Potency vs efficacy: what the dose-response curve really tells you
Pharmacology — Dose-Response, Efficacy, Potency and Therapeutic Index
The question
Two intravenous analgesics, drug X and drug Y, are compared using log dose-response curves in the same patient population. Drug X reaches its maximum effect at a lower dose than drug Y, but drug Y produces a greater maximum effect than drug X. Which statement best describes the pharmacological relationship between the two drugs?
- Drug X is more potent and more efficacious than drug Y
- Drug X is more potent but less efficacious than drug Y
- Drug X is less potent but more efficacious than drug Y
- Drug X is more potent than drug Y, and both drugs have the same efficacy
- Drug X has a wider therapeutic index than drug Y
The answer
Drug X is more potent but less efficacious than drug Y
Drug X is more potent and more efficacious than drug Y — Drug X is more potent (lower ED50), but drug Y has the greater maximum effect, so drug Y is more efficacious.
Drug X is more potent but less efficacious than drug Y — Correct. Potency is about the dose required — drug X needs less drug to produce its effect (its curve is shifted to the left). Efficacy is the maximum response achievable — drug Y reaches a higher ceiling. These are independent properties.
Drug X is less potent but more efficacious than drug Y — This reverses both relationships. Drug X reaches its effect at a lower dose (more potent), and drug Y has the greater maximum effect (more efficacious).
Drug X is more potent than drug Y, and both drugs have the same efficacy — The stem states that drug Y produces a greater maximum effect, so their efficacy is not the same.
Drug X has a wider therapeutic index than drug Y — The therapeutic index (TD50/ED50) cannot be determined from the information given. No toxic dose data is provided for either drug.
Explanation
Potency and efficacy are independent properties of a drug, and confusing the two is one of the commonest errors in pharmacology.
Potency refers to the amount of drug required to produce a given effect. It is measured by the ED50 — the dose that produces 50% of the maximum response. A drug with a lower ED50 is more potent. On a log dose-response curve, a more potent drug's curve lies to the left. Potency is largely a function of receptor affinity: the tighter a drug binds, the less of it is needed.
Efficacy (more precisely, maximal efficacy) is the greatest response a drug can produce regardless of dose. It is read off the top of the dose-response curve. A drug with a higher plateau is more efficacious. Efficacy depends on intrinsic activity — how effectively receptor binding is converted into a cellular response — and on the number of receptors activated.
A drug can be highly potent but have low efficacy: morphine is more potent than paracetamol (a far smaller dose is needed) and also more efficacious (it can relieve more severe pain). But fentanyl is more potent than morphine (lower ED50) while both are full mu-agonists with similar maximal efficacy — potency changed, efficacy did not.
The therapeutic index (TI = TD50/ED50) compares the toxic dose to the effective dose and is a measure of safety, not of potency or efficacy. It cannot be calculated without information about the drug's toxic effects.
Tips for the candidate
When a stem mentions dose-response curves and two drugs, read the curve for two separate facts: WHERE the curve sits on the x-axis (left = more potent) and HOW HIGH the curve reaches (higher plateau = more efficacious). These are independent — knowing one tells you nothing about the other.
The classic trap is an option that says "more potent therefore more efficacious". Potency is about milligrams; efficacy is about ceiling. A drug can be exquisitely potent (active in micrograms) and still hit a low ceiling, or need large doses but produce an enormous maximum effect.
If the question mentions therapeutic index, check whether the stem gives you toxic dose data. Without it, the TI cannot be calculated and any option claiming to compare therapeutic indices is wrong. This is a common distractor.