Editorial EDITIORIAL COMMITTEE CHEUNG, Hon-Yeung 5 Editor-in-Chief CHEUNG, Hon-Yeung Managing Editors CHENG, Mary News & Short Communications TSANG, Warren Warning on Orally Consumed Product Containing Banned and Undeclared Western Drug 6 Secretary WONG, Johnny Ingredients Treasurer TAI, Candy Commencement Notice for the Regulation of Health Claims of Orally Consumed Products Gazette 6 Business Manager YUNG, Gloria KWAN, Wanda Alert on Aconitum Alkaloid Poisoning 6 Section Editors Recall of Allopurinol-Teva Tablets 6 Pharmacy Education & Practice CHONG, Donald Warning on Slimming Product Found with Banned Drug Ingredients 7 CHAN, Timothy Drugs & Therapeutics LEUNG, Wilson Contaminant in Drinking Water Linked to Mental Illness 7 OTC & Health CHEUUNG, Foster Recall of Two Unregistered Pharmaceutical Products 7 Pharmaceutical Techniques & Technology CHECHEUNG, HY TONG, Henry Suspension of Use of Chinese Herb Mislabeled as “FlosCampsis” 7 Herbal Medicines & Nutraceuticals CHEUNG, HY Another Three Cancer Cures Added to the Subsidized Drug List by Hospital Authority 8 Society Activities WONG, Helen New Products CHAN, Ivy Arsenic Present in Organic Brown Rice Syrup 8 PANG, Bobby Woman Arrested for Allegedly Selling a Slimming Product with Undeclared and Banned Drug 8 Representatitives from SHP LEE, Ken Ingredients EDITTORIAL ADVISORY BOARD Woman Died of Legionnaires Disease after Dental Visit 8 Prof. CHAN, Hak-Kim Prof. CHANG, Pong Recall of MylifeTMPura® Blood Glucose Strips in France 8 Prof. CHERN, Ji-Wang Prof. CHIANG, Chiao-Hsi Dr. CHING, Wei-Mei Prof. CHO, Chi-Hin Results of Hong Kong Chinese Materia Medica Standards (Phase IV) Announced 9 Prof. CHOW, SS Moses Prof. HUI, SC Sarah Import into China by Travelers or by Mail of Raw Bird’s Nest and Material Medica Derived from 9 Prof. LI, CH Paul Prof. LI, Wan-Po Alain Prof. LEE, An-Rong Dr. MORGAN, Rae M. Animals Banned Dr. TIAN, Hui Prof. YANG, Chih-Hsin David Market Boom for Generics and Biosimilar Drugs in Europe 9 Prof. O’TOOLE, Desmond K Prof. LEE, Hon-leung Vincent Total Recall of Albumex 5 and Albumex 20 Infusion 9 The Hong Kong Pharmaceutical Journal, the publisher, the editorial Coca-Cola and Pepsi Caramel Color Is Carcinogenic 10 board and the respective member societies are nootret responsible for the completeness and accuracy of the articlees and advertisements Results of Registration Examination for Pharmacists Announced 10 contained in the Hong Kong Pharmaceutical Journal. The Journal will Low-dose Hormone Combo for Menopause Symptoms Approved by FDA 10 not be liable to any damages to perpersons and properties. Readers are advised to approach the rerespective authors and advertisers for China to Help TCM Extends Global Reach 10 information in case of doubts. Lower Citalopram Dose Needed in Older Patients 11 Copyright © 2010 by Hong Kong Pharmaceutical Journal Total Recall of Carboplatin Injection (Ebewe) 11 All rights reseserved. No part of this publication or its supplement may be repeproduced or transmitted in any form or by any means, Man Arrested for Allegedly Selling Unregistered Pharmaceutical Products 11 eelectronic or mechanical, including photocopying, recording, or any Neurotoxin Found in Shark Fins 11 information storage and retrieval system, without permission in writing from the Publisher. Pharmacy Education & Practice All communications and enquiries should be directed to: Impact of Pharmacist Counseling Service on Blood Pressure Control of 12 The Secretary, Hong Kong Pharmaceutical Journal, Borderline Hypertensive Patients G.P.O. Box 3274, General Post Officece, Hong Kong LEE, Vivian WY; CHAN, Belinda MC; CHEUN, Ken TK; SO, Renwick KH; YU, CM For all enquiries regarding advertissemement, please contact: Ms Gloria Yung (Tel. 9552 24588) at the following email address: A Pilot Implementation of Decentralized and Automated Dispensing System 16 [email protected] by Omnicell – from Challenging to Benefi t Realization YUNG, Kit-Man; TAM, Ka-Ming; TSE, Pascal; WONG, Kei INSTRUCTIONS FOR AUTHORS Drugs & Therapeutics The Hong Kong Pharmaceutical Journal is a journal of the pharmacists, Immunization in Hong Kong 20 for the pharmacists and by the pharmacists. Submissions are welcome TSE, Kit-Ying; CHAN, Hoi Lam for the following sections: ‡3KDUPDF\(GXFDWLRQ 3UDFWLFH ‡'UXJV 7KHUDSHXWLFV Emergency First Aid for poisoning and for Alkaloid Poisoning in Particular 25 ‡27& +HDOWK ‡ Pharmaceutical Techniques & Technology O’Toole, Desmond Keith; CHEUNG, Hon-Yeung ‡0HGLFDWLRQ6DIHW\ ‡ +HUEDO 0HGLFLQHV  1XWUDFHHXWLFDOV ‡6RFLHW\$FWLYLWLHV ‡ 1HZ 3URGXFWV Pharmaceutical Techniques & Technology Comments on any aspects of the profession are also welcome as Letter Method Development for the Colorimetric Determination of Total Alkaloids 28 to the Editor. in Herbal Medicine There is no restriction on the length of the articles to be submubmitted. CHEUNG, Hon-Yeung; BAIBADO, Joewel Tarra; CHAN, Gallant GL; ZHANG, Zhi-feng They can be written in Englilish or Chinese. The Editorial Committee may make editorial changges to the articles but major ameam ndments will be Herbal Medicines & Nutraceuticals communicated withth the authors prior to publishinhingg. Turtle Shell Extract as a Functional Food and Its Component-based 33 It is preferferabable to have original articles submitted as an electronic file, in Comparison among Different Species Micrcrososoft Word, typed in Arial 9ptpt. Files can be sent to the following LI, Lin-Qiu; CHEUNG, Hon-Yeung address: e-mail: [email protected] Society Activities Hong Kong Pharmacy Conference 2012 38 address: G.P.O. Box No. 3274, Road Traffi c (Amendment) Ordinance 2011: Briefi ng Seminars for Transport 39 General Post Office, Trades in March 2012 Hong Kong PSHK Forensic Lectures 40 For detail instructions for authors, please refer to the first issue of each volume of HKPJ. New Products Avonex™(Biogen Idec (Hong Kong) Limited) 42 Prolia® Injection (GlaxoSmithKline)/ PRADAXA® (Boehringer Ingelheim) 44 Aims and Scope of the Journal Hong Kong Pharmaceutical Journal: For Detailed Instructions for Authors 45

Editorial

Healing a Wound with the Right Remedy and Error Free Medication

The Hong Kong Leung was representing the long wish for with the immunization schemes in Hong Pharmaceutical change from the poor, the exploited and the Kong. Indeed, there is quite a lot of free Journal has moderate reformers. In other words, it is the information and government-sponsored entered its 19th privileged and the rich verses the exploited services available for eligible people. The Volume by this and the poor. This situation is almost the authors have raised a few ideas about how year, 2012. It same in many other places and that explains pharmacists in Hong Kong could make their is a year to be why there are so many demonstrations contribution in this healthcare work. Hence, fi lled with lots and uprisings in many countries in the last it is worthwhile for all pharmacists to read of changes, couple of years because people have lost and to think about. uncertainties and their patience. maybe even Healing a disease does not simply turmoil in Hong Perhaps on a more mundane level, rely on therapeutics alone but it also Kong and elsewhere. There will be many people should ask themselves what is requires a good working spirit and political elections which will mean transition the cause of the rift between the rich and system. In the Pharmacy Education of power in many countries. One of the the poor? Was Hong Kong really in such and Practice Section of this issue, two recent hot issues in the mass media in a state of blissful equilibrium 50 years ago, working teams have thrown together their Hong Kong was defi nitely the election of when there was as much inequality and far experiences and ideas on what a good the Chief Executive (CE) of the Hong Kong worse social deprivation than today? Until medication practice would be in their daily Government SAR. Whether it was guessing the answers to some key questions are work. Lee et al. share how borderline who would be the CE aspirants or who would found, it is quite impossible to give the hypertensive patients are benefi ted win the election attracted many people’s correct remedy to the problems that by a counseling service that has been attention. From the very beginning of the people are facing. initiated by her and her associates (p12) offi cial launch of the campaign for the post of while Yung et al. share with us how a CE last October, no one would expect that the This is exactly the same when a decentralized and automated dispensing two candidates from the establishmentarian substance is to be prescribed to a patient system was designed and installed in their camp would fi ght each other so severely for treatment of a disease or for nourishing hospital. The authors commented that that from time to time someone would the body. Before it can be used, suffi cient nursing effi ciency and patient safety were unexpectedly blow the whistle in relation to background information about its biological signifi cantly enhanced since this electronic the integrity of the opponent. Certainly the effects as well as its qualitative and control system was introduced (p16). Both campaign resulted in a series of shocks to quantitative determination is necessary. articles reveal that advancement and new the whole society. But we have witnessed Without this information, it is dangerous breakthroughs could only be made if we the facts and sensed the pain not only and risky to prescribe the substance as a dare to try. Certainly, it requires everyone’s pouring upon the two candidates but also for cure. Chinese medicines have been used participation and contribution. many people involved. Lurking suspicion is for thousands of years, yet many of them always damaging between people. For the have not been systematically characterized However, like the sky that may be majority of Hong Kong citizens, we were hurt or standardized using contemporary raining sometimes, things are not always too as long as we care about the harmony methodologies. The offi cial release of right. During the last three months, we have of the society. This is probably the price for Volume IV of the Hong Kong Chinese been told of a number of malpractices during a democratic election even though it was a Materia Medica Standards announced by drug manufacturing and of illegal sales of small-circle exercise. This election reminds the Department of Health exemplifi es the products containing some unregistered us whoever wants to be a public fi gure in an concerted efforts between the Hong Kong drugs or the wrong material medica. The open society, you must be clean. Otherwise, government and scholars from six local situation of malpractice by people seems you won’t have a chance to be entrusted tertiary institutions. Although it merely covers to be deteriorating. News associated with with power. the standardization of 36 commonly used recalls or being caught doing the wrong herbs, at least these people have made thing has been frequently heard. Some Fortunately, right after the election, some contributions to the modernization of of the representative news is reprinted in Mr. LEUNG Chun-Ying, the Chief- Chinese medicines (p.9). In page 28, a more the News and Communication Section of Executive-elect, immediately declared specifi c example about the determination the current issue for readers’ reference. It that there is no more a Tang or Leung of total alkaloids in herbs is described is not diffi cult to conclude that the majority camp but only a Hong Kong camp. He by Cheung and his associates. As many of recalls were attributed to the sales of also suggested we look forward and work alkaloids have potent biological activities health products containing some banned together for Hong Kong. His speech was so while being present in minute quantities, or undeclared drug ingredients while a touching and hopefully could bring about their assays, in many cases, are quite few cases were due to some mistakes reconciliation with Mr. Henry Tang. We diffi cult. This article describes an alternative introduced during manufacturing. Whatever sincerely hope that it can be realized and easy method that could overcome the the cause, they may be harmful to the user and Mr. Leung should honor what he problem of alkaloid determination for quality and, therefore, they were ordered to be has said by taking a few steps forward to control of herbs. removed from the shelves by the authorities heal the wounds in the coming months. or on a voluntary basis by the manufacturer. Apart from the determination method, Nevertheless, let us always look forward an article in the Drugs & Therapeutics Straightly speaking, what we have and work together to build a prosperous Section on the emergency treatment seen in this CE election actually represents Hong Kong. two different approaches to the deep social of alkaloid poisoning is included in this confl ict that has spread and worsened in issue (p.25). This is a topic which we as Hong Kong in the last two decades, but we pharmacists in our daily pharmacy practice, prefer to remain blissfully unaware of what is may be asked about or come across. The going on. Mr. Tang was merely representing article on “Immunization in Hong Kong”, Cheung Hon-Yeung the extension of the current rule-by-the-rich, which was written by Tse & Chan, is quite Editor-in-Chief the tycoons and the conservatives, while Mr. informative for persons who are unfamiliar 11th April, 2012

HKPJ VOL 19 NO 1 Jan-Mar 2012 5 News & Short Communications

Warning on Orally Consumed Product Containing Banned and Undeclared Western Drug Ingredients

Date: January 11, 2012

The Department of Health (DH) mellitus admitted to hospital on 26 banned drug, phenformin. All three appealed to members of the public not December 2011 because of dizziness, drugs are hypoglycaemic agents. to buy or consume an oral product, nausea and vomiting. He had a history Improper use of hypoglycaemic agents “TangBaoKouFuYiDaoSuJiaoNang”, of consuming the above product. may cause low blood sugar, which in as it has been found to contain three Investigation found that he suffered from serious cases, can be fatal. Metformin undeclared Western drugs, one hypoglycemia and renal failure. The and glibenclamide are prescription of which is a banned item in Hong patient was treated and discharged on drugs, meaning that they should be used Kong. The product is not a registered 30 December 2011. under medical supervision. Phenformin, pharmaceutical product or a registered because of the possibility of causing proprietary Chinese medicine in Hong Results from the Government fatal lactic acidosis, has already been Kong. The appeal followed DH’s receipt Laboratory revealed that the product banned in Hong Kong since 1985. of notifi cation from the Hospital Authority contained the Western medicines about a 69-year-old man with diabetes metformin and glibenclamide, and a Source: www.chp.gov.hk

Commencement Notice for the Regulation of Health Claims of Orally Consumed Products Gazette

Date: January 13, 2012

The Secretary for Food and Health makes proposes to commence the extension of of protecting public health through notice to commence the provisions the prohibition/ restriction on advertising prohibiting/restricting advertisements related to the control of health claims orally consumed products for six groups which may induce the seeking of of orally consumed products under the of health claims from June 1, 2012. The improper management of certain health Undesirable Medical Advertisements Undesirable Medical Advertisements conditions. (Amendment) Ordinance 2005. The Ordinance (Cap 231) (UMAO) was Notice is gazetted today (January 13). It fi rst enacted in 1953 with the purpose Source: www.chp.gov.hk

Alert on Aconitum Alkaloid Poisoning

Date: January 13, 2012

It was reported that on December went to the Mainland on the same day prescribed by a registered Chinese 28, 2011, a 35-year-old Chinese and subsequently sought emergency medicine practitioner stationed in Po male developed symptoms and signs care from United Christian Hospital on Yan Tong Medical Company, a licensed Chinese herbal retailer in Sai Wan before compatible with aconitum alkaloid December 30. It was reported that the developing the symptoms. poisoning, including perioral numbness, man had consumed some Chinese shortness of breath and palpitations. He herbal medicines for health maintenance Source: www.chp.gov.hk

Recall of Allopurinol-Teva Tablets

Date: January 16, 2012

A batch of Allopurinol-Teva Tablets 100mg no fungal elements were found. The of tablets. The affected batch was (registration number: HK-57739; batch report from the Government Laboratory manufactured by Teva Pharmaceutical number: 1580211) has been withdrawn revealed that the black substances, Works Private Ltd Co. in Hungary. A total of 22,965 boxes had been imported into from the shelf on quality grounds as which adhered on the surfaces of some Hong Kong and were supplied to HA, black substances were found on some tablets, bear similar features as used local pharmacies and private doctors. tablets in two blisters of the product. hydrocarbon oil.Hydrocarbon oil might Offi cial investigation results showed that be used in equipment for the production Source: www.chp.gov.hk

HKPJ VOL 19 NO 1 Jan-Mar 2012 6 Warning on Slimming Product Found with Banned Drug Ingredients

Date: January 19, 2012

Through its surveillance network, DH poison and was once a western medicine drug. It was used previously for treating found the slimming product named used as an appetite suppressant. Since constipation, but has been banned for its “FAT 2 AND 1 BURNERS III” offered November 2010, products containing cancer-causing effect.The spokesman of DH Department urged people not again for sale on the Internet.The sibutramine have been banned by the to purchase products of unknown or Government Laboratory confi rmed that Pharmacy and Poisons Board because doubtful composition. the product contained sibutramine and of the increased cardiovascular risk. phenolphthalein. Sibutramine is a Part I Phenolphthalein is another banned Source: www.chp.gov.hk

Contaminant in Drinking Water Linked to Mental Illness

Date: January 30, 2012

Exposure to tetrachloroethylene (PCE) lipophilic tissues in the central nervous of certain psychiatric illnesses, particularly has been shown to cause mood changes, system. A study published recently online bipolar disorder, post-traumatic stress anxiety and depression in people who in Environmental Health reveals that disorder and schizophrenia. work with it. PCE readily crosses the blood- prenatal and early childhood exposure to brain barrier and has a high affi nity for the the organic solvent, PCE may raise the risk Source: www.medscape.com

Recall of Two Unregistered Pharmaceutical Products

Date: February 1, 2012

Allways (Germany) Medicine Ltd. Allways upon the DH’s investigation into a public pharmaceutical product trader.According was instructed by the Department of enquiry about the products. to information obtained so far, Allways had Health (DH) to recall from the consumers not authorized any person to import and two unregistered pharmaceutical products Investigation reveals that Allways sell Centiplex B-Tab and Abacod Cod Liver namely Centiplex-B Tab (HK-58444) and is the product registration certifi cate Oil Cap 300’s. Allways imported unlabeled Abacod Cod Liver Oil Cap (HK-59342, holder of the two products. However, the cod liver oil cap 100’s and transferred them 100’s and 300’s) as the products bear two unregistered products were sold to to W&S. unapproved labels and render them local pharmacies by W&S International unregistered. The matter came to light Medicine Ltd (W&S) which is an unlicensed Source: www.chp.gov.hk

Suspension of Use of Chinese Herb Mislabeled as “FlosCampsis”

Date: February 3, 2012

The Department of Health (DH) The precautionary alert is considered developed some symptoms compatible appealed to the public who have bought indicated as the latter is a known with anti-cholinergic poisoning, including the Chinese herb “FlosCampsis” from a poisonous herb. palpitations and dilated pupils, after licensed retailer, Cheong Kee Medicine taking herbal medicines including Co in Yen Chow Street, Sham Shui Po, The suspicion arises as the DH “FlosCampsis” purchased from the to stop using the product immediately investigates a suspected Chinese above retailer. The patient’s condition as mislabelling might have occurred, herbal poisoning incident notifi ed by stabilized after hospital treatment. such that what was dispensed could Queen Elizabeth Hospital earlier on be another herb, FlosDaturaeMetelis. today. A 27-year-old Chinese male Source: www.chp.gov.hk

HKPJ VOL 19 NO 1 Jan-Mar 2012 7 Another Three Cancer Cures Added to the Subsidized Drug List by Hospital Authority

Date: February 9, 2012

The Hospital Authority expanded its In future, the patients need not pay for expected to benefi t after the drug list is drug list, adding three drugs used for the drugs on their own. Mr Cheung Wai- expanded. treating rectal cancer, multiple sclerosis, lun, Director of Cluster Services, Hospital pancreatic cancer and bladder cancer. Authority, said that 23,000 patients are Source: Sing Tao Daily

Arsenic Present in Organic Brown Rice Syrup

Date: February 16, 2012

Organic brown rice syrup, a sweetener containing the syrup and compared water with a certain level of arsenic, used in many organic foods including them with other similar products without consumers should be cautious and cereal bars and baby formulas, may be the sweeteners. They found that the reduce their exposure to these items as a hidden source of arsenic, according to former contained arsenic levels 20 times much as they can. a new study published in Environmental greater than the later. Because the risk Health Perspectives. Dartmouth College of certain cancers or heart disease are Source: http://www.nlm.nih.gov/ researchers tested commercial products said to be slightly elevated in drinking medlineplus/news/fullstory_122036.html

Woman Arrested for Allegedly Selling a Slimming Product with Undeclared and Banned Drug Ingredients

Date: February 17, 2012

A 30-year-old woman was arrested in a slimming product with undeclared and an Internet auction website during DH’s a joint operation by the Police and the banned drug ingredients. The operation surveillance operation, were found to Department of Health (DH) at Sham Shui followed laboratory test fi ndings today contain sibutramine, phenolphthalein. Po for suspected illegal sale of one box of that revealed that the slimming product, Lexscl Fat Rapid Loss Capsule, which is which had been obtained earlier from Source: www.chp.gov.hk

Woman Died of Legionnaires Disease after Dental Visit

Date: February 17, 2012

An Italian woman is dead after having dentist’s offi ce. Testing on the woman’s quickly developed septic shock and died dental surgery and contracting home and the dental offi ce showed that two days after her diagnosis. This is the fi rst reported case of legionnaire infection the infection came from the dentist’s offi ce Legionnaires’ disease, also known as via medical service. Legionellosis.The woman, who was 82, water supply. Despite treatment with contracted Legionnaires’ disease at her Cipro, a powerful antibiotic, the woman Source: www.abcnews.go.com › Health

Recall of MylifeTMPura® Blood Glucose Strips in France

Date: February 22, 2012

The Department of Health (DH) drew the Agence Française de Sécurité Sanitaire distributor in France to the pharmacies. public’s attention to the recall of certain des Produits de Santé (AFSSAPS) As the test strips are very sensitive lots of a blood glucose test strips in France. about the recall. According to AFSSAPS, towards air exposure, they may lose The affected product is MylifeTMPura® the problem came to their notice when their performance, giving falsely high (box of 100’s) manufactured by Bionime several reports of overestimation of readings. The manufacturer has since Corporation. The test strips may give blood glucose levels were received. falsely high blood glucose readings. Further investigation revealed that the then, taken preventive action by sealing problem was due to the accidental all the vials with a protective fi lm. DH was informed by the French opening of the unsealed vials of the medical device regulatory authority, test strips during transportation from the Source: www.chp.gov.hk

HKPJ VOL 19 NO 1 Jan-Mar 2012 8 Results of Hong Kong Chinese Materia Medica Standards (Phase IV) Announced

Date: February 23, 2012

The Department of Health (DH) offi cially Herba, Cnidii Fructus, Corni Fructus, Fructus, Schizonepetae Spica, launched the reference standards on Corydalis Rhizoma, Curculiginis Rhizoma, Scrophulariae Radix, Scutellariae safety and quality for 36 commonly used Curcumae Longae Rhizoma, Dictamni Barbatae Herba, Smilacis Glabrae Chinese Materia Medica (CMM) in Phase Cortex, Ecliptae Herba, Fritillariae Rhizoma, Sophorae Flavescentis Radix IV of the Hong Kong Chinese Materia Hupehensis Bulbus, Houttuyniae and Stephaniae Tetrandrae Radix. Medica Standards (HKCMMS). Herba, Hydrargyri Oxydum Rubrum, The standards for these 36 CMMs Hydrargyrum Chloratum Compositum, will be put into use for a trial period of The 36 herbs are Arctii Fructus, Isatidis Folium, Isatidis Radix, Orpiment, 12 months, starting from April 2012, upon Arsenicum, Arsenolite, Artemisiae Peucedani Decursivi Radix, Peucedani completion of all briefi ng sessions for Annuae Herba, Atractylodis Rhizoma, Radix, Polygoni Cuspidati Rhizoma et traders and laboratories. Aurantii Fructus, Aurantii Fructus Immaturus, Radix, Realgar, Schisandrae Chinensis Calomelas, Cinnabaris, Cistanches Fructus, Schisandrae Sphenantherae Source: www.chp.gov.hk

Import into China by Travelers or by Mail of Raw Bird’s Nest and Material Medica Derived from Animals Banned

Date: February 27, 2012

CUBILOSE, a type of bird’s nest issued by the Ministry of Agriculture and previous list issued in 1992, the new list considered a delicacy in China, cannot be the General Administration of Quality has a broader range of banned products, brought in by travelers or mailed into the Supervision, Inspection and Quarantine, such as leaf tobacco and genetically modifi ed food. country, according to a newly amended has 16 categories of banned animal list of prohibited items. The list, jointly and plant products. Compared with the Source: Ming Po

Market Boom for Generics and Biosimilar Drugs in Europe

Date: March 1, 2012

According to Frost & Sullivan’s report, to carefully consider their product million in 2017, with the industry growing Generic Pharmaceuticals Market — segments and the appropriate time for at a compound annual growth rate of A Global Analysis, pharmaceutical market launch. Companies will also have approximately 56.7%. According to products worth $150 billion will go off to deal with increasingly harsher cost Frost & Sullivan’s Analysis of European patent between 2010 and 2017, which cutting measures from governments and Biosimilars Market report, impending patent expiries are expected to provide will propel the generic-drugs market healthcare service providers. impetus to the market development of from revenues of $123.85 billion in 2010 several new biosimilars. to an estimated $231 billion by 2017. The global biosimilars market earned However, as competition intensifi es, revenues of around $172 million in 2010, Source: Pharmaceutical Technology generic drug manufacturers will need but this is estimated to jump to $3987 Europe, Vol. 24(3)

Total Recall of Albumex 5 and Albumex 20 Infusion

Date: March 8, 2012

A licensed drug wholesaler, Hong Kong a follow up investigation of a small leak temperature during the manufacturing Red Cross Blood Transfusion Service of ethylene glycol (in late January 2012) process. Toxic effects of ethylene glycol (HK Red Cross), was told to recall in a pasteurization vessel used in the include CNS effects similar to ethanol, all Albumex 5 Infusion 12.5g/250ml manufacture of the products. anion gap metabolic acidosis, and acute (HK-58570) and Albumex 20 Infusion renal failure. Toxicity due to ethylene 10g/50ml (HK-58571), due to quality Albumex 5 Infusion and Albumex 20 glycol occurs acutely and delayed effects issue. DH received notifi cation from Infusion, containing human albumin, are beyond 72 hours would not be expected. the HK Red Cross that they were used for shock or in plasma exchange. Safety assessment of the products is informed by the product manufacturer They can only be sold on prescription being investigated by the Australian in Australia, CSL Limited, that some and under the supervision of pharmacists regulatory authority. of the Albumex products were found at registered pharmacies. Ethylene contaminated with ethylene glycol after glycol is a substance used to control Source: www.chp.gov.hk

HKPJ VOL 19 NO 1 Jan-Mar 2012 9 Coca-Cola and Pepsi Caramel Color Is Carcinogenic

Date: March 10, 2012

High levels of a chemical that causes Pepsi and is part of caramel coloring 4-Methylimidazole (4-MI) is used tumors in animals were found in Coca- used in the beverages, according to in a various processes, including Cola Co. and Pepsi Co. Inc. sodas, a study released on March 5 by the manufacturing of dyes, pharmaceuticals, according to a consumer advocacy Center for Science in the Public Interest. and rubber, as well as a byproduct of group pressing U.S. regulators to The group petitioned the U.S. Food and food fermentation. ban a color additive.The chemical Drug Administration in February to ban 4-methylimidazole was found in Coca- the ammonia-sulfi te coloring, which is Source: www.businessweek.com/ Cola, Pepsi Cola, Diet Coke and Diet found in most colas. news/2012-03-05/

Results of Registration Examination for Pharmacists Announced

Date: March 12, 2012

The Pharmacy and Poisons Board of respectively, with corresponding passing pharmacist in Hong Kong is required Hong Kong announced today (March rates of 39 per cent, 88.2 per cent and to pass the above three subjects. 12) the results of the Pharmacists 8.9 per cent. The Board conducts its Registration Registration Examination held in Examination twice a year, normally in December 2011.There were 82, 76 and In addition to meeting other 90 candidates sitting for examinations in requirements prescribed by the Board, June and December. “Pharmacy Legislation in Hong Kong”, any pharmacy graduate outside Hong “Pharmacy Practice” and “Pharmacology” Kong intending to be registered as a Source: www.chp.gov.hk

Low-dose Hormone Combo for Menopause Symptoms Approved by FDA

Date: March 12, 2012

The FDA has approved 0.25-mg and vaginal atrophy in menopausal combo had a statistically signifi cant drospirenone/0.5-mg estradiol, a low- women. Approval was based on reduction in frequency and severity of dose hormone combo to treat moderate fi ndings from a randomized trial, which the symptoms. to severe hot fl ashes, night sweats and showed that compared with women moderate to severe symptoms of vulvar receiving placebo, those receiving the Source: Medscape.com

China to Help TCM Extends Global Reach

Date: March 14, 2012

China plans to open more Confucius date, there are more than 350 Confucius States. On June 20, Vice-President Xi Institutes to teach traditional Chinese Institutes and 500 Confucius Classrooms Jinping inaugurated the TCM Confucius medicine overseas and promote the in 101 countries and regions, offi cial Institute in Melbourne, saying it opened Eastern medical science, Deputy statistics showed. a new window for foreigners to learn Minister of Health Wang Guoqiang said about Chinese culture. At present, on March 12. Two Confucius Institutes are specially such institutes are committed mainly dedicated to teaching TCM - at the Royal to spreading Chinese culture, with a “TCM, particularly its preventive Melbourne Institute of Technology in focus on TCM, rather than training TCM aspect, is very well received abroad, Melbourne, Australia, and London South doctors, Wang said. regardless of nationality or ideology,” Bank University. Source reveals that the Wang told China Daily in an interview.To third institute is being setup in the United Source: China Daily/Asia News Network

HKPJ VOL 19 NO 1 Jan-Mar 2012 10 Lower Citalopram Dose Needed in Older Patients

Date: March 28, 2012

The use of normal dosage of a selective the maximum recommended dose or another CYP2C19 inhibitor, because serotonin reuptake inhibitor, Citalopram citalopram is 20 mg per day for patients these factors lead to increased blood (Celexa, Forest Laboratories) is with hepatic impairment, patients who levels of citalopram, increasing the risk for QT interval prolongation and torsades discouraged in patients with certain are older than 60 years, patients are de pointes. conditions because of the risk of CYP2C19 poor metabolizers, or patients QT prolongation. FDA warns that who are taking concomitant cimetidine Source: www.medscape.com

Total Recall of Carboplatin Injection (Ebewe)

Date: March 29, 2012

The Department of Health (DH) supervision of pharmacists at registered the precipitates were likely from today endorsed the recall of Novartis dispensaries. either the active drug ingredient or Pharmaceutical (HK) (Novartis), a its degradation produce. Further, licensed drug wholsaler, of all batches Novartis notifi ed that the above preliminary assessment indicated that of its Carboplatin 10mg/ml Injection product’s Austrian manufacturer, the precipitates were probably results of (Ebewe) (registration no: HK-43913) EbewePharma, decided to recall the stability issues, although the root cause from shelf as part of a multinational effort product as a precautionary measure to curb quality failure in the product. because precipitates were identifi ed in remained to be identifi ed. Carboplatin injection is indicated for the several batches of samples retained treatment of various cancers. It can only routinely as part of good manufacturing Source: www.dh.gov.hk/english/ be sold on prescription and under the practice. According to EbewePharma, press/2012/120329-2.html

Man Arrested for Allegedly Selling Unregistered Pharmaceutical Products

Date: March 30, 2012

A 53-year-old man was arrested in a fi ndings that revealed that the cold and high dosage may result in liver damage. joint operation by the Police and the fl u medicine, which had been obtained Sale of an unregistered pharmaceutical Department of Health (DH) at Mongkok for earlier from an Internet auction website product is offence under the Pharmacy and Poisons Ordinance. The maximum suspected illegal sale of two boxes of cold during DH’s surveillance operation, was penalty is a fi ne of $100,000 and two and fl u medicine manufactured by Taisho found to contain paracetamol, which is years’ imprisonment. Pharmaceutical Co., Ltd., which were a western medicine and is used for the unregistered pharmaceutical products. management of pain and fever. Although Source: www.dh.gov.hk/english/ The operation followed laboratory test the side effects are usually mild, taken in press/2012/120330-2.html

Neurotoxin Found in Shark Fins

Date: March 30, 2012

A study conducted by Dr. Deborah is a cause of concern as it may link to threat to people who are having long term C. Mash revealed that high amount neurodegenerative diseases, including exposure to it in fresh water systems. The of a neurotoxin, β-N-methylamino-L- Alzheimer’s disease, amyotrophic toxin can be bioaccumulated in nerve cell alanine (BMAA), was found fi n clips lateral sclerosis (ALS) and parkinsonism and causes neurodegeneration. from sharks in Florida waters.The dementia. BMAA, which is produced by concentration of BMAA in the shark fi ns cyanobactreria (a blue green algae), is a Source: Medscape.com

HKPJ VOL 19 NO 1 Jan-Mar 2012 11 Pharmacy Education & Practice

Impact of Pharmacist Counseling Service on Blood Pressure Control of Borderline Hypertensive Patients

LEE, Vivian WYa*; CHAN, Belinda MCa*; CHEUN, Ken TKa*; SO, Renwick KHa*; YU, CMb a School of Pharmacy, Faculty of Medicine, Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China b Division of Cardiology, Department of Medicine and Therapeutics, Faculty of Medicine, Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China (* Corresponding author)

ABSTRACT could help them manage their health followed.(4) Therefore, patients’ problems. They generally agreed knowledge and awareness of Objective: To investigate the clinical pharmacist had the best role for drug hypertension play important roles impact of pharmacist counseling counseling. Conclusion: Patients to achieve successful BP control. It service in borderline hypertensive with borderline hypertension may not is essential for patients to receive patients. Methodology: This was a be sensitive to pharmacist counseling clear information about both the 9-month, open, prospective trial. service for blood pressure control. risks associated with uncontrolled Borderline hypertensive patients However, pharmacist interventions hypertension, and the benefi ts expected attending the outpatient hypertension signifi cantly improved drug from anti-hypertensive treatments and clinic were recruited in this study. compliance. Most patients welcomed therapeutic lifestyle changes. Possible They were assigned to meet the pharmacy service in the management drug-related adverse effects also pharmacists before usual physician of hypertension. have to be explained. Physicians, with consultation. Enrolled patients no doubt, should be involved in this received hypertension education, Keywords: borderline hypertension, educational process. However, they drug compliance checking and clinical pharmacy, patient counseling and may not have enough time in the busy lifestyle modifi cation during two compliance outpatient setting. In fact, patient face-to-face interview sessions. A management time constraint has been telephone follow up was arranged in identifi ed to be one of the barriers to between the interviews. At the end INTRODUCTION the effective management of patients of the study, mean blood pressure with uncontrolled hypertension.(5) This is was compared with baseline as Hypertension is one of the most particularly true in the busy outpatient the primary outcome. Secondary prevalent chronic diseases worldwide.(1) setting in Hong Kong with such a large outcomes included compliance rate, Inadequate control of hypertension can patient load. Pharmacists, as drug drug-related problems identifi ed and lead to many complications including professionals, are thus in a very good pharmacist interventions provided cardiovascular, renal and optical position to help optimize BP control in the study. Patient satisfaction was diseases.(1) However, many patients by providing patient education and also surveyed. Results: After 9 month are not aware of hypertension since it enhancing drug compliance. Various study period, 47 patients completed is asymptomatic before complication studies demonstrated that clinical the study. Mean systolic and diastolic manifestations. In Hong Kong, about pharmacy services can have a signifi cant blood pressure declined by 2.81 20% of adults are hypertensive,(2) and a impact on compliance and patient mmHg and 1.94 mmHg respectively. study conducted locally showed about satisfaction, and thus on drug therapy The results were not statistically 75% of hypertensive patients had outcomes.(6-15) The objective of our study signifi cant when compared with inadequate blood pressure (BP) control was to investigate the clinical impact of the baseline blood pressure. (>140/90mmHg).(2) pharmacist counseling service among Percentage of patients achieving the borderline hypertensive patients. blood pressure goal was 39% with Noncompliance with prescribed statistically signifi cance (p <0.05). antihypertensive regimens has been The mean compliance rate was known to be one of the reasons of METHODOLOGY increased from baseline 83.16 ± suboptimal BP control.(3) The most 30.52% to 93.44 ± 18.38% at the signifi cant factors in noncompliance are It was a 9-month, prospective, open- end of study (p=0.017). A total a lack of knowledge about prescribed labeled study conducted in the outpatient of 588 pharmacist interventions drugs and their side effects, and a lack of hypertension clinic at the Prince of Wales were made. Most patients agreed understanding about the consequences Hospital (PWH) from August 2008 to pharmacist service was useful and if a prescribed drug regimen is not May 2009. Eligible subjects were under

HKPJ VOL 19 NO 1 Jan-Mar 2012 12 the usual physician follow ups in addition Patients were interviewed twice second follow up. Pharmacists mainly to counseling service by pharmacists. (assuming a 3-4 month separation focused on problems identifi ed in the Patients were eligible in the study if between follow-ups) by pharmacists previous visit or provided advice in case 1) they were diagnosed with essential during the study period. In each of drug-related queries arose. A checklist hypertension with borderline BP control follow up, patients were seen by the was used to make sure important and in 2 consecutive clinic visits during the pharmacists prior to physicians. Blood necessary areas were covered in the past 6 months (defi ned as systolic BP pressure measurement was done by telephone follow-up. At the end of the 140-150 mmHg and/or diastolic BP 90- the trained healthcare assistants before study, patients received a satisfaction 100 mmHg in 2 visit records, or one clinic the interview with automatic BP monitor survey to assess their satisfaction on this visit with controlled BP [<140/90] while (Manufacturer: A&D; Model: TM-2655P). clinical pharmacist service.(16) the other with uncontrolled BP [>140/90]) During the interview, pharmacists and, 2) they were receiving one or more assessed their drug compliance, Demographic data including age, antihypertensive drugs and followed educated on lifestyle changes (benefi ts gender, history of hypertension, anti- up regularly at the hypertension clinic of exercises, diet modifi cation, home BP hypertensive regimens, and baseline for at least 6 months. Patients were monitoring, and smoking cessation) and BP were collected. The primary outcome excluded if they were under 18 years old, evaluated if there was any side effect was the absolute BP change between the pregnant, were not able to communicate related to the patients’ drug regimen. BP measured before and after the study verbally, had secondary hypertension Brief information about hypertension period. Secondary outcomes included with underlying causes, hypertensive including BP goal, complications of the mean difference in compliance rate emergency, diabetes mellitus, or were uncontrolled hypertension, benefi t and any potential drug-related problems enrolled in other clinical trials. of BP decrease and the associated identifi ed, pharmaceutical interventions cardiovascular disease risk modifi cation made as well as patient’s satisfaction During the recruitment period, were discussed. Educational leafl ets towards our service would also be pharmacists were provided with the published by the Hospital Authority documented. patients’ list one week prior to the follow about hypertension were also provided. up dates by the head nurse. Eligible Leafl ets covered classifi cation and Blood pressure change throughout patients were invited to participate defi nition of hypertension, hypertension- the study was analyzed by Student’s in the study when they attended the related complications, drug treatment paired t-test. Proportion of patients hypertension clinic before they met the options and their potential side effects. achieving the JNC7 BP goal was physician. Demographic data included analyzed by McNemar test (used for age, gender, past medical history, history Any observed drug-related paired proportions). Compliance rate of hypertension, anti-hypertensive problems were documented. During difference, which was not usually regimen, baseline BP were collected from the assessment, patient’s compliance normally distributed, was analyzed by medical charts or the Hospital Authority’s on each drug was evaluated. The Wilcoxon test. Descriptive statistics was Clinical Management System (CMS). pharmacist asked the patients to used to describe identifi ed drug-related All patients’ data were recorded on an describe their regimens by drug dosages problems, pharmacist interventions and individual patient assessment form. Other (number of pills), frequencies (number patient satisfaction survey. Statistical relevant informations such as laboratory of doses), and number of pills taken signifi cance was taken at the 5% level data, social history, readings of home BP measurement and concomitant use of at different times of the day. Patients and the test was two-tailed. Data would over-the-counter medications and herbal were asked whether they had missed be analyzed using SPSS version 17 agents were recorded. Each pharmacist any dosage, changed their regimens in (Chicago, USA). who participated in the study followed terms of doses, frequency and timing, a standardized protocol throughout or had drugs left over. We defi ned the study to ensure consistency of patients as compliant with a drug if they RESULTS interventions and services provided to remembered their prescribed regimen each patient. All pharmacist interventions correctly and complied with it for at least A total of 67 patients were enrolled in (17) performed were documented. 80% of time. Their overall compliance the study. However, 20 patients dropped rate was calculated as the total number out from the study due to lost to follow We used comparative method on the of prescribed hypertensive drugs divided up; the date of second follow up was not same group of patients on their baseline by the number of hypertensive drugs within the study period; patients were and fi nal BP. The result was paired to that the patient was compliant with and referred to another clinic, excluded due each other and pair t-test was used to was expressed as a percentage.(17) For to diagnosis of diabetes on the day of fi rst estimate sample size. We assumed the example, a patient who complied with all interview, and passed away. Therefore, mean difference of decrease in BP to be prescribed drugs had a compliance score 47 patients completed the study. The 10 mmHg, and the standard deviation to of 100%, while one complied with only mean age was 60.45 ± 13.73 years old. be 20 mmHg based on previous study two out of four drugs had a compliance Over 60% of them were males. The study conducted locally.(16) The number of score of 50%. cohort was on an average of 2.19 ± 0.97 patients to be enrolled was estimated types of hypertension medications. The on the basis of statistical power of 90% In the second follow up, pharmacists mean baseline systolic and diastolic (β=0.1), with an error of 5% (α= 0.05). As followed up on any drug-related problems blood pressures were 138.28 ± 18.26 a result, 44 patients were targeted based identifi ed previously. A telephone follow mmHg and 78.15 ± 12.15 mmHg on the sample size calculation tool.(17) up was conducted in between the fi rst and respectively. Baseline compliance

HKPJ VOL 19 NO 1 Jan-Mar 2012 13 rate was 83.16 ± 30.52 %. The 4 most patients’ satisfaction survey performed uncontrolled hypertension.(4,14,19) In commonly prescribed blood pressure during the last follow up, patients were contrast, our patients had a relatively lowering medications were beta-blocker satisfi ed with our service and had positive stable and controlled disease state. (66%), calcium channel blockers feedbacks (Table 2). They mostly agreed Fifty-one percent of subjects had (44.0%), angiotensin converting enzyme that the pharmacist was the most suitable achieved controlled hypertension at inhibitor (ACEI) (36.2%) and diuretics person to provide drug counseling. the fi rst interview. Therefore, the effect (36.2%). Others included angiotensin of pharmacist intervention was not as receptor blocker (ARB) (14.9%), alpha- prominent as compared to other overseas blocker (14.9%), methyldopa (6.4%) and DISCUSSION studies. We therefore performed a hydralazine (4.3%). subgroup analysis in patients who were Studies demonstrated that additional not at BP goal at the fi rst interview. At the end of the study, the mean clinical pharmacy service can improve In these patients, our pharmaceutical reductions in SBP and DBP were 2.81 disease outcomes in hypertension.(6-11) service was able to achieve a signifi cant ± 18.17 mmHg and 1.94 ± 10.07 mmHg However, patients who received reduction of 11.96 mmHg and 4.91 mmHg respectively. Both of them did not show additional care by pharmacists in this in SBP and DBP, respectively. The result statistical difference (p > 0.05). However, study did not achieve a better BP control. was comparable to the overseas studies. when we excluded the patients who However, our fi ndings did not show the The BP reduction achieved was clinically initially presented with controlled BP clinical signifi cance in the management meaningful, as a 10 mmHg reduction (SBP<140 mmHg and DBP<90 mmHg) of borderline hypertensive patients. in SBP was able to achieve 36% lower in the fi rst interview and performed a Borderline hypertension is not usually stroke risk, 24% lower ischemic heart subgroup analysis to investigate the BP attended when compared with stage disease risk in Asian hypertension difference, the results were statistically patients.(20) After the study period, our signifi cant (p < 0.05). The mean reductions 1 and 2 hypertension classes. Other in SBP and DBP were 11.96 ± 16.94 pharmacist-involved hypertension intervention helped 39.1% of these (21) mmHg (p = 0.003) and 4.91 ± 11.05 programs showed positive results patients to achieve the JNC VII BP goal. mmHg (p = 0.044) respectively. In were mainly focused on patients with In our previously published data, the addition, among the patients not at goal in the fi rst interview, 39.1% of them (9 out Table 2. Patient satisfaction summary of 23) were able to achieve the JNC VII Questions N (%) goal after our study period (p=0.004). In (total 48) addition, the mean compliance rate was 1. Overall, are you satisfi ed with pharmacist counseling? increased from baseline 83.16 ± 30.52% Very satisfi ed 15 (31) to 93.44 ± 18.38% at the end of study Satisfi ed 32 (67) No comment 1 (2) (p=0.017). A number of drug related Dissatisfi ed 0 problems were identifi ed and a total of Very dissatisfi ed 0 588 interventions were done (Table 1). 2. Do you understand drug and disease knowledge educated by the pharmacist? Completely understood 22 (46) The most common problem identifi ed Mostly understood 25 (52) was related to adverse drug reactions. Understood half of the content 0 Patients were reminded to discuss with Mostly not understood 1 (2) Totally not understood 0 physicians regarding such potential 3. Do you think pharmacist education is useful? adverse drug reactions. According to the Very useful 15 (31) Useful 31 (65) No comment 2 (4) Table 1. Summary of pharmacist interventions Very un-useful 0 Totally un-useful 0 Pharmacist intervention N (%) 4. Do you agree pharmacists can help you better manage your health problems? Possible adverse drug reaction Totally agree 10 (21) ♦ identifi cation and advice given 18 (3.1) Agree 32 (67) ♦ referral to doctor 8 (1.4) No comment 5 (10) Disagree 1 (2) Drug compliance Totally disagree 0 ♦ compliance assessment 134 (22.8) ♦ correct the compliance 64 (10.9) 5. Would you like to spend more time to receive counseling from pharmacists? Strongly willing 11 (23) Lifestyle modifi cation Willing 27 (56) ♦ diet 68 (11.6) No comment 8 (17) ♦ exercise 68 (11.6) Unwilling 2 (4) ♦ smoking cessation/alcohol 69 (11.7) Totally unwilling 0 consumption 6. Do you agree such pharmacist service be promoted to other patients with hypertension? Education Totally agree 16 (33) ♦ drug knowledge 76 (12.9) Agree 30 (63) ♦ disease knowledge 67 (11.4) No comment 2 (4) Drug interactions Disagree 0 ♦ drug/herb interactions 3 Totally disagree 0 ♦ drug/drug interactions 5 7. Do you agree pharmacist has the best role to provide drug counseling? Pharmacotherapy suggestion Totally agree 17 (35) ♦ duplication of drug class identifi ed 3 Agree 27 (57) ♦ dosage choice/drug dosage 5 No comment 4 (3) recommendation Disagree 0 Total 588 Totally disagree 0

HKPJ VOL 19 NO 1 Jan-Mar 2012 14 incidence of cardiovascular events in Author’s background 13. Borenstein JE, Graber G, Saltiel E, et al. patients with inadequately controlled LEE, Wing Yan Vivian is currently Associate (2003). Physician-pharmacist comanagement hypertension was positively related to Professor in the School of Pharmacy and of hypertension: a randomized, comparative the extent and duration of BP deviation Assistant Dean (Student Affairs), Faculty of trial. Pharmacotherapy, 23(2):209-216. Medicine, Chinese University of Hong Kong. from treatment goals. Furthermore, Both CHAN, Belinda MC and CHEUNG 14. McConnell KJ, Zadvomy EB, Hardy AM, pharmacist counseling services helped Ken TK are pharmacists at the Department et al. (2006). Coronary artery disease and patients to achieve a better compliance of Health of Hong Kong. SO, Renwick KH hypertension: outcomes of a pharmacist- managed blood pressure program. rate of 93.44% from a baseline of 83.16% is currently a pharmacist at the Prince of Wale’s Hospital, Hospital Authority, Hong Pharmacotherapy, 26(9):1333-1341. (p=0.017). Compliance was believed Kong. YU, CM is currently Professor and 15. Erickson SR, Slaughter R, Halapy H (1997). to be one of the causes for resistant Head of the department of medicine and Pharmacists’ ability to infl uence outcomes (21) therapeutics and Assistant Dean (External hypertension. In the current study, the of hypertension therapy. Pharmacotherapy, Affairs), Faculty of Medicine, Chinese 17(1):140-147. most commonly prescribed drug class University of Hong Kong. At the time of this was beta-blockers. First line treatment study, Ms. Belinda M.C. Chan, Mr. Ken T.K. 16. Winnie Chan Kit Yu (2007). A study of for hypertension recommended by the Cheung, and Mr. Renwick K.H. So were Pharmacist’s Impact on the Blood Pressure JNC VII guidelines and the ALLHAT students of the Master of Clinical Pharmacy Control in Patients with Uncontrolled Programme, School of Pharmacy, CUHK. Hypertension. Paper presented and published (23) study was thiazide diuretic. Calcium Corresponding author’s email address is at School of Pharmacy, Chinese University of channel blockers and ACEI are [email protected]. Hong Kong. (24) preferred treatments in the ANBP-2 17. Sample size calculation. http://department. and ASCOT-BPLA.(25) obg.cuhk.edu.hk/researchsupport/Sample_ References size_CompMeanIndependent.asp [accessed May 11, 2009] There were a number of limitations 1. Kearney PM, Whelton M, Reynolds K, et in our study. Firstly, small sample size al. (2005). Global Burden of Hypertension: 18. Wu JYF, Leung WYS, Chang S, et al. (2006). Analysis of Worldwide Data. Lancet, Effectiveness of telephone counseling by a 365: 217-223. was due to high dropout rate. Future pharmacist in reducing mortality in patients studies involving a greater sample size 2. Cheung BM, Law FC, Lau CP (2002). The receiving polypharmacy: randomized might be necessary to draw a signifi cant rule of halves applies in Chinese hypertensive controlled trial. British Medical Journal, result of pharmacist counseling service patients. Am J Hypertens, 15:209A. (333):522. on BP control. Secondly, the current 3. Burt VL, Whelton P, Roccella EJ, et al. 19. Paul E. Bogden, Robert D. Abbott, Pam (1995). Prevalence of hypertension in the study has no control group to perform Williamson et al. (1998). Comparing standard U.S. population: results from the third national care with a physician and pharmacist team unpaired analysis. Thirdly, the long health and nutrition examination survey, 1988- approach for uncontrolled hypertension. J Gen 1991. Hypertension, 25:305-313. term impact of pharmacist intervention Intern Med, 13:740–745. 4. Vivian EM (2002). Improving blood pressure cannot be observed due to a short study 20. Lawes CM (2003). Blood pressure control in a pharmacist-managed hypertension period. It usually takes a few years for clinic. Pharmacotherapy, 22(12):1533-1540. and cardiovascular disease in the Asia patients with uncontrolled hypertension Pacifi c region. J Hypertens. 21(4): 5. Susan A, Pablo Lapuerta, Bruce D, et al. 673-675. to develop complications such as stroke (2002). Physician-Related Barriers to the or myocardial infarction. Finally, the Effective Management of Uncontrolled 21. The Seventh Report of the Joint National Hypertension. Arch intern Med., 162:413-420. Committee on Prevention, Detection, reduction of BP may not be solely due to Evaluation, and Treatment of High Blood 6. Sczupak CA, Conrad WF (1977). Relationship pharmacist interventions but change of Pressure. http://www.nhlbi.nih.gov/guidelines/ between patient-oriented pharmaceutical BP lowering drug management. services and therapeutic outcomes of hypertension/. [Accessed April 9, 2009] ambulatory patients with diabetes mellitus. Am 22. Lee VWY, Chan THW, Ko TTL, et al. J Hosp Pharm, 34:1238-1242. (2008). Clinical Outcome of Hypertension CONCLUSION 7. Carmichael JM (1995). Do pharmacists Management- A Five-Year Observational Study. need prescribing privileges to implement Journal of Medical Economics,11(1):101-118. pharmaceutical care? Am J Health-Syst This study suggested patient with Pharm, 52:1699-16701. 23. The ALLHAT offi cers and Coordinators for the ALLHAT Collaborative Research borderline hypertension may not be 8. Alsuwaidan S, Malone DC, Billups SJ, et Group (2002). Major Outcomes in High- as sensitive to additional pharmacy al., for the IMPROVE Investigators (1998). Risk Hypertensive Patients Randomized to Characteristics of ambulatory care clinics Angiotensin-Converting Enzyme Inhibitor counseling service although improvement and pharmacists in veterans affairs medical or Calcium Channel Blocker vs. Diuretic: of BP control was observed. Drug centers. Am J Health-Syst Pharm, 55:68-72. The Antihypertensive and Lipid-Lowering compliance was signifi cantly improved 9. Carter BL, Malone DC, Valuck RJ, et al. (1987). Treatment to Prevent Heart Attack Trial after pharmacist intervention. Careful The IMPROVE study: background and study (ALLHAT). JAMA, 288: 2981-2997. design. Am J Health-Syst Pharm, 55:62-67. allocation of pharmacy resources should 24. Dahlof B, Sever PS, Poulter NR, et al. be considered for the management of 10. Lip GY, Beevers DG (1997). Doctors, nurses, (2005). ASCOT Investigators. Prevention pharmacists and patients -- the rational of Cardiovascular Events with an borderline hypertensive patients when evaluation and choice in hypertension Antihypertensive Regimen of Amlodipine resources are scarce. (REACH) survey of hypertension care delivery. Blood Pressure, 6(suppl 1):6-10. adding Perindopril as required versus Atenolol adding Bendrofl umethiazide as required, in 11. Walneia ADS, Juan CYT, Gun BM, et al. the Anglo-Scandinavian Cardiac Outcomes (2007). Effect of pharmaceutical care on blood ACKNOWLEDGEMENT Trial- Blood Pressure Lowering Arm (ASCOT- pressure control and health-related quality of BPLA): A Multicentre Randomised Controlled life in patients with resistant hypertension. Am Trial. Lancet, 366: 895-906. J Health-Syst Pharm, 64(18):1955-1961. This study was supported by the School 25. Wing LM, Reid CM, Ryan P, et al. (2003). of Pharmacy, The Chinese University of 12. Lee VWY, Chu KKY, Lam SSK, et al. (2010). Impact of Pharmacist Intervention Second Australian National Blood Pressure Hong Kong. All authors declared that on Cardiovascular Risks Management in Study Group. A Comparison of Outcomes with there was no confl ict of interest during Hypertensive Type 2 Diabetic Patients in Angiotensin-Converting Enzyme Inhibitors and Primary Care Setting. (Presented at the Hong Diuretics for Hypertension in the Elderly. N Eng the study and the preparation of the Kong Pharmacy Conference 2010) J Med, 348: 583-592. manuscript.

HKPJ VOL 19 NO 1 Jan-Mar 2012 15 A Pilot Implementation of Decentralized and Automated Dispensing System by Omnicell – from Challenging to Benefi t Realization

YUNG, Kit-Mana*; TAM, Ka-Mingb; TSE, Pascalc; WONG, Keid a Pharmacist, Pharmacy Department, St. Teresa’s Hospital, 327 Prince Edward Road, Kowloon, Hong Kong b Senior Analyst Programmer, Information Technology Services Department, St. Teresa’s Hospital, 327 Prince Edward Road, Kowloon, Hong Kong c Chief Information Technology Offi cer, Information Technology Services Department, St. Teresa’s Hospital, 327 Prince Edward Road, Kowloon, Hong Kong d Chief Pharmacy Offi cer, Pharmacy Department, St. Teresa’s Hospital, 327 Prince Edward Road, Kowloon, Hong Kong (* Corresponding author)

ABSTRACT As a vicious cycle, the pharmacy has to the point of care. User identifi cation handle repeat orders every three days (password/ fi ngerscan) is required for A pilot project of decentralized and manage drug returns from the ward the users to get access to the system, automated dispensing system by as well. In addition, every ward has a list the patients for whom medications are Omnicell has been implemented in of ward stock medications which aims to removed, and provide usage data to the a medical ward M5B of St. Teresa’s shorten the time to receiving drugs for hospital’s fi nancial department for the Hospital since May 2011. An electronic administration. However, nurses have patients’ bills (Fig. 1). active drug list (ADL) interfaced with to dispense those ward stock items from Omnicell cabinet was also introduced several designated cupboards without Omnicell medication dispensing to ensure a reconciled medication guiding directions and restrictions. cabinets are locked systems that are profi les for patients. The objectives Hence, this increases the likelihood of loaded with the medications. The of the pilot project were improving medication selection errors, especially stocked medications are kept in the nursing effi ciency and patient safety. with sound-alike, look-alike items. compartmentalized cabinets. At the In conclusion, the pilot project was appropriate dosing time, nurses can successful and aspects for further In order to enhance nursing logon with username and fi ngerprint or development were identifi ed. effi ciency and patient safety, a pilot password to retrieve patients’ medication project of a decentralized automated profi les from the cabinet computer and Keywords: decentralized and automated pharmacy system by Omnicell has been remove medications by following the dispensing system, Omnicell, electronic implemented in a medical ward M5B since guiding lights to the specifi c drug storage location. The new system provides active drug list, patient safety, HL7 May 2011. Additionally, an electronic increased control and accountability active drug list (ADL) interfaced with over dangerous drugs and fl oor stock Omnicell cabinet was also introduced medications in patient care areas. INTRODUCTION to ensure a reconciled medication profi les for patients. Patient ADL is BACKGROUND OF WARD M5B Traditionally, inpatient medications maintained by nurses, pharmacists and are dispensed by centralized distribution doctors collaboratively. Lessons learnt M5B is a 47-bed medical ward. We systems. Pharmacy processes (i.e. from project initiation, preparation and chose M5B as the pilot ward as it is data entry, drug pick, verifi cation) the implementation are discussed and the one of the wards with high workload. medication orders received from wards way forward for further improvement is Therefore, we could challenge the and fi nally dispatches the dispensed identifi ed. system with high activity in addition to medications back to the ward. St. the new workfl ow. In the pilot study, we Teresa’s hospital (STH) is a private installed a 2-cell Omnicell cabinet station general hospital and all patients are CONCEPT OF DECENTRALIZED AND in M5B, accommodating over 90% of self-fi nanced. Nurses have to review AUTOMATED DISPENSING SYSTEM formulary injectable drugs which need the continued medication order every to be dispensed based on past usage three days in order to avoid unnecessary Automated dispensing systems are records. orders. Since the maintenance typically installed in hospitals on patient medications are not available at the point care units, and are connected via a real- of care, nurses always need to order time interface to the hospital’s Pharmacy CONCEPT AND APPLICATION OF surplus to avoid running out of drugs Information System in order to maintain ACTIVE DRUG LIST (ADL) at administration times. As a result, control over drug dispensing. Their nurses have to handle a lot of drug major advantage lies in allowing nurses In a close-loop drug distribution returns when patients are discharged. to obtain medications for inpatients at system, nurses should only administer

HKPJ VOL 19 NO 1 Jan-Mar 2012 16 1HZ:RUNIORZZLWK$'&

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Figure 1: New workfl ow with automated dispensing cabinet (ADC) and benefi ts medication-orders that have been pharmacy, nurses and the IT department. Even though the technology of verified by pharmacy except in In the kick-off meeting, we defi ned the decentralized automated dispensing is emergency situations. Therefore, an objectives and timeline of the projects. very mature and widely adopted in US ADL is essential for ensuring Omnicell and vendor representatives and many European countries, STH is drugs administered by nurses are were provided with ward site visit and the the innovator in using this technology prescribed by physicians and reviewed current STH drug distribution system and in Hong Kong. Similar to many health- by pharmacists. Currently, electronic the nursing practices were explained. Mr. related IT projects, we are facing some inpatient medication order entry (MOE) John Rosen helped us understand the common risks in project implementation is still not available in our hospital. We database structure requirement and also such as delivery, business impact, make use of the dispensing records to the operation of Omnicell console. Mr. business support, technology and construct a drug list (medication profi le). Dean Martin, who is a pharmacist from project management, etc. Among all Attending doctors are responsible Australia, helped us develop the policies of them, achieving successful change to review the ‘active’ drug and make and procedures for ADC use in STH. management is the most challenging. On orders to ‘continue’, ‘discontinue’ and top of the general resistance to change, ‘add new drug’. Nurses are responsible the application of health IT increases Follow-up meetings were held in to update the ADL according to doctors’ the accountability on all staff, especially March and May respectively for interface instructions. The active drugs are clearly nursing, which can make them reluctant testing, cabinet setup and fi nalization of presented in ADL so that doctors can to use. Because nurses are one of policies and procedures. get their patients’ complete medication the major stakeholders in the project, profi les easily. It is ultimately benefi cial the project team made great efforts to for doctors who are taking care of increase their knowledge, acceptance, RISK AND PROJECT MANAGEMENT patients intended for long-stay; patients and comfort with the technology. who are on multiple drugs and those who are consulting multiple doctors. As defi ned in the PMBOK 2008, projects In order to increase the users’ are temporary endeavours undertaken to acceptance, nurse representatives create unique project, services or results. actively participated in requirement PREPARATION OF IMPLEMENATION Project management is the application of collection process. The Chief Nursing knowledge, skills, tools and techniques Offi cer and all senior nursing offi cers The kick-off project meeting was held in to project activities to meet project were invited to express their concerns January 2011. It was a 5-day meeting requirements. In the real world, project and opinions on the new system. which involved two experts from Omnicell, development is risky in nature; therefore, User requirements were collected and Mr. John Rosen and Mr. Dean Martin, risk management is managing and prioritized throughout the preparation representatives from vendor Deltason, mitigating the risks. and implementation process. The

HKPJ VOL 19 NO 1 Jan-Mar 2012 17 involvement of M5B ward-in-charge internationally, it is a new experience Since all dangerous drugs are nurse as a project governance committee to integrate STH hospital information locked in high security bins individually member also ensured there was systems (HIS) with a third-party and all transactions are accountable effi cient communication among nurses, application. Therefore, IT has done and traceable with a recorded witness, Pharmacists and the IT department. research on HL7 standards before and inventory counts confi rmed on each interface development. It is understood access, no cycle count is required during that HL7 version 2 is just an interchange each shift handover. In addition, the SYSTEM TRAINING standard but not an interoperability ADC can free nurses’ time in triweekly standard. HL7 version 2.3.1 was stock taking, requisition and ward stock Hands-on training was provided to selected because it is commonly used expiry date checking. As the cabinet pilot ward nurses and pharmacy staff in Hong Kong. For this project, a new stocked medications can be available at immediately before the system Go-Live. Gateway has been built to exchange HL7 the point of care, the implementation of Eight training sessions were conducted messages between Omnicell server and ADC greatly eliminates the process of by Mr. John Rosen and representatives HIS applications. Several information drug return and saves much time for both from Deltason. In training sessions, systems of STH have also been revamped nursing and pharmacy staff. the general operation and functions in order to make them exchange data in HL7 standards. In addition, the IT of cabinets were demonstrated. The In term of patient safety, the ADC department has developed a new trainers also resolved many users’ reduces ward stock drug dispensing module in Nursing service system that concerns and questions immediately errors through the application of the allow nurses to maintain the ADL. They in an interactive way. Participants had guiding light directed removal and safety also provided training to nurses on the a chance to understand the benefi ts of principles involved in defi ning drug new applications. the system and be more confi dent in the locations within the cabinet. use of the new system within their own clinical environment. DISCUSSION Feedback from users Benefi ts of ADC use in term of saving CHALLENGES FROM IT ASPECTS nurses’ time A survey on the nurse satisfaction level with the use of the ADC was conducted Apart from hardware support, the IT The instant benefi t of using the ADC is the in late July (60 days after system go live). department played a crucial role in shortening of time between making new In the trial, thirty nurses had participated developing interfaces in Health Level order to pharmacy and receiving drugs in using the ADC and twenty-fi ve Seven (HL7) standard to allow the back from pharmacy for administration (83.3%) completed questionnaires were Omnicell server and STH computer (i.e. reduction in prescription turn around received. From the results, most of the systems to communicate. time). There is virtually ‘zero’ time lag nurses agree that the ADC is easy to for receiving the continued doses. use and they feel satisfi ed in general Health Level Seven International Nurses can also save manpower in (Figure 2). Because the cabinet (HL7) are the global authority on documenting the procedure fee charging medication profi le is updated immediately standards for interoperability of health on the system electronically. When once the pharmacist validates the information technology. Even though removing medications from cabinets, the prescription, it greatly reduces the time HL7 standards are very common within procedure fee can be captured and billed taken to administer the fi rst dose of and among healthcare organizations to patient’s account electronically. injectable drugs.

67+1XUVLQJ)HHGEDFNRQ7ULDORI2PQLFHOO$'& PRQWKVDIWHU$'&JROLYH 'LVFXVVLRQVZLWK6WDII%HQHILWV %HQHILWVLGHQWLILHGWKURXJKGLVFXVVLRQVZLWKVWDII SKDUPDF\DQGQXUVLQJ  Ease of use 5V[LK! □ $FFHVVWRILUVWGRVHTXLFNHU  -\SSTHYR! □ 5HGXFHGSUHVFULSWLRQWXUQDURXQGWLPH Overall satisfaction Usefulness of ;V[HSUVVMU\YZLZ □ 0LQLPL]HVRYHUVWRFNLQJ PU]VS]LKPU[YPHS! □ %HWWHUVWRFNFRQWURO Training □ 'HFUHDVHGZRUNWRGLVSHQVHVWRFN FIPXOWLSOHGD\GLVSHQVLQJV    ;V[HSUVVM □ 5HGXFHGUHWXUQVRILQMHFWLRQV X\LZ[PVUUHPYL □ &DSWXUHFKDUJHVDFFXUDWHO\ □ ,QMHFWLRQVDYDLODEOHLQVKRUWHUWLPH □ ,PSURYHGVDIHW\WKURXJKXVHRIEDUFRGHWRUHVWRFN □ 1RQHHGWRUHZULWHRUGHUV □ 0RUHGUXJVDYDLODEOHDWZDUGOHYHO Feel disappointed Improve accuracy of □ 6DYHWLPHRQQXUVLQJLQYROYHPHQWRQPHGPDQDJHPHQW    FIWRSUHYLRXVV\VWHP if fall back drug picking □ ,PSURYHGVHFXULW\DFFRXQWDELOLW\

'LVFXVVLRQVZLWK6WDII ,VVXHV3UREOHPV ,VVXHVUDLVHGLQGLVFXVVLRQVZLWKVWDII Time to first     Time saving in □ )LQJHUVFDQGLIILFXOWWRXVHUHOLDEO\ dose medication drug management □ ,QYHQWRU\LQFDELQHWPXVWEHDFFXUDWH □ 5HWXUQELQLVVXHZLWKRSHQLQJZLWKNH\ □ 6WRFNELQVWRRIOLPV\ □ ,QWHUIDFHPRQLWRULQJGRZQWLPHSURFHGXUHV    XQFOHDUZKDWWRGR Reduce manual documentation Usefulness of MUP program Figure 3: Summary of discussions with staff: Figure 2: Results of STH Nursing Feedback on Trial of Omnicell ADC (2 month after ADC go live) Benefi ts and issues/ problems

HKPJ VOL 19 NO 1 Jan-Mar 2012 18 There is also support from nurses stock-keeper directly. A pharmacy reconcile the patient drug profi le that the application of active drug list technician picks the items according to more proactively though profi le-based (ADL) has reduced the manual process the restock pick list and affi xes restock dispensing. of repeating doctors’ drug orders and barcode labels to the verifi ed items. greatly reduced the chance of transcribing With the Omnicell SafetyStock barcode Most of the benefi ts discussed in errors. However, before profi le-based feature, a pharmacy technician has to the pilot cannot be quantifi ed because dispensing implementation, nurses still scan the restock barcode label to confi rm the baseline information before have to work to update the medication correct bin during restocking. implementation had not been captured. profi le. In the subsequent ADC installations, Moreover, the inventory management baseline information (e.g. turnaround During post installation review is enhanced through review of electronic time, total dispensing time, and cost (24th -29th July 2011), Mr. Dean Martin usage transactions and alerts. The regular capture for ward stock administration) interviewed nursing and pharmacy staff review of inventory reports e.g. PAR should be collected for further analysis. vs usage report provides reference to (end users). The benefi ts and issues/ pharmacy for optimizing the stock level of CONCLUSIONS problems associated with ADC uses cabinet items in order to prevent overstock/ were discussed (Figure 3). under-stock. The pilot project has been successful since the ADC and ADL use have Benefi ts of ADC use in term of Further improvement improved nursing effi ciency and patient improving pharmacy inventory control safety. The acceptance of ADC use In the pilot, we only stocked non by nurses is high because it is easy to The inventory monitoring function of -refrigerated injectable items in operate. ADC enhances patient safety by Omnicell system has enhanced the cabinets. We propose to add oral drugs guiding nurses’ drug selection in a more effi ciency of the restocks process and in the future when unit dose package controlled manner. It frees nurses’ time cabinet inventory control. Every cabinet techniques are introduced. Moreover, from tedious manual documentations to stocked item has a unique item code. The we would utilize Omnicell Flexi-lock perform their clinical services. Patients PAR/Restock/Critical low levels of each technology to link refrigerated items with benefi t from receiving their fi rst dose item are defi ned in the Omnicell console. the ADC in the future. of medication with minimal time delay. Once the stock level hits the restock Inventory control is optimized by regular level, restock order is created and sent to In order to improve the accuracy analytical reports review to reduce drug STH top-up system at a scheduled time. of patient drug profi le, the interface for expenditure resulting from overstocking. In addition, critical low or stock-out alerts pharmacy data entry will be revamped. In the pilot, aspects for further will continue to be sent to pharmacy Pharmacy will be able to update and development are identifi ed.

HKPJ VOL 19 NO 1 Jan-Mar 2012 19 Drugs & Therapeutics

Immunization in Hong Kong

TSE, Kit-Yinga; CHAN, Hoi Lamb* a Hong Kong Sanatorium and Hospital, 2 Village Road, Happy Valley, Hong Kong SAR, China; b Pfi zer Corporation Hong Kong Limited, 16/F, Stanhope House, 736 King’s Rd, North Point, Hong Kong SAR, China (* Corresponding author)

ABSTRACT been successful with the worldwide have already been approved and implementation of the polio vaccination marketed. In Hong Kong, the Childhood Vaccines are an effective means to programme.(4) Emerging and re-emerging Immunization Programme (CIP) prevent diseases. Several trends can infectious disease have made the role of implemented by the government also be observed in the development of immunization an increasingly important includes the diphtheria, tetanus, acellular vaccines in the 21st century. Various focus in preventative health. New pertussis & inactivated poliovirus government funded immunization possibilities in vaccine development such combination vaccine and measles, schemes are in place in Hong Kong as new targets, combinations and novel mumps & rubella vaccine.(7) and eligible citizens can enjoy routes of administration have helped free or subsidized immunization. to feed such a demand. Therefore, The routes of immunization are Pharmacists are expected to pharmacists have the responsibility to being extended to many nonparenteral have knowledge on vaccines and keep themselves familiar with the latest methods.(5) A new live, attenuated immunization programs; however vaccination technologies, available influenza vaccine administered local information resources are vaccines and immunization programmes. intranasally to cause both systemic and often limited or the access to them local responses has been registered are unfamiliar. Pharmacy-based in Hong Kong. Aerosol, oral and vaccination is currently being DISCUSSION transcutaneous vaccines have also been practiced in some countries, which developed to reduce the invasiveness may become a trend in immunization 21st Century vaccination of immunization while maintaining the delivery in the future. effectiveness of vaccines at the same The vaccine market is an ever changing time. Keywords: Vaccine, vaccination, environment. Compared to the vaccines immunization, immunization programme in early days, we can observe several The purpose of immunization new trends in vaccine development. has been confi ned to the prevention of infectious diseases.(5) However, INTRODUCTION Adolescents and adults have vaccinations against various displaced infants and children as the noninfectious diseases are being Vaccines are biological preparations major market of vaccines.(5) Aggressive developed. Vaccines can become a very which enhance a person’s immunity pediatric immunization programmes are useful means to prevent or treat many to a specifi c disease.(1) An agent still a health priority worldwide to eradicate kinds of diseases. A lot of effort has that resembles a disease-causing polio, mumps, pertussis, measles and been made in the development of cancer microorganism is contained in either a live other diseases. However, in year 2007, vaccines which contains proteins and or inactivated vaccine. When the vaccine adult vaccine sales increased slightly but peptides from cancer antigens.(5) Cancer is administered to the human body, the signifi cantly overtook pediatric sales.(6) prophylaxis for people with inherited immune system recognizes the agent Vaccinations for adults with infl uenza carcinogenic mutations may be possible as foreign, destroys it and “remembers” vaccine, human papillomavirus (HPV) in the future. Active immunization against it. When the body encounters the vaccine and traveller vaccines have angiotensin II is a new strategy against disease-causing microorganisms later, become an important contributor to the high blood pressure.(8) Alzheimer’s fast recognition and destruction of them vaccine sales. Adults are now considered disease can possibly be controlled by becomes possible. as the driver for vaccine market growth. immunization against amyloid protein.(5)

Since its invention by Edward Combination vaccines which target Technology advancement also Jenner in late 17th century,(2) vaccines multiple diseases are becoming more allows safer and more effective have become an important method common in many parts of the world.(5) immunization. In recent years, there of reducing infections and diseases. Pentavalent vaccines are available in have been new fi ndings suggesting that Immunization with smallpox vaccine many parts of the world. Also, hexavalent sex and pregnancy differences may has caused the successful global combinations containing diphtheria, affect the immune response as well as eradication of fatal smallpox infection.(3) tetanus, pertussis, H. infl uenza type b, the occurrence of adverse effect to the The control of polio virus infection has hepatitis B and inactivated polio vaccines vaccines.(9) Women were found to have

HKPJ VOL 19 NO 1 Jan-Mar 2012 20 a greater humoral immune response infectious diseases, including hepatitis conjugate vaccine (PCV13) in the CIP and more adverse reactions to vaccines B, diphtheria, tetanus, measles, mumps of Hong Kong. PCV13 is expected to when compared to men. However, sex- and rubella. From 1 September 2009 replace PCV10, which is currently being specifi c effects in vaccine effi cacy and onwards, pneumococcal vaccine has used, by the end of 2011.(10) safety are usually not documented. been introduced into the Childhood To initiate a better immunization Immunization Programme. The Scientifi c The Government Vaccination programme, the effects of sex and Committee on Vaccine Preventable Programme (GVP) provides free pregnancy on immune responses need Diseases (SCVPD) under the Centre seasonal infl uenza vaccination and to be further understood. for Health Protection has recommended pneumococcal vaccination to eligible the use of 13-valent pneumococcal people.(11) People such as healthcare When more new vaccines are developed, pharmacists, as the primary healthcare providers, should know the Table 1. Recommended Vaccination Schedule7 emerging trends so as to deliver correct AGE IMMUNIZATION RECOMMENDED and up-to-date information to the patients B.C.G. Vaccine Newborn and customers who make the enquiries. Hepatits B Vaccine - First dose 1 month Hepatitis B Vaccine - Second dose Immunization scheme in Hong Kong DTaP-IPV Vaccine - First Dose 2 months Pneumococcal Vaccine - First Dose DTaP-IPV Vaccine - Second Dose There are several free vaccination 4 months Pneumococcal Vaccine - Second Dose programme or subsidy schemes DTaP-IPV Vaccine - Third Dose conducted by Hong Kong Centre of 6 months Pneumococcal Vaccine - Third Dose Health Protection. Hepatitis B Vaccine - Third Dose MMR Vaccine (Measles, Mumps & Rubella) - First Dose 1 year The Childhood Immunization Pneumococcal Vaccine - Booster Dose Programme (CIP) is provided by the 1 1/2 year DTaP-IPV Vaccine - Booster Dose MMR Vaccine (Measles, Mumps & Rubella) - Second Dose Primary 1 Family Health Service of the Department DTaP-IPV Vaccine - Booster Dose of Health which offers free vaccinations Primary 6 dTap-IPV Vaccine - Booster Dose to children from newborn to their DTaP-IPV Vaccine: Diphtheria, Tetanus, acellular Pertussis & Inactivated Poliovirus Vaccine primary 6.(7) It protects children from ten dTap-IPV Vaccine: Diphtheria, Tetanus, acellular Pertussis (reduced dose) & Inactivated Poliovirus Vaccine

Table 2. Immunization schemes in Hong Kong

Vaccination programme Characteristics of the programme Persons with free or subsidized vaccination provided by the Government Childhood Infl uenza Subsidise HK$80 per dose of infl uenza Children between the age of 6 months and less than 6 years; or attending a Vaccination Subsidy vaccine given to children eligible kindergarten or child care centre in Hong Kong. Scheme (CIVSS) under the Scheme Childhood Immunization Offer free vaccinations to children * Please see the above vaccination schedule Programme (CIP) from newborn to their primary 6 Elderly Vaccination Subsidise HK$130 per dose of seasonal Hong Kong residents AND aged 65 years or above Subsidy Scheme infl uenza vaccination and HK$190 per (EVSS) dose of pneumococcal vaccination given to eligible elders by private medical doctors enrolled in the Scheme Government Provide free seasonal infl uenza • Residents of RCHEs & RCHDs (under Residential Care Home Vaccination Programme) Vaccination vaccination to eligible people • Healthcare workers of RCHEs & RCHDs (under Residential Care Home Vaccination Programme Programme) • Community living persons aged 65 years or above with chronic illness attending public clinics • Community living persons aged 65 years or above receiving CSSA • CSSA recipients aged below 65 years with chronic illness attending public clinics • In-patients under HA : hospitalized patients (including paediatric patients) with chronic illness, infi rmary psycho-geriatric, mentally ill and mentally handicapped units/wards • Paediatric out-patients with chronic illness or on long-term aspirin • Healthcare workers working in DH, HA or in the public service • Poultry workers or workers who may be involved in poultry-culling operations • Children between the age of 6 months and less than 6 years from families receiving CSSA • Pregnant women receiving CSSA • Pig farmers / pigslaughtering • industry personnel Provides free pneumococcal • Residents of RCHEs & eligible residents of RCHDs (under Residential Care Home vaccination to eligible elders Vaccination Programme) aged 65 or above • Community living persons aged 65 years or above with chronic illness attending public clinics • Community living persons aged 65 years or above receiving CSSA • In-patients under HA : • hospitalized patients aged 65 years or above with chronic illness, infi rmary psychogeriatric, • mentally ill and mentally handicapped units/wards CSSA: Comprehensive Social Security Assistance; DH: Department of Health; EHCs: Elderly Health Centers; EVSS: Elderly Vaccination Subsidy Scheme; GOPCs: General Outpatient Clinics; GVP: Government Vaccination Program; HA: Hospital Authority; MCHCs: Maternal & Child Health Center; PDQA: Professional Development and Quality Assurance; RCHDs: Residential Care Homes for Persons with Disabilities; RCHEs: Residential Care Homes for the Elderly; SCVPD: Scientifi c Committee on Vaccine Preventable Disease; SOPCs: Special Outpatient Clinics; SPP: Special Preventive Programme (adapted from http://www.chp.gov.hk/en/view_content/17980.html)

HKPJ VOL 19 NO 1 Jan-Mar 2012 21 workers, poultry workers, pregnant enquiries on immunization. Access to women, people living or working in reputable and reliable local information personal care institutions, elderly resources about immunization is aged 65 or above with chronic illness essential. However, they may not or receiving Comprehensive Social be widely accessed or known by our Security Assistance, can receive professional body. free seasonal infl uenza vaccine for year 2010/11 from respective service The website of Center for Health providers from 1 November 2010. Free Protection provides information of the pneumococcal vaccination is also offered vaccination scheme in Hong Kong. Figure 1. Website of Centre for Health to eligible elders aged 65 or above to Details of immunization programme Protection. (http://www.chp.gov.hk/tc/view_ prevent hospitalization, and to reduce for different age groups, pregnant content/17980.html) complication and mortality caused by women, healthcare workers and pneumococcal infection. workers in the poultry or pig-farming The Travel Health Service of industry are uploaded to the website. the Department of Health provides Elderly persons aged 65 years Moreover, the summaries of various information on travel-related diseases, or above living in the community who communicable diseases in Hong Kong, list of affected areas, travel health advice are not eligible for the free vaccination recommendations to the general public, and traveller vaccines. The information may go to private doctors enrolled in institutions and businesses, education is available on its website (http:// Elderly Vaccination Subsidy Scheme resources, and safety updates of www.travelhealth.gov.hk/cindex.html) to receive seasonal infl uenza vaccine vaccines are also available on the and at the two Travel Health Centres with Government subsidy of $130 and website. situated in Wan Chai and Cheung Sha pneumococcal vaccine with Government subsidy of $190.(12) Children between the age of 6 months and less than 6 years Table 3. Online overseas resources about vaccines may go to private doctors enrolled in the Center for Disease http://www.cdc.gov/vaccines/default.htm Childhood Infl uenza Vaccination Subsidy Control and Prevention ● Immunization Schedules Scheme to receive seasonal infl uenza (US) ● Recommendations and Guidelines ● Vaccine Administration and Storage & Handling vaccine with Government subsidy of ● Requirements and Laws $80.(13) ● Vaccination Records ● Information for Specifi c Groups of People ● Information for Travelers If citizens are recommended to ● Vaccines & Preventable Diseases have immunization but are not eligible ● Publications ● Vaccine Safety & Adverse Events under the free or subsidy programmes, ● Research and Development they should have the vaccination at their ● News and Media Resources family doctor for personal protection. ● Calendars and Events ● Education & Training for Providers Apart from the vaccines included in ● Programs & Software/Tools the programmes, other vaccines for ● Statistics & Surveillance protection against certain infectious ● Partners’ & Related Sites diseases are available at private doctors. Department of Health http://www.dh.gov.uk/en/Publichealth/Immunisation/index.htm (UK) ● Latest News For example, people should consult their ● Key Documents family doctors for chickenpox vaccine, ● Immunization Usefulness Links Haemophilus infl uenzae type b vaccine, ● Vaccine Uptake Survey meningococcal vaccine, hepatitis A Health Protection Agency http://www.hpa.org.uk/ (UK) ● Infectious Disease Topics vaccine and rotavirus vaccine if they ● Publications want a more complete health protection. ● Products and Services ● News Centers ● Events and Professional Trainings Working pharmacists should Department of Health http://www.health.gov.au/internet/main/publishing.nsf/Content/ohp-communic-1 constantly check the updates posted and Aging (Australia) ● Communicable diseases control on the website of the Center for Health ● Communicable diseases information Protection to equip themselves with Public Health Agency http://www.phac-aspc.gc.ca/im/index-eng.php of Canada ● Canadian Immunization Guide suffi cient knowledge on local vaccination ● Immunization Competencies programmes which can facilitate their ● Immunization Registries interaction with patients. ● Immunization Schedules ● Infl uenza ● National Advisory Committee on Immunization (NACI) Information resources for pharmacists ● National Immunization Strategy ● Travel Vaccines ● Vaccine-Preventable Diseases Pharmacists, being primary health ● Vaccine Safety professionals, are expected to advocate, Centers for Disease http://www.cdc.gov.tw/mp.asp?mp=1 facilitate and provide health education to Control, R.O.C. (Taiwan) ● News the public. With the increasing popularity ● Health topics ● Programs & Campaigns of various kinds of vaccines and higher ● International Cooperation level of public awareness on personal ● Statistics & Analysis health, pharmacists need to handle more ● Publication

HKPJ VOL 19 NO 1 Jan-Mar 2012 22 Wan. These centers provide services What will be the adverse reactions giving immunizations to the public.(16) including health risk assessment, health after immunization? The adverse Vaccination by pharmacists can education, vaccinations and medications effects to various vaccines are different. effectively raise the immunization rate that travelers might need while travelling Healthcare professionals should refer because pharmacy-based immunization abroad. to the package insert for the specifi c is convenient. People can get immunized reactions. Dizziness, low-grade fever, at the community pharmacies at any These internet resources may not injection site pain and swelling are time and do not need to make an provide enough clinical information on the mild and common reactions after appointment for vaccination at the each individual vaccine. There is a lack immunization. The pain and fever can clinics. This advantage is especially of comprehensive local resources on be relieved by self-administration of obvious in the rural areas where clinics specifi c vaccine. Pharmacists often have paracetamol. However, if the reactions may not be accessible and clinic hours to refer to the primary resource from persist, like for more than 24 hours, or may be restricted and have been willingly overseas databases and the reports become worse, the immunized individual accepted by patients.(20-22) and updated news by overseas health should consult the doctor.(14) authorities. The table below shows some This represents an evolving and examples of useful overseas resources Rarely there are severe adverse changing practice role of the pharmacist on vaccines. reactions such as convulsion and severe combined with an increasing public health allergic reaction after immunization. need. Apart from the US, pharmacy- Frequently asked questions about Immunized individuals should be based immunization services have (23) vaccination admitted to the Accident and Emergency started to develop in Australia, as well Department immediately if they have as in the UK.(24) Although pharmacists Pharmacists may come across some diffi culty in breathing, rapid pulse, skin in Hong Kong are not authorized to people or patients who enquire about rash and shock after vaccination. Such administer vaccinations at the moment, vaccination. Here are some of the reactions should be recorded for future the efforts in improving vaccination rates frequently asked questions and the brief reference to take necessary precautions amongst adults via pharmacist-managed before other vaccinations.(14) vaccination programs represents a answers. recognition of the role of pharmacists When is the appropriate time to in providing primary healthcare. Why are there boosters for some receive seasonal infl uenza vaccine? If pharmacy-based vaccination is types of the vaccines? Booster doses The seasonal outbreak of infl uenza implemented in Hong Kong in future, should be given at specifi c intervals usually occurs from January to March a comprehensive training programme to maintain the immunity which may in Hong Kong. To ensure protection must be in place. decrease with time after some types of against seasonal infl uenza, the vaccine vaccination. should be taken at least 2 weeks before the outbreak for immunity to develop. CONCLUSIONS Where should the children receive People should get immunized before the immunization service included in the mid-December every year.(15) The ever-growing demand of government CIP? Children from birth to immunization for various types of 5 years of age can get immunized at any New trend in vaccination: communicable diseases has caused the Maternal and Child Health Center of the administration of vaccines by rapid need to develop more vaccines. The Department of Health. The Department pharmacists Hong Kong Government offers several of Health also arranges inoculators to immunization programmes to its citizens, visit primary schools to provide school In recent years, pharmacists are getting especially the children and elderly who children free immunization. Parents may involved in immunization as immunizers. are at risk of having serious infections. also bring their children to private doctors In the United States, changes in pharmacy Pharmacists should equip themselves (14) for vaccination. practice laws have allowed pharmacists with suffi cient resources, be aware to administer vaccines at non-traditional of updates to the local immunization Under what circumstances are sites such as pharmacies and it has been schemes and keep up with clinical people not suitable for vaccination? recognised as a method to increase knowledge of immunization in order Special arrangement for immunization vaccination rates. Pharmacists are to achieve effective patient education is needed under certain circumstances. legally authorized to deliver infl uenza and and interactions. Several reputable People should seek medical advice pneumonia vaccinations in some areas in references are available from Hong before receiving immunization if they the US.(16-18) The American Pharmacists Kong and overseas which pharmacists have the following conditions. Association has adopted guidelines for can easily refer to in their daily practice. ● History of serious reaction to a pharmacy-based immunizations through New trends in immunization practices previous vaccine a national certifi cate training program for such as the administration of vaccines ● History of severe hypersensitivity to pharmacists and other training providers by pharmacists may potentially impact any substance include National Community Pharmacists our role as health care providers. ● Immunodefi ciency conditions: Association (NCPA) and Centers Pharmacists have a responsibility to ■ Congenital immunodefi ciency for Disease Control and Prevention keep themselves familiar with the latest ■ Leukaemia, cancer (CDC).(16,19) Pharmacists have to learn vaccination technologies, available ■ Chronic disease with long term about vaccines, adverse reactions, vaccines and immunization programmes treatment, e.g. chemotherapy or emergency issues, legal and regulatory in order to provide the best care to the taking corticosteroids.(14) issue and practice the injections before community.

HKPJ VOL 19 NO 1 Jan-Mar 2012 23 Author’s background 8. Ola Samuelsson, et al. (2008) Vaccination Against 17. Krysten A. Modrzejewski. (2003). Pharmacists’ TSE Kit Ying Helena was a pharmacy intern high blood pressure: a new strategy. The Lancet, involvement with vaccinations leads to preventive working in Hong Kong Sanatorium & Hospital. 371:788-9. health care role. American Journal of Health-System Pharmacy, 60:1726-1728 Her email address is: helena_0124@ 9. Klein SL, et al. (2010) The Xs and Y of immune hotmail.com CHAN Hoi Lam is currently the responses to viral vaccines. Lancet Infectious 18. Sharya Vaughan Bourdet, etal. (2003) Effect of a Associate Manager - Medical Affairs of Pfi zer Disease,10(5): 338–49. pharmacist-managed program of pneumococcal and infl uenza immunisation on vaccination rates among Hong Kong. For more information about this 10. Press release. New pneumococcal vaccine adult inpatients. American Journal of Health-System article, please contact her through her email recommended for children immunisation Pharmacy, 60:1767-1768. address: hoilam.chan@pfi zer.com programme. Centre of Health Protection website. 19. Khalid M. Kamal, et al. (2003). Impact of the American http://www.chp.gov.hk/en/content/116/23024.html Pharmacists Association’s (APhA) Immunisation Accessed May 10, 2011. Training Certifi cation Program. American Journal of Pharmaceutical Education, 67(4):124. References 11. Centre of Health Protection. Government Vaccination Programme 2010/11. Who is it for and when is it 1. What are vaccines? News Medical. http://www. 20. Emily M. Ambizas. Value of Community Pharmacist. news-medical.net/health/What-are-Vaccines.aspx available? Available on http://www.pssny.org/documents/pdfs/ Accessed May 10, 2011. leg_docs/rphvalue_whitepaper.pdf. [Accessed June 12. Elderly Vaccination Subsidy Scheme. Centre of 22, 2011] 2. The Life of Edward Jenner. Edward Jenner Museum. Health Protection website. http://www.chp.gov. http://www.jennermuseum.com/edwardjenner. hk/en/view_content/21839.html Accessed May 10, 21. Annie Wong, et al. (2003). Pneumococcal vaccination html Accessed May 10, 2011. 2011. in hospitalized elderly patients: role of the pharmacist. Pharmacotherapy, 23(2) 3. Statue commemorates smallpox eradication. 13. Childhood Infl uenza Vaccination Subsidy Scheme. WHO website. http://www.who.int/mediacentre/ 22. David T. Bearden. (2005) Statewide impact of Centre of Health Protection website. http://www.chp. news/notes/2010/smallpox_20100517/en/index.html pharmacist-delivered adult infl uenza vaccinations. gov.hk/en/view_content/17984.html Accessed May Accessed May 10, 2011. American Journal of Preventive Medicine, 10, 2011. 4. Global Polio Eradication Initiative - April 2010. 29(5):450-452. WHO website. http://www.afro.who.int/index. 14. Child Health: Immunisation. Family Health Service, 23. Position statement on immunisation in pharmacies. php?option=com_content&view=article&id=2290&It Department of Health website. http://www.fhs.gov. Pharmaceutical Society of Australia website. emid=2669 Accessed May 10, 2011. hk/english/health_info/class_topic/ct_child_health/ http://www.psa.org.au/site.php?id=3672. [Accessed 5. Stanley A Plotkin. (2005). Vaccines: past, present ch_immunisation_i1.html Accessed May 10, 2011. May 10, 2011] future. Nature Medicine,11(4): S5-11 15. Centre of Health Protection. Frequently Asked 24. Mary Francis, et al. Vaccination services through 6. Carlson B. (2008). Adults now drive growth of vaccine Question on Seasonal Infl uenza Vaccine. Available at community pharmacy: a literature review. Public market. Genetic Engineering & Biotechnology News, http://www.chp.gov.hk/files/pdf/faq_gvp_eng.pdf Health Wales. Available at http://www2.nphs.wales. 28(11): 22–3. Accessed May 10, 2011. nhs.uk:8080/pharmaceuticalphtdocs.nsf/c944d98bd 7. Childhood Immunisation Programme. Centre fffc718802570050043d5cd/b16d4a1e2295dcbf8025 of Health Protection website. http://www.chp. 16. Scott A. (2009). Vaccination by pharmacists: New 77830030f109/$FILE/Vaccination%20services%20 gov.hk/en/view_content/17982.html Accessed York pharmacists train to give fl u and pneumonia through%20community%20pharmacy%20v1a.pdf. May 10, 2011. shots. Drug Topics,153(3):. Accessed May 10, 2011.

CE Questions Answer for 184-S3(D&T) Drug Administration in Enteral Tube Feeding 1. A 2. D 3. D 4. B 5. A 6. C 7. C 8. A 9. C 10. B

HKPJ VOL 19 NO 1 Jan-Mar 2012 24 Emergency First Aid for poisoning and for Alkaloid Poisoning in Particular

O’Toole, Desmond Keith; CHEUNG, Hon-Yeung* Research Group for Bioactive Products, Department of Biology & Chemistry, City University of Hong Kong, Hong Kong SAR, China. (* Corresponding author)

ABSTRACT the biological responses, the poison effective if the poison has been diluted is classifi ed into one of the following with a demulcent drink such as those Poisoning due to ingestion of a range types; namely, the corrosive poisons, already mentioned. of chemicals and natural toxic materials the narcotic poisons, the irritant poisons requires swift responses to help the and the excitants. The last three types The most convenient emetic method victim of poisoning. The general of poison are also known as the non- is to tickle the back of the throat with a approach to handling these kinds of corrosive poisons. Although treatment for feather, which can be done without risk of poisonings are reviewed and then the each kind of poisoning may be different, choking an unconscious patient who is not particular problem of alkaloid poisoning the common practices of handling a in a fi t condition to swallow a liquid emetic discussed. Poisoning of certain plants poisoned patient are about the same. such as a tablespoonful of salt in half a containing a naturally occurring pint of lukewarm water, or a teaspoonful alkaloid substance requires prompt of mustard in half a pint of warm water, or action to minimize the poisonous COMMON PRACTICES OF HANDLING a tablespoonful of an ipecac preparation (8) effect on a patient. Although each type NON-CORROSIVE POISONING (although there are doubts about its of alkaloid may have its own specifi c usefulness) or thirty grams of zinc sulfate antidotes, they may not be immediately First of all, cases of poisoning can be in a tea-cupful of warm water. available. Tannic acid or a cup of strong recognized by certain well-defi ned tea could be used as the universal symptoms occurring soon after the act As mentioned above, under the antidote. Besides, activated charcoal in of eating or drinking. The training of a category of non-corrosive poisonings liberal doses could also be a choice to doctor or a pharmacist should cover there are three types of poisons, each eliminate the poisons from the body. the knowledge of antidotes for every of which should be handled in slightly kind of poison, and accordingly their different ways, in addition to the general Keywords: alkaloid poisoning, fi rst aid, services should be sought if poisoning is treatment just described. tannic acid, tea, activated charcoal, suspected. Information about the patient universal antidote conveyed to the practitioner should be 1. The narcotic poisons are those which as accurate as possible, in particular the induce torpor, which gradually becomes suspected kind of poison to be treated, INTRODUCTION deeper, until unconsciousness merges so that the most appropriate antidote into death. Such poisons include can be determined. As a fi rst step, the A poison is a substance that causes death chloroform, ether, the many preparations lips and tongue of the patient must be of opium, sometimes known as laudanum or harm if it is swallowed or absorbed into examined. If they are not marked so as to chlorodine, paregoric, syrup of poppies, the body.(1) It could be a chemical or toxins appear seared or have white markings, morphia lozenges, Godfrey’s cordial, produced by living organisms including this suggests that a non-corrosive poison infant soothing syrup, pain-killer, and microbes, animals or plants. has been consumed, and so special many cough medicines. Symptoms of handling for corrosive poisoning is not narcotic poisoning may be recognized Food poisoning is one of the most required. commonly known illnesses. It occurs by unconsciousness, a cold and clammy skin, a feeble and slow pulse, a dark line after eating at picnics, restaurants, school While awaiting the arrival of the along the middle of the tongue, and by the cafeterias or large social functions. In doctor, no time must be lost to prevent the contraction of the pupils of the eyes to a most cases, one or more people may further action of the poison in the system, become sick within two to six hours of and this can fi rst be done by diluting or pin point. eating some food or drink because the removing as much as possible of the food has been contaminated with certain poison so as to arrest the progress of the The chief aim must be to get rid of types of bacteria, parasites, viruses, poison. Dilution may be brought about the poison by vomiting, and then to fi ght or toxins.(2) However, food poisoning by giving a copious draught of a bland, against the increasing stupor by trying does not necessarily originate only from soothing (demulcent) drink, which will to keep the patient awake. Strong coffee contaminated food. Sometimes it is due also ease the pain and alleviate irritation. should be given to the patient, who to consuming some confusing poisonous The remedies in the home which are most should be made to walk up and down, materials, such as poisonous fungi,(3) or likely to be at hand are milk, beaten egg, supported by one or two helpers, while due to improper preparation of the puffer oil from tinned sardines (unless sardines another helper occasionally dashes cold fi sh (fugu).(4,5) are suspected as the cause of ptomaine water on the patient’s face, or fl icks the poisoning), olive oil, cod-liver oil, fl our patient’s chest and face with a wet towel. When a therapeutic substance is and water, weak tea, warm water, barley Slapping the bare soles of the feet with improperly taken at a wrong time or water, thin gruel (congee), linseed tea, or a slipper is useful when the patient is dosage or a combination of both, it can a small dose of castor oil. Depending on unable to be walked about the room, and also cause poisoning.(6) For example, the individual case, these remedies can if the breathing threatens to stop, artifi cial when a person takes a larger-than- be used as a diluting agent. respiration must be applied. If medical prescribed dose of barbiturates or aid is not forthcoming, and the patient is combines the barbiturates with alcohol deeply unconscious, an attempt should even at the proper dose, it can lead to a TREATMENT FOR NON-CORROSIVE be made to wash out the stomach. This coma and death. Sometimes if a drug is POISONING(8) is done by taking a clean piece of rubber taken on an empty stomach it may result gas tubing, and passing one end as far in severe pain or strong reactions.(7) Non-corrosive poisoning can be best as possible down the gullet. A funnel treated by giving an emetic to promote is then put into the other end, the tube Whatever the poison is, based on vomiting, which is less painful and more and funnel held upward and warm water

HKPJ VOL 19 NO 1 Jan-Mar 2012 25 poured gently into the funnel until it is full turn black. In such a case, an antidote mustard in warm water, or have the to overfl owing. The free end of the tube is should be given promptly. Fortunately, patient place their index fi nger far then lowered and the stomach empties by acids and alkalis neutralize each other, so back on the tongue and stroke from syphon action. that alkaline poisons can be neutralized side to side. Vomiting should also with doses of a weak acid, such as be induced after each dose of the 2. The irritant poisons are of a metallic vinegar, or lemon-juice and water, in antidote. Caution: with strychnine, nature, and include arsenic, phosphorus, the proportion of two tablespoonfuls strongly caustic, or corrosive poisons, tartar emetic (potassium antimony to half pint of water. Acid poisons can DO NOT induce vomiting. tartrate), sugar of lead (lead acetate), be neutralised by the consumption 7. Give the patient the Universal Antidote corrosive sublimate (mercuric chloride), of an alkali, such as a tablespoonful as shown below. and copper sulfate. of magnesia, bicarbonate of soda, or 8. Get medical attention as soon as common whiting in half a pint of water, possible. Do not interrupt the above The effect of such poisons may or with ordinary lime water. In oxalic acid procedures. be recognized by a metallic taste in the poisoning, potash, soda, and ammonia mouth, running eyes and nose, pain in must be avoided, and only magnesia, Paramedics who respond to this the pit of the stomach, vomiting, and whiting, or lime water should be used. sort of incident are, in most cases, only violent purging. Such cases are treated minutes away and should have been according to the general directions, but On no account must an emetic be trained and equipped to handle these the administration of oil must be avoided given. With cases of corrosive poisoning sorts of emergencies. in a case of phosphorus poisoning. After there is always the risk that during vomiting ceases the patient’s strength retching the stomach may press against must be kept up by giving the patient the diaphragm and rupture its weakened UNIVERSAL ANTIDOTE FOR stimulating beverages. walls, which would result in peritonitis. ALKALOID POISONING

3. The excitants give rise to mental When alkaloids have been swallowed, excitement followed by delirium or TREATMENT FOR ALKALOID give 0.6 to 2.0 gm of tannic acid in a half convulsions. The most common poisons POISONING glass of warm water immediately, followed of the class are belladonna with its by another glass of water; or give strong alkaloid atropine, henbane and its Many people often consume plants or black tea, or potassium permanganate extracts, woody nightshade, poisonous Chinese medicines thinking they are (1:5,000 solution) as an alternative. fungi, laburnum seeds, prussic acid natural substances and they are not When a specifi c antidote is not available, contained in laurel leaves and almond poisonous. It is true in general; yet, as is give one teaspoon to one table spoon of essences, and strychnine, which may be well known, some botanical components activated charcoal in liberal doses. If the recognized by its effect on the sufferer’s are extremely poisonous. As a pharmacist nature of the poison is unknown, give and paramedical health caretaker, it is back, which is bent inwards. repeated doses of 15 gm of the following important to know the symptoms in cases mixture or a like mixture, stirred in half of alkaloid poisoning and other kinds of If the patient is not strongly convulsed a glass of warm water as the universal poisoning. The initial treatment consists an emetic is given, otherwise cold water is antidote for alkaloid poisoning. in chemical destruction or obstruction splashed over the face, and the patient is - Pulverized, activated charcoal (burnt and subsequent evacuation of the toxic kept in a dark room. toast as an alternative) - 2 parts material. While each alkaloid, when - Tannic acid (strong black tea as an taken by mouth, requires its own special alternative) - 1 part 4. Alcoholic poisoning. – The symptoms antidote, if any is known, the following of this form of poisoning include coma, - Magnesium oxide (milk of magnesia as general procedure and drugs can be an alternative) - 1 part seizures, slow breathing and hypothermia applied. (low body temperature). The general A poison control kit for fi rst-aid treatment for poisoning is followed, If a person is suspected of overdosing but vomiting is promoted, there is no emergency use, containing ipecac syrup on any alkaloid that can cause death from and the activated charcoal is possibly attempt to dilute the alcohol, the patient overdose one should call an ambulance is kept covered, and when consciousness available in some pharmacy stores. immediately and take the following Never give oils, fats, or alcohol; tannin returns the patient should be given a hot actions: drink. (tannic acid powder or common black tea) 1. If possible, positively identify the precipitates most alkaloids (as well as noxious agent the patient has certain toxic glycosides and many metals). SPECIAL TREATMENT FOR overdosed on and give this information However, the precipitates could dissolve CORROSIVE POISONING(8) to the ambulance operator. in the acidic gastric juice. Hence, the 2. Remove the noxious agent from antidote should be given with an alkaline During the examination of the lips and contact with the patient. substance, such as sodium carbonate or tongue of a patient, if they are seared 3. Keep the patient on their back with bicarbonate, milk of magnesia, or the like, and white markings are present, then a the head tilted back so that the airway which neutralize acids. Stomach contents corrosive poison is likely to have been of the patient remains open. If the can then be removed by vomiting or with taken, and the following special treatment patient vomits turn the patient’s head a stomach pump. is required. to the side and assist the patient in removing the vomitus from the mouth. Iodine in the form of tincture of Iodine Corrosive poisonings are attributed An unconscious or near-conscious diluted, or Lugol’s Solution (iodine with to strong acids and alkalis, such as person should be placed on their potassium iodide) could also be given as vitriol (sulphate salts of various metals), abdomen, head turned to one side a general antidote. But the precipitates spirits of salt (HCl), aqua fortis (nitric and tongue pulled forward. may dissolve in alkaline juices in the acid (HNO3)), carbolic acid, and oxalic 4. If the patient is conscious and has a gag intestines, so to hurry the poison through acid among the acids; and caustic soda, refl ex then it is fi ne to give him water the bowels if vomiting or a stomach pump potash (soluble potassium salts), and or milk. The way to test a person’s gag is not possible to rely on, a purgative lime among the alkalis. The symptoms of refl ex is to apply pressure to the back should be administered. this type of poisoning are intense burning of their tongue. Normally they will gag pain from mouth to stomach, the inside of when you do this. According to Stedman’s medical the mouth appears blistered or covered 5. Give 2-4 glasses of water immediately dictionary, the “universal antidote” with loosely-hanging white skin, the voice but milk can be substituted. described above is considered ineffective, is hoarse, and the pulse feeble, and the 6. Induce vomiting immediately by giving except for the activated charcoal patient retches. The vomited food matter 1-2 tablespoons of salt in a full glass which absorbs and obstructs alkaloids. contains whitish fl akes or shreds, which of warm water, or a tablespoon of However, it could be very dangerous to

HKPJ VOL 19 NO 1 Jan-Mar 2012 26 administer. If the victim is drowsy any with vomiting and the development of consumption have increased signifi cantly vomitus could end up in the lungs which ascites. Death may ensue from 2 weeks in recent years. Unlike the period prior to could result in death. But quick removal to more than 2 years after poisoning, but 1940, of all the recent casualties most from the stomach is desirable. patients may recover almost completely if were not attributed to alkaloid poisoning. the alkaloid intake is discontinued and the Nevertheless, poisoning due to alkaloids liver damage has not been too severe. still repeatedly happens and most alkaloid EXAMPLE OF ALKALOIDS POISONING: poisonings are recoverable if prompt - PYRROLIZIDINE COMPOUNDS Diagnosis fi rst aid is given. Pharmacists should be knowledgeable about these kinds Background Evidence of toxicity may not become of poisonings so they can give advice apparent until sometime after the on the right antidotes to use for alkaloid Pyrrolizidine alkaloids are a large, alkaloid is ingested. Early clinical signs poisoning so that a poisoned life may be varied class of naturally occurring, include nausea and acute upper gastric rescued. stereochemically diverse monoesters, pain, acute abdominal distension with diesters and macrocyclic diesters of prominent dilated veins on the abdominal 1-hydroxymethyl-7-hydroxy-1,2-dehydro wall, fever, and biochemical evidence of ACKNOWLEDGEMENTS pyrrolizidines (e.g. esters of the diastereo a dysfunctional liver. Fever and jaundice isomeric necine bases heliotridine and may be present. In some cases the lungs This paper has drawn substantially on the retronecine) or their N-methylated, ring are affected; pulmonary edema and material published at chestofbooks.com/ opened (otonecine) analogues.(9-11) pleural effusions have been observed. food/household/Woman-Encyclopaedia, These alkaloids and their N-oxides occur Lung damage may be prominent and has see reference 8 below. as natural components of many herbal been fatal. Chronic illness from ingestion preparations, cooking spices and honey, of small amounts of the alkaloids Author’s background and can contaminate food crops (e.g. over a long period proceeds through O’Toole, DK, is an Australian. He holds a cereals) and animal-derived food (e.g. BSc and MSc degrees from Qld University in fi brosis of the liver to cirrhosis, which is Microbiology and Food Microbiology. He was milk, eggs) destined for the human food indistinguishable from cirrhosis of other supply.(10,12) (See associated foods below.) awarded a PhD in 2001 from Griffi th University aetiology. on factors affecting the quality of milk and dairy products. Dr O’Toole has appeared as In vivo, the esterifi ed dehydro Associated foods an Expert Witness in a number of court cases pyrrolizidine alkaloids form hepatic, in Hong Kong involving food and microbiology. didehydro pyrrolizidine metabolites Many plants from the Boraginaceae, He has extensive experience with practical (i.e. dihydro pyrrolizine esters) that are Compositae, and Leguminosae families aspects of food production and has been hepatotoxic and can be pneumotoxic, contain well over 100 hepatotoxic an active member of committees that have genotoxic and carcinogenic.(10,11,13) pyrrolizidine alkaloids. Pyrrolizidine developed standards for microbiological Although pyrrolizidine alkaloid poisoning due to the consumption of testing for the Dairy Industry. Dr CHEUNG, intoxication is a rare toxicosis, it can be the alkaloid-containing plants as food, HY is associate professor of pharmaceutics in caused by consumption of plant material contaminants of food, or as medicinals the City University of Hong Kong. His email containing these alkaloids. The plants has occurred. address: [email protected] may be consumed as food, for medicinal purposes, or as contaminants of other Most result from the use of medicinal agricultural crops. Cereal crops and preparations as home remedies. References forage crops are sometimes contaminated 1. Hornby AS (2004). Oxford Advanced Learner’s English- However, intoxications of animals th with pyrrolizidine-producing weeds, and Chinese Dictionary, 6 Ed. Publisher: Oxford. grazing on pasture sometimes occurs 2. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002618/ the alkaloids fi nd their way into fl our and in areas under drought stress, where (reviewed: January 10, 2011 and accessed on March 3, 2012) other foods, including milk from cows plants containing alkaloids are common. 3. http://familydoctor.org/familydoctor/en/diseases-conditions/ food-poisoning/mushroom-poisoning.html [accessed on feeding on these plants. Milk from dairy animals can become March 3, 2012] contaminated with the alkaloids, and 4. Centers for Disease Control (1996-05-17). Tetrodotoxin Poisoning Associated With Eating Puffer Fish Transported While hepatic N-oxidation of alkaloids have been found in the honey from Japan. Morbidity and Mortality Weekly Report pyrrolizidine alkaloidsis a recognised collected by bees foraging on toxic plants. 45(19):389–412. detoxifying mechanism in mammals,(14,15) 5. Noguch T, Arakawa O (2008). Tetrodotoxin – Distribution and Mass human poisonings have occurred in Accumulation in Aquatic Organisms, and Cases of Human it has been shown that orally ingested other countries when cereal crops used Intoxication. Marine Drugs, 6(2):220-242. N-oxides of the pyrrolizidine alkaloids to prepare food were contaminated with 6. CASSIDY S, HENRY J (1987). Fatal toxicity of antidepressant can have hepatotoxicity similar to that drugs in overdose. British Medical Journal, 295:1021-1024. seeds containing pyrrolizidine alkaloid. 7. Fleisher D, Li C, Zhou Y,Pao L,Karim A (1999). Drug, Meal of the parent free base alkaloids due to and Formulation Interactions Infl uencing Drug Absorption After Oral Administration: Clinical Implications. Clinical reduction in the alimentary tract prior to Prevention Pharmacokinetics, 36(3):233-254. (9) absorption. Furthermore, Molyneux et 8. http://chestofbooks.com/food/household/Woman- Encyclopaedia-1/How-To-Treat-Cases-Of-Poisoning. al. showed that, in calves, intra-ruminal Avoiding the plants containing the html#ixzz1rGbw2PLC [accessed on March 3, 2012] infusion of riddelliine-N-oxide alone, at substances is the only way of prevention. 9. Mattocks AR (1986). Chemistry and toxicology of pyrrolizidine the same rate as calculated for a toxic However, these plants are not normally alkaloids. Academic Press: London. 10. International Program on Chemical Safety (IPCS) (1988). dose of the whole plant, resulted in consumed in a European diet. Pyrrilizidine alkaloids. Environmental Health Criteria 80. toxicity on a par with the whole plant.(16) WHO, Geneva. By contrast, they also showed that 11. Wiedenfeld H, Roeder E, Bourauel T, Edgar J (2008). Risk populations Pyrrolizidine alkaloids. Structure and Toxicity. V&R Unipress, infusion of the riddelliine free base, Bonn University Press: Göttingen. again at the rate calculated for a toxic All humans are believed to be susceptible 12. Edgar JA (2003). Pyrrolizidine alkaloids and food safety. dose of the whole plant, was not toxic. Chemistry Australia, 70:4-7. to the hepatotoxic pyrrolizidine alkaloids. 13. Fu PP, Xia Q, Lin G (2004). Pyrrolizidine alkaloids – However, others have shown that, given Home remedies and consumption of genotoxicity, metabolism enzymes, metabolic activation, and mechanism. Drug Metabolism Review, 36:1-55. intravenously, or studied in vitro using herbal teas in large quantities can be a 14. Jago MV, Edgar JA, Smith LW, Culvenor CCJ (1970). liver microsomes, the N-oxides are less risk factor and are the most likely causes Metabolic conversion of heliotrine based pyrrolizidine alkaloids to dehyroheliotridine. Molecular Pharmacology, toxic than the parent free base alkaloids. of alkaloid poisonings. 6:402-406. 15. Miranda CL, Chung W, Reed RE, Zhao X, Henderson Poinsoning symptoms MC, Wang JL, Williams DE, Buhler DR (1991). Flavin- containing monooxygenase: a major detoxifying enzyme for CONCLUSION the pyrrolizidine alkaloid senecionine in guinea pig tissues. Biochemical Biophysical Research Communications, Most cases of pyrrolizidine alkaloid 178:546-552. toxicity result in moderate to severe liver Death or sickness caused by a toxic 16. Molyneux RJ, Johnson AE, Roitman JN, Benson ME (1979). Chemistry of toxic range plants. Determination of pyrrolizidine damage. Gastrointestinal symptoms are substance either intentionally for alkaloid content and composition in Senecio species by nuclear magnetic resonance spectroscopy. Journal of usually the fi rst sign of intoxication, and the purpose of murder or suicide, or Agriculture and Food Chemistry, 27:497-499. consist predominantly of abdominal pain unintentionally due to accidental contact or

HKPJ VOL 19 NO 1 Jan-Mar 2012 27 Pharmaceutical TechniqueTechniques & & Technology Technology

Method Development for the Colorimetric Determination of Total Alkaloids in Herbal Medicine

CHEUNG, Hon-Yeunga*; BAIBADO, Joewel Tarraa,b; CHAN, Gallant GLa; ZHANG, Zhi-fenga,c a Research Group for Bioative Products, Department of Biology and Chemistry, City University of Hongkong, 83 Tat Chee Avenue, Hongkong SAR, China (* Corresponding author) b Iloilo Doctors’ College, College of Sciences & Nursing, 5000 West Avenue, Molo, Iloilo City, Philippines c Ethnic Pharmaceutical Institute of Southwest University for Nationalities, Chengdu 610041,Sichuan, China

ABSTRACT to be determined. The quantity may determination of total alkaloids in this be so low that it cannot be assayed study has also been endorsed and Herbal plants contain many bioactive individually. Shams et al. (2009) reported adapted as the assay method for components that are responsible for that vincristine and vinblastine alkaloids Fritillaria spp. in Phase III of the Hong their bioactivities. These compounds in Catharanthus roseus L. Don are as Kong Chinese Materia Medica Standards are very complex and closely related low as 0.001 and 0.002% respectively.(1) (HKCMMS) in 2010.(6) in structure making them diffi cult to Among wild morning-glory species isolate qualitatively and quantitatively. (Ipomoea spp.), the range of the total Numerous studies have demonstrated ergot alkaloids is between 0.0029% to MATERIALS AND METHODS that isosteroidal alkaloids are the 0.0059%.(2) The scopolamine alkaloids major active components in medicinal in Atropa belladona were found to be as Apparatus and reagents plants. However, the content of low as 0.00168 (% dry wt).(3) individual alkaloid components vary The UV absorbance of alkaloid-dye among species and the content of any adducts was measured with a Hitachi On one hand, the amount and potential marker is present at very low U-2810 UV-Vis spectrophotometer type of bioactive isosteroidal alkaloids level (less than 0.01%) so that it can (Lab Recyclers, Inc., Gaithersburg, varies among different Fritillaria species not be quantifi ed by High Performance America). Potassium biphthalate, and the content of potential marker Liquid Chromatography (HPLC). It was bromothymol blue, dichloromethane, alkaloid(s) may be lower than 0.01%, found that using a specifi c marker for ammonium hydroxide, ethanol, ethyl which is the criterion set down by the the assay is not an ideal choice for acetate, anhydrous sodium sulfate were many herbs. Hence, the total alkaloid committee of the Hongkong Chinese purchased from Shenzhen Zhongyuan content was used as an index for Materia Medica Standards (HKCMMS) Chemical & Glass Instruments Company the quality control of the herb. The for the selection of marker compounds (China). Peimisine (purity >98%) was (4-5) aim of this study was to optimize for the quality control of herbs. To purchased from Hai Chan Biotechnology an acid-dye colorimetric method for extract and produce suffi cient quantities Limited (Hong Kong). Seven batches of the quantitative determination of the of a purifi ed bioactive component, the Fritillaria ussuriensis Bulbs (FUB) were total alkaloids in herbal medicines. quality of raw herb is a determining purchased or collected freshly from The method developed shows good factor. Thus, it is necessary to determine various cities/counties in China in May reproducibility and high reliability. the alkaloid contents at the start. Hence, 2007. Details of their origin are listed This quantitative method is useful for this study aims to optimize a simple and in Table 1. All collected samples were the quality control of herbal medicine reliable quality control method for herbal authenticated by Prof. Wang Qiuling with low alkaloid content. medicines with low contents of active (Beijing University of Chinese Medicine, alkaloids. The reported colorimetric Beijing, China). Keywords: Herbal medicine; Total alkaloids; Colorimetric method; Acid-dye; Table 1. Source Information and Total Alkaloid Content of Different Batches of Fritillaria Quality control ussuriensis bulb Batch No. Sample ID Source Amount±SD (%w/w) 1 FUB 01-01 Tonghua, Jilin 0.2426±0.0056 INTRODUCTION 2 FUB 03-01 Baishan, Jilin 0.2826±0.0081 Alkaloids are secondary metabolites 3 FUB 04-01 Tieli, Heilongjiang 0.2516±0.0036 in plants that are complex but closely 4 FUB 05-01 Heilongjiang 0.2826±0.0081 related in structure. A certain herb may 5 FUB 06-01 Jilin, Jilin 0.2826±0.0081 contain many similar alkaloids. However, 6 FUB 07-01 Northeastern, China 0.2246±0.0079 their contents may not be high enough 7 FUB 08-01 Heilongjiang 0.2840±0.0108

HKPJ VOL 19 NO 1 Jan-Mar 2012 28 Initial procedure for the acid-dye The dried extract was further dissolved M), respectively, for later colorimetric colorimetric method in 10 mL of dichloromethane. One mL of analysis as mentioned above. the dissolved sample extract was taken The colorimetric method for out and added with another 7 mL of Investigation of the effect of residual determination of total alkaloids is dichloromethane for the determination of water based on the conjugation reaction total alkaloids according to the method between total alkaloids in sample described above. As the remaining water present after the extracts and bromothymol blue, forming partition of sample extract with dye might colored alkaloid-dye adducts which Extraction method interfere with the absorbance of the can be measured quantitatively with sample-dye solution, anhydrous sodium a UV spectrophotometer. The initial One mL of ammonium hydroxide was sulfate was used to remove the residual colorimetric method was carried out added to half gram of powdered FUB water in the dichloromethane layer to according to the method described by Liu sample in a 50-mL round bottom fl ask see the possible infl uence from residual & Xie (1995) with minor modifi cation.(7) and left to stand for 30 min at room water. In brief, the dichloromethane layer Peimisine was selected as a standard as temperature. Ten mL of dichloromethane/ was collected in a test tube containing it is a typical active alkaloid in Fritillaria methanol (4:1,128 v/v) was added into the 0, 2 or 4 g of anhydrous sodium sulfate. spp. and the average content is slightly round bottom fl ask. Then, an extraction The solution was shaken and fi ltered to larger than 0.01% (Table 2). Briefl y, method applied including sonication (for a 25-mL volumetric fl ask for subsequent 2 mL of 0.2 M potassium biphthalate 30 min or 60 min) or refl uxing (60 or colorimetric analysis. buffer solution (pH 5.0) and 2 mL of 120 min) was adapted. After extraction, 0.001 M bromothymol blue solution were sample solutions were further processed Validation of optimized method transferred into a 50-mL separating funnel according to the procedure described containing 8 mL of standard solution in the preceeding paragraph on the Calibration curve or sample extract in dichloromethane. optimization of extraction solvent. Two mg of peimisine was dissolved to Then, the mixture solution was shaken 10 mL of dichloromethane in a volumetric vigorously and allowed to stand for 10 Soaking time in ammonium hydroxide fl ask as a stock of standard solution min. The number of partitionings of the (standard stock). The calibration curve sample solution in bromothymol blue dye One mL of ammonium hydroxide was was prepared using 0.2, 0.4, 0.8, 1.0 and with dichloromethane was investigated. added to half gram of powdered FUB 1.2 mL of standard stock solution, which The partition steps were repeated from sample in a 50-mL round bottom fl ask were then supplemented with 7.8, 7.6, one to four times. Subsequently, the and left to stand for 30 or 60 min at room 7.2, 7.0 and 6.8 mL of dichloromethane temperature. The following steps were dichloromethane layer was collected and processed accordingly. and fi ltered into a 10-mL volumetric the same as mentioned above while fl ask. Filtrates were combined in the using dichloromethane/methanol (4:1, Reproducibility, repeatability and same 10-mL volumetric fl ask, to which v/v) as the extracting solvent and refl uxing recovery was added dichloromethane to make up (120 min) as the extraction method. a total volume of 10 mL. After standing The reproducibility test of the method for 30 min, the UV absorbance of the Optimization of the ratio of dye to was examined by analyzing fi ve replicate solution was measured at 410 nm. The sample extract standard solutions of 16 mg/L peimisine. absorbance of the solution was diluted if The repeatability test was carried necessary to give an absorbance value To ensure the homogeneity of the out through the measurement of fi ve in the range from 0.2 to 0.8. analyte, all the sample extract needs to replicates of the same batch of Fritillaria be collected and analyzed as only one sample (Table 3). To evaluate the Optimization of sample extraction mL of sample extract was taken out for recovery test of the developed method, the analysis in previous experiments and fi ve replicates of Fritillaria samples spiked Extraction solvent all the sample extract re-dissolved in with 0.7 mg of peimisine were measured dichloromethane (total in 10 mL) should with eight times dilution. Concentrations To a 0.5 g sample of powdered FUB in be used. Accordingly, the ratio of dye to of the analytes were calculated from the a 50-mL centrifugal tube was added 1 sample extract needs to be optimized. established calibration curve. mL of ammonium hydroxide and it was Briefl y, 0.5 g of sample was extracted left for 30 min under room temperature. with dichloromethane:methanol (4:1). Application to Fritillaria spp. samples Then, 10 mL of fi ve solvents, namely After soaking in ammonium hydroxide dichloromethane, dichloromethane/ for 30 min and subsequent 120-min Briefl y, 0.2 g of each 20 Beimu sample methanol (4:1, v/v), methanol, ethanol refl uxing, the extract was dried and re- was soaked in 1 mL of ammonium or ethyl acetate, was added into the dissolved in 8 mL of dichloromethane. hydroxide solution for 30 min. It was then centrifugal tube, respectively, for the Different amounts of sample extract extracted using 120 min refl ux with the later comparison of their extraction (corresponding to 0.125, 0.25, 0.375 addition of 10 mL of dichloromethane/ capabilities. After sonicating for 30 min, and 0.5 g sample used) were then methanol (8:2v/v) solution. After the above mixture solution was fi ltered partitioned with three concentrations evaporation, the extract was dissolved in and fi ltrate was evaporated to dryness. of the dye (0.001, 0.0025 and 0.005 8 mL of dichloromethane for subsequent colorimetric analysis. The colorimetric method for determination of alkaloids Table 2. Results of the marker selection assay in the determination of components of FUB using HPLC described by Liu & Xie, 1995(7) was adapted with minor modifi cations. Compound A Compound B Pingbeimine A 3-acetate Peimisine Peimisine was selected as a standard as Mean 0.005 0.0054 0.0099 0.0163 it is a typical active alkaloid in Fritillaria RSD 44.00909 30.62562 60.5193 90.67995 with the average content of slightly

HKPJ VOL 19 NO 1 Jan-Mar 2012 29 larger than 0.01% (Table 2). Briefl y, 60 or 120 min refl ux) is shown in Fig. 1C. increase proportionally to the amount 2 mL of 0.2 M Potassium biphthalate It is clear that using 120-min refl ux as of sample used Fig. 2A(b). This might buffer solution (pH 5.0) and 2 mL of the extracting method gave the highest be attributed to the interference with 0.0025 M Bromothymol blue solution were extraction effi ciency of total alkaloids in absorbance of the sample-dye complex transferred into a 50 mL separating funnel FUB. Thus, 120 min refl ux was selected caused by the redundancy of the dye. containing 8 mL of standard solution as the extraction method in the optimized While the concentration of bromothymol or sample extract in dichloromethane. method. blue lowered down to 0.0025 M Then, the mixture was shaken vigorously Fig. 2A(c), the absorbance of the complex and stood for 10 min. Subsequently, the Optimization of soaking time in rose linearly. Through correlating the dichloromethane layer was collected and ammonium hydroxide absorbance of the solution on the basis fi ltered into a 10 mL volumetric fl ask. of the calibration curve of initial acid-dye Filtrates were combined in the same 10 In Fig. 1D, no signifi cant difference was colorimetric method (data not shown), mL volumetric fl ask, and were added observed when samples were treated the amount of total alkaloids determined with dichloromethane to make up a total with ammonium hydroxide for 30 and 60 by this method exhibited a good linear volume of 10 mL. After standing for 30 min, respectively, indicating that 30-min relationship with the amount of sample min, the UV absorbance of the solution deposition time is enough for the sample ranged from 0.1 to 0.5 g Fig. 2A(d). was measured at 410 nm (UV 1201 UV- solution to reach stable absorbance. The result indicated that 0.0025 M was Vis Spectrophotometer; Shimadzu). The a proper concentration for bromothymol absorbance of the solution was diluted Optimization of the ratio of dye to blue used in the optimized method. by 5 (if necessary) to give an absorbance sample extract value from 0.2 to 0.8. Removal of residual water in sample- As shown in Fig. 2A(a), when bromothymol dye solution blue was at the concentration of 0.001 RESULTS M, the absorbance of the sample-dye The result of Fig. 2B showed that after solution increased linearly with the the addition of anhydrous sodium Optimization of the number of sample amount initially and decreased sulfate (ASS), the absorbance of blank partitionings at the point of 0.375 g of FUB sample. dichloromethane fl uctuated a lot, and a It might be due to the inadequacy of similar phenomenon was observed for When comparing the infl uence of the the bromothymol blue dye present in the sample extract. The absorbance of number of partitions on the partition the alkaloid-dye reaction. When the the solutions decreased substantially effi ciency (Fig. 1A), it is clear that three concentration of the dye was increased after the addition and the maximum partitionings with dichloromethane was to 0.005 M, the absorbance did not absorbance of the solution also shifted enough to extract total alkaloids as the content of total alkaloids reaches a stable level. Thus, three partitionings was 0.16 adapted in the succeeding experiments. 2600 0.14 2400 A C Optimization of extracting solvent 2200 0.12 2000 0.1 The extraction yield of total alkaloids 1800 1600 0.08

with different solvents including Content (mg/kg) 1400

Amount (%) 0.06 dichloromethane: methanol (4:1), 1200 dichloromethane, methanol, ethanol 1000 0.04 0 1 2 3 4 5 and ethyl acetate is displayed in Fig. 0.02 Number of times of Partitioning 1B. The contents of total alkaloids 0 were calculated through the calibration Sonicate 30min Sonicate 60min Reflux 60min Reflux 120min curve of peimisine, and the extraction 0.10 0.16 effi ciency of total alkaloids from B D FUB samples with different solvents 0.14 was evaluated using the parameter 0.08 amount (%) which was calculated as 0.12 0.1 total alkaloid weight (equivalent amount 0.06 of peimisine) percentage of the sample. 0.08 By comparing extraction effi ciency of Amount (%) different solvent systems, it was found Amount (%) 0.04 0.06 that dichloromethane: methanol (4:1) 0.04 was the most effective system for the 0.02 extraction of total alkaloids of FUB 0.02 samples. Therefore, dichloromethane: 0.00 0 methanol (4:1) was chosen as the Dichloromethane Methanol Ethanol Ethyl acetate Dichloromethane: 30 min 60 min extracting solvent in the optimized Methanol = 4:1 method. Figure 1. Method development for determination of total alkaloids in Fritillaria samples. A = Effi ciency of extraction using an increasing number of partitioning. B = Extraction effi ciency Optimization of extraction method of total alkaloids with different solvents. C = Extraction effi ciency of total alkaloids with different methods. D = Extraction effi ciency of total alkaloids from FUB samples with 30 or 60 min after The performance of different extraction the addition of ammonium hydroxide to the sample. (Each set of data or column represents the methods (30 or 60 min sonication, mean ± SD of fi ve independent experiments)

HKPJ VOL 19 NO 1 Jan-Mar 2012 30 to different wavelengths. On the other DISCUSSION alkaloids. Based on the initial acid-dye hand, direct measurement of UV colorimetric method mentioned above, absorption for the blank dichloromethane So far, few approaches have been a series of experimental conditions were and sample-dye solution without the developed for the determination of total further optimized and satisfactory results addition of ASS gave a more reproducible alkaloids in plant materials, such as were obtained. and stable reading with consistent UV gravimetric method, titrimetric method, maximum absorption. Therefore, the and colorimetric method.(8-13) When Sonicated solution containing a organic layer could be directly used for compared to the colorimetric method, surfactant as extracting agent was used UV measurement and there is no need to gravimetric and titrimetric approaches by Djilani et al. (2006) in the extraction remove residual water. show weaker sensitivity. In most of alkaloids from natural products gravimetric methods, impurities were such as Hyoscyamus muticus, Datura (14) Linearity, reproducibility, repeatability found to be present in the residue as stramonium and Ruta graveolens. The and recovery more than one spot is displayed by extracting reagent used was chloroform TLC.(13) The titrimetric assays may not and precipitated with Mayer’s reagent be able to refl ect the reality as the end- dissolved in a basic solution.(14) In As shown in Fig. 3, the calibration curve point could be obscured by the color of Fig. 1C, it is clear that using 120-min of peimisine exhibited a good linear the extract. Thus, a colorimetric method refl ux as the extracting method gave regression (R2 = 0.9992): y= 0.0263x + adapted in this study is more sensitive the highest extraction effi ciency of total 0.0964. The results of reproducibility, and reliable for the determination of total alkaloids as compared to sonication. repeatability, and recovery tests of the optimized method are displayed in Table 3, which shows that the developed Calibration curve for peimisine colorimetric method for the determination 0.8 of total alkaloids are reproducible with 0.7 good repeatability and recovery. 0.6 0.5 Application to Fritillaria spp. 0.4 y= 0.0263x + 0.0964 2 0.3 R = 0.9992 The optimized protocol was applied to 0.2 Fritillaria samples. The total alkaloid 0.1 content of Fritillaria ussurienses bulb is 0 0 5 10 15 2025 30 presented in Table 1. The total alkaloid Conc. (mg/1) among Fritillaria samples is between 0.2246-0.2840 (%w/w). Figure 3. Calibration curve for peimisine determined by acid-dye colorimetric method.

A (a) 0.001M Bromothymol blue B 1.2 1 0.8 0.6 2 g ASS Abs 0.4 0.80 0.2 4 g ASS 0 0.125 0.200 0.375 0.500 0.70 0 g ASS Corresponding amount of sample/g

(b) 0.005M Bromothymol blue 4’g ASS 1.2 0.60 1 0’g ASS 0.8 0.6 0.4 Abs 0.2 0.50 0 0.125 0.200 0.375 0.500 Corresponding amount of sample/g 0.40 (c) 0.0025M Bromothymol blue 1 Absorbance 0.8 0.30 0.6

Abs 0.4 0.2 0.20 0 0.125 0.200 0.375 0.500 Corresponding amount of sample/g

(d) 0.0025M Bromothymol blue 0.10 1.6 1.4 1.2 1 0.00 0.8 y = 2.615x + 0.016

Abs 0.6 R2 – 0.9995 0.4 1 2 3 0.2 0 0.125 0.200 0.375 0.500 Measuring times Corresponding amount of sample/g Figure 2. Absorbance of the sample-dye solutions. A = Sample prepared with different amounts of acid dye using 0.001 M (a), 0.005 M (b) and 0.0025 M (c) bromothymol blue, and the corresponding amount of total alkaloids (d) in the colorimetric method. B = Absorbance of the mixture of blank dichloromethane solution and 0 /2 / 4 g of anhydrous sodium sulfate (solid lines), and the mixture of sample-dye solution and 0 / 4 g of anhydrous sodium sulfate (dashed lines).

HKPJ VOL 19 NO 1 Jan-Mar 2012 31 Table 3. Results of reproducibility, repeatability, and recovery tests in the determination of total References alkaloid contents in Fritillaria samples using acid-dye colorimetric method 1. Shams KA, Nazif NM, Azim NSA, Shafeek KAA, Test Mean SDa RSDb (n=5) El-Missiry MM, Ismail SI, Nasr MMSE (2009). Isolation and Characterization of Antineoplastic Absorbance Reproducibility 0.45 0.01 2.62 Alkaloids from Catharanthus Roseus L. Don. (16 mg/L peimisine) Cultivated in Egypt. Afr J Tradit Complement Amount (mg/Kg) Altern Med. 2009; 6(2):118–122. Repeatability 2616.54 91.25 3.49 (0.2 g of FUB sample) 2. Wilkinson RE, Hardcastle WS, McCormick CS Recovery (%) Recovery 96.33 3.71 3.85 (1988). Psychotomimetic ergot alkaloid contents of (0.2 g of FUB sample spiked with 0.7 mg of peimisine) seed from Calonyction muricatum, Jacquemontia a Standard deviation; b Relative standard deviation tamnifolia, Quamoclit lobata, and Quamoclit sloteri. Bot. Gaz. 149(1):107-109 3. Fatemeh A, Fatemeh S (2011). Tropane alkaloids Thus, 120 min refl ux was selected as the can be a suitable quality control tool of Atropa belladonna L. and Atropa acuminata extraction method instead of sonication. for medicinal plants especially those Royle ex Miers Plants. J Med Plant Res Shams et al. (2009) utilized different containing a variety of small amounts of 5(29):6515-6522 methods of preparation of total alkaloids active alkaloids. 4. Yu, H, Jiang, Y, Li, P, Li, SP, & Wang, YT (2005). Study on analytical method for alkaloids in Bulbus using different solvents like benzene, Fritillariae cirrhosae. China journal of Chinese methanol, ethyl acetate, chloroform, Materia Medica 30:572-575. (1) and methylene chloride. It was found ACKNOWLEDGMENT 5. Ding, K, Lin, G, Ho, YP, Cheng, TY, & Li, P (1996). that vincristine and vinblastine alkaloids Prederivatization and high-performance liquid chromatographic analysis of alkaloids of bulbs in Catharanthus roseus L. Don are as This study arose from partial work on of Fritillaria. Journal of Pharmaceutical Sciences low as 0.001 and 0.002% respectively.(1) the projects (CityU Project No. 9210026 85:1174-1179. Among wild morning-glory species and No. 9211007) of Hong Kong Chinese 6. Hong Kong Chinese Materia Medica Standards (Ipomoea spp.), the range of the total Materia Medica Standards (HKCMMS) (2008) Hong Kong: Department of Health, Hong ergot alkaloids is between 0.0029% to funded by the Department of Health, Kong Government SAR. 4:195-205 0.0059%.(2) The scopolamine alkaloids in Hong Kong SAR Government. The 7. Liu, J, & Xie, Jintao (1995). Determination of total alkaloids and trace elements in Fritillaria. Atropa belladona were determined as low funding support is highly appreciated. Guangdong Trace Elements Science 2:63-66. as 0.00168 (% dry wt) using chloroform- 8. Kumar, R, & Hemalatha, S (2010). (3) methanol-ammonia extraction. Various Author’s background Pharmacognostical standardization of leaves of solvents including diethyl ether, Dr. CHEUNG Hon-Yeung, who is an associate Alangium lamarckii Thwaites. Pharmacognosy Journal 2:19-26. chloroform, and methanol were used professor of Pharmaceutics at the City University of Hong Kong, is a manufacturing 9. Wu, H, Tang, Z, Qiu, L, & Ye, D (1999). The to extract alkaloids from Fritillaria pharmacist and biotechnologist. He has more comparison of component contents and with the quantity of the analyte varied than 30 years of working experiences in pharmacological actions between two kinds of markedly.(15-18) In the present study, industries, academic and consultancy jobs. processed products of Pinellia rhizoma prepared He was an expert witness in court and a by ginger juice and alum. China journal of Chinese it was shown that dichloromethane: member of the Biotechnology Committee for Materia Medica 24:25-28, 63. methanol (4:1) is the most effi cient Hong Kong and Shenzhen Government. Dr. 10. Davidson, AG & Hassan, SM (1984). The extraction solvent coupled with 120 min Cheung has published more than 200 papers simultaneous assay of emetine and cephaeline refl ux. It yielded 0.2246-0.2840% total and articles in many prestigious international in Ipecacuanha and its preparations by journals. He is frequently interviewed by the spectrofl uorimetry. Journal of Pharmaceutical and alkaloids. This simply shows that this mass media. He can be contacted through his Biomedical Analysis 2:441-448. email address: [email protected] extraction method has higher effi ciency 11. Derya, C, Nehir, US, & Gulen, IK (2010). Prof. Joewel Tarra Baibado is a doctor of compared to others. Table 2 shows the Quality control and anticholinesterase activity Public Health Medical Microbiology student result of marker selection assay in the determinations on Sternbergia sicula. Marmara at the University of the Philippines. He Pharmaceutical Journal 14:121-124. determination of alkaloids in FUB. In this obtained his Master of Science in Biology case, it can be inferred that HPLC is not (Microbiology), BS in Biology, and Professional 12. Saleh, MR, El-Masry, S, & El-Shaer, N Education from the same university. He is an (1979). Colorimetric and spectrophotometric the method of choice. Although the mean assistant professor of medical microbiology, determination of total and non-phenolic alkaloids peimisine was slightly higher than 0.01%, parasitology and human biology at Iloilo in ipeca and its formulations. Journal Association of Offi cial Analytical Chemists 62:1113-1115. the variation of the content is very large Doctors’ College, College of Sciences as refl ected by large RSD values. It has and Nursing in Philippines. His research 13. Shamsa, F, Monsef, H, Rouhollah, R, & Verdian- interests include screening of antimicrobial rizi, M (2008). Spectrophotometric determination been depicted by various results that the properties of bioactive compounds of of total alkaloids in some Iranian medicinal alkaloid contents of different herbs varied Philippine mangroves and indigenous plants. Thai Journal of Pharmaceutical Sciences remarkably and that the amount may Philippine herbs. Recently, he is a research 32:17-20. associate at the City University of Hongkong be so low that it can hardly be assayed 14. Djilani A, Legseir B, Soulimani R, Dicko A, doing histologic sectioning and imaging Younos C (2006). New Extraction Techniques for individually even with HPLC. Therefore, microscopy of Traditional Chinese Medicines. Alkaloids. J. Braz. Chem. Soc. 17:3 Correspondence to: Joewel20022002@ determination of the total alkaloids is still 15. Li SL, Chan SW, Li P, Lin G, Zhou G, Ren YG, yahoo.com; [email protected] necessary in this scenario. Chiu FCK (1999). Precolumn derivatisation and CHAN, Gallant GL obtained his BSc and MPhil gas chromatographic determination of alkaloids degrees from CityU and worked as Research in bulbs of Fritillaria. J Chromatogr A 859:183-192 Assistant when this work was pursued. He is CONCLUSION currently doing his PhD project in the HKUST. 16. Li SL, Li P, Lin G, Chan SW, Ho YP 2000. Dr. Zhi-feng Zhang is an associate professor Simulataneous determination of seven major of Pharmacognosy and Pharmaceutical isosteroidal alkaloids in bulbs of Fritillaria by gas In this study, a colorimetric method for the Botany at the Ethnic Pharmaceutical Institute chromatography. J Chromatogr A 873:221-228 determination of total alkaloids has been of Southwest University for Nationalities, 17. Li SL, Lin G, Chan SW, Li P (2001). Determination Chengdu, Sichuan, China. His research of the major isosteroidal alakaloids in bulbs optimized and has been successfully interest is on microscopic studies and isolation of Fritillaria by high performance liquid applied to quantify the total alkaloids and purifi cation of bioactive compounds chromatography coupled with evaporative light in some samples of herbal medicine in Traditional Chinese Medicines. He is scattering detector. J Chromatogr A 909:207-214 (i.e., Fritillaria bulb). The method gave currently, a post doctoral fellow at the City 18. Xu DM, Huang EX, Wang SQ, Wen XG, Wu University of Hongkong. He can be contacted XY (1990). Studies on the alkaloids of Fritillaria satisfactory reproducibility. Therefore, at [email protected]. pallidifl ora. Acta Bot Sin 32:789-793 this method with minor modifi cations

HKPJ VOL 19 NO 1 Jan-Mar 2012 32 Herbal Medicines & Nutraceuticals

Turtle Shell Extract as a Functional Food and Its Component-based Comparison among Different Species

LI, Lin-Qiu; CHEUNG, Hon-Yeung* Research Group for Bioactive Products, Department of Biology & Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, China. (*Correspondence author) Tel.: +852 3442 7746; Fax: +852 3442 0522 Email address: [email protected]

Scientifi c Names: Chinemys reevesii Plastron has been prescribed to of turtle could be used as material (Gray); Cuora trifasciata; Cuora nourish yin and suppress the sthenic medica. In this review article, aurocapitata; Cuora galbinifrons, yang. It benefi ts kidney, invigorates sources, identifi cation and chemical Trachemys scripta; Hardella thurjii the bone, relieves metrorragia and composition of some turtle shells, Family: Emydidae (includes Chinemys can regulate menstruation. In recent as well as their biological effects spp., Cuora spp., Trachemys spp.); decades, many studies have been and medical uses are reviewed. Its Common Names: Chinese Pond done to ensure that diverse species addition to a few popular functional Turtles (Chinemys reevesii (Gray); foods by the Chinese herbalist are Asian Box Turtles (Cuora. trifasciata; C. also described. aurocapitata; C. galbinifrons); Crowned River Turtle (Hardella thurjii); Slider Keywords: turtle shell, plastron, Turtles (Trachemys scripta) functional food, guiling gao, gui lu erxian Chinese Names: 烏龜；閉殼龜；金頭閉 Contraindications jiao, cell proliferation 殼龜；黃額閉殼龜巴西龜；冠背龜 Turtle shell could excite the uterus. Part Usually Used: Plastron Therefore, it should not be used by Common Uses: sthenic yang pregnant women. In addition, for those INTRODUCTION suppression, bone invigoration, people with cold stomach and yin defi ciency it may not be good because it menstruation regulation, metrorrhagia is extremely yin.(1,2) Animals of the Order Testudines are relief, anti-aging classed as reptiles, whose common Undesirable Effects names may be different from country to Nil, but parasites may be present. country.(3) According to Animals: A visual ABSTRACT encyclopedia, Hand Book of Turtles Interaction with Conventional Drugs and Turtles of The World, testudinates Turtle shell is a traditional Chinese At the time of publication, no interaction that live on dry land and have round, with conventional drugs has been medicine, which has been used for stumpy legs are called tortoise, while reported. thousands of years by the Chinese. turtles spend most of their time in water and have fl ipper-like limbs. Freshwater turtles are often called terrapins.(4-6) For the sake of easy description, “turtle shell” is used in this review as a general name that means all types of shells of testudine BB11 BB22 CC11 animals.

The turtle shell is a highly complicated shield for the ventral and dorsal parts of the turtle, completely enclosing all the A1 BB33 BB44 CC22 vital organs of the turtle and in some cases even the head. It is constructed of modifi ed bony elements such as the ribs, parts of the pelvis and other bones found in most reptiles. The bone of the shell consists of both skeletal and dermal bone, showing that the complete AA22 D E enclosure of the shell probably evolved Figure 1. Pictures of Turtles. A1 = Chinemys reevesii (Gray) (烏龜), A2 = plastron; B1-3 = by including dermal armor into the rib Cuora trifasciata (三線閉殼龜,金錢龜), B4 = plastron; C1 = Cuora aurocapitata (金頭閉殼龜), C2 = plastron view; D = Trachemys scripta (巴西龜); E = Hardella thurjii (冠背龜,草龜) cage.

HKPJ VOL 19 NO 1 Jan-Mar 2012 33 It is widely accepted that turtle shells metrorragia. There is a legend that China along with the environmental have broad functional effects. It has been plastron of Cuora trifasciata, as shown in disruption, even these land tortoises used by Chinese people as a medicine Fig. 1, plates B1-4, has a higher nutritive will become endangered in the future. for thousands of years, and the shell value and is believed effective to heal Increasing efforts, therefore, are being of Chinemys reevesii (Gray) (Fig. 1-A1 certain tumours. If it is added to Guiling made to raise the tortoise by farming in & -A2) was fi rst recorded as Guijia in Gao, the best medical treatment can be China. Shen Nong Ben Cao Jing.(7) Turtle achieved. However, Cuora trifasciata is shell is mostly utilized in Rehmannia- classifi ed as a “critically endangered” As mentioned above, the offi cial based formulae that nourishes yin and species, and trading this species is totally listed shell recorded in the Chinese suppresses the sthenic yang. Meanwhile, prohibited. Pharmacopoeia (2010) comes from herbalists believe that it can benefi t Chinemys reevesii (Gray). This is a kidneys, invigorate bone, and regulate What is Gui Lu Erxian Jiao? land tortoise, found in rivers, lakes, and, menstruation and relieve metrorrhagia.(7-9) marshes, which is known in the west as the Until now most shells used as medicine Gui Lu Erxian Jiao (龜鹿二仙膠) is a Reeve’s tortoise. Two substitute species and functional food belong to Chinemys semifl uid extract of turtle plastron and obtained from Anhui Province, Cuora reevesii (Gray); which is recorded in deer-antler. It is a tonic decoction usually amboinensis and Cuora fl avomarginata, the Chinese Pharmacopoeia (2010) as mixed with some other herbal ingredients have been raised and sold on the market, the only recommended source of turtle such as ginseng and Lycium berries but they are not offi cially-recognized as (11-12) shell. Thus, demand for this species is (Goji). Gui Lu Erxian Jiao tonifi es qi and substitutes. The latter species is growing, resulting in a dramatic drop in blood, supplements kidney yin and yang, thought to be the one denoted as shuigui (13) the number of wild Chinemys reevesii and replenishes jing (essence). The in Li Shizhen’s Ben Cao Gang Mu. (Gray). In other cases, such as Guiling imbalance between the yin and yang can Other substitutes include Mauremys (14) Gao (sometimes referred to as Turtle lead to fatigue, lack of energy, dizziness, mutica and Testudo elongata. Another Jelly) and Gui Lu Erxian Jiao , turtle shell sweating, easy to catch a fl u and feeling tortoise, Eretmochelys imbricata, is used is an important component. cold. The Gui Lu Erxian Jiao has been as a separately listed item in the Chinese (10) claimed capable to improve overall Materia Medica, known as daimao. What is Guiling Gao? health, ensuring vitality at all times. It Although the Reeve’s tortoises can enhance a signifi cant improvement and some of the substitute species are Guiling Gao (or “Kwei Ling Ko” in in gynecological condition including raised in China for their shells,(15) there Cantonese) is a glue-like food produced menstrual pain, breast pain, excessive is still a huge natural supply and the by long-term boiling of turtle shells along secretion, feeble conditions, etc. Clinical majority of the shells are obtained from with some other herbal ingredients. It applications include weight loss, seminal wild resources. They can be collected all originated during the Ham Fung Era of emissions, impotence, dizziness, and year round, but are preferably obtained the Ching Dynasty in China between 16- soreness and weakness of the lower in autumn and winter. Tortoise collection, 19th Century, AD. It is an extravagant back and knees. It is regarded as a warm like that of fi sh in the same region, is food originally prepared for the nobles tonic. mainly accomplished by use of nets.(16) and the Emperor. No one knows who invented the prescription of Guiling Gao. Due to burgeoning demand in the What people know is that the recipe market, more than half of freshwater MEDICAL USE OF THE DORSAL AND was passed to farmers by a doctor of turtle and tortoise species from Southeast THE VENTRAL SHELL the emperor after his retirement and it and East Asia have been severely subsequently became a popular herbal threatened by over exploitation for food Turtle shell has two sections: the dorsal functional food amongst Chinese people. and traditional medicines. Therefore, in shell is known as the carapace, and the It is claimed to have wide application recent decades, many studies have been ventral shield is called the plastron.(17-18) to different diseases. It has a diuretic carried out aiming to fi nd substitutes for From the very fi rst time they were effect that may dissipate wetness, and these turtles in danger of extinction with introduced for use as medicinal medica remove toxic wastes from the body. It the same biological functions. Literature in Shen Nong Ben Cao Jing in the nourishes vital essences and cures spots surveys reveal that the results of most Han Dynasty,(7) both carapace and or blemishes on the skin. published works were conducted in plastron were recommended. However, China. In this review, the component after Zhu Dan Xi (a medical scientist of Guiling Gao contains some twenty based comparison of different turtle the Yuan dynasty) proposed a theory to thirty herbal drugs without a defi nite shells and the progress of recent study of nourishing yin,(19) folk began to use formula except that plastron and Poria will be described. plastron only. Hence, for a very long are the main components. Other time people believed that only plastron common ingredients include Lobeliae was suitable for medicinal uses and for chinensis, Akebia trifoliata, Dictammus SPECIES AND SOURCES OF TURTLE functional purposes, resulting in a huge dasycarpus and Hedyotis diffusase etc. SHELL waste of carapace. But some recent According to the 1998 edition of the research indicated that the carapace and Chinese-English manual of commonly The turtle shells used in Chinese plastron gave similar results in terms of used traditional Chinese Medicines, medicine are obtained from aquatic or nourishing yin.(20,21) It was only after 1990 plastron is described to (1) nourish yin land-based tortoise. Unlike sea turtles that the dorsal and ventral shells were and suppress the sthenic yang; (2) or some desert species, they are not employed as a whole again when the benefi t kidney and invigorate bone and included in the endangered species list.(10) Chinese Pharmacopoeia (1990) was (3) regulate menstruation and relieve However, due to the modernization of published.(22-23)

HKPJ VOL 19 NO 1 Jan-Mar 2012 34 AUTHENTICATION OF TURTLE Co, Ni, V, Si and Se etc.[Table 2],(33-36) in cholester-4-ene-3-one were claimed to SHELLS which Se is an anticancer element.(37-38) exist in shells of Mauremys mutica.(39) Although some toxic heavy metals were Fatty acid compounds of shells of In recent years, many adulterants have found in some turtle shells, the amount Chinemys reevesii (Gray) and Mauremy appeared in the turtle shell trading was very low and they were within smutica were determined by using GC- market. Hence, various techniques are acceptable ranges.(34) MS, and 32 kinds (with content of 49% required to identify the real ones from their of unsaturated fatty acid) of these acids adulterants. Mostly, people employ the In addition, some organics also were found in the previous one while 28 appearance-feature based methods for were found in turtle shells. Cholesterol, (with content of 66% of unsaturated fatty identifi cation: the color, the shape, odour, eicosenoic acid cholesterol ester and acid) were found in the latter species.(40) hardness,(24,25) and formula methods such (26) as the ratio diagrammatic method, the Table 1. Contents of amino acids in different species of turtle shell (%)(35) similarity factor of standard mode,(27) and the clustering method etc.(28) Amino Acids Different Species of Turtle Shell Chinemy sreevesii Testudo elongata Testudo elongata Ocadia sinensis Ocadia sinensis Asp 1.91 1.87 1.69 1.92 1.95 In order to identify the shells more Thr 0.80 0.68 0.55 0.81 0.82 precisely, on top of morphological Ser 1.34 1.30 1.03 1.41 1.38 examination (Fig. 1), biological and Glu 3.31 3.30 3.02 3.35 3.40 Gly 6.41 6.42 6.10 6.73 6.60 chemical methods have also been Ala 2.52 2.53 2.40 2.41 2.52 applied. A PCR technique was Cys 0.38 0.33 0.21 0.33 0.33 introduced to detect DNA of Colla Val 0.99 0.99 0.78 1.24 1.06 Met 0.22 0.18 0.17 0.22 0.22 Carapax et plastrum testudinis (shell Ile 0.63 0.61 0.50 0.68 0.64 of Chinemys reevesii ) glue Leu 1.31 1.25 1.05 1.68 1.50 Tyr 1.09 1.04 0.77 1.84 1.33 from six commercial tortoise shell glue Phe 0.5 0.77 0.72 0.96 0.91 products.(29) UV spectrum was also Lys 1.03 1.05 0.88 0.87 0.96 used for the identifi cation while Guo Amide 0.35 0.35 0.34 0.37 0.36 His 0.50 0.48 0.39 0.66 0.56 et al. employed UV-cluster analysis Arg 2.41 2.41 2.06 2.40 2.47 methods for the identifi cation of six Pro 3.59 3.64 3.38 3.73 3.68 types of turtle shell, namely shells of trp / / / / / Total 29.29 28.58 25.70 31.24 30.33 Chinemys reevesii (Gray), Cuora spp., Geoemyda grandis, Trxtudo elongata (Blyth), Clemmy smutica (Can tor) and Table 2. Parts per million (ppm) contents of trace elements in three species of turtle shell(36) (30) Platysternon megacephalum. Elements Species Chinemys reevesii (1) Chinemys reevesii (2) Cuora amboirenaia Si 6440 5133 4946 CHEMICAL COMPOSITION OF Ca 133300 123200 149000 Fe 1056 770 2593 TURTLE SHELL Al 1660 1419 1220 Mg 1056 1008 116 It is widely known that turtle shell is rich in K 340 340 174 (31,32) Na 6464 6167 4057 various kinds of amino acids. Fan et Ti 36110 13910 49710 al compared 9 types of turtle shells and Mn 5.60 1210 28101 found 18 essential amino acids with total Cr 61.80 35.00 70.40 Sr 1773 4928 6090 (33) content of 30.7%-39.6%. Cheung & Rb 3.80 3.60 9.10 Cheung were able to identify and analyse Ni 14.00 14.50 14.00 Co 20.50 23.20 23.50 sixteen amino acids in the plastrons Zn 473 251 342 and found that the content of glycine Pb 95.60 58.20 44.50 and glutamic acid was extra-ordinally Cu 834 150 144 Zr 0.50 0.36 0.16 high followed by proline, asparagine Y 19.40 2.10 0.17 and arginine.(34) This was subsequently Cl 364010 676000 319000 confi rmed by Gu after analysing the Cs 5.80 6.20 5.11 V 57.80 24.20 79.80 shells of Chinemys reevesii (Gray), Ce 61.10 36.90 69.80 Cuora amboinensis (Guenther), Tesrudo Ba 56110 19010 86100 As 77.40 43.20 37.60 elongate (Blyth), Ocadia sinensis (Gray), Ga 9.00 6.10 6.73 and Trachemys scripta elegans and Hf 14.50 162.00 169.00 reporting that all these shells contained La 32.30 4.60 6.97 Mo 5.30 5.70 4.83 amino acids ranging from 25.7% - Nb 7.90 2.70 0.36 31.24% with a higher content of glycine, P 424000 425000 449000 proline, glutamic acid, alanine, arginine S 188000 282000 221000 Sc 9.60 11.10 9.67 (35) and aspartic acid [Table 1]. Th 8.90 6.60 4.10 Se 0.150 0.030 0.066 B 0.36 0.35 0.21 Both macroelements and trace Hg 0.012 0.015 0.160 elements were found in turtle shells, Cd 0.016 0.043 0.280 such as P, K, Ca, Mg, Fe, Cu, Mn, Mo, Be 0.45 ------

HKPJ VOL 19 NO 1 Jan-Mar 2012 35 Lei et al. applied TLC scanning for growth in culture whenever plastron was defi cient rats were given a turtle shell studying of cholesta-4, 6-dine-3-ol in shell supplemented [Fig. 3] The control culture decoction. Besides, cell numbers of of Chinemys reevesii (Gray), and different did not show such a response. the peritoneal macrophages increased, species were found to differ in content.(41) the atrophic thymus gland recovered, Proteome and peptide in Colla Carapax Turtle extract can improve the et plastrum testudinis were studied by condition of the immune system. the conversion rates of lymphocytes using SELDI-TOF-MS (surface enhanced Recovery of the cell and hormonal increased and the aging of normal cells laser desorption/ionization time- of- fl ight immunity has been reported after yin was slowed down.(46) mass spectrometry). There was one peak for each interval of 1500-3000, 8000-8600, 10000-13000, and three A B peaks for interval 4800-5400 with different relative Mol Wt of 410.8 and 151.7.(42) Our group studied the protein extracts of plastron by using SDS gel. As shown in Fig.2, all sorts of plastron contain various proteins and peptides with their size continuously ranging from small to large.

Figure 3. Effect of plastron extract on the growth of NBT-II cells. Plate A: control culture; Plate B: in the presence of plastron extract.





Figure 2. SDS electrophoretogram of protein  extracts of plastron from different species. 

BIOLOGICAL FUNCTION AND  PHARMACOLOGICAL EFFECTS 5HODWLYHYLDELOLW\   Recent research showed that turtle shell has the effect of tonifying the blood,  enhancing immunity, reducing the speed  of aging, promoting development of the 76H[WUDFW XJPOSURWHLQ body, protecting the nerves, being an KU KU KU anti-cancer agent and regulating and controlling energy metabolism rate, and Figure 4. Effect of TS plastron extracts on the viability of HL-60 cells with various protein so on. concentrations; i.e. 5, 25 and 50 μg/ml of protein for 6, 12 or 24 hr.

Chen et al. identifi ed proliferation of mesenchymal stem cells (MSCs) after the culture was treated with plastrum testudinis extracts (PTE). They pointed out that the mechanism of PTE action may be associated with the up-regulation of MBP4.(43) Besides, this group also ACBD conducted some work on injured neural Figure 5. Morphology alternation of HL-60 after treatment with TS extract with (A) control, stem cell of focal cerebral ischemia and (B) 5, (C) 25 and (D) 50 μg/ml of protein. Yellow arrows indicate collapse of cell. injured spinal cord. According to their study, the turtle shell decoction could ease the neurologic defi cit and promote the expression of protein (Nestin).(44,45) As one of the major components of turtle jelly (Gui Ling Gao, 龜苓膏), turtle shell was found to be good for cell growth. We compared the effect of different ACBD ingredients of turtle jelly on NBT-Ⅱ cells Figure 6. Morphology of HL-60 after 24 h treatment with 50 μg/ml protein of turtle shells extracts. (A) Trachemys scripta, (B) Chinemys reevesi, (C) Cuoraauroc apitata, and (D) Cuora trifasiata. and found that signifi cantly beautiful Yellow arrows indicate collapse of cells.

HKPJ VOL 19 NO 1 Jan-Mar 2012 36 The anticancer effects of turtle Author’s background 21. Miao YL, Yang MX, Liu E, Yang Y (1988). Impact shells had also been explored LI, Lin-Qiu is a full-time PhD student at the of carapace and plastron on the weight, amount by Bayazit et al. Female rabbits City University of Hong Kong. She received her of water intake, amount of urine, and blood Master of Science in Analytical Chemistry and viscosity of thyroid-induced hyperthyroidism (Lepus capensis) were injected with yin-defi ciency model of rats. Bulletin of Chinese Bachelor of Science in Chemistry at Guangxi Materia Medica, 13(3):42-44. one mL dimethylbenzanthracene/kg/day University. Her research interests are mainly between 36 and 42 days in order to focused on biochemical characterization and 22. Chen QJ, Yu DF, Feng DK (2009). A research evidence-based study of traditional herbs. overview on turtle shell. Strait Pharmaceutical obtain tumor cells. Then the tumor was Journal, 21(6):105-1106. Dr. CHEUNG Hon-Yeung, who is an removed and tumor cells were incubated Associate Professor of Pharmaceutical 23. 鄭金生 (1982). “龜甲、敗龜、龜板”考辯—論龜 in RPMI-1640 medium. Results of the Microbiology & Biotechnology at the City 甲當用上、下甲. 中醫雜誌, 3:56-58. survival time and cell count indicated University of Hong Kong, is a manufacturing 24. 陸敏儀, 鐘麗新 (1986). 四種龜板的鑒別和化學成 pharmacist and biotechnologist. He has more 份含量測定的比較. 中藥通報, 11(11):15-19. that the ethanolic extract of turtle than 35 years of work experience in industry, 25. 李忠林，朱志峰 (2010). 龜板及其混偽品性狀鑒 shell possessed signifi cant anticancer academic and consultancy jobs. He has been 別. 傳統醫藥，19(14):74-75. activities.(47) We investigated the effect an expert witness in court and a member of the Biotechnology Committee for Hong Kong 26. 李水福，胡清宇，吳慧清 (1995). 比值圖示法鑒 別龜板及其混淆品. 中藥材，18(9):449-451. of aqueous extracts from plastron of and Shenzhen Government. 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Pharmacology and from: http://www.itmonline.org/arts/tortois2.htm Therapeutics. 79:179-192. sinensis (Gray), Cuora amboinensis [accessed on March 30, 2012] 39. 孫蘇亞，李發美 (2000). 黃喉擬水龜板中三種出體 (Guenther), Trachemys scripta elegans, 11. Zhang NR (1985). Identifi cation and criticism 化合物的分離和鑒定. 中國中藥誌，25(3):165- Chinemys reevesii (Gray). They found of two kinds of tortoise close-shell. Bulletin of 166. Chinese Medicinal Herbs (10):253. that all these shells except Ocadia 40. 孫蘇亞，李發美 (1999). 龜板中脂肪酸的GC一 MS分析. 藥物分析雜誌，19(6):406-409. sinensis improved the weight loss of 12. Chen BH, Li BH (1979). Ecological material from Cuora fl avomarginata. Journal of Zoology 41. 蕾鈞濤，蔡柏玲 (2005). 薄層掃描法測定龜甲中膽 rats that were yin defi cient. The anoxia 1:22-24. 甾4, 6-二烯-3 醇的含量. 醫藥導報，24(11):1051. tolerance of rats was also enhanced by 13. Li SZ. Ben Cao Gang Mu. People’s Medical 42. 李春梅，王若光，王陸穎，劉小麗 et al. (2007). turtle extract except that from Testudo Publishing House: Beijing, 1982. 基於鐳射解析/離子化飛行時間質譜技術的中藥 龜甲膠蛋白質組分析. 湖南中醫藥大學學報， (48) 14. Zhang E. English-Chinese Rare Chinese Materia elongate (Blyth). 27(6):21-29. Medica, Publishing House of Shanghai College of Traditional Chinese Medicine: Shanghai, 1990. 43. Chen DF, Zeng HP, Du SH, Li H et al. (2007). Extracts from plastrum testudinis promote 15. Li J et al. (1986). Report on the survey of proliferation of rat bone-marrow-derived CONCLUSION the cultication of tortoise. Bulletin of Chinese mesenchymal stem cells. Cell Prolifi cation, Medicinal Herbs, 11: 583. 40:196–212. The turtle shell is an interesting area to 16. 石青，方前波 (2001). 各種龜板的鑒別. Primary 44. 陳東風，杜少輝，李伊為 (2001). 龜板對局灶性腦 Journal of Chinese Materia Medica, 15(5):34. 缺血後神經幹細胞的作用. 廣州中醫藥大學學報， be studied. It is not merely because of 17. Zangerl R. The turtle shell. In: Gans, C., Bellairs, 18(4):328-332. its usefulness in taxonomic identifi cation D.d’A. and Parsons, T.A. (Eds). Biology of the 45. 李伊為，崔曉軍，陳東風 (2003). 龜板對脊髓 and evolutionary relationship, but also Reptilia, Vol 1, Morphology A Academic Press: 損傷大鼠神經幹細胞的作用. 解剖學雜誌，19(3): London. 1969, p311-340. 321-324. of its usefulness in understanding its 18. Alderton D. Turtles & Tortoises of the World. 46. 李長泉 (2003). 龜甲藥理作用及臨床應用的現代 importance as a source of functional Facts on File, New York,1988. 研究. 長春中醫學院學報，19(4):55. food and medicine. 19. 朱震亨 (元). 本草衍義補遺，丹溪心法附餘本. 47. Bayazit V, Khan KM (2005). Anticancerogen 墨潤堂印，卷首: 11, 1920. activities of biological and chemical agents on lung carcinoma, breast adenocarcinoma and 20. Yang MX, Yang Y (1988). Pathological impact leukemia in rabbits. Journal of the Chemical of carapace and plastron on the thyroid, Society of Pakistan, 27(4):413-422. thymus, adrenals, and spleen of thyroid-induced hyperthyroidism yin-defi ciency model of rats. 48. 顧迎寒，盧先明，蔣桂華 (2007). 不同品種龜甲 Bulletin of Chinese Materia Medica, 13(3):41-43. 滋陰作用對比研究. 時珍國醫國藥，18(16):1417.

HKPJ VOL 19 NO 1 Jan-Mar 2012 37 Society Activities

Hong Kong Pharmacy Conference 2012

Reporter: Gloria Hung, Programme Coordinator, Hong Kong Pharmacy Conference 2012

“Pharmacist: your Healthcare medications and medication safety in Manufacturers Association, Pharmaceutical Partner 藥劑師 — 健康之侶” was the hospital pharmacies in China. The Day Distributors Association of Hong theme of the 24th Hong Kong Pharmacy 2 program encompassed information Kong and Hong Kong Association of Conference 2012 which took place at the technology, elderly care, community Pharmaceutical Industry contributed Hong Kong Convention and Exhibition and hospital practices. Ms. Linda Woo in a Q&A session facilitated by Centre on 4th to 5th February, 2012. and Mr. Lot Chan, Chief Pharmacist Mr. Michael Ling. It was organized by The Pharmaceutical and Senior Pharmacist respectively, The Conference dinner on 4th Society of Hong Kong, The Practising from the Drug Offi ce were invited to February was defi nitely a highlight. Pharmacists Association of Hong Kong, speak in the plenary session on the Talents from our young pharmacists The Society of Hospital Pharmacists of regulation of pharmaceutical products and students were uncovered in the Hong Kong, School of Pharmacy of the post-75-recommendations by the review drama performance and games, and Chinese University, Department of Health committee in 2009. Representatives the site organization of the event. All and Hospital Authority. The Organizing from the three pharmacist societies/ the participants and guests thoroughly Committee of the Conference was led association, Hong Kong Pharmaceutical enjoyed the occasion.” by Mr. SO Yiu Wah, the chairperson and Ms. Ritchie KWOK, the vice-chairperson. We were glad to have Mr. Richard Yuen Ming-fai, Permanent Secretary for Food and Health (Health) to be our offi ciating guest.

The Conference attracted over 400 participants from Hospital, Community, Industry, Government and Education sectors. We saw a technology breakthrough this year. An on-line registration system was set up. It was highly popular with almost half of the registrants registered on-line. Plate-2: Opening ceremony of the HK Pharmacy Conference 2012. From left to right: Mr. William CHUI, Vice-President, Society of Hospital Pharmacists of Hong Kong; Ms. Mary CHENG, President, The Day 1 theme speeches covered Pharmaceutical Society of Hong Kong; Ms. Iris CHANG, President, Practising Pharmacists a wide scope of topics, including needs, Association of Hong Kong; Mr. Richard YUEN, Permanent Secretary for Food and Health (Health); skills and value based pharmacist Mr. Y W SO, Chairperson of the Hong Kong Pharmacy Conference 2012; Ms. Anna LEE, Chief Pharmacist, Chief Pharmacist’s Offi ce, Hospital Authority, Hong Kong; Dr. Heston KWONG, education, environmental toxins, Drug Offi ce, Department of Health, Hong Kong; Prof. Joan ZUO, Associate Director (Research and enhancement of compliance to chronic Graduate Affairs), School of Pharmacy, The Chinese University of Hong Kong.

Plate-1: The organizing committee with the student helpers at the conference dinner

HKPJ VOL 19 NO 1 Jan-Mar 2012 38 Road Traffi c (Amendment) Ordinance 2011: Briefi ng Seminars for Transport Trades in March 2012

Reporters: CHAN Henry; CHAN Shirley; CHEUNG Peggy; LAM Daisy

Representatives, namely from the were responsible to answer inquiries information to the authority to support the Pharmaceutical Society of Hong Kong related to drug treatment and side effects development of these leafl ets. (PSHK), the Practising Pharmacists encountered by drivers. Association of Hong Kong (PPAHK) and the Society of Hospital Pharmacists of Hong Kong (SHPHK) joined as medicines advisers of the captioned event on 1st March 2012 and 10th March 2012, organized by the Transport Department.

The purposes of these seminars are to introduce the enforcement procedures Plate-4: Leafl et distributed to the attendees against drug driving under the Road Traffi c (Amendment) Ordinance 2011 Plate-3: Mr Yiu-Wah So is giving the speech on and to brief effects of common medicinal drugs may affect driving ability drugs on driving ability. Plate-4 shows leafl ets containing The chairman of SHPHK, Mr. SO information about legal advice and side Yiu Wah (Plate-3) was responsible to effects of selected medicines that may conduct a speech on “Common medicinal pose a risk to driving were distributed drugs that may have side effects on to all attendants. The 3 pharmacist Plate-5: Fellow pharmacists who helped to driving ability”. Other representatives organizations provided drug related organize the seminar

The Pharmaceutical Society of Hong Kong Pharmacy Legislation Lectures 2012 Registration Form

Surname First Name

Contact No.

Name of Place of Work (If any)

Membership

Member/ Non-member PSHK 2011/2012 Membership No

Membership Type

Voting/ Pre-reg/ Associate/ Student

Lectures Attending

⃞ L1 ⃞ L2 ⃞ L3 ⃞ L4 ⃞ L5 ⃞ All

Payment Method

⃞ Online ⃞ Cheque ⃞ Cash (on site only) Total Amount: HK$

Cheque No Bank Name:

Payment Methods: (1) Online Payment http://www.pshk.hk/ (2) Make cheque payable to “The Pharmaceutical Society of Hong Kong” and send by mail to Kowloon Post Offi ce, P.O. Box 73552, Yaumatei, Kln. (3) Deposit the appropriate fee into our account HSBC 0022-163-166 and send bank-in receipt by mail to Kowloon Post Offi ce, P.O. Box 73552, Yaumatei, Kln. PSHK Forensic Lectures

Dear Members / Fellow Pharmacists,

PSHK Forensic Lectures on Pharmacy Legislation 2012

Drug Offi ce, The Department of Health, and The Pharmaceutical Society of Hong Kong will co-organise a series of fi ve lectures on Pharmacy Legislation of Hong Kong. This will be a good learning opportunity for anyone who is interested in gaining knowledge and latest updates in this aspect and for the candidates who will be sitting in the Hong Kong Pharmacist Registration Examination on Pharmacy Legislation.

Venue: PSHK Headquarters, 1303 Rightful Centre, 12 Tak Hing Street, Jordan, Kln. Time: 6:30 pm – 8:30 pm, please arrive at 6:00 pm for registration

Date Topic Lecturer 20.4.2012 Wholesale & Retail Sale of Poisons Kevin LO (Friday) Undesirable Medical Advertisements Labelling of Poisons and Pharmaceutical Products Arkie LO 27.4.2012 Control of Antibiotics Charlotta CHAK (Friday) Classifi cation of Poisons Karena Lee 4.5.2012 Registration of Pharmaceutical Products Iris LEE (Friday) Manufacture of Pharmaceutical Products Agnes TSE 11.5.2012 Licensing of Authorised Sellers of Poisons and Listed Sellers of Poisons Tony CHAN (Friday) Import/Export Control of Pharmaceutical Products and Dangerous Drugs Brenda LAM 18.5.2012 Classifi cation and Sale of Dangerous Drugs Mandy Ho (Friday) Questions and Answers

All members and non-members are welcome to attend the lectures. Each individual lecture is offered at HK$200 for non-members. Members will enjoy a special privileged deal of HK$150 for all the 5 lectures, only to online payment or by cheque in advance. On-site cash payment would be $200.

Registration Methods: (1) Registration on Line: Members & Non members joining the lectures can register and pay on line. You will receive a registration confi rmation and receipt after payment has been made. (Please refer to our website: www.pshk.hk) (2) Registration by Mail: Members & Non-Members joining the lectures can also register by fi lling in the registration form and write a cheque payable to “The Pharmaceutical Society of Hong Kong” and send by mail to Kowloon Post Offi ce, P.O. Box 73552, Yaumatei, Kln. (3) Registration on site: Members & Non members joining the lectures can register on-site by completing the registration Form & payment by cash or cheque.

Joining as PSHK Member: All non-members who would like to join us as new voting & pre-reg members have to pay non-member fee HKD$1,000 at fi rst & you will receive the reimbursement [$250 for new voting members & $450 for new pre-reg members] with the membership card after successfully joining our membership.

For non-members who wanted to join our society, please be reminded to bring along the following: (1) Pharmacy Legislation Lectures 2012 Registration Form & PSHK Membership Application Form which can be downloaded from the “downloads” section of our web site: http://www.pshk.hk/ (2) One recent passport-size photograph (3) Photocopy of certifi cate of academic qualifi cation (4) Photocopy of certifi cate of overseas professional qualifi cation if available (5) Photocopy of Hong Kong Certifi cate of Pharmacist Registration (to join the voting membership) (6) Payment :

Normal Membership Fee: Entrance Fee: HK$200 (for all membership except CUHK & HKU student chapter membership) Annual Fee: HK$200 (for pre-registration membership) HK$400 (for voting membership) HK$600 (for associate membership) HK$20 (for CUHK & HKU student chapter membership)

Lecture Fee: Member: HK$150 for 5 lectures Non Member: HK$200 per lecture For payment by cheque, please make cheque payable to “The Pharmaceutical Society of Hong Kong”.

Please refer to the following table for fees calculation. Fees Calculation Member Type Entrance Fee Membership Fee per Lecture Total Fee Refund Member Status Fee 2012 for 5 Lectures Old Member All Paid Up Paid Up $150 $150 N/A New Member Voting $200 $400 $150 $750 $250 New Member Pre-Reg $200 $200 $150 $550 $450 New Member Associate $200 $600 $150 $950 $50 New Member CUHK/ HKU N/A $20 $150 $170 $830 Non Member N/A N/A N/A $200 $1,000 N/A THE 12TH ASIAN CONFERENCE ON CLINICAL PHARMACY 7 – 9 July 2012, Hong Kong SAR, China

www.accp2012.org

“Citius, Altius, Fortius” appraising clinical excellence, nurturing eminent practice

Important Dates Abstract submission deadline: 31 January 2012 ︳Early bird registration deadline: 31 March 2012 Topics Keynote Lecture Plenary Lectures Symposia Development of Clinical Pharmacy - Nurturing Eminent Practice - Ambulatory Care East Meets West Strategies to Success Cardiology Appraising Clinical Excellence - Geriatrics and Patient Education What Have We Achieved and How Medication Reconciliation Do We Measure It? Oncology Paediatrics Pharmaceutics Psychiatry Renal

Hosts: Enquiry: UBM Medica Pacific Ltd. Tel: (852) 2155 8557 or 3153 4374 HKPJ VOL 19 NO 1 Jan-Mar 2012 41 Fax: (852) 2559 6910 Email: [email protected] New Products

Indications can be made. The safety and of suicidal ideation (see Treatment of patients effi cacy of Avonex in children Contraindications). Depression diagnosed with relapsing <12 years have not yet been and suicidal ideation are known multiple sclerosis. In clinical established. No data are to occur in increased frequency Avonex™ trials, this was characterized available. in the MS population and in (Biogen Idec (Hong Kong) Limited) by ≥2 acute exacerbations association with interferon use. (relapses) in the previous Elderly: Clinical studies did Patients should be advised 3-years without evidence not include a suffi cient number to immediately report any Product Name of continuous progression of patients ≥65 to determine symptoms of depression and/ Avonex Solution For Injection between relapses. Avonex whether they respond or suicidal ideation to their 30mcg / 0.5ml slows the progression of differently than younger physician. disability and decreases the patients. However, based Patients exhibiting depression frequency of relapses. on the mode of clearance should be monitored closely Presentation It can be used among patients of interferon β-1a, there are during therapy and treated Injection each 0.5ml containing with single demyelinating event no theoretical reasons for appropriately. Cessation 30mcg of Interferon β-1a with an active infl ammatory any requirement for dose of therapy with Avonex process, those who severely adjustments in the elderly. should be considered (see Pharmacology warrant treatment, those The IM injection site should Contraindications and Adverse Interferons are a family of whose alternative diagnosis be varied each week (see Reactions). naturally occurring proteins have been excluded, and Toxicology under Actions). Avonex should be administered that are produced by those who are determined to Doctors may prescribe a with caution to patients with eukaryotic cells in response be at high risk of developing 25 mm, 25 gauge needle a history of seizures, to those to viral infection and other clinically defi nite MS (see to patients for whom such receiving treatment with biological inducers. Interferons Pharmacology under Actions). a needle is appropriate to antiepileptics, particularly if are cytokines that mediate Avonex should be discontinued administer an IM injection. their epilepsy is not adequately antiviral, anti-proliferative, and in patients who develop Prior to injection and for an controlled with antiepileptics immunomodulatory activities. progressive MS. additional 24 hrs after each (see Interactions and Adverse Three major forms of interferons injection, an antipyretic Reactions). have been distinguished: α, Dosage and Administration analgesic is advised to decrease Caution should be used and β, and γ. Interferons-α and Adults: The recommended fl u-like symptoms associated close monitoring considered β are classifi ed as type I dosage for the treatment with Avonex administration. when administering Avonex to interferons, and interferon-γ of relapsing MS is 30 mcg These symptoms are usually patients with severe renal and is a type II interferon. These (0.5 mL), administered by present during the fi rst few hepatic failure and to patients interferons have overlapping IM injection once a week. At months of treatment. with severe myelosuppression. but clearly distinguishable the initiation of the treatment, At the present time, it is Hepatic injury including biological activities. They can patients may either be started not known for how long elevated serum hepatic also differ with respect to their on a full dose of 30 mcg (0.5 patients should be treated. enzyme levels, hepatitis, cellular sites of synthesis. mL) or on approximately half Patients should be clinically autoimmune hepatitis and Interferon-β is produced by the dose once a week to help evaluated after 2 years of hepatic failure has been various cell types including them to adjust to treatment treatment and longer-term reported with interferon-β in fi broblasts and macrophages. and thereafter increased to the treatment should be decided post-marketing (see Adverse Natural interferon-β and full dose of 30 mcg (0.5 mL). on an individual basis by the Reactions). In some cases, Avonex (interferon β-1a) are In order to obtain adequate physician. Treatment should these reactions have occurred be discontinued if the patient glycosylated and have a single effi cacy, a dose of 30 mcg in the presence of other (0.5 mL) once a week should develops chronic progressive medicinal products that have N-linked complex carbohydrate be reached and maintained MS. been associated with hepatic moiety. Glycosylation of other after the initial titration injury. The potential of additive proteins is known to affect their period. A manual titration Contraindications effects from multiple medicinal stability, activity, biodistribution device to enable delivery of Initiation of treatment in products or other hepatotoxic and half-life in blood. However, approximately half the dose is pregnancy. agents (eg, alcohol) has not the effects of interferon-β that available for patients initiating Patients with a history of been determined. Patients are dependent on glycosylation Avonex treatment. hypersensitivity to natural or should be monitored for signs arc not fully defi ned. No additional benefi t has been recombinant interferon-β or of hepatic injury and caution Avonex exerts its biological shown by administering a to any of the excipients of exercised when interferons are effects by binding to specifi c higher dose (60 mcg) once a Avonex. used concomitantly with other receptors on the surface of week. Patients with current severe medicinal products associated human cells. This binding depression and/or suicidal with hepatic injury. initiates a complex cascade Children: The safety and ideation (see Precautions and Patients with cardiac disease, of intracellular events that effi cacy of Avonex in Adverse Reactions). such as angina, congestive leads to the expression of adolescents 12-16 years have heart failure or arrhythmia, numerous interferon-induced not yet been established. Warnings should be closely monitored gene products and markers. Currently available data are Avonex should be administered for worsening of their clinical These include MHC class I, Mx described in Pharmacology with caution to patients with condition during treatment with protein, 2’/5’-oIigoadenylate under Actions and previous or current depressive Avonex. Flu-like symptoms disorders, in particular to associated with Avonex synthetase, β2-microglobulin Adverse Reactions but no and neopterin. recommendation on dosage those with antecedents therapy may prove stressful

HKPJ VOL 19 NO 1 Jan-Mar 2012 42 to patients with underlying capabilities were observed. symptoms that may mimic Disorders: Common: Rash, cardiac conditions. Caution should be exercised MS exacerbations may occur increased sweating, contusion. Laboratory abnormalities when Avonex is administered following injections. Transient Uncommon: Alopecia. are associated with the use in combination with medicinal episodes of hypertonia and/ Not Known: Angioneurotic of interferons. Therefore, in products that have a narrow or severe muscular weakness oedema, pruritus, vesicular addition to those laboratory therapeutic index and are that prevent voluntary rash, urticaria, aggravation of tests normally required for largely dependent on the movements may occur at psoriasis. monitoring patients with MS, hepatic cytochrome P450 any time during treatment. Musculoskeletal and complete and differential white system for clearance such These episodes are of limited Connective Tissue Disorders: blood cell counts, platelet as antiepileptics and some duration, temporally related to Common: Muscle cramp, neck counts, and blood chemistry, classes of antidepressants. the injections and may recur 2 including liver function tests, pain, myalgia , arthralgia, pain after subsequent injections. in extremity, back pain, muscle are recommended during Pregnancy and lactation The frequencies of adverse Avonex therapy. Patients with Use in pregnancy: There stiffness, musculoskeletal reactions are expressed in stiffness. Not Known: Systemic myelosuppression may require is limited information on the patient-years, according to more intensive monitoring of use of Avonex in pregnancy. lupus erythematosus, muscle the following categories: Very complete blood cell counts, Available data indicates that weakness, arthritis. common (≥1/10 patient-years); with differential and platelet there may be an increased Endocrine Disorders: Not common (≥1/100 to <1/10 counts. risk of spontaneous abortion. Known: Hypothyroidism, patient-years); uncommon Patients may develop Initiation of treatment is hyperthyroidism. (≥1/1000 to <1/100 patient- antibodies to Avonex. The contraindicated during years); rare (≥1/10,000 to Metabolism and Nutrition antibodies of some of those pregnancy. Disorders: Common: Anorexia. patients reduce the activity Women of Childbearing <1/1000 patient-years); very rare <1/10,000 patient- Infections and Infestations: Not of interferon β-1a in vitro Potential: Women of Known: Injection site abscess. (neutralizing antibodies). childbearing potential have to years); not known (cannot be Vascular Disorders: Common: Neutralizing antibodies are take appropriate contraceptive estimated from the available Flushing. Not Known: associated with a reduction in measures. If the patient data). Vasodilation. the in vivo biological effects of becomes pregnant or plans Within each frequency Avonex and may potentially to become pregnant while grouping, undesirable effects General Disorders and be associated with a reduction taking Avonex, she should are presented in order of Administration Site Conditions: of clinical effi cacy. It is be informed of the potential decreasing seriousness. Very Common: Flu-like estimated that the plateau for hazards and discontinuation of symptoms, pyrexia, chills, the incidence of neutralizing therapy should be considered Investigations: Common: sweating. Common: Injection antibody formation is reached (see Toxicology under Actions). Decreased lymphocyte count, site pain, injection site after 12 months of treatment. In patients with a high relapse decreased white blood cell erythema, injection site Recent clinical studies with rate before treatment started, count, decreased neutrophil bruising; asthenia2, pain, patients treated up to 3 years the risk of a severe relapse count, decreased hematocrit; fatigue2, malaise, night with Avonex suggest that following discontinuation of increased blood potassium, sweats. Uncommon: Injection approximately 5-8% develop Avonex in the event of increased blood urea nitrogen. site burning. Not Known: neutralizing antibodies. pregnancy should be weighed Uncommon: Decreased Injection site reaction, injection The use of various assays to against a possible increased platelet count. Not Known: site inflammation, injection detect serum antibodies to risk of spontaneous abortion. Decreased weight, increased site cellulitis1, injection interferons limits the ability to weight, abnormal liver function site necrosis, injection site compare antigenicity among Use in lactation: It is not tests. bleeding; chest pain. different products. known whether Avonex is Cardiac Disorders: Not Known: Immune System Disorders: excreted in human milk. Cardiomyopathy, congestive Interaction Because of the potential for Not Known: Anaphylactic heart failure (see Precautions), reaction, anaphylactic shock, No formal interaction studies serious adverse reactions in palpitations, arrhythmia, hypersensitivity reactions have been performed in nursing infants, a decision tachycardia. humans. should be made either to (angioedema, dyspnoea, Blood and Lymphatic System The interaction of Avonex discontinue breastfeeding or urticaria, rash, pruritic rash). Disorders: Not Known: with corticosteroids or Avonex therapy. Hepatobiliary Disorders: Pancytopenia, thrombocytopenia. adrenocorticotropic hormone Not Known: Hepatic failure Nervous System Disorders: (ACTH) has not been studied Side effects Very Common: Headache2. (see Precautions), hepatitis, systematically. The clinical The highest incidence of Common: Muscle spasticity, autoimmune hepatitis. studies indicate that MS adverse reactions associated Reproductive System and patients can receive Avonex with Avonex therapy is related hypoesthesia. Not Known: Neurological symptoms, Breast Disorders: Uncommon: and corticosteroids or ACTH to fl u-like symptoms. The most Metrorrhagia, menorrhagia. during relapses. commonly reported fl u-like syncope, hypertonia, dizziness, Psychiatric Disorders: Interferons have been reported symptoms are myalgia, fever, paraesthesia, seizures, migraine. Common: Depression (see to reduce the activity of hepatic chills, sweating, asthenia, Respiratory, Thoracic and cytochrome P450-dependent headache and nausea. Flu- Mediastinal Disorders: Precautions), insomnia. Not enzymes in humans and like symptoms tend to be most Common: Rhinorrhoea. Rare: Known: Suicide, psychosis, animals. The effect of high-dose prominent at the initiation Dyspnoea. anxiety, confusion, emotional AVONEX administration on of therapy and decrease in Gastrointestinal Disorders: lability. P450-dependent metabolism frequency with continued Common: Vomiting, diarrhoea, in monkeys was evaluated and treatment. nausea. Forensic Classication: no changes in liver metabolising Transient neurological Skin and Subcutaneous Tissue P1S1S3

HKPJ VOL 19 NO 1 Jan-Mar 2012 43 thigh, or the abdomen. All Dosage and Administration: Prolia® Injection patients should receive PRADAXA may be taken with (GlaxoSmithKline) calcium 1000 mg daily and at food, or on an empty stomach least 400 IU vitamin D. Prolia with water. The capsule should PRADAXA® be swallowed intact. Active Ingredient: should be administered by a (Boehringer Ingelheim) VTE prevention following Denosumab healthcare professional. If a dose is missed, administer elective knee replacement surgery: The recommended Presentation: the injection as soon as the Active ingredient: dose of PRADAXA is 220 mg 1 mL of a 60 mg/mL solution in patient is available and every Dabigatran etexilate daily, taken orally as two (2) a single-use prefi lled syringe. 6 months from the date of the capsules of 110 mg once a last injection. Presentation: day in patients with intact renal Prolia should be clear, Capsules of 75 mg, 110 mg Pharmacological Properties: function. Treatment should and 150 mg Prolia (denosumab) is a human colorless to pale yellow normally be initiated within 1-4 IgG2 monoclonal antibody solution that may contain trace hours of completed surgery Pharmacological Properties: with affi nity and specifi city amounts of translucent to once hemostasis is secured. Dabigatran etexilate is a for human RANKL (receptor white proteinaceous particles. Start with a single capsule prodrug which does not exhibit activator of nuclear factor Do not use if the solution of 110 mg, and continue with anticoagulant activity itself. kappa-B ligand). Prolia binds is discolored or cloudy or if two (2) capsules once daily Following oral administration, to RANKL, a transmembrane the solution contains many thereafter for a total of 10 days. dabigatran etexilate is rapidly particles or foreign particulate If hemostasis is not secured, or soluble protein essential absorbed and converted matter. Prior to administration, initiation of treatment should for the formation, function, to dabigatran by esterase- be delayed. If treatment is not and survival of osteoclasts, Prolia may be removed from catalysed hydrolysis in plasma started on the day of surgery the cells responsible for bone the refrigerator and brought and in the liver. for whatever reason, then resorption. to room temperature (up to Dabigatran is a competitive, treatment should be initiated It prevents RANKL from 25°C/77°F) by standing in reversible direct thrombin with 2 capsules at once. activating its receptor, the original container. This inhibitor, and is the main active VTE prevention following RANK, on the surface generally takes 15 to 30 principle in plasma. Since elective hip replacement of osteoclasts and their minutes. Do not warm Prolia in thrombin (serine protease) surgery: The recommended precursors. Prevention of the any other way. enables the conversion of dose of PRADAXA is 220 mg fi brinogen into fi brin during RANKL/RANK interaction daily, taken orally as two (2) the coagulation cascade, inhibits osteoclast formation, Contraindications: its inhibition prevents the capsules of 110 mg once a function, and survival, thereby Pre-existing hypocalcemia development of thrombus. day in patients with intact renal decreasing bone resorption must be corrected prior to Dabigatran also inhibits function. Treatment should and increasing bone mass and initiating therapy with Prolia free thrombin, fi brin-bound normally be initiated within 1-4 strength in both cortical and thrombin and thrombin- hours of completed surgery Precautions: trabecular bone. induced platelet aggregation. once hemostasis is secured. Hypocalcemia, serious In-vivo and ex-vivo animal Start with a single capsule of Indications: infections, concomitant studies have demonstrated 110 mg, and continue with 2 Prolia is indicated for the immunosuppressant agents antithrombotic effi cacy and capsules once daily thereafter treatment of postmenopausal or with impaired immune anticoagulant activity of for a total of 28-35 days. If women with osteoporosis at systems may be at increased dabigatran after intravenous hemostasis is not secured, high risk for fracture, defi ned risk for serious infections, administration and of initiation of treatment should be delayed. If treatment is not as a history of osteoporotic Osteonecrosis of the Jaw dabigatran etexilate following started on the day of surgery fracture, or multiple risk factors and Suppression of Bone oral administration in various for whatever reason, then for fracture; or patients who Turnover. animal models of thrombosis. treatment should be initiated have failed or are intolerant to Indications: with 2 capsules at once. other available osteoporosis Drug Interactions: Prevention of venous Prevention of stroke and therapy. No drug-drug interaction thromboembolic events systemic embolism in studies have been conducted (VTE) in patients who have patients with atrial fi brillation: Dosage and Administration: with Prolia undergone elective total hip The recommended dose of The recommended dose is 60 replacement or total knee PRADAXA is 300 mg daily, mg administered as a single Side Effects: replacement surgery. taken orally as one 150 mg subcutaneous injection once Abdomen, urinary tract, ear Prevention of stroke and capsule twice a day. every 6 months. Administer infections, endocarditis, systemic embolism in patients via subcutaneous injection cellulitis, dermatitis, eczema, with atrial fi brillation, in whom Forensic Classication: in the upper arm, the upper rashes and pancreatitis anticoagulation is appropriate. P1S1S3

HKPJ VOL 19 NO 1 Jan-Mar 2012 44 Aims and Scope of the Journal

Hong Kong Pharmaceutical Journal: For Detailed Instructions for Authors

INTRODUCTION Three copies of the manuscript are paragraphs, fi gure and table call-outs. required on either 8.5”x11” or A4 paper Most formatting codes will be removed or Hong Kong Pharmaceutical Journal (two copies are used for review purposes replaced on processing your article. Please (HKPJ) is the offi cial publication of the and the original is kept on fi le at the do not use options such as automatic word Pharmaceutical Society of Hong Kong, Section Editor). Copies must be produced breaking, justifi ed layout, double columns or the Practising Pharmacists Association on a high-quality printer, and originals and automatic paragraph numbering (especially of Hong Kong and the Society of Hospital copies of all Figures and Schemes must be for numbered references). However do use Pharmacists of Hong Kong. It is a journal fully legible. Initially only send hard copies bold face, italic, subscripts, superscripts of the pharmacists, for the pharmacists of the paper; when it has been refereed, etc. The Editors reserve the right to adjust and by the pharmacists. The Journal is revised if necessary, and accepted, you style to certain standards of uniformity. If currently divided into several sections: will be requested to send a disk containing authors are unfamiliar with HKPJ, they Editorial Comment; News & Short the fi nal version with the fi nal hard copy should consult a recent copy (or the free Communications; Pharmacy Practice; to the appropriate Editor. Make sure that online sample copy available from www. Over-the-Counter & Health; Drugs the disk and the hard copy match exactly. HKPS.com/HKPJ) to see the conventions & Therapeutics; Herbal Medicines The revised manuscript must be returned currently followed for guidance in preparing & Nutraceuticals; Pharmaceutical to the Editors within one month, otherwise submissions. Technology and New Products. It it may be deemed to be new and subject publishes review articles or original to further review. When submitting the The content of manuscripts must be papers relevant to these different fi elds fi nal version with a disk please label all arranged as follows: (1) a Title Page with of pharmacy. In addition to the regular disks with “HKPJ”, your name, software authors name(s) and address(es); (2) four issues of the Journal per year, there (e.g. word 2000), hardware used (e.g. an Abstract, in which contents are briefl y are issues dedicated solely to reports on PC or Macintosh) and fi le names with the stated; (3) a 4 to 6 Key Word Index, (4) special function of the society. The Aims correct extension (e.g. Fig 1.cdx, Table 1-6. Introduction, and (5) the Results and and Scope of the Journal are published xls). Save text on a separate disk from the Discussion (preferably combined). Although on the inside back cover of each issue. graphics, include the text and tables in one each section may be separated by fi le, and provide graphics and structures headings, they should form one continuous in separate numbered fi les. Please narrative and only include details essential Submission of Manuscript remember to keep a backup copy of both to the arguments presented. If a discussion the electronic fi les and original manuscript is separately provided, it should not include Submission of a paper implies that it has for reference and safety since we cannot a repetition of the results, but only indicate not been published previously, that it is accept responsibility for damage or loss of conclusions reached on the basis of them, not under consideration for publication papers. Original manuscripts are discarded and those from other referred works; (6) elsewhere, and that if accepted it will three months after publication unless Conclusions or Concluding Remarks; (7) not be published elsewhere in the the Publisher is asked to return original the Experimental should include brief details same form, in English or in any other material after use. of the methods used such that a competent language, without the written consent researcher in the fi eld may be able to of the publisher. Authors are specifi cally Suggested Referees repeat the work; (8) Acknowledgments; discouraged from submitting papers as (9) References; (10) Legends, Formulae, fragmented studies of a particular topic. Please submit, with your manuscript, Tables and Figures. A manuscript must be indicated which the names and addresses of 2 potential section it is belonged. Upon received, it referees. You may also mention persons Title Page and Author Names: Titles must will be screened by a Sectional Editor who you would prefer not to review your be as brief as possible, consistent with of HKPJ for initial consideration before it paper. clarity, and should not exceed 10 words is sent out for further review or comment. in length. Uninformative phrases such as Editorial Authority “Chemical examination of”, “Studies For online submission: on”, “Survey of”, “New”, “Novel” etc. will Authors are encouraged to submit The Editors of HKPJ reserve the right to be deleted. If a paper is part of a series, manuscripts using the online submission make alterations to manuscripts submitted this must not be given in the heading, but system. Access to the system, and full for publication. Such alterations will be referred to in a footnote in the form: *Part instructions on its use, can be found on made if manuscripts do not conform with 9 in the series “The Role of Pharmacists the HKPS website at: http://www.HKPS. accepted scientifi c standards or if they in Medical Care of Patients” followed by org/HKPJ/Guidelines. In creating the contain matter which in the opinion of a numbered reference to the previous electronic version of their manuscript, the Editors is unnecessarily verbose or part. Author names should be typed right authors are requested to follow the unclear. Alterations may be queried, but underneath the article title. Each author guidelines for submitting fi les. The paper this will inevitably delay publication. should identify himself or herself with should be submitted as a single fi le, Surname in capital letters, followed by the prepared with a standard word-processor Preparation of manuscript fi rst name. All names are separated by a such as Microsoft Word, with embedded semicolon ( ; ). An asterisk should be placed tables and graphics. Please note that The manuscript is required to be written following the name of the author to whom any embedded graphics must also be in English, with numbered pages, single- correspondence inquiries should be made. submitted as separate, original fi les. spaced, using Arial 9 point font, and in a Full postal addresses must be given for The preferred formats for graphics fi les suitable word-processing format. Each all co-authors. Superscript letters; a, b, c are tiff or postscript. All correspondence page should have adequate margins (4 should be used to identify authors located at between Editor and author is performed cm) and liberal spaces at top and bottom of different addresses. by email. Authors are reminded that the manuscript. All textual elements should the copyright of their article or paper is begin fl ush left, with the second paragraphs An Author’s background box at the automatically transferred to HKPJ once it onwards indent, and should use the wrap- end of each article is mandatory to include is accepted for publication in the journal. around end-of-line feature, i.e. no returns the author’s job title and the affi liated at the end of each line. Place two returns institutle or organization. Full details For hardcopy submission: after every element such as title, headings, of telephone, fax numbers and e-mail

HKPJ VOL 19 NO 1 Jan-Mar 2012 45 address should also be indicated for the code. The Experimental Procedures (2) Mabry T, Markham KR, Thomas MB. corresponding authors. No academic or employed should be concise but suffi ciently (1970). The Systematic Identifi cation professional membership title is allowed. detailed that a qualifi ed researcher will be of Flavonoids. 2nd Ed, pp. 79-105. able to repeat the studies undertaken, and Springer Verlag, New York. ABSTRACT: The abstract should be on these should emphasize either truly new a separate page and briefl y describe the procedures or essential modifi cations of (3) Harborne JB. (1999). Plant chemical results obtained and conclusions reached, existing procedures. Experimental details ecology. In: Barton D, Nakanishi K, not the methods used, or speculations on normally omitted include: (I) method of Meth-Cohn 0, (Eds.), Comprehensive any other matter. They are not expected preparation of common chemical and Natural Products Chemistry, Vol. 8. to be a complete summary but only an biochemical derivatives, (2) excessive pp. 137-196. Pergamon, Oxford. outline of the main fi ndings. The abstract details of separation of compounds, Preparation of Illustrations: All illustrations should be contained within 250 words and proteins and enzymes, e.g. preparation of should be provided in camera-ready form, should be readable without reference to columns, TLC plates, column and fraction suitable for reproduction (which may include size. Compound Characterization: Physical the rest of the paper. reduction) without retouching. Illustrations and spectroscopic data for new compounds must be comprehensive, and follow the (fi gures, tables, etc.) should be prepared Key Words: Authors must give four to for either single or double column format. six “key words” or phrases, which identify order shown below: compound name (and assigned number in text); physical state For online submission illustrations should the most important subjects covered by be included in the manuscript and also be the paper. of compound (e.g. oil, crystal, liquid, etc.), melting and/or boiling point; optical rotation submitted separately as high resolution fi les. For hardcopy submission illustrations INTRODUCTION should give the and/or circular dichroism measurements, if optically active; UV; JR, lH NMR; 13C should be submitted on separate pages minimum historical data needed to in camera-ready format with legends on give appropriate context to the author’s NMR; MS. For all new compounds, either high-resolution mass spectral or elemental separate pages. Hardcopy illustrations investigation and its relationship to other supplied by authors are digitally scanned similar research previously or currently analysis data is required. See later section for method of data presentation. into the appropriate page and must therefore being conducted. Only information be of the highest quality. Where possible essential to the arguments should be the original electronic fi les are used, fi gures presented. Much data can be taken for Nomenclature: Chemical nomenclature, abbreviations and symbols must follow produced by computer must therefore be granted or quoted in abbreviated form. prepared at a minimum resolution of 300 Specifi c term (genus, species, authority) IUPAC rules. Whenever possible, avoid coining new trivial names; every effort dpi. Refer to all photographs, charts and of all experimental works must be given diagrams as “Figure(s)” and number them at fi rst mention and preferably be in should be made to modify an existing name. For example, when a new consecutively in the order to which they the form adopted by the International are referred. They should accompany the Scientifi c Community. compound is described, it should be given a full systematic name according to IUPAC manuscript, but should not be included nomenclature and this should be cited in the within the text. All illustrations should be RESULTS AND DISCUSSION: These Abstract or in the Experimental section. clearly marked with the fi gure number sections should be carefully prepared and the author’s name (either on the back with discussions of the results being ACKNOWLEDGMENTS: This section if submitting on paper or with a clear fi le compared with existing and/or previous is used to provide brief credit for name if submitting online). All fi gures are to knowledge within the fi eld. Authors scientifi c and technical assistance, have a caption, which should be supplied are, however, encouraged to combine and in recognition of sponsorship on a separate page. Note: Illustrations the Results and Discussion sections through fi nancial support and any other of the following type generally will not be wherever possible. appropriate form of recognition. accepted for publication: (1) diagrams or photographs of chromatograms (PC EXPERIMENTAL: Subsections on the References: All publications cited in and TLC), electrophoretic separations, or Experimental Procedures should be the text should be presented in a list recorder traces of GC and HPLC data which italicized and inserted as part of the of references following the text of the are given merely to prove identifi cation; (2) fi rst line of the text to which they apply. manuscript. In the text refer to the straight-line graphs; (3) generalized pH HKPJ encourages an extensive use of author’s name (without initials) and year and temperature-denaturation curves of abbreviations (these are listed at the back of of publication (e.g. “Since Peterson enzymes; (4) illustrations of IR, UV, NMR the Instructions to Authors, or the reader is (1993) has shown that ...” or “This is in or MS (values can be quoted in the text or referred to other sources). The Experimental agreement with results obtained later by Experimental); (5) fl ow sheets illustrating should begin with a subsection entitled Kramer.(4)” For two authors both authors isolation of compounds; (6) expectable MS General Experimental Procedures. This are to be listed, with “and” separating the fragmentation patterns; (7) formulae of well- subsection will typically contain brief details two authors. For more than two authors, known compounds or reaction schem~s; of instruments used, and identifi cation use the fi rst author’s surname followed (8) tables giving either single values for of sources of specialized chemicals, by et al. The list of references should be each parameter which could be easily biochemicals and molecular biology kits. arranged according to the order of their quoted in the text, or repeating data shown The next subsection describes the source(s) appearance in the text with no more than elsewhere. and documentation of biological materials three authors listed. If number of authors used, whether in reference to whole plants of a reference exceeds three, “et al” is Illustrations should be drawn on separate or parts there from, crude drugs, or any used followed by year of publication pages and prepared with good contrast other plant material from which identifi able in bracket after the fi rst author. Journal (black on a white background). Lettering chemical substances are obtained for the titles should be completely shown in tables, fi gures, etc: lettering in formulae, fi rst time. Documentation must also include followed by the volume, issue number fi gure axes etc. must be large enough to a reference to voucher specimen(s) and in bracket if included, colon and start be legible after reduction. Lettering should voucher number(s) of the compounds, – fi nal page number. The manuscript be drawn in 6-7pt Helvetica (Arial) font plants or other material examined. If should be carefully checked to ensure to ensure optimum visibility. Chemical available, authors should quote the name that the spelling of authors’ names and formulae must be made absolutely clear; and address of the authority who identifi ed dates are exactly the same in the text as printers are not chemists and much delay each sample investigated. Specimens in the reference list. Some examples of is caused by poor drawing. Aromatic rings should preferentially be deposited in a major references are shown below: must be drawn with alternate double bonds regional herbarium where the collection is and conformation of single bonds shown by maintained by state or private institution and (1) Cabello-Hurtado F, Durst F, Jorrin thickened or dashed (III) lines according to which permits loan of such materials. With JV, Werck-Reichhart D. et al. (1998). convention. Formulae should be numbered other microorganisms, the culture collection Coumarins in Helianthus tuberosus: consecutively in Arabic numerals. If from which they were either accessed and/ characterization, induced graphics are created using ChemDraw or or deposited should be included, together accumulation and biosynthesis. ISISDraw the preferred settings are: font with identifi cation of the strain designation Biochemistry, 49(1):1029-1036. 10 pt Helvetica (Arial), chain angle 120o

HKPJ VOL 19 NO 1 Jan-Mar 2012 46 bond spacing 18% of length, fi xed (bond) Errata and Corrigenda to publish (sodium borohydride), NaCl, Nal04 (sodium length 14.4 pt (0.508 cm), bold width (bond articles will be included, at the discretion periodate), NaOH, Na2S03(sodium sulphite), thickness) 2.0 pt (0.071 cm), line width 0.6 of the Section Editors and the publisher. Na2S04 (sodium sulphate), Na2S203 (sodium pt (0.021 cm), margin width 1.6 pt (0.056 thiosulphate), 03, PPi (inorganic phosphate), 2− cm), and hash spacing 2.5 pt (0.088 cm). Abbreviations SO4 ., Tris (buffer). The overall size should be not more than About, approximately: ca. 95mm (single column) or 194mm (double Anhydrous: dry (not anhyd.) Organics, e.g. Ac20 (acetic anhydride), column) by 285 mm. Aqueous: aq. n-BuOH (butanol), C6H6 (benzene), CCl4 Circular dichroism: CD (carbon tetrachloride), CH2Cl2 (methylene Tables must be typed on separate Concentrated (or mineral acids): conc. chloride), CHCl3 (chloroform), CH2N2 pages, numbered consecutively, given a Concentrations: ppm (or ppb), μM, mM, (diazo-methane), CM (carboxymethyl), suitable caption and arranged to be viewed M, %, mol DEAE (diethylaminoethyl), DMF vertically. They must be so constructed Dry weight: dry wt; fresh weight: fr. wt (dimethylformamide), DMSO (dimethyl as to be intelligible without reference to Electricity: V, mA, eV sulphoxide), EDTA (ethylene-diaminetetra- the text. Every table must have an Arabic Force due to gravity (centrifugation): g; acetic acid), Et20 (diethyl ether), EtOAc -1 number and a title, and each column must rpm (revolutions min ) (ethyl acetate), EtOH (ethanol), HC02H be provided with an explanatory heading. Gas chromatography: GC (formic acid), HOAc (acetic acid), iso-PrOH No vertical rules should be used. Tables Gas chromatography-mass spectrometry: (iso-propanol), Me2CO (acetone), MeCOEt should not duplicate results presented GC-MS Trimethylsilyl derivative: TMSi (methyl ethyl ketone), MeOH (methanol), elsewhere in the manuscript (e.g. in graphs). (TMS cannot be used as this refers to the NaOAc (sodium acetate), NaOMe (sodium Footnotes may be used to expand column internal standard tetramethylsilane used methoxide), petrol (not light-petroleum or headings, etc. and should be referenced by in 1H NMR) petroleum ether), PhOH (phenol), PrOH superscript lowercase letters a,b,c rather High performance liquid chromatography: (propanol), PVP (polyvinylpyrrolidone), than symbols. Results should be cited HPLC TCA (trichloroacetic acid), TFA Infrared spectrophotometry: IR (trifl uoroacetic acid), THF (tetrahydrofuran). only to the degree of accuracy justifi ed on 1 Length: nm, μm, mm, cm, m H NMR solvents and standards: CDCl3 the basis of the errors of the method and (deutero-chloroform), D O, DMSO-d usually only to three signifi cant fi gures. Literature: lit. 2 6 + [deuterodimethylsulphoxide not (CD ) S0], Units must always be clearly indicated and Mass spectrometry: m/z [M] (molecular 3 2 ion, parent ion) pyridine-d5 (deuteropyridine), TMS chosen so as to avoid excessively high (tetramethylsilane). (>100) or low (<0.01) values. The fi gure Melting points: uncorr. (uncorrected) Molecular mass: Da (daltons), kDa zero should precede the decimal point for For further terms used in biochemistry all numbers below one (e.g. 0.1). Molecular weight: Mr Nuclear magnetic resonance: 1H NMR, and molecular biology the authors should 13 see the websites of the nomenclature Half-tone photographs must have C NMR, Hz, δ Numbers: e.g. 1, 10, 100, 1000, 10000; committees (www.chem.qmul.ac.uk/iubmb/). good contrast and not be more than 25 -1 cm wide and not more than 30 cm high. per or Optical rotatory dispersion: ORD Page charges. Original photographs (or high resolution There is no page charges for HKPJ. graphic fi les of at least 500 dpi) must be Paper chromatography: PC Precipitate: ppt. supplied as they are to be reproduced (e.g. Preparative thin-layer chromatography: Proofs and Articles in Press black and white or colour). If necessary, prep. TLC Proofs will be despatched via e-mail to the a scale should be marked on the Radioactivity: dpm (disintegrations corresponding author, by the Publisher photograph. Please note that photocopies per min), Ci (Curie), sp. act (specifi c and should be returned with corrections of photographs are not acceptable. activity), Bq (1 becquerel = 1 nuclear as quickly as possible, normally within 48 transformation sec-1) hours of receipt. Proofreading is solely Colour charges Repetitive manipulations: once, twice, the author’s responsibility. Authors should Authors are encouraged to submit their x3, x4, etc. ensure that corrections are returned in works in colour. There is no charge for one communication and are complete, RRt (relative retention time), R1 (Kovat’s colour print. retention index), ECL (equivalent chain as subsequent corrections will not be length- term frequently used in fatty acid possible. Any amendments will be Supplementary data work) incorporated and the fi nal article will then HKPJ now accepts electronic Saturated: satd. be published online as an Article in Press. supplementary material to support Solution: soln. and enhance your scientifi c research. Solvent mixtures including Offprints Supplementary fi les offer the author chromatographic solvents: abbreviate Two copies containing the offprints will additional possibilities to publish be supplied free of charge. Additional as follows n-BuOH-HOAc-H2O (4:1:5) supporting applications, movies, Statistics: LSD (least significant offprints and copies of the issue can be animation sequences, high-resolution difference), s.d. (standard deviation), s.e. ordered at a specially reduced rate using images, background datasets, sound (standard error) the order form sent to the corresponding clips and more. Supplementary fi les Temperature: (with centigrade), mp, mps, author after the manuscript has been supplied will, subject to peer review, be mmp, bp accepted. Late orders for reprints will published online alongside the electronic Temperature: temp. incur a 50% surcharge. version of your article in HKPS website. Thin-layer chromatography: TLC, Rf The presence of these fi les will be Time: s, min, h, day, week, month, year Copyright signifi ed by a footnote to the article Ultraviolet spectrophotometry: UV, A Upon acceptance of an article, Authors will be assumed to transfer copyright title, and by a description included in a (absorbance, not aD-optical density) unconditionally to HKPJ. This transfer will ‘Supplementary Data’ section at the end Volume: 1, (litre), μ1, ml ensure the widest possible dissemination of the paper. In order to ensure that your Weight: wt, pg, ng, μg, mg, g, kg submitted material is directly usable, of information. If excerpts from other please ensure that data is provided in copyrighted works are included, the Inorganics, e.g. AICl3 (aluminum Author(s) must obtain written permission one of our recommended fi le formats chloride), BF3 (boron trifl uoride), Cl., CO3, and supply a concise and descriptive from the copyright owners and credit the H2, HCl, HCIO4 (perchloric acid), HNO3. source(s) in the article. caption for each fi le. Please also clearly H2O, H2O2, H2SO4, H3B03 (boric acid), He, indicate whether data fi les are either i) for KHCO3 (potassium bicarbonate), KMn04 Author enquiries publication online or ii) only to be used as (potassium permanganate;), KOH, K-Pi For enquiries relating to the submission of an aid for the refereeing of the paper. For buffer (potassium phosphate buffer), articles (including electronic submission) please 2+ more detailed instructions please visit our LiAIH4 (lithium aluminium hydride), Mg , send your query by email to [email protected] + Author Gateway at htto://authors.HKPJ.org MgCI2, N2, NH3, (NH4)2S04, Na , NaBH4

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