Pharmacology Basics

Two questions: what the body does, and what the drug does

Pharmacology splits into two big ideas. Pharmacokinetics (PK) is what the body does to a drug: how it gets in, where it goes, how it is changed, and how it leaves. Pharmacodynamics (PD) is what the drug does to the body: which target it acts on and what effect that produces. ^[1]

Almost every dosing decision combines the two. PK tells you how much drug reaches its target and for how long; PD tells you how strong the effect will be at that concentration.

ADME: the four steps of pharmacokinetics

A useful way to remember pharmacokinetics is ADME — absorption, distribution, metabolism, and excretion.

• Absorption — how the drug enters the bloodstream. An intravenous dose goes straight in; an oral dose has to cross the gut wall first.
• Distribution — how the drug spreads into tissues. Only the unbound (free) fraction in plasma can leave the blood and act, so heavy protein binding matters. ^[2]
• Metabolism — how the drug is chemically changed, mostly in the liver, often by cytochrome P450 (CYP) enzymes. Some drugs are inactive until metabolised (prodrugs).
• Excretion — how the drug and its metabolites leave the body, mainly through the kidneys, and also in bile and faeces.

Bioavailability and first-pass metabolism

Bioavailability is the fraction of a dose that reaches the systemic circulation unchanged. By definition it is 100% for an intravenous dose. ^[2]

Oral drugs travel from the gut through the portal vein to the liver before reaching the rest of the body. Some of the dose can be metabolised on that first pass, which is why the oral and IV doses of the same drug can be very different.

Half-life and steady state

The elimination half-life is the time it takes for the plasma concentration to fall by half. It drives how often a drug needs to be given.

With regular dosing, a drug reaches steady state — where the amount going in balances the amount being cleared — after about 4 to 5 half-lives. ^[1,3] The same rule describes how long it takes for most of a drug to wash out after it is stopped.

How drugs act on receptors

Many drugs work by binding to receptors. An agonist binds and activates the receptor. An antagonist binds without activating it, which blocks the natural agonist. A partial agonist activates the receptor, but less than a full agonist can.

The therapeutic index compares the dose that causes toxicity with the dose that produces the wanted effect. Drugs with a narrow therapeutic index — such as warfarin, digoxin, lithium, and phenytoin — need careful dosing and often blood-level monitoring. ^[2,3]