Pharmacology is the science of how drugs interact with living systems. It sits right on the border between chemistry and biology, and a surprising amount of it can be understood with ideas you already use in chemistry lessons: equilibrium, rates, pH and pKa, solubility and half-life. This guide introduces the core vocabulary and shows where the chemistry comes in.
Pharmacology is usually split into two halves:
- Pharmacodynamics — what the drug does to the body.
- Pharmacokinetics — what the body does to the drug.
Part 1: pharmacodynamics
Receptors and binding
Most drugs act by binding to a protein. Many of those proteins are receptors — molecules that normally respond to the body’s own signals, such as neurotransmitters or hormones. Binding is usually reversible and can be treated as an equilibrium:
drug + receptor ⇌ drug–receptor complex
Just like any equilibrium, the position depends on concentration. More drug means more receptors occupied, up to the point where almost all are filled. The concentration that occupies half the receptors is the dissociation constant, K_d. A drug with a low K_d has high affinity: it binds strongly even at low concentrations.
Agonists, antagonists and partial agonists
Binding is only half the story. What happens next determines the type of drug:
- An agonist binds and activates the receptor, mimicking the natural signal. Morphine is an agonist at opioid receptors, the same receptors activated by endorphins.
- An antagonist binds but doesn’t activate. By sitting in the site, it blocks the natural signal. Naloxone, used to reverse opioid overdoses, is an opioid antagonist that pushes morphine-like drugs off their receptors.
- A partial agonist activates the receptor but can’t produce the full response, even when every receptor is occupied.
The ability to activate once bound is called efficacy. Affinity and efficacy are separate properties: an antagonist can have very high affinity and zero efficacy.
Competitive vs non-competitive blocking
This mirrors the chemistry of enzyme inhibition:
- A competitive antagonist binds the same site as the natural signal. Enough agonist can outcompete it, just as adding more reactant shifts an equilibrium.
- A non-competitive (or allosteric) antagonist binds elsewhere and changes the receptor’s shape, so adding more agonist can’t fully overcome it.
- Irreversible blockers form a covalent bond. The effect lasts until the body makes new protein. Aspirin works this way on the cyclooxygenase enzyme in platelets, which is why a single low dose affects clotting for days.
Dose–response curves
If you plot the size of a drug’s effect against the logarithm of its concentration, you usually get an S-shaped (sigmoidal) curve. Two numbers summarise it:
- Emax: the maximum effect the drug can produce (a measure of efficacy).
- EC₅₀: the concentration giving half the maximum effect (a measure of potency).
A more potent drug has a lower EC₅₀ — its curve sits further left. But potency isn’t the same as being “stronger” in a useful sense. A drug that needs 100 mg to work isn’t worse than one that needs 1 mg, provided both reach the same maximum effect safely.
The therapeutic index
Every drug has a dose that helps and a dose that harms. The therapeutic index compares them — traditionally the ratio of the toxic dose to the effective dose. A large ratio means a wide safety margin; a small one means the dose must be carefully controlled and often monitored with blood tests. Lithium (used in bipolar disorder) and digoxin (a heart drug) are classic narrow-margin examples. The old saying attributed to Paracelsus — “the dose makes the poison” — is really a statement about this ratio.
Part 2: pharmacokinetics
Pharmacokinetics follows the drug’s journey through four stages, often shortened to ADME.
Absorption: pKa and pH
For a tablet to work, the drug must dissolve and then cross the gut wall into the bloodstream. Cell membranes are made of phospholipids, with a fatty interior, so uncharged molecules cross much more easily than ions.
Many drugs are weak acids or weak bases, so their charge depends on pH. The Henderson–Hasselbalch equation tells you the ratio:
For a weak acid: pH = pKa + log([A⁻]/[HA])
Take aspirin (acetylsalicylic acid, pKa ≈ 3.5):
- In the stomach, pH ≈ 2: log([A⁻]/[HA]) = 2 − 3.5 = −1.5, so [A⁻]/[HA] ≈ 0.03. About 97 % is in the neutral HA form — ready to cross membranes.
- In the small intestine, pH ≈ 6.5: the ratio is 10³ = 1,000, so almost all of it is ionised.
In practice, though, most absorption still happens in the small intestine, because its surface area is enormous. The pH calculation explains tendencies, not the whole picture. For weak bases, such as many antihistamines and antidepressants, the pattern is reversed: they’re more ionised in the acidic stomach and less ionised in the intestine. (For more on these calculations, see buffer calculations and pH of weak acids.)
Bioavailability is the fraction of an oral dose that reaches the general circulation unchanged. Drugs given intravenously have 100 % bioavailability by definition. Oral drugs lose some to poor absorption and to the first-pass effect: blood from the gut goes to the liver before the rest of the body, and the liver may break down part of the dose straight away.
Distribution
Once in the blood, a drug spreads into tissues. Fat-soluble drugs spread widely; very polar drugs stay mostly in the blood and extracellular fluid. Many drugs bind to plasma proteins such as albumin, and only the unbound fraction is active. The blood–brain barrier — tightly joined cells lining brain capillaries — keeps out many polar molecules, which is why drugs meant for the brain tend to be small and fat-soluble.
Metabolism
The liver’s job is to make foreign molecules easier to excrete, usually by making them more polar. It works in two phases:
- Phase I: oxidation, reduction or hydrolysis, often by the cytochrome P450 family of enzymes, which introduce or expose groups such as –OH.
- Phase II: conjugation — attaching a large polar group such as glucuronic acid, sulfate or glutathione.
Metabolism usually deactivates a drug, but not always. Some drugs are prodrugs, given in an inactive form that the body converts into the active one. Codeine, for instance, is partly converted to morphine in the liver. Paracetamol shows the other side: at normal doses it’s safely conjugated, but in overdose a minor pathway produces a reactive product that can damage the liver.
Excretion and half-life
Most drugs and their metabolites leave through the kidneys in urine; some leave through bile. For many drugs, elimination follows first-order kinetics: the rate of removal is proportional to the concentration, so a constant fraction is removed per unit time. This gives a constant half-life, t½ — exactly the same mathematics as radioactive decay (try the half-life calculator).
t½ = ln 2 / k = 0.693 / k
After one half-life, 50 % of the drug remains; after two, 25 %; after five, about 3 %. That’s why doctors say a drug is essentially cleared after about five half-lives.
Worked example. A drug has a half-life of 6 hours, and a patient has 80 mg in their body. How much remains after 24 hours?
24 h ÷ 6 h = 4 half-lives, so the amount is 80 × (½)⁴ = 80 ÷ 16 = 5 mg.
Half-life also sets dosing. With repeated doses, the drug accumulates until it reaches a steady state, where the amount eliminated between doses equals the amount given. It takes about four to five half-lives to get there. For a drug with a long half-life, doctors sometimes give a larger first “loading dose” to reach effective levels quickly.
Alcohol is a notable exception: at typical concentrations its main metabolising enzyme is saturated, so it’s removed at a roughly constant amount per hour (zero-order kinetics) rather than a constant fraction (see how the body metabolises alcohol).
Common mistakes
- Confusing potency with efficacy. Potency is how much you need; efficacy is how big the maximum effect can be.
- Thinking half-life means the drug is “half gone” in one step. It’s an exponential process: the same fraction goes in every half-life.
- Forgetting pH. Whether a drug is charged depends on the pKa and the pH of the compartment.
- Assuming metabolism always inactivates. Prodrugs are activated by metabolism, and some metabolites are toxic.
Key takeaways
- Pharmacodynamics: drugs bind targets with a given affinity and produce effects with a given efficacy; agonists activate, antagonists block.
- Dose–response curves give EC₅₀ (potency) and Emax (efficacy); the therapeutic index measures safety.
- Pharmacokinetics (ADME): uncharged forms cross membranes; pKa and pH decide the charge.
- The liver makes drugs more polar; most drugs are eliminated with first-order kinetics and a constant half-life.
For how chemists build the molecules in the first place, read how drugs are designed.
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