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American College of Medical Toxicology 2012 www.acmt.net ACMT Medical Toxicology Board Review Course ARE YOU PREPARED? Astor Crowne Plaza Hotel New Orleans, LA September 8-10, 2012 SYLLABUS Day Two - 3 slides per page Sponsored by the University of Alabama School of Medicine Division of Continuing Medical Education American College of Medical Toxicology Medical Toxicology Board Review Course September 8-10, 2012 - New Orleans, LA Day 1 - Saturday, September 8, 2012 7:00-7:50am Breakfast & Stimulus Room 7:50-8:20am Welcome & Introductions 8:20-9:10am Pharmacokinetics/Toxicokinetics Howard A. Greller, MD, FACMT 9:10-10:00am Molecular Mechanisms William P. “Russ” Kerns II, MD, FACMT 10:00-10:20am Break 10:20-11:10am Analytical/Forensics Evan S. Schwarz, MD 11:10-12:00pm Autonomics/Neurotransmitters G. Patrick Daubert, MD 12:00-1:30pm Lunch –n-Learn: Mushrooms & Fish-borne Howard A. Greller, MD, FACMT 1:30-2:20pm Psychotropics G. Patrick Daubert, MD 2:30-3:20pm Cardiovascular Toxins Trevonne M. Thompson, MD 3:20-3:40pm Break 3:40-4:05pm Hydrocarbons Trevonne M. Thompson, MD 4:05-4:30pm Pharmaceutical Additives G. Patrick Daubert, MD 4:30-4:55pm Endocrine Trevonne M. Thompson, MD 6:00-7:30pm Welcome Reception - Napoleon House, 500 Chartres Street in the French Quarter Day 2 - Sunday, September 9, 2012 7:00-8:00AM Breakfast & Stimulus Room 8:00-8:50am Pesticides J. Dave Barry, MD, FACMT 8:50-9:15am Terrorism Hazmat J. Dave Barry, MD, FACMT 9:15-9:40am Antimicrobials Michael Policastro, MD 9:40-10:00am Break 10:00-10:50am GI/Heme Michael Policastro, MD 10:50-11:15am Chemotherapeutics Michael Policastro, MD 11:15-12:05pm Plants Thomas C. Arnold, MD, FACMT 12:05-1:30pm Lunch-n-Learn: Historical Outbreaks Stephen W. Munday, MD, MPH FACMT 1:30-2:20pm Envenomations Thomas C. Arnold, MD, FACMT 2:20-3:10pm Carcinogens Stephen W. Munday, MD, MPH, FACMT 3:10-3:30pm Break 3:30-4:20pm Misc Toxins 1 Brandon K. Wills, DO, FACMT 4:20-4:45pm Misc Toxins 2 Brandon K. Wills, DO, FACMT Day 3 - Monday, September 10, 2012 7:00-8:00am Breakfast & Stimulus Room 8:00-8:50am Anesthetics; Drugs of Abuse & Withdrawal Kurt C. Kleinschmidt, MD, FACMT 8:50-9:15am Herbal/Supplemental Tox Kurt C. Kleinschmidt, MD, FACMT 9:15-10:05am Industrial Poisons Jefrey Brent, MD, PhD, FACMT 10:05-10:25am Break 10:25-11:15am Assessment/Population Health/Risk Jefrey Brent, MD, PhD, FACMT 11:15-12:05pm Metals/Metalloids 1 Cyrus Rangan, MD 12:05-12:30pm Metals/Metalloids 2 Cyrus Rangan, MD John G. Benitez, MD, MPH, FACMT 12:30-3:00pm Stimulus Room Russ Kerns, MD, FACMT Pesticides ACMT Board Review Course J. Dave Barry Naval Medical Center Portsmouth Portsmouth, VA 2 Pesticides Insecticides Fungicides Rodenticides Fumigants Herbicides Others 3 1 Pesticides Insecticides Cholinesterase Inhibitors Organophosphates Carbamates Organochlorines Pyrethrins/Pyrethroids Newer Insecticides 4 Insecticides Cholinesterase Inhibitors O Carbamates R1 Ordeal (Calabar) Bean R-O C N (or S) R2 Carbamates Organophosphates O (or S) Synthesized R2 P R1 X Organophosphates 5 Insecticides Cholinesterase Inhibitors 6 Goldfrank’s Toxicologic Emergencies – 8th Ed (2006) 2 Pesticides sympathetic Autonomic Nervous System parasympathetic N M M C N T ne N ne L N M S N 7 Sympathetic Parasympathetic (cholinergic) agit N M Sz M C sec mio N T sec rr ne sec vasoconstr hr N hr ne L mot N M S sec Fasic N 8 paraly mict Insecticides Organophosphates Delayed Syndromes Intermediate Syndrome Weakness 1-4d after exposure peripheral NMJ dysfunction ineffective AChE reactivation OPIDN Neuropathy target esterase (NTE) Lysophospholipase (lysoPLA) TOCP (tri-ortho cresyl phosphate) Jamaican ginger paralysis (1930’s) Cooking oils (1950’s) 9 3 Pesticides Insecticides Organophosphates Diagnosis RBC Cholinesterase Butyrylcholinesterase (pseudocholinesterase) Better reflection of Falls first synaptic inhibition Recovers rapidly (few days) Regenerates more Wide daily variation slowly than neuronal in other disorders AchE Liver dysfunction Wide variations Malnutrition in RBC disorders Drugs Pregnancy 10 Genetic deficiency Insecticides Cholinesterase Inhibitor Treatment Decontamination Protect Providers Glove Bag Skin Triple wash – soap/water Shave scalp? GI Gastric? AC? 11 Insecticides Cholinesterase Inhibitor Treatment Decontamination Antimuscarinic Agents Atropine Infusion 0.02 – 0.08 mg/kg/hr Bolus 2mg q 2-15 min / double dose Glycopyrrolate Scopolamine 12 4 Pesticides Insecticides Cholinesterase Inhibitor Treatment Decontamination Antimuscarinic Agents Benzodiazepine Diazepam 13 Insecticides Cholinesterase Inhibitor Treatment Decontamination Antimuscarinic Agents Benzodiazepine (Organophosphates) Oximes Pralidoxime Bolus: 600mg q ?4hr Infusion: 1-2g load f/b Obidoxime, HI-6 500mg/hr ?carbaryl? 14 Insecticides Organophosphates Aging & Oximes R “Aging” 15 5 Pesticides Insecticides Organochlorines Large family of neuroexcitatory toxins DDT and analogues Cyclodienes Hexachlorocyclohexane (lindane) Mirex and chlordecone 16 Insecticides Organochlorines Large family of neuroexcitatory toxins DDT and analogues Most banned from industrialized countries Na Ch Blockade Neuroexcitation 17 Insecticides Organochlorines Large family of neuroexcitatory toxins DDT and analogues Cyclodienes Most banned from industrialized countries GABA Antagonists neuroexcitation 18 6 Pesticides Insecticides Organochlorines Large family of neuroexcitatory toxins DDT and analogues Cyclodienes Hexachlorocyclohexane (lindane) Scabicide GABA Antagonist Seizures, neuroexcitation 19 Insecticides Organochlorines Large family of neuroexcitatory toxins DDT and analogues Cyclodienes Hexachlorocyclohexane (lindane) Mirex and chlordecone Hopewell Epidemic (1974) “Kepone Shakes” 20 Insecticides Pyrethrins/Pyrethroids Pyrethrins Naturally occuring NaCh openers Rapidly decompose Pyrethroids Synthetic derivatives More persistent, potent Piperonyl butoxide P450 inhibitor 21 7 Pesticides Insecticides Pyrethrins/Pyrethroids Toxicity Pyrethrins Allergic Pyrethroids Type 1 Type II Non-CN -CN “T” Syndrome More potent Tremor “CS” Syndrome Low tox in humans Choreoathetosis, salivation GI (saliv, n/v/d), pulmonary neuroexcitation 22 Insecticides Pyrethrins/Pyrethroids Treatment Supportive Decontamination Skin GI - AC 23 Insecticides Others Boric Acid Ant/cockroach killer Mechanism unclear Symptoms GI (blue-green emesis/diarrhea) Kidney CNS/Neuro Derm (boiled lobster rash) 24 8 Pesticides Insecticides Others Amitraz 2-agonism Treatment Fipronil supportive GABA antagonist Insect:Human 1000:1 Imidacloprid Nicotinic Avermectins (abamectin, ivermectin) Fermentation of Streptomyces avermitilis 25 Rodenticides 26 Rodenticides Compound 1080/1081 Sodium Monofluoroacetate (SMFA) Compound 1080 Flouroacetamide Compound 1081 Inhibit aconitase in Krebs cycle “lethal synthesis” 27 9 Pesticides Compound 1080/1081 28 Rodenticides Compound 1080/1081 Symptoms apprehension dysrhythmias, seizures, coma, ↓ Ca Not flouride toxicity Treatment Unknown Ethanol, Glycerol 29 monoacetate, Rodenticides PNU (Vacor) n-3-pyridylmethyl-N-p-nitrophenyl urea Interferes with nicotinamide activity in pancreas, brain, liver Rapid development of Diabetes mellitus (DKA) Orthostatic hypotension CNS toxicity GI perforation 30 10 Pesticides Rodenticides PNU (Vacor) Treatment Aggressive Decontamination Nicotinamide Niacin 31 Rodenticides Phosphine Rodenticide (Zinc Phosphide) Fumigant (Aluminum Phosphide) Phosphine gas Cellular poison Inhibits cytochrome oxidase and ETC Rotten fish / garlic-like odor 32 Rodenticides Phosphene Symptoms Low level exposure Pulmonary edema (delayed) High level exposure Multisystem failure N/V, coma, seizures, hypertension, pulmonary edema 33 11 Pesticides Rodenticides Phosphene Treatment Inhalation – supportive Ingestion Intubation lavage/suction diluted HCO3 solution, milk Supportive NAC, Mg 34 Rodenticides Strychnine Strychnos nux vomica Glycine inhibition Involuntary generalized muscular contractions Opisthotonos, trismus, risus sardonicus Treatment Benzodiazepines NM Blockade 35 Rodenticides ATNU α-naphthyl-thiourea Acute pulmonary edema Mechanism unknown 36 12 Pesticides History ‘superwarfarins’ Longer T1/2 100X more potent Same mechanism 37 Warfarins Exogenous Vitamin K Vit K (phytonadione) Quinone Vit Ki (inactive) Vit Ka (active) Vit K 2,3 epoxide hydroquinone FFP Factors II,VII,IX,X Factors Iia,VIIa,Ixa,Xa (active)38 Diagnosis & Treatment Child/unintentional none Suicidal/other Labs Vit K1 (phytonadione) IV, PO, IM FFP 39 13 Pesticides Bromethalin Uncouples oxidative phosphorylation AMS, myoclonus, seizures, coma Norbormide (dicarboximide) Norway rat selective smooth muscle constriction Death from profound vasoconstriction Other rats, rodents, humans don’t have the same receptor or transporter 40 Herbicides Bipyridyl herbicides Paraquat Diquat Chlorphenoxy herbicides 2,4-D, 2,4,5-T and Agent Orange Glyphosate Anilide derivatives 41 Paraquat/Diquat Redox cycling 1 – depletion of NADPH 2 – superoxide formation 3 – lipid peroxidation cascade 4 – glutathione & NADPH depletion 42 14 Pesticides Paraquat Active transport into Type I & II alveolar epithelial cells Surfactant depletion, destruction of alveoli 43 Symptoms Dependant on amount ingested May be delayed, especially with dilute products Caustic (Skin, GI Mucosa) Renal Toxicity/Failure ARDS Paraquat
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  • (DMT), Harmine, Harmaline and Tetrahydroharmine: Clinical and Forensic Impact

    (DMT), Harmine, Harmaline and Tetrahydroharmine: Clinical and Forensic Impact

    pharmaceuticals Review Toxicokinetics and Toxicodynamics of Ayahuasca Alkaloids N,N-Dimethyltryptamine (DMT), Harmine, Harmaline and Tetrahydroharmine: Clinical and Forensic Impact Andreia Machado Brito-da-Costa 1 , Diana Dias-da-Silva 1,2,* , Nelson G. M. Gomes 1,3 , Ricardo Jorge Dinis-Oliveira 1,2,4,* and Áurea Madureira-Carvalho 1,3 1 Department of Sciences, IINFACTS-Institute of Research and Advanced Training in Health Sciences and Technologies, University Institute of Health Sciences (IUCS), CESPU, CRL, 4585-116 Gandra, Portugal; [email protected] (A.M.B.-d.-C.); ngomes@ff.up.pt (N.G.M.G.); [email protected] (Á.M.-C.) 2 UCIBIO-REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal 3 LAQV-REQUIMTE, Laboratory of Pharmacognosy, Department of Chemistry, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal 4 Department of Public Health and Forensic Sciences, and Medical Education, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal * Correspondence: [email protected] (D.D.-d.-S.); [email protected] (R.J.D.-O.); Tel.: +351-224-157-216 (R.J.D.-O.) Received: 21 September 2020; Accepted: 20 October 2020; Published: 23 October 2020 Abstract: Ayahuasca is a hallucinogenic botanical beverage originally used by indigenous Amazonian tribes in religious ceremonies and therapeutic practices. While ethnobotanical surveys still indicate its spiritual and medicinal uses, consumption of ayahuasca has been progressively related with a recreational purpose, particularly in Western societies. The ayahuasca aqueous concoction is typically prepared from the leaves of the N,N-dimethyltryptamine (DMT)-containing Psychotria viridis, and the stem and bark of Banisteriopsis caapi, the plant source of harmala alkaloids.