Pharmacology and Toxicology
What the exam tests
Pharmacology and Toxicology tests receptor theory, dose–response, pharmacokinetic variability, and poisoning management. Questions often ask you to distinguish potency from efficacy or to select the correct antidote.
Core rules
- Occupancy: for a simple bimolecular interaction, fractional occupancy = [L]/(Kd + [L]). A competitive antagonist raises the apparent Kd and shifts the curve right without lowering maximal response; a noncompetitive antagonist lowers Emax.
- Potency vs efficacy: EC50 describes potency; Emax describes efficacy. A partial agonist has lower Emax but may have high affinity; an inverse agonist reduces constitutive activity.
- Therapeutic index: TI = LD50/ED50 in animals; it is not a human safety margin. Warfarin has a narrow TI; penicillin has a wide one.
- Induction and inhibition: rifampin induces CYP3A4 and lowers many drug levels; azole antifungals and macrolides inhibit CYP3A4. Inhibition is usually faster than induction.
Worked example
A full agonist has Kd = 5 nM. At [L] = 10 nM, occupancy = 10/(5 + 10) = 0.667, so about 67% of receptors are occupied. If the same concentration produces only 30% of maximal response, the tissue may have high receptor reserve or the compound may be a partial agonist; receptor occupancy alone does not prove full agonism. Adding a competitive antagonist would increase the EC50, but at sufficient agonist concentration the same Emax remains reachable.
Traps
Do not equate Kd with EC50 in intact tissues; do not call a competitive antagonist irreversible; do not use TI as a clinical index; and remember that N-acetylcysteine treats acetaminophen toxicity, atropine plus pralidoxime treats organophosphate poisoning, and naloxone reverses opioids.