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Updated: Dec 31 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
      • Metallic Poisoning
      • Treatment
      • Poison(s)
      • Notes
      • 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
      • 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)
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