Toxicology Drug Introduction Toxicology medications can be broken down into the following categories metallic poisoning gas poisoning prescription drugs overdose illegal drugs overdose household substance overdose Metallic Poisoning Treatment Poison(s) Notes Deferoxamine Iron Used for aluminum poisoning in renal failure Used in iron overload with repeat transfusions (thalssemia) Iron over load, hemochromatosis Deferasirox Iron Used for aluminum poisoning in renal failure Used in iron overload with repeat transfusions (thalssemia) Iron over load, hemochromatosis Prussian blue Cesium Thallium Used in the case of a radioactive incident Penicillamine Copper (Wilson's disease) Water-soluble form of penicillin Avoid in patients who have penicillin allergy Chelates copper EDTA Lead Can chelate and deplete calcium ions Dimercaprol (BAL) Arsenic Lead Mercury Used in conjunction with EDTA for lead poisoning Arsenic poisoning garlic odor, cardiovascular instability, Mees lines Succimer Arsenic Lead Mercury Used more commonly in children Gas Poisoning Treatment Poison(s) Notes 100% O2 (consider hyperbaric O2) Carbon monoxide (CO) CO binds with much greater affinity (in particular to HbF) than O2 Amyl and sodium nitrite Sodium thiosulfate Hydroxocobalamin Cyanide Cyanide found in rodenticides "gopher goitter", released in burning of plastics and wool, and plants such as cassava Cyanide binds Fe3+ of cytochrome oxidase a3 of the electron transport chain (ETC) arresting cellular respiration Nitrites create methemoglobin (Fe3+) intentionally to compete for and bind cyanide so it does not get to the ETC Prescription Drug Overdose Treatment Poison(s) Notes N-acetylcysteine Acetaminophen Best if given with 8-10 hours Also a mucolytic Initial management: N-acetylcysteine, charcoal, and acetaminophen level Sodium bicarbonate Salicylates Tricyclic antidepressants (TCA) First sign of OD is hyperventilation and respiratory alkalosis Do not give with physostigmine First check an EKG for QRS prolongation, then treat with sodium bicarbonate in TCA overdose Potassium iodide Radioactive iodine (I-131) Given to prevent the uptake of I-131 Ammonium chloride (NH4Cl, acidic) Amphetamines (basic) Eliminates amphetamines by acidifying urine which results in a charged amphetamine molecule which is excreted Atropine Anticholinesterases Organophosphates Sarin (nerve gas) Removed contaminated clothing if patient was exposed to insectisides Atropine as an anti-cholinergic and combats the excess Ach Pralidoxime if given in a timely manner regenerates acetylcholinesterase reversing the condition (timing is critical) Pralidoxime Anticholinesterases Organophosphates Sarin (nerve gas) Removed contaminated clothing if patient was exposed to insectisides Atropine as an anti-cholinergic and combats the excess Ach Pralidoxime if given in a timely manner regenerates acetylcholinesterase reversing the condition (timing is critical) Physostigmine Antimuscarinic Anticholinergic agents Atropine overdose Do not give if patient may have TCA OD as it may lead to heart block or asystole Tertiary amine that can cross the blood brain barrier and reverse anticholinergic effects in the CNS Toxidrome: hot as a hare, dry as a bone, full as a flask, blind as a bat, red as a beet, and mad as a hatter Naloxone/naltrexone Opioids Precipitates withdrawal symptoms in chronic opioid users Use in patients with respiratory depression Opioid withdrawal will NOT kill a patient it is just unpleasant Flumazenil Benzodiazepines May cause seizures in addicted benzodiazepine users Rarely used with benzodiazepine overdose unless concerned for respiratory depression Otherwise let the patient "sleep off" the benzodiazepines Supportive/observation Gamma hydroxybutyrate (GHB) GABA analog Anabolic properties (used by bodybuilders) Date rape drug Agitation, bradycardia, respiratory depression, pinpoint pupils, somnolence, amnesia, and 6-8 hour duration of symptoms Glucagon β-blockers Glucagon, insulin, dextrose, calcium, lipid emulsion, and epinephrine are antidote Calcium, epinephrine, insulin, dextrose, and glucagon Calcium channel blockers (verapamil and diltiazem) Bradycardia Hypotension Hyperglycemia Heart block Supportive, naloxone Clonidine Methyldopa Similar toxidrome with miosis, bradycardia, hypotension, and somnolence Cessation of offending agent, dialysis Propylene glycol Solvent for phenytoin, diazepam/lorazepam, nitroglycerin Cardiovascular collapse (bradycardia, hypotension, vasodilation, increased vagal tone) Seizure, coma, lactic acidosis Osm gap and anion gap acidosis β-blockers (propranolol, esmolol) Theophylline Adenosine antagonist OD symptoms are due to β2 activation: hypotension, tachycardia, hypokalemia, hyperglycemia Digitalis antibody, lidocaine, Mg2+ Digitalis Visual and GI symptoms classically seen in overdose Octreotide , dextrose, steroids Sulfonylureas Persistent hypoglycemia that recurs after treatment with dextrose Methylene blue Methemoglobin Iron in the heme molecule is Fe3+ which cannot bind oxygen until it is reduced to Fe2+ by treatment Vitamin C Methemoglobin Iron in the heme molecule is Fe3+ which cannot bind oxygen until it is reduced to Fe2+ by treatment Aminocaproic acid tPA Streptokinase Vitamin K Warfarin Bridge with heparin as warfarin can deplete protein C and S first (anticoagulants) leading to an initial prothrombotic state Plasma infusion Warfarin Bridge with heparin as warfarin can deplete protein C and S first (anticoagulants) leading to an initial prothrombotic state Protamine Heparin Protamine is a highly positively charged peptide which strongly binds to the negatively charged heparin Argatroban Heparin Direct thrombin inhibitor Household Substance Overdose Treatment Poison(s) Notes Ethanol IV infusion Fomepizole Antifreeze (ethylene glycol) Methanol Think antifreeze when ingested substance is said to be sweet and individual appears "drunk without the typical smell of alcohol" Fomepizole should be followed by dialysis Caustic fluid Perform endoscopy Irrigation for ocular exposure Do not try to induce vomiting in patient Could perhaps use small amount of diluent Hydrofluoric acid Irrigation Calcium gluconate (topical) Swelling and tenderness Hyperkalemia, hypocalcemia, hypomagnesemia Other Treatment Poison(s) Notes Antivenin Crotaline envenomation (rattlesnake bite) Small parallel bite marks that ooze suggest envenomation Erythema, edema, swelling, and pain Antivenin, supportive Elapidae (coral snakes) Descending flaccid paralysis Respiratory failure Lethargy Bite is often painless Supportive Amanita phalloides Inhibits RNA polymerase Course nausea and vomiting symptom remission toxic appearance, nausea/vomiting, and elevated liver enzymes with stigmata of liver failure Supportive Amanita muscaria Hallucinogenic Delrium Sympathomimetic Agitation Synesthesia Removal of nematocysts/stinger Warm water immersion Rinsing with vinegar Jellyfish stings Pain Erythema Edema Cord like lesions Supportive therapy Caffeine overdose adenosine antagonist Tachycardia Palpitations Anxiety Supraventricular tachycardia Seizures Iron Poisoning Most deaths due to iron poisoning (ingestion of iron tablets) occur in children between 12 - 24 months of age Symptoms occur within 30 min to several hours abdominal pain, diarrhea, vomiting, cyanosis, drowsiness, and hyperventilation resulting from acidosis Death can result in six hours, but an apparent recovery may happen from 6 - 12 hours with death ensuing in the next 12 hours If not treated early, damage to the stomach can lead to pyloric stenosis or gastric scarring Early treatment with deferoxamine can reduce mortality significantly from 45% to 1% Mechanism of action of iron related damage iron overdose results in the peroxidation of membrane lipids leading to cell death uncouples oxidative metabolism => anaerobic metabolism => lactic acidosis Toxic Alcohols Each are competitive substrates for alcohol dehydrogenase (ADH) Methanol metabolized by ADH to formaldehyde followed by aldehyde dehydrogenase to form formic acid which is toxic to the optic nerve early toxicity of formic acid is metabolic acidosis by formic acid itself formic acid also binds to cytochrome oxidase blocking oxidative phosphorylation resulting in lactic acidosis which is the latter and leading cause of the metabolic acidosis signs and symptoms appear within 12 - 24 hours after ingestion CNS depression methanol acts similarly as ethanol as a CNS depressant metabolic acidosis visual changes blindness occurs with as little as 30 mL and death at 100 mL ingestion Ethylene glycol colorless, odorless, sweet-tasting liquid toxicity derives from the hepatic oxidation of ethylene glycol to glycolic and oxalic acid degraded by same pathway as methanol the glycolic acid produced by aldehyde dehydrogenase is converted in oxalic acid oxalic acid binds calcium and forms calcium oxalate crystals that damage the heart, brain, lungs, kidneys signs and symptoms develop in stages after ingestion first stage: 0.5 - 12 hours stronger inebriant than methanol and ethanol causing mild depression of CNS resulting in seizures and coma patients appear "drunk without smelling like alcohol" within 4 - 12 hours, calcium oxalate crystals deposit in the brain causing CNS toxicity, cerebral edema, meningismus (nuchal rigidity, photophobia, headache without infection or inflammation) hypocalcemia occurs due to binding of calcium by oxalic acid and can cause prolonged QT, arrhythmias, myocardial depression second stage: 12 - 24 hours tachypnea occurs to offset the metabolic acidosis due to the toxic metabolites produced multiorgan failure (CHF, lung injury, myositis) due to widespread crystal deposition NOTE: most deaths occur in the second stage third stage: 24 - 72 hours acute anuric renal failure from crystal deposition but full recovery occurs within weeks to months Treatment IV ethanol (used historically) competitive substrate for ADH and has greater affinity for ADH than methanol and ethylene glycol fomepizole (best initial therapy) inhibits ADH preventing production of toxic metabolites should be followed by dialysis Isopropyl alcohol (isopropanol) common in alcoholics who have ran out of alcohol found in rubbing alcohol, disinfectants, and hand sanitizers signs and symptoms profoundly intoxicated (much more stuporous/ataxic than ethanol) nausea, vomiting, and abdominal pain (from gastritis) smell of acetone osmolar gap without an anion gap acidosis Treatment supportive care Miscellaneous When behavioral changes are recognized in adolescents screen for substance use Seafood-Associated Toxins Tetrodotoxin Scombroid presentation peppery/bitter fish taste when consuming tuna, mahi mahi, herring, and mackerel symptoms GI abdominal pain diarrhea dermatologic urticaria flushed and warm skin pulmonary wheezing neurologic dizziness Ciguatoxin heat-stable neurotoxin inhibits voltage gated sodium channels symptoms GI (vomiting, diarrhea, and abdominal pain) neurologic (perioral paresthesias, pruritus, metallic taste, painful dentition, sensation that teeth are loose, temperature related dysesthesias, and blurry vision) cardiac (bradycardia, heart block, and hypotension)