Please confirm topic selection

Are you sure you want to trigger topic in your Anconeus AI algorithm?

Please confirm action

You are done for today with this topic.

Would you like to start learning session with this topic items scheduled for future?

Updated: May 11 2024

Toxicology

Images
https://upload.medbullets.com/topic/121613/images/ethylene glycol metabolism - moises dominguez.jpg
https://upload.medbullets.com/topic/121613/images/methanol metabolism - moises dominguez.jpg
  • 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
      • 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)
Card
1 of 0
Question
1 of 56
Private Note