Top High Yield Pharmacology Concepts and Keywords

Pharmacokinetics: “What the Body Does to the Drug”

Absorption

• First-pass metabolism significantly reduces bioavailability of orally administered drugs that are highly extracted by the liver (propranolol, morphine, nitroglycerin)
• Weak acids (aspirin) are better absorbed in the acidic stomach; weak bases in the alkaline intestine
• Bioavailability = (AUC oral / AUC IV) × 100

Distribution

• Volume of distribution (Vd) = dose / plasma concentration. High Vd means extensive tissue distribution
• Only unbound (free) drug is pharmacologically active and can be filtered/metabolized
• Drugs don’t cross blood-brain barrier if they’re ionized, highly polar, or large

Metabolism

• Phase I reactions (CYP450): oxidation, reduction, hydrolysis – often create active or toxic metabolites
• Phase II reactions: conjugation (glucuronidation, sulfation) – generally produce inactive, water-soluble products
• CYP3A4 metabolizes ~50% of all drugs – major site of drug interactions
• Zero-order kinetics (alcohol, phenytoin, aspirin at high doses): constant amount metabolized per unit time regardless of concentration

Elimination

• Most drugs follow first-order kinetics: constant fraction eliminated per unit time
• Half-life = 0.693 × (Vd / Clearance)
• Steady state reached in ~4-5 half-lives
• Loading dose = Vd × target concentration; Maintenance dose = Clearance × target concentration

Pharmacodynamics: “What the Drug Does to the Body”

Receptor Concepts

• Efficacy (Emax): maximum effect a drug can produce. Partial agonists have lower efficacy than full agonists
• Potency (EC50): concentration needed for 50% of maximal effect. Less clinically important than efficacy
• Competitive antagonists shift dose-response curve right (can be overcome with more agonist)
• Non-competitive antagonists decrease maximum response (cannot be overcome)

Therapeutic Index

• TI = TD50 / ED50 (or LD50 / ED50). Narrow therapeutic index drugs require monitoring: warfarin, digoxin, lithium, phenytoin, theophylline, aminoglycosides

Autonomic Pharmacology

Cholinergic Drugs

• Muscarinic effects: DUMBBELSS (Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Emesis, Lacrimation, Salivation, Sweating)
• Atropine reverses muscarinic effects; pralidoxime reverses nicotinic effects of organophosphates (must give early before “aging”)
• Nicotinic receptors: Nn at ganglia, Nm at neuromuscular junction

Adrenergic Drugs

• α1: vasoconstriction, mydriasis, urinary retention
• α2: decreased sympathetic outflow (central), decreased insulin release
• β1: increased heart rate and contractility (cardiac)
• β2: bronchodilation, vasodilation, tremor, hyperglycemia
• β3: lipolysis

Cardiovascular Drugs

Antihypertensives

• ACE inhibitors cause dry cough (bradykinin accumulation) and hyperkalemia; contraindicated in pregnancy
• ARBs are like ACE inhibitors but without the cough
• Thiazides cause hypokalemia, hyperglycemia, hyperlipidemia, hyperuricemia, hypercalcemia
• β-blockers mask hypoglycemia symptoms (except sweating) in diabetics

Anticoagulants

• Heparin: monitor with aPTT, reversed by protamine sulfate, can cause HIT (heparin-induced thrombocytopenia)
• Warfarin: monitor with PT/INR, reversed by vitamin K (slow) or fresh frozen plasma (fast), crosses placenta
• Warfarin inhibits vitamin K epoxide reductase, affecting factors II, VII, IX, X and proteins C & S

CNS Drugs

General Principles

• Benzodiazepines potentiate GABA-A receptors (increase frequency of opening); barbiturates increase duration of opening
• Flumazenil reverses benzodiazepines; naloxone reverses opioids
• SSRIs take 2-4 weeks for antidepressant effect but side effects occur immediately
• Antipsychotics block D2 receptors; extrapyramidal side effects related to nigrostriatal pathway blockage

Antimicrobials

Key Principles

• Bactericidal: β-lactams, vancomycin, aminoglycosides, fluoroquinolones
• Time-dependent killing: β-lactams (keep concentration above MIC for >40% of dosing interval)
• Concentration-dependent killing: aminoglycosides, fluoroquinolones (maximize peak concentration)
• β-lactams require actively dividing bacteria to work

Resistance Mechanisms

• β-lactamase production (add β-lactamase inhibitor: clavulanate, sulbactam, tazobactam)
• Altered penicillin-binding proteins (MRSA – use vancomycin)
• Decreased permeability or efflux pumps

Drug Interactions

CYP450 Inducers (decrease other drug levels): CRAP GPS – Carbamazepine, Rifampin, Alcohol (chronic), Phenytoin, Griseofulvin, Phenobarbital, St. John’s Wort

CYP450 Inhibitors (increase other drug levels): SICKFACES.COM – Sodium valproate, Isoniazid, Cimetidine, Ketoconazole, Fluconazole, Acute alcohol, Chloramphenicol, Erythromycin, Sulfonamides, Ciprofloxacin, Omeprazole, Metronidazole

Toxicology Antidotes

• Acetaminophen → N-acetylcysteine
• β-blockers → Glucagon
• Benzodiazepines → Flumazenil
• Carbon monoxide → 100% O2, hyperbaric O2
• Digoxin → Anti-digoxin Fab fragments
• Iron → Deferoxamine
• Lead → EDTA, dimercaprol, succimer
• Methanol/ethylene glycol → Fomepizole, ethanol
• Opioids → Naloxone
• Organophosphates → Atropine + pralidoxime
• Warfarin → Vitamin K, fresh frozen plasma

These concepts form the foundation for understanding most pharmacological principles and are frequently tested in medical examinations.