2804NRS · Human Pathophysiology And Pharmacology 1
Pharmacology Principles
All of pharmacology splits into two questions. Pharmacokinetics (PK) = what the body does to the drug — how it moves in, around, gets broken down and out (ADME: Absorption, Distribution, Metabolism, Excretion). Pharmacodynamics (PD) = what the drug does to the body — how it binds receptors to produce an effect. This chapter is the conceptual spine every other drug in the unit hangs from: the ADME pipeline and key PK parameters (bioavailability, volume of distribution, half-life, steady state, the therapeutic window), then the PD core — the graded dose-response curve (ED50, Emax, potency vs efficacy), agonists, antagonists and partial agonists, the therapeutic index as a safety margin, and tolerance, adverse drug reactions and interactions. In 2804NRS this toolkit is woven through Modules 5–7 and examined throughout: get the PK/PD split straight and every drug fact slots onto one side or the other.
What this chapter covers
- 01PK vs PD — the two questions
- 02Pharmacokinetics 1 — ADME, the drug's journey
- 03Pharmacokinetics 2 — the concentration-time curve & dosing
- 04Pharmacodynamics 1 — receptors & the dose-response curve
- 05Pharmacodynamics 2 — agonists, antagonists & partial agonists
- 06Pharmacodynamics 3 — therapeutic index & the safety picture
Potency vs efficacy — and why the therapeutic index matters
- +1(a) Potency: drug A works at a lower dose, so its dose-response curve sits further left — drug A is more POTENT.
- +1Efficacy: drug B reaches a higher plateau (Emax), so drug B is more EFFICACIOUS — efficacy is the ceiling, potency is the dose to get there.
- +1(b) Therapeutic index: TI = TD50/ED50, the gap between the effective and the toxic dose. A NARROW index means a small margin for error.
- +1For the patient: a narrow-TI drug (warfarin, digoxin, lithium, gentamicin) needs blood-level monitoring and careful dosing, because the effective and toxic doses are close.
Key terms
- Bioavailability (F)
- The fraction of an administered dose that reaches the systemic circulation unchanged. Intravenous = 100% (F = 1); an oral drug is reduced by first-pass hepatic metabolism.
- Half-life (t½)
- The time for plasma concentration to fall by 50%. It takes about 4–5 half-lives to clear a drug or to reach steady state, where the rate of administration equals the rate of elimination.
- Agonist vs antagonist
- An agonist binds AND activates a receptor (affinity + efficacy) → response on; an antagonist binds but does not activate, blocking the agonist (affinity, no efficacy) → response off. A partial agonist activates only submaximally.
- Therapeutic index (TI)
- TD50/ED50 (or LD50/ED50) — the safety margin. A larger index is safer; a narrow index (warfarin, digoxin, lithium, gentamicin) means levels must be monitored.
- Adverse drug reaction (ADR)
- A harmful, unintended response to a drug. Type A is dose-related and predictable; Type B is idiosyncratic and unpredictable. CYP450 inhibitors raise another drug's level (toxicity); inducers lower it (treatment failure).
Pharmacology Principles FAQ
What is the difference between pharmacokinetics and pharmacodynamics?
Pharmacokinetics (PK) is what the body does to the drug — Absorption, Distribution, Metabolism and Excretion (ADME) — and it governs the drug concentration at the site over time. Pharmacodynamics (PD) is what the drug does to the body — receptor binding and the resulting effect. PK sets up PD: it decides how much active drug reaches the receptor and for how long.
What is the difference between potency and efficacy?
Potency is the dose needed for a given effect (a more potent drug works at a lower dose, so its curve sits further left). Efficacy is the maximum effect the drug can produce (the plateau height, Emax). A drug can be very potent but have low efficacy, or vice versa — they are independent.
What does the therapeutic index tell you?
It is the safety margin, TD50/ED50 — the gap between the dose that works and the dose that harms. A larger index is safer. A narrow index means the effective and toxic doses are close, so narrow-TI drugs (warfarin, digoxin, lithium, gentamicin) need monitoring and careful dosing.
What is first-pass metabolism and why does it matter?
First-pass metabolism is the hepatic breakdown of an oral drug, carried via the portal vein, before it reaches the systemic circulation — so it lowers oral bioavailability. An intravenous dose bypasses it (F = 100%). It is a key reason the same drug needs a different dose by mouth versus by injection.
Exam move
Make the PK/PD split your first move on any drug question: a fact about movement, levels or dosing is PK; a fact about receptors, effect or safety is PD. Learn ADME as an ordered pipeline and tie each step to a parameter (bioavailability, volume of distribution, half-life, clearance). On the PD side, keep potency (dose) and efficacy (ceiling) firmly separate, know the agonist/antagonist/partial-agonist distinction, and treat the therapeutic index as the safety headline — narrow means monitor. This spine then carries straight into the COX pathway, the adrenergic and cholinergic drugs, and ageing pharmacokinetics.
