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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
 
Treatment Poison(s) Notes
Metallic Poisoning
Deferoxamine
  • Iron
  • Used for aluminum poisoning in renal failure
  • Used in iron overload with repeat transfusions (thalssemia)
  • Iron over load, hemochromatosis
Deferasirox
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
Succimer
  • Arsenic
  • Lead
  • Mercury
  • Used more commonly in children
Gas Poisoning
100% O2 (consider hyperbaric O2)
  • Carbon monoxide (CO)
  • CO binds with much greater affinity than O2
Amyl and sodium nitrite
  • 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
Sodium thiosulfate
Hydroxycobalamin
Prescription Drug Overdose
N-acetylcysteine 
  • Acetaminophen   
  • Best if given with 8-10 hours
  • Also a mucolytic
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
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
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
Glucagon
  • β-blockers 
  • IM glucagon best to reverse beta-blocker overdose
β-blockers (propranolol, esmolol)
  • Theophylline
  • OD symptoms are due to β2 activation: hypotension, tachycardia, hypokalemia, hyperglycemia

Digitalis antibody, lidocaine, Mg2+

  • Digitalis
  • Visual and GI symptoms classically seen in overdose
Methylene blue
  • Methemoglobin
  • Iron in the heme molecule is Fe3+ which cannot bind oxygen until it is reduced to Fe2+ by treatment
Vitamin C
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

Protamine

  • Heparin
  • Protamine is a highly positively charged peptide which strongly binds to the negatively charged heparin
Argatroban
  • Direct thrombin inhibitor 
Household Substance Overdose
Ethanol IV infusion
  • 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
Fomepizole  
Caustic fluid
  • Perform endoscopy 
  • Irrigation x 15mins for ocular exposure 
  • Do not try to induce vomiting in patient
  • Could perhaps use small amount of diluent
Other
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
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 (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
Acetaminophen Toxicity
  • A
Miscellaneous
  • When behavioral changes are recognized in adolescents screen for substance use 
 

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