Atropine Technical Report
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Table 2. 2012 AGS Beers Criteria for Potentially
Table 2. 2012 AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults Strength of Organ System/ Recommendat Quality of Recomm Therapeutic Category/Drug(s) Rationale ion Evidence endation References Anticholinergics (excludes TCAs) First-generation antihistamines Highly anticholinergic; Avoid Hydroxyzin Strong Agostini 2001 (as single agent or as part of clearance reduced with e and Boustani 2007 combination products) advanced age, and promethazi Guaiana 2010 Brompheniramine tolerance develops ne: high; Han 2001 Carbinoxamine when used as hypnotic; All others: Rudolph 2008 Chlorpheniramine increased risk of moderate Clemastine confusion, dry mouth, Cyproheptadine constipation, and other Dexbrompheniramine anticholinergic Dexchlorpheniramine effects/toxicity. Diphenhydramine (oral) Doxylamine Use of diphenhydramine in Hydroxyzine special situations such Promethazine as acute treatment of Triprolidine severe allergic reaction may be appropriate. Antiparkinson agents Not recommended for Avoid Moderate Strong Rudolph 2008 Benztropine (oral) prevention of Trihexyphenidyl extrapyramidal symptoms with antipsychotics; more effective agents available for treatment of Parkinson disease. Antispasmodics Highly anticholinergic, Avoid Moderate Strong Lechevallier- Belladonna alkaloids uncertain except in Michel 2005 Clidinium-chlordiazepoxide effectiveness. short-term Rudolph 2008 Dicyclomine palliative Hyoscyamine care to Propantheline decrease Scopolamine oral secretions. Antithrombotics Dipyridamole, oral short-acting* May -
4/23/2015 1 •Psychedelics Or Hallucinogens
4/23/2015 Hallucinogens •Psychedelics or This “classic” hallucinogen column The 2 groups below are quite different produce similar effects From the classic hallucinogens Hallucinogens Drugs Stimulating 5HT Receptors Drugs BLOCKING ACH Receptors • aka “psychotomimetics” LSD Nightshade(Datura) Psilocybin Mushrooms Jimsonweed Morning Glory Seeds Atropine Dimethyltryptamine Scopolamine What do the very mixed group of hallucinogens found around the world share in common? •Drugs Resembling NE Drugs BLOCKING Glutamate Receptors •Peyote cactus Phencyclidine (PCP) •Mescaline Ketamine All contain something that resembles a •Methylated amphetamines like MDMA High dose dextromethorphan •Nutmeg neurotransmitter •New synthetic variations (“bath salts”) •5HT-Like Hallucinogens •LSD History • Serotonin • created by Albert Hofmann for Sandoz Pharmaceuticals LSD • was studying vasoconstriction produced by ergot alkaloids LSD • initial exposure was accidental absorption thru skin • so potent ED is in millionths of a gram (25-250 micrograms) & must be delivered on something else (sugar cube, gelatin square, paper) Psilocybin Activate 5HT2 receptors , especially in prefrontal cortex and limbic areas, but is not readily metabolized •Characteristics of LSD & Other “Typical” •Common Effects Hallucinogens • Sensory distortions (color, size, shape, movement), • Autonomic (mostly sympathetic) changes occur first constantly changing (relatively mild) • Vivid closed eye imagery • Sensory/perceptual changes follow • Synesthesia (crossing of senses – e.g. hearing music -
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. -
Nightshade”—A Hierarchical Classification Approach to T Identification of Hallucinogenic Solanaceae Spp
Talanta 204 (2019) 739–746 Contents lists available at ScienceDirect Talanta journal homepage: www.elsevier.com/locate/talanta Call it a “nightshade”—A hierarchical classification approach to T identification of hallucinogenic Solanaceae spp. using DART-HRMS-derived chemical signatures ∗ Samira Beyramysoltan, Nana-Hawwa Abdul-Rahman, Rabi A. Musah Department of Chemistry, State University of New York at Albany, 1400 Washington Ave, Albany, NY, 12222, USA ARTICLE INFO ABSTRACT Keywords: Plants that produce atropine and scopolamine fall under several genera within the nightshade family. Both Hierarchical classification atropine and scopolamine are used clinically, but they are also important in a forensics context because they are Psychoactive plants abused recreationally for their psychoactive properties. The accurate species attribution of these plants, which Seed species identifiction are related taxonomically, and which all contain the same characteristic biomarkers, is a challenging problem in Metabolome profiling both forensics and horticulture, as the plants are not only mind-altering, but are also important in landscaping as Direct analysis in real time-mass spectrometry ornamentals. Ambient ionization mass spectrometry in combination with a hierarchical classification workflow Chemometrics is shown to enable species identification of these plants. The hierarchical classification simplifies the classifi- cation problem to primarily consider the subset of models that account for the hierarchy taxonomy, instead of having it be based on discrimination between species using a single flat classification model. Accordingly, the seeds of 24 nightshade plant species spanning 5 genera (i.e. Atropa, Brugmansia, Datura, Hyocyamus and Mandragora), were analyzed by direct analysis in real time-high resolution mass spectrometry (DART-HRMS) with minimal sample preparation required. -
Muscarinic Acetylcholine Receptor
mAChR Muscarinic acetylcholine receptor mAChRs (muscarinic acetylcholine receptors) are acetylcholine receptors that form G protein-receptor complexes in the cell membranes of certainneurons and other cells. They play several roles, including acting as the main end-receptor stimulated by acetylcholine released from postganglionic fibersin the parasympathetic nervous system. mAChRs are named as such because they are more sensitive to muscarine than to nicotine. Their counterparts are nicotinic acetylcholine receptors (nAChRs), receptor ion channels that are also important in the autonomic nervous system. Many drugs and other substances (for example pilocarpineand scopolamine) manipulate these two distinct receptors by acting as selective agonists or antagonists. Acetylcholine (ACh) is a neurotransmitter found extensively in the brain and the autonomic ganglia. www.MedChemExpress.com 1 mAChR Inhibitors & Modulators (+)-Cevimeline hydrochloride hemihydrate (-)-Cevimeline hydrochloride hemihydrate Cat. No.: HY-76772A Cat. No.: HY-76772B Bioactivity: Cevimeline hydrochloride hemihydrate, a novel muscarinic Bioactivity: Cevimeline hydrochloride hemihydrate, a novel muscarinic receptor agonist, is a candidate therapeutic drug for receptor agonist, is a candidate therapeutic drug for xerostomia in Sjogren's syndrome. IC50 value: Target: mAChR xerostomia in Sjogren's syndrome. IC50 value: Target: mAChR The general pharmacol. properties of this drug on the The general pharmacol. properties of this drug on the gastrointestinal, urinary, and reproductive systems and other… gastrointestinal, urinary, and reproductive systems and other… Purity: >98% Purity: >98% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 10mM x 1mL in DMSO, Size: 10mM x 1mL in DMSO, 1 mg, 5 mg 1 mg, 5 mg AC260584 Aclidinium Bromide Cat. No.: HY-100336 (LAS 34273; LAS-W 330) Cat. -
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. -
Viewed the Existence of Multiple Muscarinic CNS Penetration May Occur When the Blood-Brain Barrier Receptors in the Mammalian Myocardium and Have Is Compromised
BMC Pharmacology BioMed Central Research article Open Access In vivo antimuscarinic actions of the third generation antihistaminergic agent, desloratadine G Howell III†1, L West†1, C Jenkins2, B Lineberry1, D Yokum1 and R Rockhold*1 Address: 1Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA and 2Tougaloo College, Tougaloo, MS, USA Email: G Howell - [email protected]; L West - [email protected]; C Jenkins - [email protected]; B Lineberry - [email protected]; D Yokum - [email protected]; R Rockhold* - [email protected] * Corresponding author †Equal contributors Published: 18 August 2005 Received: 06 October 2004 Accepted: 18 August 2005 BMC Pharmacology 2005, 5:13 doi:10.1186/1471-2210-5-13 This article is available from: http://www.biomedcentral.com/1471-2210/5/13 © 2005 Howell et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Muscarinic receptor mediated adverse effects, such as sedation and xerostomia, significantly hinder the therapeutic usefulness of first generation antihistamines. Therefore, second and third generation antihistamines which effectively antagonize the H1 receptor without significant affinity for muscarinic receptors have been developed. However, both in vitro and in vivo experimentation indicates that the third generation antihistamine, desloratadine, antagonizes muscarinic receptors. To fully examine the in vivo antimuscarinic efficacy of desloratadine, two murine and two rat models were utilized. The murine models sought to determine the efficacy of desloratadine to antagonize muscarinic agonist induced salivation, lacrimation, and tremor. -
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. -
Drugs That Can Cause Delirium (Anticholinergic / Toxic Metabolites)
Drugs that can Cause Delirium (anticholinergic / toxic metabolites) Deliriants (drugs causing delirium) Prescription drugs . Central acting agents – Sedative hypnotics (e.g., benzodiazepines) – Anticonvulsants (e.g., barbiturates) – Antiparkinsonian agents (e.g., benztropine, trihexyphenidyl) . Analgesics – Narcotics (NB. meperidine*) – Non-steroidal anti-inflammatory drugs* . Antihistamines (first generation, e.g., hydroxyzine) . Gastrointestinal agents – Antispasmodics – H2-blockers* . Antinauseants – Scopolamine – Dimenhydrinate . Antibiotics – Fluoroquinolones* . Psychotropic medications – Tricyclic antidepressants – Lithium* . Cardiac medications – Antiarrhythmics – Digitalis* – Antihypertensives (b-blockers, methyldopa) . Miscellaneous – Skeletal muscle relaxants – Steroids Over the counter medications and complementary/alternative medications . Antihistamines (NB. first generation) – diphenhydramine, chlorpheniramine). Antinauseants – dimenhydrinate, scopolamine . Liquid medications containing alcohol . Mandrake . Henbane . Jimson weed . Atropa belladonna extract * Requires adjustment in renal impairment. From: K Alagiakrishnan, C A Wiens. (2004). An approach to drug induced delirium in the elderly. Postgrad Med J, 80, 388–393. Delirium in the Older Person: A Medical Emergency. Island Health www.viha.ca/mhas/resources/delirium/ Drugs that can cause delirium. Reviewed: 8-2014 Some commonly used medications with moderate to high anticholinergic properties and alternative suggestions Type of medication Alternatives with less deliriogenic -
PSYCHEDELIC DRUGS (P.L) 1. Terminology “Hallucinogens
PSYCHEDELIC DRUGS (p.l) 1. Terminology “hallucinogens” – induce hallucinations, although sensory distortions are more common “psychotomimetics” – to minic psychotic states, although truly most drugs in this class do not do so “phantasticums”or “psychedelics” – alter sensory perception (Julien uses “psychedelics”) alterations in perception, cognition, and mood, in presence of otherwise clear ability to sense” may increase sensory awareness, increase clarity, decrease control over what is sensed/experienced “self-A” may feel a passive observer of what “self-B” is experiencing often accompanied by a sense of profound meaningfulness, of divine or cosmic importance (limbic system?) these drugs can be classified by what NT they mimic: anti-ACh, agonists for NE, 5HT, or glutamate (See p. 332, Table 12.l in Julien, 9th Ed.) 2. The Anti-ACh Psychedelics e.g. scopolamine (classified as an ACh blocker) high affinity, no efficacy plant product: Belladonna or “deadly nightshade” (Atropa belladonna) Datura stramonium (jimson weed, stinkweed) Mandragora officinarum (mandrake plant) pupillary dilation (2nd to atropine) PSYCHEDELIC DRUGS (p.2) 2. Anti-ACh Psychedelics (cont.) pharmacological effects: e.g. scopolamine (Donnatal) clinically used to tx motion sickness, relax smooth muscles (gastric cramping), mild sedation/anesthetic effect PNS effects --- dry mouth relaxation of smooth muscles decreased sweating increased body temperature blurred vision dry skin pupillary dilation tachycardia, increased BP CNS effects --- drowsiness, mild euphoria profound amnesia fatigue decreased attention, focus delirium, mental confusion decreased REM sleep no increase in sensory awareness as dose increases --- restlessness, excitement, hallucinations, euphoria, disorientation at toxic dose levels --- “psychotic delirium”, confusion, stupor, coma, respiratory depression so drug is really an intoxicant, amnestic, and deliriant 3. -
Nomination Background: Ketamine Hydrochloride (CASRN: 1867-66-9)
KETAMINE Nomination TABLE OF CONTENTS Page 1.0 BASIS OF NOMINATION 1 2.0 BACKGROUND INFORMATION 1 3.0 CHEMICAL PROPERTIES 2 3.1 Chemical Identification 2 3.2 Physico-Chemical Properties 3 3.3 Purity and Commercial Availability 4 4.0 PRODUCTION PROCESSES AND ANALYSIS 6 5.0 PRODUCTION AND IMPORT VOLUMES 7 6.0 USES 7 7.0 ENVIRONMENTAL OCCURRENCE 7 8.0 HUMAN EXPOSURE 7 9.0 REGULATORY STATUS 7 10.0 CLINICAL PHARMACOLOGY 7 11.0 TOXICOLOGICAL DATA 13 11.1 General Toxicology 13 11.2 Neurotoxicology 14 12.0 CONCLUSIONS 15 APPENDIX A 17 APPENDIX B 23 APPENDIX C 27 1 KETAMINE 1.0 BASIS OF NOMINATION Ketamine, a noncompetitive NMDA receptor blocker, has been used extensively off - label as a pediatric anesthetic for surgical procedures in infants and toddlers. Recently, Olney and coworkers have demonstrated severe widespread apoptotic degeneration throughout the rapidly developing brain of the 7-day-old rat after ketamine administration. Recent research at FDA has confirmed and extended Olney’s observations. These findings are cause for concern with respect to ketamine use in children. The issue of whether the neurotoxicity found in this animal model (rat) has scientific and regulatory relevance for the pediatric use of ketamine relies heavily upon confirmation of these findings that may be obtained from the conduct of an appropriate study in non-human primates. 2.0 BACKGROUND INFORMATION The issue of potential ketamine neurotoxicity in children surfaced as a result of FDA’s reluctance to approve an NIH pediatric clinical trial using this compound because of its documented neurotoxic effects in young rats (published in several papers over the last ten years by Olney and co-workers).