ABP Med Toxicology cheat sheet

Toxicity is dose-dependent: Paracelsus' principle states that all substances are poisons and the right dose differentiates a poison from a remedy.

Risk is a function of hazard and exposure; a potent toxicant with no exposure pathway poses no human risk.

Therapeutic index = TD50/ED50; a larger value generally indicates a wider margin between toxic and effective doses.

NOAEL is the highest dose with no significant adverse effect; LOAEL is the lowest dose with an observed adverse effect.

Uncertainty factors, typically 10 for interspecies and 10 for intraspecies variability, convert animal NOAELs to human reference doses.

Dose-response curves may be threshold, linear, or nonlinear; genotoxic carcinogens are often modeled with linear low-dose extrapolation.

The four risk-assessment steps are hazard identification, dose-response assessment, exposure assessment, and risk characterization.

Acute exposure is a single or short-term contact; chronic exposure is repeated or continuous over a long period and may affect different target organs.

Route matters: inhalation bypasses first-pass metabolism and produces rapid systemic absorption, while dermal absorption varies with lipophilicity and skin integrity.

First-order elimination: a constant fraction is removed per unit time; half-life = 0.693 x Vd / CL, and steady state is reached after about 4-5 half-lives.

Zero-order elimination: a constant amount is removed per unit time when pathways are saturated; ethanol, phenytoin, and high-dose salicylate follow this pattern.

Vd = total body burden / plasma concentration; drugs with large Vd, such as digoxin and tricyclics, are poorly removed by hemodialysis.

Clearance = elimination rate / plasma concentration; total clearance is the sum of hepatic, renal, and other clearance pathways.

Only free unbound drug is pharmacologically active and filterable at the glomerulus; protein binding limits dialysis and distribution.

Osmolal gap = measured osmolality minus calculated osmolality (2 x Na + glucose/18 + BUN/2.8); an elevated gap suggests methanol, ethylene glycol, isopropanol, or other unmeasured osmoles.

Anion gap = Na - (Cl + HCO3); elevated gap acidosis occurs with salicylate, methanol, ethylene glycol, and other organic acids.

Immunoassays are screening tests; positive results should be confirmed by GC-MS or LC-MS/MS because of cross-reactivity and false positives.

Co-oximetry directly measures carboxyhemoglobin and methemoglobin; standard pulse oximetry cannot distinguish these dyshemoglobins from normal hemoglobin.

Acetaminophen is metabolized by CYP2E1 to NAPQI; glutathione depletion causes centrilobular hepatic necrosis, and N-acetylcysteine restores glutathione.

The Rumack-Matthew nomogram applies to single acute acetaminophen ingestions at 4 or more hours post-ingestion; NAC is most effective within 8 hours.

Salicylate poisoning causes early respiratory alkalosis and later metabolic acidosis; urine alkalinization to pH 7.5-8 enhances elimination, and hemodialysis is used for severe toxicity.

Opioid toxicity triad: miosis, respiratory depression, and CNS depression; naloxone is titrated to restore ventilation, and re-narcotization can occur because naloxone is shorter-acting than many opioids.

Benzodiazepines increase GABA-A chloride channel frequency; flumazenil can precipitate seizures in mixed overdose or chronic benzodiazepine dependence.

Beta-blocker overdose causes bradycardia, hypotension, and hypoglycemia; glucagon, high-dose insulin with dextrose, and vasopressors are treatments.

Calcium channel blocker overdose causes vasodilation, bradycardia, and hypotension; calcium salts, high-dose insulin, vasopressors, and pacing may be required.

Tricyclic antidepressants block sodium channels and cause QRS widening; sodium bicarbonate is first-line for cardiotoxicity.

Digoxin inhibits Na/K-ATPase and causes hyperkalemia and arrhythmias; digoxin-specific Fab fragments are the definitive antidote.

Alcohol withdrawal: tremor and autonomic hyperactivity at 6-24 hours, seizures at 12-48 hours, and delirium tremens at 48-96 hours; benzodiazepines are first-line and thiamine prevents Wernicke encephalopathy.

Opioid withdrawal causes yawning, lacrimation, rhinorrhea, piloerection, cramps, vomiting, and diarrhea; it is not usually life-threatening.

Benzodiazepine withdrawal can cause anxiety, insomnia, perceptual disturbances, and seizures; gradual tapering is safer than abrupt cessation.

Cocaine and amphetamines are sympathomimetics; benzodiazepines are first-line for agitation, seizures, and hypertension, and hyperthermia requires rapid cooling.

MDMA can cause hyperthermia, hyponatremia, serotonin syndrome, and rhabdomyolysis; treatment is supportive with cooling and careful sodium correction.

GHB and GBL cause CNS depression, bradycardia, and respiratory depression; flumazenil is not recommended because it may worsen outcomes.

Synthetic cannabinoids can cause severe agitation, tachycardia, seizures, and psychosis; management is supportive with benzodiazepines.

Neonatal abstinence syndrome causes irritability, tremors, feeding difficulty, and diarrhea; opioids such as morphine or methadone are used for severe cases.

Naloxone precipitates acute opioid withdrawal but is safe and indicated for opioid-induced respiratory depression.

Carbon monoxide binds hemoglobin with about 200-250 times the affinity of oxygen; standard pulse oximetry is falsely normal, and co-oximetry is required.

Carbon monoxide treatment is 100% oxygen; hyperbaric oxygen is considered for severe poisoning, syncope, neurologic deficits, or pregnancy with significant exposure.

Cyanide poisoning causes cellular hypoxia, lactic acidosis, and normal or high venous oxygen saturation; hydroxocobalamin is a preferred antidote in smoke inhalation.

Caustic ingestions cause liquefactive necrosis with alkalis and coagulative necrosis with acids; do not induce vomiting or give activated charcoal, and use early endoscopy for significant exposure.

Hydrocarbon ingestion carries a high aspiration risk; do not induce vomiting, and activated charcoal is generally avoided because of aspiration and poor adsorption.

Mixing bleach with ammonia produces chloramine gas; mixing bleach with acid produces chlorine gas; both cause irritant inhalation injury.

Methanol and ethylene glycol are household alcohols; fomepizole blocks alcohol dehydrogenase, and hemodialysis removes the parent compounds and toxic metabolites.

Occupational exposure limits such as OSHA PELs are legal airborne limits; biological monitoring may detect absorption that air sampling misses.

Volatile solvent abuse can cause arrhythmias, CNS depression, and renal tubular acidosis; management is supportive in a calm environment.

Organophosphate and carbamate insecticides inhibit acetylcholinesterase; organophosphates cause aging of the enzyme, while carbamates generally do not.

Cholinergic toxicity includes salivation, lacrimation, urination, diarrhea, bronchorrhea, bradycardia, miosis, and fasciculations; atropine treats muscarinic effects.

Pralidoxime reactivates phosphorylated acetylcholinesterase if given before aging; it is used for organophosphates but is not routinely needed for carbamates.

Pyrethroids prolong sodium channel activation and cause paresthesias, tremors, and seizures; treatment is supportive, and atropine is not indicated.

Lead poisoning causes anemia, abdominal pain, neuropathy, and encephalopathy; chelation depends on blood lead level and symptoms.

Severe lead encephalopathy is treated with dimercaprol plus calcium disodium EDTA; oral succimer is used for moderate lead elevation.

Iron overdose causes vomiting, metabolic acidosis, shock, and hepatic failure; deferoxamine is indicated for severe toxicity.

Methylmercury bioaccumulates in fish and causes paresthesias, ataxia, visual field constriction, and developmental neurotoxicity.

Cadmium inhalation causes pneumonitis and chronic renal tubular damage; chelation is not effective and avoidance is the main strategy.

Amanita phalloides amatoxins inhibit RNA polymerase; a late onset of severe gastroenteritis followed by hepatic failure is characteristic.

Amanita muscaria contains muscimol and ibotenic acid; it causes delirium, ataxia, and hallucinations, and treatment is supportive with benzodiazepines.

Datura species contain anticholinergic tropane alkaloids; dry skin, mydriasis, delirium, and urinary retention are typical.

Oleander contains cardiac glycosides that can cause bradycardia, heart block, and hyperkalemia; digoxin-specific Fab may be considered.

Ciguatera causes gastrointestinal symptoms followed by paradoxical temperature reversal, paresthesias, and sometimes bradycardia or hypotension.

Scombroid poisoning is histamine toxicity from improperly stored fish; flushing, urticaria, and headache respond to antihistamines.

Tetrodotoxin and saxitoxin block sodium channels and cause paresthesias, weakness, and respiratory paralysis; treatment is supportive.

Snake envenomation with systemic bleeding, coagulopathy, or neurotoxicity requires antivenom and supportive care; pressure immobilization is used for some elapid bites.

Scorpion stings can cause autonomic storm and cardiopulmonary failure, especially in children; antivenom is used for severe cases.

Activated charcoal adsorbs many drugs; the optimal dose is about 1 g/kg, and it is most effective within 1 hour of ingestion.

Activated charcoal is contraindicated for caustic ingestions, hydrocarbons with aspiration risk, ileus, and an unprotected airway.

Gastric lavage is reserved for recent, potentially lethal ingestions, usually within 1 hour, with a protected airway; it is not used for caustics or hydrocarbons.

Whole-bowel irrigation with polyethylene glycol is used for sustained-release products, iron, and lithium; it is contraindicated in obstruction or ileus.

Urinary alkalinization to pH 7.5-8 enhances elimination of weak acids such as salicylates and phenobarbital.

Hemodialysis is most effective for low-molecular-weight, water-soluble drugs with small Vd and low protein binding; examples include methanol, ethylene glycol, lithium, salicylate, and theophylline.

N-acetylcysteine, naloxone, fomepizole, hydroxocobalamin, deferoxamine, digoxin Fab, glucagon, and lipid emulsion are antidotes for specific poisonings.

Intravenous lipid emulsion is used for severe local anesthetic systemic toxicity and refractory cardiotoxic drug overdose.

Multiple-dose activated charcoal can enhance elimination of drugs with enterohepatic recirculation, such as carbamazepine, theophylline, and phenobarbital.

Pediatric doses are weight-based (mg/kg); using adult fixed doses or combination products can cause serious dosing errors.

Toddlers explore by mouth; one tablet of an opioid, sulfonylurea, tricyclic, or camphor can be lethal to a small child.

A button battery lodged in the esophagus can cause liquefactive necrosis within hours; urgent endoscopic removal is required.

Prevention includes child-resistant packaging, locked storage, safe disposal, and immediate poison center consultation.

Poison control centers can be reached in the US at 1-800-222-1222; consultation reduces unnecessary emergency visits and improves outcomes.

Syrup of ipecac is no longer recommended for routine pediatric poisoning because of ineffective or harmful vomiting.

Lead screening is recommended for at-risk children; blood lead levels are interpreted with age-specific reference values and repeat testing.

Pediatric vital signs vary by age; bradycardia in a child is often defined relative to age and may reflect hypoxia or poisoning.

Neonatal abstinence syndrome requires standardized scoring and nonpharmacologic care first, with opioids for severe withdrawal.

Initial toxicologic emergency management follows ABCs: secure the airway, support ventilation, and restore circulation before definitive decontamination.

Toxidromes guide early treatment: anticholinergic, cholinergic, sympathomimetic, opioid, sedative-hypnotic, serotonin, and neuroleptic malignant syndrome.

Wide-complex tachycardia from sodium channel blockade is treated with sodium bicarbonate; avoid class IA antiarrhythmics.

Severe hyperthermia requires rapid cooling; benzodiazepines control agitation and shivering, and dantrolene is used for malignant hyperthermia.

Seizures in poisoning are treated with benzodiazepines; persistent seizures may require barbiturates or propofol.

Refractory shock from beta-blocker or calcium channel blocker overdose may require glucagon, high-dose insulin with dextrose, vasopressors, pacing, or ECMO.

Methemoglobinemia causes cyanosis unresponsive to oxygen and chocolate-brown blood; methylene blue is used, but avoid it in G6PD deficiency.

Serotonin syndrome is treated by stopping serotonergic drugs, giving benzodiazepines, and using cyproheptadine in selected cases.

ECMO can support refractory cardiogenic shock or respiratory failure from poisoning while drug elimination occurs.