USMLE Step 1 Review/Pharmacology

Pharmacodynamic and pharmacokinetic processes, general principles.

Pharmacokinetics

The four stages of chemicals passing through the body

• Absorption - the process of the intake of the drug into the body
• Distribution - the process of the dispersion of the drug into the blood stream and tissues
• Metabolism - the process of the parent compounding into daughter metabolites
• Excretion - the process of eliminating the drug from the body

Dosage intervals

Zero order pharmacokinetics, the rate of reaction is independent of the concentration of the reactants:

r = k

Drugs following zero order pharmacokinetics; Mnemonic: 'Peas & WHEATS' (A Pea would look like a zero and denotes the order). Pea also stands for 'Pee'-ing out a constant amount as in zero order kinetics constant amount of the drug is eliminated per unit time. Rate of elimination is constant and does not depend on or vary with the drug intake or plasma concentration of the drug.

• Phenytoin, Phenylbutazone
• Warfarin
• Heparin
• Ethanol
• Aspirin
• Theophylline, Tolbutamide
• Salicylates

Absorption

Many abbreviations are used in writing administration routes and frequency:

• p.o.: by mouth
• IM: intramuscular injection
• SC: subcutaneous injection
• IV: intravenous
• PR: per rectum
• h.s.: at hour of sleep (bedtime)
• ac: before meals
• pc: after meals
• q: every, ie, q 8 h means every 8 hours
• q.d.: every day
• b.i.d.: twice/day
• t.i.d.: three times/day
• q.i.d.: four times/day
• q.o.d.: every other day

Distribution

The volume of distribution is given by the following equation:

$V_D=\frac{\mathrm{t}\mathrm{o}\mathrm{t}\mathrm{a}\mathrm{l}\mathrm{a}\mathrm{m}\mathrm{o}\mathrm{u}\mathrm{n}\mathrm{t}\mathrm{o}\mathrm{f}\mathrm{d}\mathrm{r}\mathrm{u}\mathrm{g}\mathrm{i}\mathrm{n}\mathrm{t}\mathrm{h}\mathrm{e}\mathrm{b}\mathrm{o}\mathrm{d}\mathrm{y}}{\mathrm{d}\mathrm{r}\mathrm{u}\mathrm{g}\mathrm{b}\mathrm{l}\mathrm{o}\mathrm{o}\mathrm{d}\mathrm{p}\mathrm{l}\mathrm{a}\mathrm{s}\mathrm{m}\mathrm{a}\mathrm{c}\mathrm{o}\mathrm{n}\mathrm{c}\mathrm{e}\mathrm{n}\mathrm{t}\mathrm{r}\mathrm{a}\mathrm{t}\mathrm{i}\mathrm{o}\mathrm{n}}$

Metabolism

Drugs undergoing complete first pass metabolism when taken orally: 'FILTHy'

• First pass metabolism
• Isoprenaline
• Lignocaine (Lidocaine)
• Testosterone
• Hydrocortisone

Drugs metabolized by acetylation, acetylator polymorphism: Some individuals are slow acetylators and some are fast acetylators.The drugs metabolized by acetylation may become ineffective in fast acetylators and cause toxicity in slow acetylators. Mnemonic: 'SHIP'

• Sulfonamides including dapsone
• Hydralazine
• Isoniazid (INH)
• Procainamide

Enzyme inducers: 'SCRAP Bar'

• Sulphonylureas
• Carbemazepine
• Rifampicin
• Alcohol
• Pheytoin
• Barbituates

Enzyme inhibitors 'COMIC CASE'

• Cimetidine
• Omeprazole
• Metronidazole
• Isoniazid
• Chloramphenicol
• Ciprofloxacin
• Allopurinol
• Sulphonamides
• Erythromycin

Elimination

Three sites where drug excretion occurs: The kidneys, the liver and the lungs.

Drug actions

• mechanisms of drug action, structure-activity relationships (including anticancer drugs)
• concentration- and dose-effect relationships, types of agonists and antagonists and their actions
• individual factors altering pharmacokinetics and pharmacodynamics
• mechanisms of drug adverse effects, overdosage, toxicology
• mechanisms of drug interactions
• regulatory issues
• signal transduction, including structure/function of all components of signal transduction pathway such as receptors, ligands
• cell cycle/cell cycle regulation