SPLE Pharmacist Exam Complete Review Guide 2026–2027

4. Structure-activity relationships (SAR): a small structural change can alter receptor affinity or metabolism. Enantiomers can differ in activity: S-warfarin is more potent than R, and esomeprazole is the S-enantiomer of omeprazole. Lipinski's rule of five predicts oral absorption: molecular weight under 500 and logP under 5.
5. Drug development: preclinical work, investigational new drug (IND) application, Phase I (safety and kinetics in healthy volunteers), Phase II (efficacy and dose in patients), Phase III (large confirmatory trials), new drug application (NDA), then Phase IV postmarketing surveillance.
6. Pharmacodynamics: a full agonist gives the maximal response, a partial agonist less, an inverse agonist lowers basal activity. A competitive antagonist raises EC50 and leaves Emax unchanged. Therapeutic index = TD50 ÷ ED50 and reflects the safety margin.
7. Receptor types: G-protein-coupled (Gs raises cAMP, Gi lowers it, Gq raises IP3 and DAG), ligand-gated ion channels, tyrosine-kinase receptors such as insulin, and intracellular nuclear receptors such as steroids.
8. Interactions: common CYP3A4 inhibitors include ketoconazole, clarithromycin and grapefruit juice; inducers include rifampin, carbamazepine, phenytoin and St John's wort. P-glycoprotein interactions and pharmacodynamic interactions, such as additive sedation, also occur.
9. Well-known teratogens: warfarin, ACE inhibitors and angiotensin receptor blockers, isotretinoin, valproate, methotrexate, thalidomide and tetracyclines.
10. Antidotes: N-acetylcysteine for acetaminophen, naloxone for opioids, flumazenil for benzodiazepines, vitamin K for warfarin, protamine for heparin, atropine with pralidoxime for organophosphates, fomepizole for methanol and ethylene glycol, deferoxamine for iron, digoxin-specific Fab fragments for digoxin.
11. Pharmacognosy: a crude drug is the plant or animal material as found, a semi-purified product is an extract, and a purified product is a single pure compound. Major classes: alkaloids such as morphine, atropine and quinine; glycosides such as digoxin from Digitalis; terpenes such as artemisinin from Artemisia annua; paclitaxel from Taxus.
12. Supplements: St John's wort induces CYP3A4 and can cause serotonin syndrome with antidepressants; ginkgo raises bleeding risk with warfarin; kava is linked to liver toxicity; high-dose vitamin B6 causes neuropathy. The fat-soluble vitamins are A, D, E and K, and high-dose vitamin A is teratogenic.
13. Dosage forms: tablets (disintegration then dissolution), hard and soft capsules, solutions, suspensions (shake before use) and emulsions (oil-in-water or water-in-oil), and semisolids such as ointments, creams and gels. The Noyes-Whitney equation shows dissolution rate rises with surface area and solubility. Enteric coating protects against stomach acid.
14. BCS: Class I high solubility, high permeability; Class II low solubility, high permeability; Class III high solubility, low permeability; Class IV both low. Controlled-release systems include matrix and osmotic pump designs, and transdermal patches include nitroglycerin, fentanyl and nicotine.
15. Stability: hydrolysis affects esters and amides such as aspirin and procaine; oxidation affects epinephrine and ascorbic acid and is limited by antioxidants; photolysis needs light-resistant containers. The Arrhenius equation links temperature to degradation rate. t90 for zero order = 0.1 × C₀ ÷ k; for first order = 0.105 ÷ k.
16. Routes: intravenous bioavailability is 100%, sublingual avoids first-pass hepatic metabolism, oral is subject to it, and rectal partly avoids it. For high-extraction drugs such as propranolol and lidocaine, clearance depends on hepatic blood flow.
17. Kinetic equations: k = 0.693 ÷ t½; CL = k × Vd; loading dose = Css × Vd ÷ F; maintenance dose rate = CL × Css ÷ F; steady state takes about 4–5 half-lives. F = (AUC oral × IV dose) ÷ (AUC IV × oral dose). Cockcroft-Gault: (140 − age) × weight ÷ (72 × serum creatinine), multiplied by 0.85 for women.
18. Nonlinear (Michaelis-Menten) kinetics: enzymes saturate at high doses, half-life lengthens and levels rise disproportionately, as with phenytoin, ethanol and high-dose aspirin. Bioequivalence: the 90% confidence interval of the AUC and Cmax ratios must fall within 80–125%.
19. Sterile compounding: work is done in an ISO Class 5 environment (laminar airflow hood or biological safety cabinet) inside an ISO Class 7 buffer room with an ISO Class 8 anteroom. Sterilizing filters are 0.22 micron; sterility testing uses membrane filtration or direct inoculation. Hazardous drugs (USP <800>) are prepared in a Class II biological safety cabinet with closed-system transfer devices. Every product is labelled with a beyond-use date (BUD).
20. Calculations: percent w/v means grams per 100 mL; 1:1000 = 0.1% = 1 mg/mL. Dilution: C₁V₁ = C₂V₂. mEq = mg × valence ÷ molecular weight. 1 kg = 2.2 lb; 1 teaspoon = 5 mL. Body surface area (m²) = square root of (height in cm × weight in kg ÷ 3600). Isotonic sodium chloride is 0.9%.

Common mistakes in this chapter

• ✕ Confusing a competitive antagonist (curve shifts right, Emax unchanged) with a noncompetitive one (Emax falls)
• ✕ Confusing potency (EC50) with efficacy (Emax): the more potent drug is not necessarily the more efficacious one
• ✕ Forgetting that clearance and Vd are the independent variables and half-life depends on them: t½ = 0.693 × Vd ÷ CL
• ✕ Assuming all drugs follow first-order kinetics: phenytoin and ethanol saturate, so levels rise more than the dose does
• ✕ Mixing up CYP inducers (rifampin, carbamazepine), which lower the other drug's level, with inhibitors (ketoconazole, clarithromycin), which raise it
• ✕ Confusing ratio strength with percent strength: 1:1000 is 0.1%, or 1 mg/mL, not 1%
• ✕ Mixing up USP <797> (sterile), <795> (nonsterile) and <800> (hazardous drugs)
• ✕ Believing extended-release tablets can be crushed: crushing releases the whole dose at once