Updated: 3/3/2021

Toxicology

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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
  • Arsenic poisoning 
    • garlic odor, cardiovascular instability, Mees lines
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 (in particular to HbF) than O
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
Hydroxocobalamin 
Prescription Drug Overdose
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 
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
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 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
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)

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