Safety: therapeutic index, dosing across species, allergy and polypharmacy

Explains how drug safety is measured (therapeutic index, ED and LD), how animal doses are converted to human doses, why allergies aren't side effects, and when combining drugs is a bad idea.

Dónde encajaSe conecta con 3 · Desbloquea 2

Se conecta con: Dose-response curves: potency, efficacy, slope and variability — The therapeutic index compares two dose-response curves.
When enzymes change: induction, inhibition and genetics — Pharmacokinetic interactions are the enzyme inhibition and induction you already met.
Therapeutic window, steady state, washout — and tolerance — The therapeutic window is the clinical cousin of the therapeutic index.
Desbloquea: Phases of drug trials: from animals to Phase IV — Animal toxicity testing and human-equivalent dosing come before Phase I trials.
The Controlled Substances Act: schedules I–V and the Analogue Act — Safety is one of the factors drug schedules are supposed to weigh.

Orientarse

Therapeutic index – ratio of lethal dose to effective dose: TI = LD50 / ED50. ED50 – the drug dose that produces desired effect in 50% of subjects; LD50 – the lethal dose for 50% of subjects. The greater the TI, the safer the drug. Also: human equivalent dose (HED), drug allergy (not a side effect) and polypharmacy.

Términos del curso

Las palabras de tu profesor, tal cual aparecen en las diapositivas. Aprende el término y esta definición; la explicación de abajo solo ayuda a entenderla.

Therapeutic index (TI): “Ratio of lethal dose to effective dose”Diapositivas 05, p. 42
TI = LD50 / ED50; the greater the TI, the safer the drug.
ED50: “The drug dose that produces desired effect in 50% of subjects”Diapositivas 05, p. 42
Can be more conservative, e.g., ED95.
LD50: “The lethal dose for 50% of subjects”Diapositivas 05, p. 42
Must be a directly biological effect of the drug; can be more conservative, e.g., LD5.
Human equivalent dose (HED): “Calculate human equivalent dose (HED) and express in mg/kg”Diapositivas 05, p. 45
Animals differ in weight, tissue distribution and body surface area; LD50 in humans is estimated, never really known.
Drug allergy: “Drug allergies work same as any allergy – idiosyncratic immune response”Diapositivas 05, p. 46
Not counted when determining side effects, toxicity, or lethality.
Polypharmacy: “Sometimes medications are combined to produce optimal therapeutic outcome”Diapositivas 05, p. 47
Bad idea with pharmacodynamic redundancy, pharmacodynamic interactions (MAOI + MDMA) or pharmacokinetic interactions.

De tu curso: Course slides 05, pp. 42–47

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