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.
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- 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.
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- 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.
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Recorrido
ED50 and LD50
ED50 is the dose that produces the desired effect in 50% of subjects. LD50 is the dose lethal to 50%. Death must be a direct biological effect of the drug — alcohol poisoning stopping breathing counts; a drunk-driving crash doesn't.
Analogía y ejemplo resuelto
Analogía: The therapeutic index is the width of a mountain road. A wide road (big TI) forgives a wobble of the steering wheel. A narrow ledge (small TI) means a small mistake sends you over. Fentanyl is a road that's wide in proportion but only a few centimeters long in absolute terms — easy to overshoot.
Drug P: ED50 10 mg, LD50 1,000 mg. Drug Q: ED50 2 mg, LD50 20 mg. Which is safer by therapeutic index?
- TI = LD50 / ED50.
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