PharmacologyTier 1Medical Sciences concept

Pharmacokinetic-pharmacodynamic relationship interpretation (tachyphylaxis, active metabolites, receptor changes)

Core concept

Pharmacokinetics (PK) = what the body does to the drug (absorption, distribution, metabolism, excretion -> concentration over time)
Pharmacodynamics (PD) = what the drug does to the body (concentration -> effect) -- the PK/PD relationship can change independent of concentration
Exam task: interpret a concentration-vs-effect graph where the relationship shifts, and identify the mechanism (tachyphylaxis, active metabolite, receptor change)

Tachyphylaxis: effect diminishes despite unchanged/rising concentration -- rapid receptor desensitisation or downregulation (e.g. nitrates, decongestants, some catecholamines)
Active metabolite accumulation: apparent effect outlasts or exceeds what parent drug concentration predicts -- effect curve does not decline in parallel with parent drug level (e.g. diazepam -> desmethyldiazepam, morphine -> M6G)
Receptor upregulation/sensitisation (e.g. after chronic antagonist exposure, beta-blocker withdrawal) -> same concentration now produces a larger effect, or withdrawal produces rebound effect at near-zero concentration

On a graph, tachyphylaxis = effect curve flattens/falls while concentration curve stays high or rises
Active metabolite = effect (or a toxicity marker) persists after parent concentration has fallen toward zero
Trap: assuming "drug level is now low, so effect/toxicity should be resolving" -- check for an active metabolite with a longer half-life before reassurance
Abrupt beta-blocker cessation -> upregulated receptors now unopposed -> rebound tachycardia/hypertension/angina despite drug concentration being essentially zero

Tachyphylaxis differs from true tolerance (gradual, over days-weeks, often receptor downregulation or metabolic) though both describe diminished effect over time
Active metabolite curves relate directly to opioid metabolite accumulation and half-life calculation
Receptor sensitisation/rebound is the same mechanism underlying clonidine and beta-blocker withdrawal syndromes

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