DABAT flashcards

32 cards. Read the term and the definition here. The deck at the top of this page is optional.

Therapeutic index

Ratio of the median toxic dose to the median effective dose (TD50/ED50). A larger value indicates a wider margin between therapeutic and toxic exposure, but it does not capture the slope or severity of the toxic response.

Hormesis

A biphasic dose-response in which low doses produce stimulation or apparent benefit while high doses produce inhibition or toxicity. It is descriptive and does not by itself establish a safe exposure threshold for regulatory decisions.

LD50

A statistically derived single-dose estimate expected to kill 50 percent of a test population. It varies with species, strain, route, vehicle, and observation period, and it does not describe mechanism, slope, or reversibility.

Reference dose

An estimate of daily oral exposure likely to be without appreciable risk over a lifetime. It is derived by dividing a point of departure by uncertainty factors, typically 10 for interspecies and 10 for intraspecies variability.

Margin of exposure

The ratio of a toxicological point of departure to estimated human exposure. Larger values indicate greater separation from hazardous doses; for genotoxic carcinogens, values of 10,000 or more are generally considered low concern.

Cancer slope factor

An upper-bound estimate of cancer risk per unit lifetime average daily dose, derived from dose-response modeling. Risk is estimated by multiplying the slope factor by the estimated average daily dose.

Toxicokinetics

The study of how absorption, distribution, metabolism, and excretion determine the concentration of a toxicant at the target site over time. It links external dose to internal dose and to observed toxicity.

Volume of distribution

The apparent volume relating the amount of drug in the body to its plasma concentration. A large value above roughly 1 L/kg indicates extensive tissue distribution and limits removal by hemodialysis.

Zero-order elimination

Elimination at a constant rate independent of concentration, occurring when metabolic or transport capacity is saturated. Half-life lengthens as concentration rises; ethanol and high-dose phenytoin are classic examples.

First-pass metabolism

Metabolism of an orally absorbed substance in the intestinal wall or liver before it reaches systemic circulation. It reduces oral bioavailability and, when saturated, can cause disproportionate increases in systemic exposure.

Michaelis-Menten kinetics

A saturable elimination model in which rate equals Vmax times concentration divided by Km plus concentration. At concentrations well above Km, elimination becomes zero-order and half-life increases with dose.

Enterohepatic recirculation

Reabsorption of a substance or its conjugate from the intestine after biliary excretion, prolonging systemic exposure. It explains the usefulness of multiple-dose activated charcoal for drugs such as carbamazepine and phenobarbital.

Reactive metabolite

A chemically unstable biotransformation product that can covalently bind macromolecules, deplete glutathione, and cause cell injury. Acetaminophen's NAPQI is the prototypical example of such a toxic intermediate.

Glutathione depletion

Loss of the principal cellular thiol antioxidant, allowing reactive electrophiles and reactive oxygen species to damage proteins, lipids, and DNA. N-acetylcysteine restores cysteine availability for glutathione synthesis.

Oxidative phosphorylation uncoupling

Disruption of the proton gradient across the inner mitochondrial membrane so that electron transport proceeds without ATP synthesis, producing heat and increased oxygen consumption. Dinitrophenol is a classic uncoupler.

Cytochrome c oxidase inhibition

Blockade of complex IV of the electron transport chain, halting oxidative phosphorylation and causing cellular hypoxia despite normal oxygen delivery. Cyanide and hydrogen sulfide act through this mechanism.

Toxidrome

A constellation of vital-sign, pupil, skin, and neurologic findings that suggests a class of intoxicant, such as cholinergic, anticholinergic, sympathomimetic, opioid, or sedative-hypnotic, and guides empiric treatment.

Anion gap

Calculated as sodium minus the sum of chloride and bicarbonate, normally about 8 to 12 mEq/L. An elevated gap suggests accumulation of unmeasured acids such as methanol, ethylene glycol, salicylate, or lactate.

Osmolal gap

The difference between measured and calculated serum osmolality, where calculated equals 2 times sodium plus glucose divided by 18 plus BUN divided by 2.8. It is elevated early in toxic alcohol ingestion.

Carboxyhemoglobin

Hemoglobin bound to carbon monoxide, measured by co-oximetry rather than standard pulse oximetry. It impairs oxygen delivery and shifts the dissociation curve leftward, and it can be normal in delayed presentation.

Rumack-Matthew nomogram

A plot of serum acetaminophen concentration against time since ingestion that identifies patients needing N-acetylcysteine. It applies to single acute ingestions with a known time, not to chronic or repeated supratherapeutic use.

Activated charcoal

A decontamination adsorbent most effective when given within about one hour of ingestion. It is avoided with an unprotected airway, gastrointestinal obstruction, and caustic or hydrocarbon ingestion because of aspiration risk.

Fomepizole

A competitive inhibitor of alcohol dehydrogenase used to treat methanol and ethylene glycol poisoning. It prevents formation of toxic metabolites and is preferred over ethanol because of simpler dosing and fewer adverse effects.

Sodium bicarbonate therapy

Alkalinization used for salicylate poisoning to enhance urinary elimination and for wide-complex tachycardia from sodium channel blockade, where it provides a sodium load and alkalinization.

Multiple-dose activated charcoal

Repeated charcoal doses that create a concentration gradient favoring diffusion of drug from blood into the gut. It enhances elimination of carbamazepine, theophylline, phenobarbital, and dapsone.

Hemodialysis indications

Removal of low-molecular-weight, water-soluble, low-volume-of-distribution, poorly protein-bound toxins such as methanol, ethylene glycol, lithium, salicylate, and theophylline, especially with severe acidosis or organ failure.

Delirium tremens

Severe alcohol withdrawal with agitation, hallucinations, tachycardia, hypertension, fever, and diaphoresis, typically beginning 48 to 96 hours after the last drink. It carries substantial mortality and is treated with benzodiazepines.

Opioid withdrawal

A self-limited syndrome of yawning, lacrimation, rhinorrhea, piloerection, mydriasis, cramps, and diarrhea after cessation of opioids. It is rarely fatal and is treated with buprenorphine or methadone.

Naloxone

A competitive opioid receptor antagonist that reverses respiratory depression and sedation in opioid overdose. Repeated doses may be required for long-acting or high-potency opioids, and withdrawal can be precipitated.

Phosphatidylethanol

A direct alcohol biomarker formed in cell membranes that reflects ethanol exposure over roughly two to four weeks. It is used to detect chronic or relapsed drinking and is less affected by liver disease than some markers.

Methylmercury

An organic mercury form that bioaccumulates in fish and causes paresthesias, ataxia, constricted visual fields, and hearing loss. The developing fetal brain is especially vulnerable to in-utero exposure.

Hydrogen sulfide

A gas that inhibits cytochrome c oxidase and causes cellular hypoxia, with high concentrations producing rapid collapse. Olfactory fatigue means absence of its rotten-egg odor does not exclude dangerous exposure.