potency

**Definition:** Potency is the amount (dose or concentration) of a drug needed to produce a specified effect, typically 50% of the maximal response (EC50 for effect, ED50 for dose in a population/quantal curve). Lower EC50 = higher potency.

**Dose-response curve:** - Plotted as response vs. log(dose). Potency is read on the x-axis (position of the curve); efficacy is read on the y-axis (height of the plateau, Emax). - A more potent drug's curve is shifted LEFT. A less potent drug's curve is shifted RIGHT. - Changing potency does not change Emax unless the mechanism of antagonism changes it.

**Determinants of potency:** - Affinity of the drug for its receptor (Kd; lower Kd = higher affinity, often higher potency) - Receptor density and efficiency of receptor-effector coupling (spare receptors increase potency of agonists) - Pharmacokinetics (absorption, distribution, bioavailability, clearance) influence the dose needed

**Potency vs. efficacy (high-yield):** - Efficacy (Emax) = maximal effect a drug can produce. It is determined by intrinsic activity. Full agonists have the highest efficacy, partial agonists have lower efficacy, and antagonists have zero. - Potency = how much drug is needed. Drug A can be more potent but less efficacious than drug B. - Clinically, efficacy generally matters more than potency. A less potent drug can simply be given at a higher dose (as long as toxicity is not limiting). Example: morphine vs. fentanyl (fentanyl is more potent, but both are full mu agonists with similar efficacy); furosemide (high efficacy, "high-ceiling" diuretic) vs. HCTZ (more potent per mg, lower efficacy). - Potency matters for dose size (mg) but does not indicate superiority.

**Effects of antagonists on the curve:** - Competitive antagonist: shifts agonist curve RIGHT (decreases apparent potency, increases EC50), Emax unchanged (can be overcome with more agonist). - Noncompetitive (irreversible) antagonist: decreases Emax (decreased efficacy), potency (EC50) generally unchanged or modestly changed. - Partial agonist: lower Emax than full agonist. Can be of high or low potency.

**Related concepts:** - Therapeutic index = TD50/ED50 (or LD50/ED50): a safety measure comparing the dose curves for toxic and effective effects. It is not the same as potency. - Spare receptors: maximal response occurs with less than 100% receptor occupancy, so the EC50 is lower than the Kd. - Don't confuse potency with "strength" of a dosage form.

**Exam pearls:** - "Left shift on dose-response curve" = increased potency. - "Higher plateau" = increased efficacy. - Competitive antagonist + agonist = right shift, same Emax. - Noncompetitive antagonist = lower Emax. - Potency is inversely related to EC50/ED50.

**Other (non-pharmacology) usage:** "Potency" can also mean male erectile capacity in older/clinical urology texts (opposite of impotence) and developmental potency of stem cells (totipotent, pluripotent, multipotent). Pharmacologic potency is the board-relevant meaning.