Overview Poisons and Treatments Treatment Poison(s) Notes Deferoxamine Iron Used for aluminum poisoning in renal failure Used in repeat transfusions that can cause iron overload (thalassemia) Used in iron overdose Deferasirox Iron Used for aluminum poisoning in renal failure Used in repeat transfusions that can cause iron overload (thalassemia) Used in iron overdose Prussian blue CesiumThallium 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 Weak association with improve outcomes in scleroderma EDTA Lead Can chelate and deplete calcium ions Only needed in moderate to severe lead poisoning Dimercaprol (BAL) Arsenic Lead Mercury Used in conjunction with EDTA for lead poisoning Succimer Arsenic Lead Mercury Chelation therapy more commonly used in children N-acetylcysteine Acetaminophen Best if given with 8-10 hours Also a mucolytic Best next step in management if you suspect acetaminophen intoxication yet have no lab results (it is a benign treatment) Sodium bicarbonate Salicylates Tricyclic antidepressants (TCA) First sign of OD is hyperventilation and respiratory alkalosis Do not give with physostigmine First do an EKG, if wide QRS (in TCA overdose) then try sodium bicarbonate Deprotonation of drugs causes improved urinary excretion Potassium iodide Radioactive iodine (I-131) Given to prevent the uptake of I-131 Can also be used in thyroid storm as iodine initially decreases thyroid hormone production Ammonium chloride (NH4Cl, acidic) Amphetamines (basic) Eliminates amphetamines by acidifying urine which results in a charged amphetamine molecule which is excreted Atropine Pralidoxime Hyoscyamine Anticholinesterases Organophosphates Sarin (nerve gas) Atropine blocks Ach receptors decreasing the effect of these drugs. Hyoscyamine is second line if atropine is not available Pralidoxime, if given in a timely manner, regenerates acetylcholinesterase reversing the initial pathology Physostigmine Antimuscarinic Anticholinergic agents Do not give if patient may have TCA OD as it may lead to heart block or asystole Tertiary amine that can cross the BBB and reverse CNS symptoms of atropine Naloxone/naltrexone Opioids Precipitates withdrawal symptoms in chronic opioid users Not indicated in neonates who may be withdrawing Indicated particularly in adult patients who have respiratory depression Naltrexone decreases alcohol cravings Flumazenil Benzodiazepines May cause seizures in addicted benzodiazepine users Not routinely used, better to let the patient "sleep off" their benzodiazepine overdose Ensure patient maintains respiratory effort and airway 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" Glucagon β-blockers IM glucagon is best initial therapy β-blockers (propranolol, esmolol) Theophylline OD symptoms are due to β2activation: hypotension, tachycardia, hypokalemia, hyperglycemia Digitalis antibody, lidocaine, Mg2+ Digitalis GI disturbance and visual halos classic in overdose Amyl and sodium nitrite Sodium thiosulfate Hydroxycobalamin Cyanide Cyanide found in rodenticides "gopher goitter",released in burning of plastics and wool, and plants such as cassava Cyanide binds Fe3+ of cytochrome c in the electron transport chain and blocks cellular respiration Nitrites generate methemoglobin, which can save the ETC by binding up the cyanide Methylene blue Vitamin C Methemoglobin Iron in the heme molecule is Fe3+ which cannot bind oxygen until it is reduced to Fe2+by treatment 100% O2 (consider hyperbaric O2) Carbon monoxide (CO) CO binds with much greater affinity than O2 Aminocaproic acid tPA Streptokinase - Vitamin K Plasma infusion Warfarin Bridge with heparin If patient suddenly has increase in PT/PTT look for other medications that are P450 inhibitors Protamine Heparin Protamine is a highly positively charged peptide which strongly binds to the negatively charged heparin Antivenin Rattlesnake bite - 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, 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 the Fenton reaction produces dangerous free radicals Methanol and Ethylene Glycol Toxicity 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 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: competitive substrate for ADH and has greater affinity for ADH than methanol and ethylene glycol fomepizole: inhibits ADH preventing production of toxic metabolites Tetrodotoxin Highly potent toxin that binds to fast voltage-gated Na+ channels, preventing depolarization Presents with nausea, diarrhea, paresthesias, weakness, dizziness, and loss of reflexes