ABEM Medical Tox key terms

Toxicokinetics describes how a poison is absorbed, distributed, metabolized, and excreted by the body over time, and how those processes change as the dose rises into the toxic range.

Volume of distribution is the apparent fluid volume that would be needed to contain the total amount of drug in the body at the measured plasma concentration; large values suggest extensive tissue binding.

Clearance is the volume of plasma completely cleared of a drug or toxin per unit time; it reflects the combined activity of hepatic metabolism, renal excretion, and other elimination pathways.

The elimination half-life is the time required for the plasma concentration of a substance to fall by half during first-order elimination; it depends on both volume of distribution and clearance.

First-order kinetics means the amount of drug eliminated per unit time is proportional to the current plasma concentration, so a constant fraction is removed during each half-life regardless of dose.

Zero-order kinetics means a constant amount of drug is eliminated per unit time because metabolic or excretory pathways are saturated; concentration falls linearly, and small dose increases can cause disproportionate rises in levels.

A toxidrome is a recognizable cluster of physical signs and symptoms caused by a class of poisons, such as opioid, anticholinergic, sympathomimetic, or cholinergic toxicity, used to guide early treatment.

Activated charcoal is a fine black powder that adsorbs many drugs and toxins in the gastrointestinal tract, reducing absorption when given early after ingestion; it does not bind metals, alcohols, or strong acids and bases.

The osmolal gap is the difference between measured and calculated serum osmolality; an elevated gap suggests the presence of unmeasured osmoles such as methanol, ethylene glycol, isopropanol, or acetone.

Naloxone is a competitive opioid receptor antagonist that rapidly reverses opioid-induced respiratory depression and sedation; repeated doses or an infusion may be needed because its duration is shorter than many opioids.

Flumazenil is a benzodiazepine receptor antagonist used to reverse benzodiazepine sedation, but it can precipitate seizures or withdrawal in dependent patients and is avoided in mixed overdose with proconvulsant drugs.

N-acetylcysteine replenishes glutathione and detoxifies the reactive metabolite NAPQI in acetaminophen poisoning; it is most effective when started early but still helps in late presentations with hepatic injury.

Acetaminophen overdose can cause severe centrilobular hepatic necrosis through accumulation of the reactive metabolite NAPQI; the Rumack-Matthew nomogram guides treatment when ingestion time is known and the patient is not chronically poisoned.

Salicylate toxicity causes vomiting, tinnitus, hyperventilation, mixed respiratory alkalosis and metabolic acidosis, hypoglycemia, and cerebral edema; treatment includes sodium bicarbonate, glucose, and hemodialysis for severe cases.

Digoxin immune Fab consists of antibody fragments that bind digoxin and related cardiac glycosides, reversing life-threatening arrhythmias and hyperkalemia; it is reserved for severe toxicity because it can cause rebound heart failure.

Serotonin syndrome is a potentially life-threatening toxidrome caused by serotonergic drugs, marked by altered mental status, autonomic hyperactivity, and neuromuscular excitation such as clonus, hyperreflexia, and tremor.

Methemoglobinemia occurs when hemoglobin iron is oxidized from ferrous to ferric, impairing oxygen delivery and causing cyanosis, chocolate-colored blood, and a saturation gap; common causes include nitrites, dapsone, and local anesthetics.

Fomepizole inhibits alcohol dehydrogenase, blocking formation of toxic metabolites in methanol and ethylene glycol poisoning; it is preferred over ethanol because dosing is predictable and it causes less hypoglycemia and sedation.

Methanol poisoning causes metabolic acidosis, visual disturbances, and blindness because methanol is metabolized to formic acid; treatment includes fomepizole, sodium bicarbonate, and hemodialysis in severe cases.

Ethylene glycol poisoning causes an osmolal gap early, then high-anion-gap metabolic acidosis, calcium oxalate crystals, renal failure, and neurologic or cardiopulmonary toxicity; fomepizole and hemodialysis are mainstays of care.

Isopropanol poisoning typically causes rapid-onset central nervous system depression, hemorrhagic gastritis, and ketosis without significant metabolic acidosis; it is managed supportively because isopropanol is metabolized to acetone.

Alcohol withdrawal is a hyperexcitable state occurring hours to days after cessation of heavy ethanol use, ranging from tremor and anxiety to seizures, hallucinations, and delirium tremens; benzodiazepines are first-line treatment.

The opioid toxidrome consists of reduced consciousness, pinpoint pupils, and respiratory depression; naloxone reverses it, but repeated dosing and observation are needed because many opioids outlast a single naloxone dose.

The anticholinergic toxidrome causes delirium, dry skin, flushing, mydriasis, urinary retention, decreased bowel sounds, and tachycardia; physostigmine can reverse central symptoms but may cause seizures and is avoided in certain poisonings.

Carboxyhemoglobin is hemoglobin bound to carbon monoxide, which shifts the oxygen dissociation curve leftward and prevents normal oxygen transport; levels guide diagnosis but do not reliably predict clinical severity.

Carbon monoxide poisoning causes headache, nausea, dizziness, confusion, syncope, and myocardial ischemia; treatment is high-flow oxygen, with hyperbaric oxygen considered for severe neurologic, cardiac, or pregnancy-related cases.

Organophosphate poisoning irreversibly inhibits acetylcholinesterase, producing a cholinergic crisis with salivation, lacrimation, urination, diarrhea, bronchospasm, bradycardia, and muscle fasciculations; atropine and pralidoxime are key treatments.

Lead poisoning causes abdominal pain, anemia, neuropathy, hypertension, and cognitive impairment; chelation is reserved for symptomatic patients or very high blood lead levels, and removing the exposure is essential.

Cyanide poisoning blocks mitochondrial cytochrome oxidase, causing tissue hypoxia, lactic acidosis, and a high mixed venous oxygen saturation; hydroxocobalamin is a preferred antidote in smoke inhalation and industrial exposures.

Nerve agents are highly toxic organophosphorus compounds that inhibit acetylcholinesterase, causing rapid cholinergic crisis; management includes decontamination, atropine, pralidoxime, and benzodiazepines for seizures.

Botulism is caused by botulinum toxin, which blocks acetylcholine release at neuromuscular junctions, producing descending flaccid paralysis, diplopia, dysphagia, and respiratory failure; antitoxin and supportive care are essential.

Atropine is a muscarinic antagonist used to treat cholinergic poisoning; large repeated doses are titrated to dry secretions and adequate heart rate, and it does not reverse neuromuscular weakness caused by nicotinic effects.

Pralidoxime is an oxime that reactivates acetylcholinesterase inhibited by organophosphates before aging occurs; it is most useful early and complements atropine, especially for nicotinic symptoms such as muscle weakness.

Hydroxocobalamin binds cyanide to form cyanocobalamin, restoring cytochrome oxidase activity; it is given intravenously for suspected cyanide poisoning and may cause reddish discoloration of skin, urine, and laboratory samples.

Methylene blue reduces methemoglobin back to hemoglobin by serving as an electron donor through NADPH-dependent pathways; it is contraindicated in G6PD deficiency and can cause serotonin toxicity at higher doses.

Succimer, or DMSA, is an oral chelator used for lead poisoning, especially in children; it increases urinary lead excretion and is generally better tolerated than dimercaprol, though it is not used for severe encephalopathy.

Sodium bicarbonate is used as an antidote for salicylate toxicity and some sodium-channel blocker overdoses; it alkalinizes serum and urine, enhances salicylate elimination, and can overcome myocardial sodium-channel blockade.

Chain of custody is the documented, unbroken record of who collected, handled, stored, and transported a forensic specimen, ensuring that evidence is admissible and has not been altered or contaminated.

Postmortem redistribution is the movement of drugs after death from tissue reservoirs into blood, which can raise or lower measured concentrations depending on sampling site and time since death, complicating forensic interpretation.