Principles of Pharmacology MCQ

Every prescription rests on a few principles. Pharmacokinetics describes what the body does to the drug, absorption, distribution, metabolism, and excretion, with first-pass metabolism, CYP450 enzymes, and half-life being the high-yield concepts. Pharmacodynamics describes what the drug does to the body, through receptors and the difference between full and partial agonists, competitive and non-competitive antagonists, and affinity versus efficacy. Dose-response curves give ED50, LD50, and the therapeutic index, which is the margin of safety. Drug interactions live at both layers, classically when a CYP inhibitor like an antibiotic shoots a warfarin INR up. Good prescribing ties it all to the patient, with the right drug, dose, route, and duration written clearly and safely.

Pharmacokinetics: ADME and Half-Life

• Pharmacokinetics is what the body does to the drug; the four steps are absorption, distribution, metabolism, and excretion (ADME).
• Absorption is influenced by the route of administration and bioavailability (the fraction of an administered dose reaching the systemic circulation); intravenous bioavailability is 100 percent, while oral bioavailability is variable and often much lower.
• Distribution depends on the volume of distribution (high in lipophilic, tissue-bound drugs) and plasma protein binding (only the free, unbound fraction is pharmacologically active).
• Excretion is mainly renal (with hepatic and biliary contributions); the half-life is the time for the plasma concentration to fall by half, and roughly five half-lives are needed to reach steady state or to clear most of a drug.

First-Pass Metabolism and Bioavailability

• Drugs absorbed from the gastrointestinal tract enter the portal vein and pass through the liver before reaching the systemic circulation; this first-pass metabolism can substantially reduce oral bioavailability.
• Routes that bypass first-pass metabolism include intravenous, sublingual, transdermal, intranasal, rectal (partly), and inhaled administration.
• Nitroglycerin is given sublingually for angina because oral nitroglycerin would be almost completely inactivated by first-pass metabolism.
• First-pass metabolism is also why some drugs are not given orally at all, or are given at a much larger oral dose than intravenous dose to achieve the same plasma level.

CYP450 Inducers, Inhibitors, and Polymorphisms

• Most drug metabolism uses the hepatic cytochrome P450 (CYP) enzymes, with CYP3A4 handling the largest share of clinical drugs.
• CYP inducers (rifampin, phenytoin, carbamazepine, St. John's wort) speed metabolism and lower the plasma levels of drugs metabolized by that enzyme.
• CYP inhibitors (azole antifungals like ketoconazole, macrolides like clarithromycin, grapefruit juice, ciprofloxacin) slow metabolism and raise plasma levels, which is how an antibiotic can push an INR up on warfarin.
• Genetic polymorphisms matter: codeine is a prodrug converted to morphine by CYP2D6, so ultra-rapid metabolizers can get toxicity and poor metabolizers get no analgesia; clopidogrel needs CYP2C19 activation and is less effective in poor metabolizers.

Pharmacodynamics: Receptors, Agonism, and Antagonism

• Pharmacodynamics is what the drug does to the body, usually by binding receptors with a certain affinity (how tightly) and efficacy (the size of the response produced).
• A full agonist produces the maximum receptor response; a partial agonist produces a submaximal response even when all receptors are occupied.
• A competitive antagonist binds reversibly at the receptor, shifting the dose-response curve to the right but preserving the maximum response, which can be overcome by enough agonist.
• A non-competitive (or irreversible) antagonist reduces the maximum achievable response and cannot be overcome by more agonist.

Dose-Response and Therapeutic Index

• The ED50 (effective dose 50) is the dose that produces the chosen effect in half the population (or half the maximum response); a smaller ED50 means a more potent drug.
• The LD50 (lethal dose 50) is the dose lethal to 50 percent of animals in toxicology; clinically, a TD50 (toxic dose 50) is more commonly cited.
• The therapeutic index (TI) is the ratio LD50 to ED50 (or TD50 to ED50); a higher TI means a wider margin of safety.
• Drugs with a narrow therapeutic index (warfarin, digoxin, lithium, phenytoin, theophylline) need monitoring because small changes in dose, absorption, or clearance can swing the patient from underdose to toxicity.

Drug Interactions and Prescribing Principles

• Drug interactions can be pharmacokinetic (changing absorption, protein binding, metabolism through CYP induction or inhibition, or excretion) or pharmacodynamic (additive, synergistic, or antagonistic effects at the same or different targets).
• A classic dental interaction is an antibiotic added to a patient on warfarin: the antibiotic kills vitamin K-producing gut flora and, for some agents, also inhibits CYP enzymes, raising the INR and bleeding risk.
• Prescribing principles include choosing the right drug for the indication, dosing for weight and organ function (start low and go slow in the elderly or in renal or hepatic impairment), and considering interactions and adherence.
• A complete prescription includes the patient and prescriber, the drug, strength and dose, the route and frequency (the sig, often in abbreviations such as BID, TID, PRN), the quantity to dispense, and refill instructions.