DOCSLIB.ORG

Primaquine Sensitivity (Glucose-6-Phosphate Dehydrogenase Deficiency)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Primaquine Sensitivity (Glucose-6-Phosphate Dehydrogenase Deficiency) PRIMAQUINE SENSITIVITY (GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY) .An Inborn Error of Metabolism of Medical and Biolo Significance Alvin R. Tarlov. M... D. .George J. Brewer, M. D. From the University of Chicago-Army Medical Research Unit, Department of Medicine, Chicago, Illinois. "he previously unpublished studies gf the authors included in this review were supported by the Medical' Research and Development Command, Office of the Surgeon General, Department of the Army, under contracts DA-49-007-MD- 566 and DA 49-007-MDWwith the University of Chicago and were supplernent- ed by grants from Burroughs- Wellcome and Company, Winthrop Laboratories, , and the Douglas Smith Foundation, SUBMITTED TO THE ARCHIVES OF INTERNAL MEDICINE 25 AUGUST I961 - 3. \, \, The potential danger of hemolysis from use of the 8-aminoquinoline antim larial drug, pamaquine (plasmoquine@J , has been known since i.\\ 1926 (l): Earle (2), in 1948, reported that pamaquine caused hemolysis . ' in 5-10 percent of American Negroes, but rarely in Caucasians. Similar observations were made in 1952 by Hockwald (3), during an evaluation of the related, but less toxic drug, primaquine; it was further noted that the severity of hemolysis was determined by the amount of drug administered. In 1954, Dern (4) discovered that the susceptibility to hemolysis by primaquine is due to an intrinsic abnormality of the erythrocyte. Dern, Beutler and Alving (5) reported that the hemolysis is self-limited in that clinical recovery occurs even if the daily dose of drug is continued. Many drugs can precipitate hemolysis (6 ) . This hypersusceptibility to hemolysis by drugs is a genetically transmitted inborn error of metabolism (7 ) , - The first biochemical abnormality to characterize drug-sensitive cells, a low content of reduced glutathione (GSH), was discovered by Beutler (8). This kind of susceptibility to drug-induced hemolysis is called primaquine-sensitivity because the initial stbdies which led to its charact- erization were made during investigations of the hemolytic property of this antimalarial drug. It has recently also been designated glucose-6- phosphate dehydrogenase (G-6-PD) deficiencx after the major known enzym- atic defect in primaquine-sensitive individuals (9) but the phenotypic name, ‘,’ primaquine sensitivity, should not be discarded until the primary genetic 9 \;. defectkor basic biochemical abnormality responsible for the destruction of erythrocytes has bcen established with certainty. Important contrib- utions to an understanding of this inborn error of metabolism have been made by many scientific workers, Intensive investigations have been carried out in the United States, Israel, Italy, Germany and, more recently, in other countries. Many drugs in common clinical use.__ may precieate hemolysis.___ ‘Nu-iIaiig(*r of ialrogc11ii::iIQ ~iiidut.cdacxitc aticmia sliould always be - ~ ~._-___-_____-. weighed by physicians in their selection-. of therapeutic agents. The possib- ility that _,some systemic discases -mznhancc the hemolytic effect of these drugs should alwTs be born in mind when an obscure hemolytic episode is encountered at the bedside. MODE- OF. IhYIERITANCE~. .. AND DISTRI- BUTION . - -- - __ Childs, Browne, and their co-workers (lo’ concluded from studies of American Negroes that primaquine-sensitivity is probably trans- mitted by a gene of partial dominance located on the X chromosome (sex- (12) linkage), Strong supporting evidence was soon presented by Gross , Szeinberg (I3), and Larizza (14). Definite proof for sex-linkage of the primaquine -sensitive gene in Sardinians was provided recently by chromosome; when colur blindness and primaquine-sensitivity coexist in a single individual the two gent’s segregate identically through succeed- ing generations in a given family (I5). Thcse conclusions are supported by the investigations of Adam (I6) in Sephardic Jews. Full expression of the genetic defect occurs in affected hemizygous males (E)because the mutant gene (2)is not opposed by a normal allele (X). Full expression is rare in females because the homozygous female -_ (XX) must inherit a mutant gene from both parents. Usually, affected females are heterozygous (e);they inherit a mutant gene from one parent and a normal allele from the 0th r, and, therefore, have partial expression of the trait. In our study of Negro* volunteers at two penal institutions in Illinois, 13 percent of the males and 3 percent of the females were fully (171 susceptible to hemolysis . Affected females manifested a wide ’ spectrum of expression of the clinical phenotype (hemolysis when 30 mg. of primaquine base was administered daily); in some hemolysis was only detectable by isotopic labeling of the erythrooytes. In iit hers the hemolytic susceptibility and the biochemical abnormalities of the erythrocytes were ~~ ~~ +This paper concerns the inherited disorder of primaquine- sensitive American Negroes unless otherwise specified. Sensitive Caucasians (Sardinians, Sephardic Jews) are more severely affected and differ in some respects from sensitive Negroes. .. c- -4- as severe, possibly even more severe, than in males with full expression. Judged by the clinical phenotype 20 percent of the Negro women were heterzygous. ** Yet, deficient G-6-PD*** in the erythrocytes could be demonstrated unequivocally only in approximately three-fourths of the heterozygous females. This may mean that several enzymatic abnormal- ities can influence the expression of the clinical phenotype or, alternatively, that the --in vitro assay of G-6-PD in hemolysates does not accurately reflect a slight decrease in the --in vivo activity of this enzyme in the circulating erythrocyte6. Primaquine- sensitiyity has a broad geographic distribution. Among Caucasians the defect is particularly concentrated in the Mediterranean area. Racial and ethnic groups having a high incidence usually are more darkly pigmented; the mutant gene rarely occurs in peoples of Northern European origin. Primaquine-sensitivity occurs in 48 percent of some Sardinian groups (") and in 2 to 36 percent of Mediterranean and Asiatic (Sephardic) Jews (13' 22); it is rare in European (Ashkenazic) Jews. The incidence in American Negro males is approximately 13 percent (1 1,17). - **This figure is slightly lower than the expected incidence of heterozygosity calculated from 13 percent incidence of sensitivity in Negro men. This may ir$Licate that som heterozygous females are so weakly expressed that detection is impossible even when primaquine is administered. ***The correlation between hemolysis and enzyme defi ienc was not improved when the Clock and McLean assay of G-6-PDb, 1% was substituted for the Kornberg method (21,23,24,25) it is even higher in some African Negro tribes . Prima- quine-sensitivity has also been reported in Greeks (26), Iranian Moslems (27), Asiatic Indians (28), Chinese (29), Filipinos(Z1) and many others (‘l). The incidence is highest in tropical and semi-tropical zones. It tends to parallel the distribution of falciparum malaria (21). GENETICAL AND ENVIRONMENTAL INFLUENCES Analysis of gene frequencies often yield information concerning the adaptive values of the trait. Many mutant genes decrease fitness; therefore, they tend to disappear from the population. A mutant gene, if it increases fitness, may exist in a population in a greater frequency than would be expected if it did not produce this biological advantage. I. Falciparum Malaria and Primaquine-Sensitivity:- The geographic distribution of primaquine-sensitivity (high frequency in tropical and semi-tropical malarious areas) suggests that the trait provides an evolutionary selective advantage against malaria*, as hypo- (31) thesized by Motulsky (‘”, and supported by the studies of Allison . Malaria parasites require glutathione (GSH). (32) and an oxidative pathway of carbohydrate metabolism (32* a3) for optimum growth. The low GSH *The incidence of the trait, however, is very low in Armenians who have lived for years in Iran where falciparum malaria is common and y&re the incidence of this trait in native Iranians varies from 5-1570. ( ) -. content and the diminished activity of the pentose phosphate pathway of primquine-sensitive erythrocytes mymake it difficult for the intracellular parasites to survive. The lower parasite density in the blood of young children whose erythrocytes are deficient in G-6-PD compared to children with normal enzyme activity has been interpreted as supporting this hypothesis. (31) Protection against malaria may similarly explain the geographic variation in frequency of sickle- (34, 35, 36) hemoglobin and thalassemia . Recently, however, caution (37, 65) has been advocated in interpreting data based on parasite densities I. II. Favism, Thalassemia and Primaquine-Sensitivity: Favism, hemolytic anemia caused by the fava bean, occurs only in primaquine- (38, 39.40.41 1 sensitive individuals . This condition is most common in Sardinians. The mortality rate in children who experience acute hemolysis after ingestion of the beans is reported to be 8 percent (42) . Clinical manifestations of acute icteric favism, however, are rare among primaquine-sensitive individuals who have thalassemia minor (41’43) and the observed frequency of individuals havinb both traits is . The erythrocytes of individuals with thalassemia minor have high\Y’ (45,46, 41.33.40) a shortened survival and consequently, a young erythrocyte population. Young cells are relatively resistant to hemolysis deficiency is rare. Similarly, Rh negativity is
Load more

Recommended publications
  • Dihydropteroate Synthase Gene Mutations in Pneumocystis
    Dihydropteroate Synthase Gene Mutations in Pneumocystis and Sulfa Resistance Laurence Huang,* Kristina Crothers,* Chiara Atzori,† Thomas Benfield,‡ Robert Miller,§ Meja Rabodonirina,¶ and Jannik Helweg-Larsen# Pneumocystis pneumonia (PCP) remains a major Patients who are not receiving regular medical care, as cause of illness and death in HIV-infected persons. Sulfa well as those who are not receiving or responding to anti- drugs, trimethoprim-sulfamethoxazole (TMP-SMX), and retroviral therapy or prophylaxis, are also at increased risk dapsone are mainstays of PCP treatment and prophylaxis. for PCP (2). PCP may also develop in other immunosup- While prophylaxis has reduced the incidence of PCP, its pressed populations, such as cancer patients and transplant use has raised concerns about development of resistant organisms. The inability to culture human Pneumocystis, recipients. Furthermore, PCP remains a leading cause of Pneumocystis jirovecii, in a standardized culture system death among critically ill patients, despite advances in prevents routine susceptibility testing and detection of drug treatment and management (3). resistance. In other microorganisms, sulfa drug resistance The first-line treatment and prophylaxis regimen for has resulted from specific point mutations in the dihy- PCP is trimethoprim-sulfamethoxazole (TMP-SMX) (4). dropteroate synthase (DHPS) gene. Similar mutations While prophylaxis has been shown to reduce the incidence have been observed in P. jirovecii. Studies have consistent- of PCP, the widespread and long-term use of TMP-SMX in ly demonstrated a significant association between the use HIV patients has raised concerns regarding the develop- of sulfa drugs for PCP prophylaxis and DHPS gene muta- ment of resistant organisms. Even short-term exposure to tions.
    [Show full text]
  • Pharmaceutical Compositions Comprising Hydroxychloroquine (HCQ), Curcumin, Piperine/ Bioperine and Uses Thereof in the Medical Field
    (19) TZZ 56_8A_T (11) EP 2 561 868 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 27.02.2013 Bulletin 2013/09 A61K 31/12 (2006.01) A61K 31/4706 (2006.01) A61K 45/06 (2006.01) A61P 35/00 (2006.01) (21) Application number: 11178638.0 (22) Date of filing: 24.08.2011 (84) Designated Contracting States: (72) Inventor: Van Oosten, Anton Bernhard AL AT BE BG CH CY CZ DE DK EE ES FI FR GB 3920 Lommel (BE) GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR (74) Representative: DeltaPatents B.V. Designated Extension States: Fellenoord 370 BA ME 5611 ZL Eindhoven (NL) (71) Applicant: Van Oosten, Anton Bernhard 3920 Lommel (BE) (54) Pharmaceutical compositions comprising hydroxychloroquine (HCQ), Curcumin, Piperine/ BioPerine and uses thereof in the medical field (57) The present invention concerns a pharmaceuti- of a premalignant plasma cell proliferative disorder like cal composition containing HCQ, curcumin and BioPer- a monoclonal gammopathy of undetermined significance ine/piperine and its application in the medical field. In (MGUS) and/or smoldering (asymptomatic) multiple my- particular, the composition according to the invention can eloma (SMM) and/or Indolent multiple myeloma (IMM) be advantageously employed in the prevention or treat- and/or to cause remission of a cancer arising from a pre- ment of a subject presenting with a proliferative disorder, malignant plasma cell proliferative disorder like multiple to slow the progression of and/or or to cause regression myeloma (MM).
    [Show full text]
  • The Safety and Effectiveness of Single Dose Primaquine As a P
    Malaria Policy Advisory Committee Meeting 11-13 September 2012, WHO HQ Session 5 WHO Evidence Review Group: The Safety and Effectiveness of Single Dose Primaquine as a P. falciparum gametocytocide Pullman Hotel, Bangkok, Thailand, 13-15 August 2012 Meeting Report Background Deployed since the early 1950s primaquine is the most Glossary: widely used 8-aminoquinoline antimalarial drug. It has been used extensively in the radical treatment of P. vivax G6PD: Glucose-6-phosphate dehydrogenase and P. ovale malaria, and as a single dose G6PDd: G6PD deficient gametocytocide in falciparum malaria. The main limitation to its use has been haemolytic toxicity. The 8- AHA: Acute haemolytic anaemia aminoquinoline antimalarials produce dose dependent acute haemolytic anaemia (AHA) in individuals who have ACT: Artemisinin combination treatment G6PD deficiency, an inherited X-linked abnormality. The MDA: Mass drug administration prevalence of the underlying allelic genes for G6PD deficiency varies typically between 5 and 32.5 % in POC: Point of care malaria endemic areas of Asia and Africa. Use of primaquine as a gametocytocide has great potential to reduce the transmission of falciparum malaria in low transmission settings, and in particular to help contain the spread of artemisinin resistant falciparum malaria in SouthEast Asia. The World Health Organisation currently recommends addition of primaquine 0.75 mg base/kg (adult dose 45 mg) to treatment regimens for P. falciparum malaria in areas of low transmission, particularly in areas where artemisinin resistant falciparum malaria is a threat, “when the risk for G6PD deficiency is considered low or testing for deficiency is available”. Unfortunately there is often uncertainty about the prevalence and severity of G6PD deficiency, and testing for it is usually not available in these areas.
    [Show full text]
  • A Suitable RNA Preparation Methodology for Whole Transcriptome Shotgun Sequencing Harvested from Plasmodium Vivax‑Infected Patients Catarina Bourgard1, Stefanie C
    www.nature.com/scientificreports OPEN A suitable RNA preparation methodology for whole transcriptome shotgun sequencing harvested from Plasmodium vivax‑infected patients Catarina Bourgard1, Stefanie C. P. Lopes2,3, Marcus V. G. Lacerda2,3, Letusa Albrecht1,4* & Fabio T. M. Costa1* Plasmodium vivax is a world‑threatening human malaria parasite, whose biology remains elusive. The unavailability of in vitro culture, and the difculties in getting a high number of pure parasites makes RNA isolation in quantity and quality a challenge. Here, a methodological outline for RNA‑ seq from P. vivax isolates with low parasitemia is presented, combining parasite maturation and enrichment with efcient RNA extraction, yielding ~ 100 pg.µL−1 of RNA, suitable for SMART‑Seq Ultra‑Low Input RNA library and Illumina sequencing. Unbiased coding transcriptome of ~ 4 M reads was achieved for four patient isolates with ~ 51% of transcripts mapped to the P. vivax P01 reference genome, presenting heterogeneous profles of expression among individual isolates. Amongst the most transcribed genes in all isolates, a parasite‑staged mixed repertoire of conserved parasite metabolic, membrane and exported proteins was observed. Still, a quarter of transcribed genes remain functionally uncharacterized. In parallel, a P. falciparum Brazilian isolate was also analyzed and 57% of its transcripts mapped against IT genome. Comparison of transcriptomes of the two species revealed a common trophozoite‑staged expression profle, with several homologous genes being expressed. Collectively, these results will positively impact vivax research improving knowledge of P. vivax biology. Plasmodium vivax is the most prevalent malaria parasite outside Sub-Saharan Africa, causing the most geographi- cally widespread type of malaria, placing millions of people at risk of infection 1.
    [Show full text]
  • Review of Mass Drug Administration and Primaquine
    Contents Acknowledgements ...................................................................................................................................... 2 Acronyms ...................................................................................................................................................... 3 Introduction .................................................................................................................................................. 4 Methods ....................................................................................................................................................... 4 Findings ......................................................................................................................................................... 6 Study objectives and design ............................................................................................................ 9 Contextual parameters - endemicity, seasonality, target population .......................................... 10 Outcome measures ....................................................................................................................... 13 Drug regimens ............................................................................................................................... 13 Co-Interventions ............................................................................................................................ 15 Delivery methods and community engagement ..........................................................................
    [Show full text]
  • Estonian Statistics on Medicines 2016 1/41
    Estonian Statistics on Medicines 2016 ATC code ATC group / Active substance (rout of admin.) Quantity sold Unit DDD Unit DDD/1000/ day A ALIMENTARY TRACT AND METABOLISM 167,8985 A01 STOMATOLOGICAL PREPARATIONS 0,0738 A01A STOMATOLOGICAL PREPARATIONS 0,0738 A01AB Antiinfectives and antiseptics for local oral treatment 0,0738 A01AB09 Miconazole (O) 7088 g 0,2 g 0,0738 A01AB12 Hexetidine (O) 1951200 ml A01AB81 Neomycin+ Benzocaine (dental) 30200 pieces A01AB82 Demeclocycline+ Triamcinolone (dental) 680 g A01AC Corticosteroids for local oral treatment A01AC81 Dexamethasone+ Thymol (dental) 3094 ml A01AD Other agents for local oral treatment A01AD80 Lidocaine+ Cetylpyridinium chloride (gingival) 227150 g A01AD81 Lidocaine+ Cetrimide (O) 30900 g A01AD82 Choline salicylate (O) 864720 pieces A01AD83 Lidocaine+ Chamomille extract (O) 370080 g A01AD90 Lidocaine+ Paraformaldehyde (dental) 405 g A02 DRUGS FOR ACID RELATED DISORDERS 47,1312 A02A ANTACIDS 1,0133 Combinations and complexes of aluminium, calcium and A02AD 1,0133 magnesium compounds A02AD81 Aluminium hydroxide+ Magnesium hydroxide (O) 811120 pieces 10 pieces 0,1689 A02AD81 Aluminium hydroxide+ Magnesium hydroxide (O) 3101974 ml 50 ml 0,1292 A02AD83 Calcium carbonate+ Magnesium carbonate (O) 3434232 pieces 10 pieces 0,7152 DRUGS FOR PEPTIC ULCER AND GASTRO- A02B 46,1179 OESOPHAGEAL REFLUX DISEASE (GORD) A02BA H2-receptor antagonists 2,3855 A02BA02 Ranitidine (O) 340327,5 g 0,3 g 2,3624 A02BA02 Ranitidine (P) 3318,25 g 0,3 g 0,0230 A02BC Proton pump inhibitors 43,7324 A02BC01 Omeprazole
    [Show full text]
  • 1 Antimalarial Activity of the 8 - Aminoquinolines Edward A
    University of Nebraska - Lincoln DigitalCommons@University of Nebraska - Lincoln US Army Research U.S. Department of Defense 1991 1 Antimalarial Activity of the 8 - Aminoquinolines Edward A. Nodiff Franklin Research Center, Arvin Calspan Corporation, Valley Forge Corporate Center, Norristown, PA Sankar Chatterjee Department of Medicinal Chemistry, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Washington, DC Hikmat A. Musallam Department of Medicinal Chemistry, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Washington, DC Follow this and additional works at: http://digitalcommons.unl.edu/usarmyresearch Nodiff, Edward A.; Chatterjee, Sankar; and Musallam, Hikmat A., "1 Antimalarial Activity of the 8 - Aminoquinolines" (1991). US Army Research. 337. http://digitalcommons.unl.edu/usarmyresearch/337 This Article is brought to you for free and open access by the U.S. Department of Defense at DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in US Army Research by an authorized administrator of DigitalCommons@University of Nebraska - Lincoln. Progress in Medicinal Chemistry - Vol. 28, edited by G.P. Ellis and G.B. West 0 1991, Elsevier Science Publishers, B.V. 1 Antimalarial Activity of the 8- Aminoquinoline s EDWARD A. NODIFF, B.A. SANKAR CHATTERJEE, Ph.D. and HIKMAT A. MUSALLAM, Ph.D.2 Franklin Research Center, Arvin Calspan Corporation, Valley Forge Corporate Center, 2600 Monroe Boulevard, Norristown, PA 19403 and 'Department of Medicinal Chemistry, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Washington, DC 20307-5100, U.S.A. INTRODUCTION 2 THE PARASITE Exoerythrocytic phase Erythrocytic phase Sporogony THE DISEASE 4 CLASSIFICATION OF ANTIMALARIAL DRUGS 4 HISTORY 5 METHODS FOR ANTIMALARIAL DRUG EVALUATION 8 Rane blood schizontocidal screen (P.
    [Show full text]
  • Mefloquine Poisoning and VA Service Connection
    Mefloquine Poisoning and VA Service Connection Presentation to the State Bar of Texas Military and Veterans Law Section March 29, 2019 Salado, Texas Remington Nevin, MD, MPH, DrPH Executive Director Photo credit: Dr. Remington Nevin Photo credits: Dr. Remington Nevin Background • Mefloquine was developed by the U.S. military as an antimalarial drug – Origins in the late 1960s during a Vietnam War-era program • Widespread use in the U.S. military beginning in the early 1990s (e.g. Somalia, SOCOM, OIF/OEF, AFRICOM) – Tens (hundreds?) of thousands of veterans have been exposed • Recently deprioritized for use by DoD – Followed U.S. and international “black box” warnings and recognition of chronic psychiatric and neurologic effects 2013 “Drug of Last Resort” Policy Memorandum “Mefloquine is the drug of last resort for malaria chemoprophylaxis and should only be used in persons with contraindications to chloroquine, doxycycline and atovaquone- proguanil.” Declining Use of Mefloquine within DoD Woodson J. Memorandum. Subject: Notification for Healthcare Providers of Mefloquine Box Warning. August 12, 2013. Emphasis added. “[Mefloquine] may cause long lasting serious mental problems… Some people who have taken [mefloquine] developed serious neuropsychiatric reactions…” Roche UK. Lariam product documentation, June 2018. Emphasis added. “Psychiatric symptoms such as insomnia, abnormal dreams/nightmares, acute anxiety, depression, restlessness or confusion have to be regarded as prodromal for a more serious event.” Roche UK. Lariam product documentation, June 2018. Emphasis added. “In a small number of patients, it has been reported that neuropsychiatric reactions (e.g. depression, dizziness, or vertigo and loss of balance) may persist for months or longer, even after discontinuation of the drug.” Roche UK.
    [Show full text]
  • TREATMENT GUIDELINE • Drug Schedule for Treatment of Malaria Under NVBDCP
    TREATMENT GUIDELINE • Drug Schedule for treatment of Malaria under NVBDCP. • Treatment of P.vivax cases: • Chloroquine: 25mg/kg body weight divided over three days i.e. 10mg/kg on day 1, 10mg/kg on day 2nd and 5mg/kg on day 3rd. • Primaquine: 0.25mg/kg body weight daily for 14 days. Age-wise dosage schedule for treatment of P. vivax cases Age Tab. Chloroquine Tab. Primaquine* (2.5 mg base) (in years) Day-1 Day-2 Day-3 Day – 1 to Day - 14 < 1 ½ 1/2 ¼ 0 1 - 4 1 1 ½ 1 5 - 8 2 2 1 2 9 - 14 3 3 11/2 4 15 & above 4 4 2 6 Primaquine is contraindicated in infants. Pregnant women and individuals with G&PD deficiency. 14 day regimen of Primaquine should be given under supervision Treatment of uncomplicated P. falciparum cases: • Artemisinin based Combination therapy (ACT)* • Artesunate 4 mg/kg body weight daily for 3 days Plus • Sulphadoxine (25 mg/kg body weight) – Pyrimethamine (1.25 mg/kg body weight) on first day. And • Primaquine 0.75 mg/Kg body weight on day 2 Caution:- • Act is not tobe given in 1st trimester of pregnancy. • SP is not to be given to child of age under 5 month and s/he should be treated with Alternate ACT. The Programme has introduced five different age-group specific Combi Blister packs foe SP-ACT. The age group wise dose schedule for the same and the colour of each combipack is given as follows: Age-wise dosage schedule for treatment of P. falciparum cases: Age Group 1st day 2nd day 3rd day (Years) AS SP AS SP AS 0-1 Pink Blister 1 (25 mg) 1 (250 1 (25 mg) NIL 1 (25 mg) mg+12.5mg) 1-4 Yellow 1 (50 mg) 1 (500+25 mg 1 (50 mg) 1 (7.5 mg) 1 (50 mg) Blister each) 5-8 Green 1 (100 mg) 1 (750+37.5 1 (100 mg) 2 (7.5 mg base 1 (100 mg) Blister mg each) each) 9-14 Red 1 (150 mg) 2 (500 mg+ 25 1 (150 mg) 4 (7.5 mg base 1 (150 mg) Blister mg each) each) 15 & above 1 (200 mg) 2 (750+37.5 1 (200 mg) 6 (7.5 mg base 1 (150 mg) white Blister mg each) each • Caution: • ACT is not to be given in pregnancy.
    [Show full text]
  • Current Antimalarial Therapies and Advances in the Development of Semi-Synthetic Artemisinin Derivatives
    Anais da Academia Brasileira de Ciências (2018) 90(1 Suppl. 2): 1251-1271 (Annals of the Brazilian Academy of Sciences) Printed version ISSN 0001-3765 / Online version ISSN 1678-2690 http://dx.doi.org/10.1590/0001-3765201820170830 www.scielo.br/aabc | www.fb.com/aabcjournal Current Antimalarial Therapies and Advances in the Development of Semi-Synthetic Artemisinin Derivatives LUIZ C.S. PINHEIRO1, LÍVIA M. FEITOSA1,2, FLÁVIA F. DA SILVEIRA1,2 and NUBIA BOECHAT1 1Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos Farmanguinhos, Fiocruz, Departamento de Síntese de Fármacos, Rua Sizenando Nabuco, 100, Manguinhos, 21041-250 Rio de Janeiro, RJ, Brazil 2Universidade Federal do Rio de Janeiro, Programa de Pós-Graduação em Química, Avenida Athos da Silveira Ramos, 149, Cidade Universitária, 21941-909 Rio de Janeiro, RJ, Brazil Manuscript received on October 17, 2017; accepted for publication on December 18, 2017 ABSTRACT According to the World Health Organization, malaria remains one of the biggest public health problems in the world. The development of resistance is a current concern, mainly because the number of safe drugs for this disease is limited. Artemisinin-based combination therapy is recommended by the World Health Organization to prevent or delay the onset of resistance. Thus, the need to obtain new drugs makes artemisinin the most widely used scaffold to obtain synthetic compounds. This review describes the drugs based on artemisinin and its derivatives, including hybrid derivatives and dimers, trimers and tetramers that contain an endoperoxide bridge. This class of compounds is of extreme importance for the discovery of new drugs to treat malaria. Key words: malaria, Plasmodium falciparum, artemisinin, hybrid.
    [Show full text]
  • Primaquine Phosphate)
    Primaquine may be taken with or the form of hemoglobin that cannot PRIMAQUINE without food. You may take primaquine carry oxygen). These effects are related PHOSPHATE with food to avoid an upset stomach. to the amount of primaquine taken and to persons who may already be Other NAMES: Primaquine What should you do if you FORGET a experiencing low red blood cell levels. dose? WHY is this drug prescribed? Rarely, primaquine may cause If you miss a dose of primaquine, take it leukopenia (a decrease in your white Primaquine is an antibiotic used to treat as soon as possible. However, if it is blood cells which are necessary to help different types of infections. time for your next dose, do not double fight bacterial infections). the dose, just carry on with your regular It can be given in combination with schedule. To ensure that you do not develop these clindamycin (Dalacin C) for the adverse effects, it is important that you treatment of Pneumocystis carinii Why should you not forget to take come to your regular blood tests. pneumonia (PCP). This combination is this drug? Please notify your doctor if you develop usually used for people who have the following symptoms: fatigue, experienced adverse effects to sulfa If you miss doses of primaquine, your weakness, shortness of breath, rapid drugs such as trimethoprim- infection may continue or worsen. In heartbeat, dark– coloured urine, fever sulfamethoxazole (TMP/SMX, such a situation, you may need to take or chills . Bactrim , Septra ) or dapsone. This other drugs. Therefore, it is extremely combination is a safe and effective important that you take primaquine for It is important that you keep your alternative.
    [Show full text]
  • Quantification of Chloroquine by LC-MS and the Macular Degeneration Disease
    Universidade de Lisboa Faculdade de Farmácia Quantification of Chloroquine by LC-MS and the Macular Degeneration Disease David Miguel Cunha Pereira Mestrado Integrado em Ciências Farmacêuticas 2017 1 Universidade de Lisboa Faculdade de Farmácia Quantification of Chloroquine by LC-MS and the Macular Degeneration Disease David Miguel Cunha Pereira Monografia de Mestrado Integrado em Ciências Farmacêuticas apresentada à Universidade de Lisboa através da Faculdade de Farmácia Orientadora: Professora Doutora Isabel Ribeiro 2017 2 The work accomplished on this monograph was possible thanks to University of Eastern Finland (UEF), under Eramus+ Programme. Advisor: Professor Seppo Auriola 3 4 Abstract Age-related macular degeneration is a visual disease that involves a progressive loss of central vision which its consequences are dramatic for the patient’s quality of life. Age is a major risk factor for macular degeneration. Other risk factors include, ethnicity, genetics, smoking and drugs. Chloroquine appears to be the most toxic drug to the retina, which might be explained by the extensive accumulation and very long retention of chloroquine bound to melanin. Chloroquine is used for malarial prevention and treatment, as well to various inflammatory diseases such as rheumatoid arthritis and lupus erythematosus. Chloroquine toxicity in age-related macular degeneration is of serious ophthalmologic concern because it is not treatable. Nonetheless, it has been demonstrated that central vision can be preserved if damage is recognized before there
    [Show full text]