An Overview of Tropane Alkaloids from Datura Stramonium L
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Module Two the Clinical Neurotoxicology of Chemical Terrorism
Chemical Agents of Opportunity for Terrorism: TICs & TIMs! Module Two The Clinical Neurotoxicology of Chemical Terrorism Training Support Package 1 Chemical Agents of Opportunity for Terrorism: TICs & TIMs Goals and Objectives • Recognize toxic syndromes that effect the nervous system – Sedation – Convulsions – Hallucinations • Know unique clinical effects of toxins that cause sedation syndromes • List examples of agents of opportunity for each syndrome • Know initial treatment strategy Module Two - The Clinical Neurotoxicology of Chemical Terrorism 2 Chemical Agents of Opportunity for Terrorism: TICs & TIMs Central Nervous System • The CNS is immensely complex – Great target for terrorism • The CNS is central to both our function and our thinking Module Two - The Clinical Neurotoxicology of Chemical Terrorism 3 Chemical Agents of Opportunity for Terrorism: TICs & TIMs The Balance of the Brain • The brain is a fine balance of excitatory and inhibitory influences – Slight alterations in either direction are significant Excitation Inhibition Glutamate Gamma-aminobutyric acid Catecholamines (GABA) Module Two - The Clinical Neurotoxicology of Chemical Terrorism 4 Chemical Agents of Opportunity for Terrorism: TICs & TIMs The Balance of the Brain • In addition, other neurotransmitters influence our mood, our ability to think, remember, etc. Excitation Inhibition Modulators of Thought Processes Serotonin Acetylcholine Module Two - The Clinical Neurotoxicology of Chemical Terrorism 5 Chemical Agents of Opportunity for Terrorism: TICs & TIMs Clinical -
Protabase Record Display Datura Stramonium L
Protabase Record display www.prota.org Datura stramonium L. Protologue Sp. pl. 1: 179 (1753). Family Solanaceae Chromosome number 2n = 24 Vernacular names Thorn apple, green thorn apple, Jimson weed, Jamestown weed, devil’s apple, devil’s trumpet, stramonium (En). Pomme épineuse, stramoine, datura, feuille du diable, herbe du diable (Fr). Figueira do inferno, pomo espinhoso, erva dos bruxos, palha verde, estramonio (Po). Muranha (Sw). Origin and geographic distribution Datura stramonium is native to the Americas and has been introduced in many tropical, subtropical and even temperate regions. It is a naturalized weed in many African countries, but is probably seriously under-reported. Uses Datura stramonium and Datura metel L. have largely similar medicinal uses throughout the world. The most widely known use of Datura stramonium and of other Datura species is for relieving asthma, cough, tuberculosis and bronchitis by smoking the dried leaves, roots or flowers. ‘Asthma cigarettes’ have been shown to be very effective in some cases, but in other cases they had little or no effect. Cigarettes made with the leaves are also used to treat Parkinson’s disease. A decoction or infusion of leaves is given as a sedative to mental and schizophrenic patients. The leaves are applied as a dressing to cure rheumatic pain, swellings, wounds, gout, burns, ingrown toe-nails, fungal infections, tumours and ulcers. Dried pulverized leaves are dusted on wounds or applied after mixing the powder with fat or Vaseline. In DR Congo pounded fresh root and fresh leaves are soaked in water and the liquid is given in enema as an abortifacient. -
Consumer Medicine Information
New Zealand Datasheet Name of Medicine DOZILE Doxylamine Succinate 25 mg Capsules Presentation Liquid filled soft gel capsules, purple, containing 25 mg doxylamine succinate. Uses Actions Doxylamine succinate is a white or creamy white powder with a characteristic odour and has solubilities of approximately 1 g/mL in water and 500 mg/mL in alcohol at 25°C. It has a pKa of 5.8 and 9.3. A 1% aqueous solution has a pH of 4.8 - 5.2. Doxylamine succinate is an ethanolamine derivative antihistamine. Because of its sedative effect, it is used for the temporary relief of sleeplessness. The drug is also used in combination with antitussives and decongestants for the temporary relief of cold and cough symptoms. It is not structurally related to the cyclic antidepressants. It is an antihistamine with hypnotic, anticholinergic, antimuscarinic and local anaesthetic effects. Duration of action is 6-8 hours. Pharmacokinetics Following oral administration of a single 25 mg dose of doxylamine succinate in healthy adults, mean peak plasma concentrations of about 100 ng/mL occur within 2- 3 hours after administration. The drug has an elimination half-life of about 10 hours in healthy adults. Absorption It is easily absorbed from the gastrointestinal tract. Following an oral dose of 25 mg the mean peak plasma level is 99 ng/mL 2.4 hours after ingestion. This level declines to 28 ng/mL at 24 hours and 10 ng/mL at 36 hours. Distribution The apparent volume of distribution is 2.5 L/kg. Metabolism The major metabolic pathways are N-demethylation, N-oxidation, hydroxylation, N- acetylation, N-desalkylation and ether cleavage. -
(Antimuscarinic) Drugs?
© July - August 2018 How well do you know your anticholinergic (antimuscarinic) drugs? nticholinergic drugs, prescribed for a variety of clini- Acal conditions, are amongst the most frequently used prescription drugs in BC (Table 1). Also referred to as “an- timuscarinics,” such drugs specifically block muscarinic receptors for acetylcholine (ACh).1 Muscarinic ACh recep- tors are important in the parasympathetic nervous system that governs heart rate, exocrine glands, smooth muscles, clude drugs whose active metabolites are potent- as well as brain function. In contrast, nicotinic ACh recep- ly antimuscarinic,5 or which often cause typical tors stimulate contraction of striated muscles. This Letter is AC adverse effects such as dry mouth or urinary intended to remind clinicians of commonly used drugs that retention.6 People taking antihistamines, antide- have anticholinergic (AC), or technically, antimuscarinic pressants, antipsychotics, opioids, antimuscarinic properties, and of their potential adverse effects. inhalers, or many other drugs need to know that Beneficial and harmful effects of anticholinergic drugs have blockade of ACh receptors can cause bothersome been known for centuries. In Homer’s Odyssey, the nymph or even dangerous adverse effects (Table 3). pharmacologist Circe utilized central effects of atropinics Subtle and not-so-subtle toxicity in the common plant jimson weed (Datura stramonium) to cause delusions in the crew of Odysseus. Believing they Students often learn the adverse effects of anticho- had been turned into pigs, they could be herded.2 linergics from a mnemonic, e.g.: “Blind as a bat, Sometimes a drug is recommended specifically for its an- mad as a hatter, red as a beet, hot as a hare, dry as ticholinergic potency. -
Potentially Harmful Drugs in the Elderly: Beers List
−This Clinical Resource gives subscribers additional insight related to the Recommendations published in− March 2019 ~ Resource #350301 Potentially Harmful Drugs in the Elderly: Beers List In 1991, Dr. Mark Beers and colleagues published a methods paper describing the development of a consensus list of medicines considered to be inappropriate for long-term care facility residents.12 The “Beers list” is now in its sixth permutation.1 It is intended for use by clinicians in outpatient as well as inpatient settings (but not hospice or palliative care) to improve the care of patients 65 years of age and older.1 It includes medications that should generally be avoided in all elderly, used with caution, or used with caution or avoided in certain elderly.1 There is also a list of potentially harmful drug-drug interactions in seniors, as well as a list of medications that may need to be avoided or have their dosage reduced based on renal function.1 This information is not comprehensive; medications and interactions were chosen for inclusion based on potential harm in relation to benefit in the elderly, and availability of alternatives with a more favorable risk/benefit ratio.1 The criteria no longer address drugs to avoid in patients with seizures or insomnia because these concerns are not unique to the elderly.1 Another notable deletion is H2 blockers as a concern in dementia; evidence of cognitive impairment is weak, and long-term PPIs pose risks.1 Glimepiride has been added as a drug to avoid. Some drugs have been added with cautions (dextromethorphan/quinidine, trimethoprim/sulfamethoxazole), and some have had cautions added (rivaroxaban, tramadol, SNRIs). -
PRESCRIBING INFORMATION (Dicyclomine Hydrochloride USP
PRESCRIBING INFORMATION BENTYLOL® (dicyclomine hydrochloride USP) Tablets 10 mg and 20 mg Syrup 10 mg/5 mL Antispasmodic APTALIS PHARMA CANADA INC. Date of Revision: 597 Laurier Blvd. July 16, 2012 Mont-St-Hilaire, Quebec J3H 6C4 Control number: 156699 BENTYLOL® (dicyclomine hydrochloride, USP) Prescribing Information Tablets & Syrup PRESCRIBING INFORMATION BENTYLOL® (dicyclomine hydrochloride USP) 10 mg and 20 mg Tablets Syrup, 10 mg/5 mL Antispasmodic ACTION AND CLINICAL PHARMACOLOGY Bentylol (dicyclomine) relieves smooth muscle spasm of the gastrointestinal tract. Animal studies indicate that this action is achieved via a dual mechanism: (1) a specific anticholinergic effect (antimuscarinic) at the acetylcholine (ACh)-receptor sites with approximately 1/8 the milligram potency of atropine (in vitro guinea pig ileum); and (2) a direct effect upon smooth muscle (musculotropic) as evidenced by dicyclomine's antagonism of bradykinin- and histamine-induced spasms of the isolated guinea pig ileum. Atropine did not affect responses to these two agonists. Animal studies showed dicyclomine to be equally potent against ACh - or barium chloride (BaCl2) - induced intestinal spasm while atropine was at least 200 times more potent against the effects of ACh than against BaCl2. Tests for mydriatic effects in mice showed that dicyclomine was approximately 1/500 as potent as atropine; antisialagogue tests in rabbits showed dicyclomine to be 1/300 as potent as atropine. After a single oral 20 mg dose of dicyclomine in volunteers, peak plasma concentration reached a mean value of 58 ng/mL in 1 to 1.5 hours. The principal route of elimination is via the urine. __________________________________________________________________________________ Aptalis Pharma Canada Inc. -
Drugs to Avoid in Patients with Dementia
Detail-Document #240510 -This Detail-Document accompanies the related article published in- PHARMACIST’S LETTER / PRESCRIBER’S LETTER May 2008 ~ Volume 24 ~ Number 240510 Drugs To Avoid in Patients with Dementia Elderly people with dementia often tolerate drugs less favorably than healthy older adults. Reasons include increased sensitivity to certain side effects, difficulty with adhering to drug regimens, and decreased ability to recognize and report adverse events. Elderly adults with dementia are also more prone than healthy older persons to develop drug-induced cognitive impairment.1 Medications with strong anticholinergic (AC) side effects, such as sedating antihistamines, are well- known for causing acute cognitive impairment in people with dementia.1-3 Anticholinergic-like effects, such as urinary retention and dry mouth, have also been identified in drugs not typically associated with major AC side effects (e.g., narcotics, benzodiazepines).3 These drugs are also important causes of acute confusional states. Factors that may determine whether a patient will develop cognitive impairment when exposed to ACs include: 1) total AC load (determined by number of AC drugs and dose of agents utilized), 2) baseline cognitive function, and 3) individual patient pharmacodynamic and pharmacokinetic features (e.g., renal/hepatic function).1 Evidence suggests that impairment of cholinergic transmission plays a key role in the development of Alzheimer’s dementia. Thus, the development of the cholinesterase inhibitors (CIs). When used appropriately, the CIs (donepezil [Aricept], rivastigmine [Exelon], and galantamine [Razadyne, Reminyl in Canada]) may slow the decline of cognitive and functional impairment in people with dementia. In order to achieve maximum therapeutic effect, they ideally should not be used in combination with ACs, agents known to have an opposing mechanism of action.1,2 Roe et al studied AC use in 836 elderly patients.1 Use of ACs was found to be greater in patients with probable dementia than healthy older adults (33% vs. -
Diphenhydramine Hydrochloride Oral Solution USP Rx ONLY
DIPHENHYDRAMINE HYDROCHLORIDE- diphenhydramine hydrochloride solution Pharmaceutical Associates, Inc. ---------- Diphenhydramine Hydrochloride Oral Solution USP Rx ONLY DESCRIPTION Diphenhydramine hydrochloride is an antihistamine drug having the chemical name 2- (diphenylmethoxy)-N,N -dimethylethylamine hydrochloride and has the molecular formula C 17H 21NO•HCI (molecular weight 291.82). It occurs as a white odorless, crystalline powder and is freely soluble in water and alcohol. The structural formula is as follows: Each 5 mL contains 12.5 mg of diphenhydramine hydrochloride and alcohol 14% for oral administration. Inactive Ingredients: Citric acid, D&C Red No. 33, FD&C Red No. 40, flavoring, purified water, sodium citrate, and sucrose. CLINICAL PHARMACOLOGY Diphenhydramine hydrochloride is an antihistamine with anticholinergic (drying) and sedative effects. Antihistamines appear to compete with histamine for cell receptor sites on effector cells. A single oral dose of diphenhydramine hydrochloride is quickly absorbed with maximum activity occurring in approximately one hour. The duration of activity following an average dose of diphenhydramine hydrochloride is from four to six hours. Diphenhydramine is widely distributed throughout the body, including the CNS. Little, if any, is excreted unchanged in the urine; most appears as the degradation products of metabolic transformation in the liver, which are almost completely excreted within 24 hours. INDICATIONS AND USAGE Diphenhydramine hydrochloride in the oral form is effective for the following indications: Antihistaminic For allergic conjunctivitis due to foods; mild, uncomplicated allergic skin manifestations of urticaria and angioedema; amelioration of allergic reactions to blood or plasma; dermatographism; as therapy for anaphylactic reactions adjunctive to epinephrine and other standard measures after the acute manifestations have been controlled. -
The Anticholinergic Toxidrome
Poison HOTLINE Partnership between Iowa Health System and University of Iowa Hospitals and Clinics July 2011 The Anticholinergic Toxidrome A toxidrome is a group of symptoms associated with poisoning by a particular class of agents. One example is the opiate toxidrome, the triad of CNS depression, respiratory depression, and pinpoint pupils, and which usually responds to naloxone. The anticholinergic toxidrome is most frequently associated with overdoses of diphenhydramine, a very common OTC medication. However, many drugs and plants can produce the anticholinergic toxidrome. A partial list includes: tricyclic antidepressants (amitriptyline), older antihistamines (chlorpheniramine), Did you know …… phenothiazines (promethazine) and plants containing the anticholinergic alkaloids atropine, hyoscyamine and scopolamine (Jimson Weed). Each summer, the ISPCC receives approximately 10-20 The mnemonic used to help remember the symptoms and signs of this snake bite calls, some being toxidrome are derived from the Alice in Wonderland story: from poisonous snakes (both Blind as a Bat (mydriasis and inability to focus on near objects) local and exotic). Red as a Beet (flushed skin color) Four poisonous snakes can be Hot as Hades (elevated temperature) found in Iowa: the prairie These patients can sometimes die of agitation-induced hyperthermia. rattlesnake, the massasauga, Dry as a Bone (dry mouth and dry skin) the copperhead, and the Mad as a Hatter (hallucinations and delirium) timber rattlesnake. Each Bowel and bladder lose their tone (urinary retention and constipation) snake has specific territories Heart races on alone (tachycardia) within the state. ISPCC A patient who has ingested only an anticholinergic substance and is not specialists have access to tachycardic argues against a serious anticholinergic overdose. -
Monographs on Datura Stramonium L
The School of Pharmaceutical and Biomedical Sciences Pokhara University, P. O. Box 427, Lekhnath, Kaski, NEPAL Monographs on Datura stramonium L Submitted By Bhakta Prasad Gaire Bachelor in Pharmaceutical Sciences (5th Batch) Roll No. 29/2005 [2008] [TYPE THE COMPANY ADDR ESS ] A Plant Monograph on Dhaturo (Datura stramonium L.) Prepared by Bhakta Prasad Gaire Roll No. 29/2005 Submitted to The School of Pharmaceutical and Biomedical Sciences Pokhara University, Dhungepatan-12, Lekhnath, Kaski, NEPAL 2008 ii PREFACE Datura was quite abundantly available in my village (Kuwakot-8, Syangja) since the days of my ancestors. Although it's medicinal uses were not so clear and established at that time, my uncle had a belief that when given along with Gaja, it'll cure diarrhea in cattle. But he was very particular of its use in man and was constantly reminding me not to take it, for it can cause madness. I, on the other hand was very curious and often used to wonder how it looks and what'll actually happen if I take it. This curiosity was also fuelled by other rumours floating around in the village, of the cases of mass hysteria which happened when people took Datura with Panchamrit and Haluwa during Shivaratri and Swasthani Puja. It was in 2052 B.S (I was in class 3 at that time) when an incident happened. One day I came earlier from school (around 2'0 clock), only to find nobody at home. The door was locked and I frantically searched for my mother and sister, but in vain. -
Duboisia Myoporoides
Principal Studies on Scopolamine Biosynthesis in Duboisia spec. for Heterologous Reconstruction of Tropane Alkaloid Biosynthesis Laura Kohnen1, Friederike Ullrich1, Nils J. H. Averesch2 and Oliver Kayser1 (1) Technical Biochemistry, Technical University Dortmund, Dortmund, Germany (2) Centre for Microbial Electrochemical Systems (CEMES), The University of Queensland, Brisbane, Australia [email protected], [email protected], [email protected], [email protected] Tropane alkaloids Objectives - Tropane alkaloids (TA), including scopolamine and hyoscyamine, are - Reconstruction of a heterologous pathway requires fundamental secondary plant components mainly occurring in the family of Solanaceae understanding of the merging pathways, the respective biosynthetic genes, - Scopolamine is an important bulk compound in the semi-synthesis of drugs their transcription and regulation - here we focus on: for clinical medicines like Buscopan® or Spiriva® I) Analysis of the principal pathway and most important enzymes for their - TA are mainly obtained via extraction from field-grown Duboisia hybrids expression and biochemical profile - Demand for scopolamine based drugs is expected to increase in the future II) Construction of a cDNA library from cytosolic root cells of Duboisia - A biotechnological process may help to compensate fluctuations in crop yield species of the medicinal plants III) Analysis of metabolic profiles of Duboisia species Introduction IV) In silico analysis of a heterologous production system utilizing metabolic network modelling Biosynthetic pathway of TA NMR-based metabolomics - Biosynthesis of TA is located in the roots[1] - Global analysis of leaf and root extracts - TA are transported to the aerial parts of the plants - Detection of primary (amino acids, sugars) as well as secondary metabolites - Storage and accumulation of hyoscyamine, 6-OH-hyoscyamine and (flavonoids, TA) scopolamine in the leaves (cf. -
Chapter 2 2. Q Labelling in Hyoscyamine
Durham E-Theses The biosynthesis of the tropane alkaloid hyoscyamine in datura stramonium Wong, Chi W. How to cite: Wong, Chi W. (1999) The biosynthesis of the tropane alkaloid hyoscyamine in datura stramonium, Durham theses, Durham University. Available at Durham E-Theses Online: http://etheses.dur.ac.uk/4310/ Use policy The full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that: • a full bibliographic reference is made to the original source • a link is made to the metadata record in Durham E-Theses • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders. Please consult the full Durham E-Theses policy for further details. Academic Support Oce, Durham University, University Oce, Old Elvet, Durham DH1 3HP e-mail: [email protected] Tel: +44 0191 334 6107 http://etheses.dur.ac.uk COPYRIGHT The copyright of this thesis rests with the author. No quotation form it should be published without prior consent, and any information derived from this thesis should be acknowledged. DECLARATION The work contained in this thesis was carried out in the Department of Chemistry at the University of Durham between October 1995 and September 1998. All the work was carried out by the author, unless otherwise indicated. It has not been previously submitted for a degree at this or any other university.