Iran Pharm.D. End-of-Course Exam cheat sheet

Bioavailability F = (AUC_oral × D_iv) / (AUC_iv × D_oral); absolute F compares oral to IV, relative F compares two non-IV routes.

Noyes–Whitney: dC/dt = (D·A·(Cs − C)) / (h·V); dissolution rate rises with surface area A and solubility Cs, falls with diffusional path h.

Stokes settling: v = d²(ρs − ρl)g / 18η; smaller particles and higher viscosity lower sedimentation, favoring suspension stability.

Hixson–Crowell cube-root law (dM/dt ∝ surface) applies to diffusion-controlled dissolution of monodisperse particles; zero-order release needs a constant-area or reservoir system.

Higuchi: Q = √(2·D·Cs·t) for matrix release; cumulative release is proportional to √t, a diagnostic for diffusion-controlled matrix tablets.

BCS: Class I high solubility/high permeability (IVIVC likely), Class II low solubility (dissolution rate-limited), Class III high solubility/low permeability (permeability-limited), Class IV both low.

Tablet compaction: brittle materials fragment (increases area, low strain-rate sensitivity); plastic materials deform; elastic recovery causes capping/lamination.

Sterilization: moist heat 121 °C, 15 min, 15 psi achieves F0 ≥ 8–12 min; dry heat 160 °C/2 h or 170 °C/1 h for glassware and oils; ethylene oxide for heat-labile devices.

Lyophilization stages: freezing, primary drying (sublimation below collapse temperature), secondary drying (desorption of bound water); collapse temperature governs primary drying shelf temperature.

Dose–response: EC50 is the concentration producing 50% of maximal effect; a rightward shift with unchanged Emax indicates competitive antagonism (increased apparent Kd).

Competitive antagonist: dose ratio − 1 = [I]/Ki (Schild); noncompetitive antagonist lowers Emax without shifting EC50.

Therapeutic index = TD50/ED50; a low index (e.g., digoxin, warfarin, lithium) mandates therapeutic drug monitoring.

Receptor families: Gs-coupled raises cAMP; Gi-coupled lowers cAMP; Gq-coupled activates PLC → IP3/DAG → Ca²⁺; ligand-gated ion channels mediate fast synaptic transmission.

Pharmacokinetic parameters: t½ = 0.693·Vd/CL; steady state reached in ~4–5 half-lives; loading dose = Vd × target concentration / F.

Enzyme inhibition: reversible competitive raises Km with unchanged Vmax; noncompetitive lowers Vmax with unchanged Km; irreversible lowers Vmax.

Antidotes: N-acetylcysteine (acetaminophen), naloxone (opioids), flumazenil (benzodiazepines), atropine plus pralidoxime (organophosphates), deferoxamine (iron), fomepizole (methanol/ethylene glycol).

Toxicity thresholds: acetaminophen nomogram (Rumack–Matthews) starts at 4 h post-ingestion; salicylate toxicity causes mixed respiratory alkalosis and metabolic acidosis.

CYP interactions: CYP3A4 inhibitors (ketoconazole, clarithromycin, grapefruit) raise substrate levels; inducers (rifampin, carbamazepine, St John's wort) lower them.

Lipinski rule of five: MW ≤ 500, logP ≤ 5, H-bond donors ≤ 5, H-bond acceptors ≤ 10; violation of two or more predicts poor oral absorption.

Veber criteria: rotatable bonds ≤ 10 and polar surface area ≤ 140 Ų predict good oral bioavailability.

Bioisosteres: replace –COOH with tetrazole, –OH with –NH2, or phenyl with thiophene to retain activity while altering metabolism and pKa.

Prodrug design: ester prodrugs (e.g., enalapril, valacyclovir) improve absorption by masking polar groups; hydrolysis by esterases releases active drug.

SAR: electron-withdrawing groups on a phenyl ring increase acidity of a neighboring carboxylic acid; alkyl branching increases logP and often metabolic stability but reduces solubility.

Chirality: only the (S)-enantiomer of omeprazole (esomeprazole) is proton-pump active; (S)-warfarin is more potent but cleared faster than (R)-warfarin.

Metabolic soft spots: benzylic and allylic positions, N-methyl groups, and para-hydroxylation of phenyl rings are common phase I oxidation sites; fluorination blocks these.

QSAR: Hansch equation log(1/C) = k·logP + ρ·σ + … relates potency to lipophilicity and electronic parameters; used to guide analog optimization.

Alkaloids are basic nitrogen-containing plant metabolites; extraction uses acid–base partitioning (alkaloid salts in acid, free base in organic solvent at alkaline pH).

Key source plants: morphine/opium (Papaver somniferum), quinine (Cinchona), atropine/hyoscine (Atropa, Datura), digoxin (Digitalis lanata), vincristine/vinblastine (Catharanthus roseus), paclitaxel (Taxus brevifolia).

Glycosides: cardiac glycosides act via Na⁺/K⁺-ATPase inhibition; anthraquinone glycosides (senna, aloe) are laxatives; saponin glycosides cause hemolysis.

Essential oils are volatile terpenoids obtained by hydrodistillation or steam distillation; menthol (Mentha), eucalyptol, and thymol are common examples.

Standardization markers: use a defined chemical marker (e.g., hypericin in St John's wort, ginkgolides in Ginkgo) with validated HPLC methods for quality control.

Herb–drug interactions: St John's wort induces CYP3A4 and P-gp (reduces cyclosporine, oral contraceptives); ginkgo and garlic increase bleeding risk; grapefruit inhibits intestinal CYP3A4.

Flavonoids and tannins: tannins precipitate proteins (astringent, used in wound healing); flavonoids are antioxidants; both complicate extraction and assay.

Hypertension: first-line for most adults is a thiazide diuretic, ACE inhibitor/ARB, or dihydropyridine CCB; ACE inhibitors/ARBs are preferred in diabetes with proteinuria.

Type 2 diabetes: metformin is first-line unless contraindicated (eGFR < 30); add SGLT2 inhibitors or GLP-1 receptor agonists for cardiovascular or renal protection.

Asthma: stepwise therapy - SABA as needed, low-dose ICS for persistent symptoms, add LABA or LTRA as needed; never use LABA monotherapy in asthma.

Heart failure with reduced EF: quadruple therapy - ACE inhibitor/ARB/ARNI, beta-blocker, MRA, and SGLT2 inhibitor - reduces mortality.

Anticoagulation: warfarin requires INR monitoring (target 2–3 for most indications); DOACs (apixaban, rivaroxaban) require renal dose adjustment and have specific reversal agents (andexanet alfa, idarucizumab for dabigatran).

Antibiotic stewardship: complete prescribed courses for confirmed bacterial infections; avoid antibiotics for viral upper respiratory infections; de-escalate based on culture results.

Pharmacovigilance: report suspected adverse drug reactions via national reporting systems; serious reactions require prompt reporting; causality assessed with Naranjo or WHO-UMC scales.

Prescription elements: patient name, date, drug name, strength, dosage form, quantity, directions (sig), prescriber signature and license; incomplete prescriptions must be clarified before dispensing.

Medication errors: use the 'five rights' (right patient, drug, dose, route, time); high-alert medications (insulin, heparin, concentrated electrolytes, chemotherapy) require independent double-checks.

Dispensing: verify dose against weight/age for pediatric patients; check for therapeutic duplication and drug–drug interactions before release.

Patient counseling: explain indication, dose, timing, common side effects, and storage; use teach-back to confirm understanding.

Adverse event reporting: document and report to the national pharmacovigilance center; serious events include death, hospitalization, and congenital anomaly.

Good storage practices: refrigerated items (2–8 °C), controlled room temperature (15–30 °C), protect from light; monitor cold-chain with temperature logs.

Compounding: follow USP <795> (nonsterile) and <797> (sterile) standards for facilities, personnel, and beyond-use dating.

Pharmacoeconomics: cost-effectiveness ratio = cost / health outcome (e.g., cost per QALY); cost-benefit compares monetary costs and benefits; cost-minimization assumes equivalent outcomes.

QALY = life years × utility (0–1); used to compare interventions across diseases and inform reimbursement decisions.

Pharmacoepidemiology: cohort studies estimate incidence and relative risk; case-control studies estimate odds ratios for rare outcomes; RCTs provide the strongest causal evidence.

Adherence measurement: pill counts, pharmacy refill records (proportion of days covered), and self-report; each has different bias profiles.

Regulatory framework: marketing authorization requires safety, efficacy, and quality data; post-marketing surveillance continues after approval.

Health literacy: low literacy is associated with poor adherence and more hospitalizations; plain-language labeling and pictograms improve comprehension.

Pharmacy workforce: scope of practice varies by jurisdiction; expanded roles include immunization, medication therapy management, and prescribing under protocol.

Glycolysis: glucose → 2 pyruvate, net 2 ATP and 2 NADH; rate-limiting enzyme phosphofructokinase-1 is activated by AMP and inhibited by ATP and citrate.

TCA cycle: acetyl-CoA → 2 CO2, 3 NADH, 1 FADH2, 1 GTP per turn; oxidative phosphorylation yields ~2.5 ATP per NADH and ~1.5 ATP per FADH2.

Reference intervals: results are compared to age- and sex-specific ranges; a value outside the interval is not automatically pathologic - interpret with clinical context.

Liver enzymes: ALT is more liver-specific than AST; AST/ALT > 2 suggests alcoholic liver disease; alkaline phosphatase rises in cholestasis and bone disease.

Renal function: eGFR from creatinine (CKD-EPI equation); creatinine is affected by muscle mass, so cystatin C is an alternative marker.

Cardiac markers: troponin I/T are the preferred biomarkers of myocardial injury; CK-MB is less specific; BNP/NT-proBNP reflect ventricular wall stress.

Diabetes diagnosis: fasting plasma glucose ≥ 126 mg/dL, 2-h OGTT ≥ 200 mg/dL, HbA1c ≥ 6.5%, or random glucose ≥ 200 mg/dL with symptoms.

Enzyme units: one IU = 1 µmol substrate converted per minute; activity depends on temperature, pH, and substrate concentration.

Cardiac output = heart rate × stroke volume; stroke volume depends on preload, afterload, and contractility (Frank–Starling relationship).

Renal handling: filtration at the glomerulus, reabsorption in the proximal tubule (~65% of Na⁺ and water), concentration in the loop of Henle, and hormonal control by aldosterone and ADH.

Acid–base: Henderson–Hasselbalch pH = 6.1 + log([HCO3⁻]/0.03 × PaCO2); compensation is respiratory (fast, via CO2) or metabolic (slow, via HCO3⁻).

Diabetes pathophysiology: type 1 is autoimmune beta-cell destruction; type 2 involves insulin resistance and progressive beta-cell failure; DKA features ketosis and anion-gap acidosis.

Hypertension: sustained elevation of systemic vascular resistance and/or volume; secondary causes include renal artery stenosis, hyperaldosteronism, and pheochromocytoma.

Inflammation: acute response involves vasodilation, increased permeability, and neutrophil recruitment; chronic inflammation features macrophages, lymphocytes, and fibrosis.

Electrolytes: hyponatremia reflects water imbalance more than sodium loss; hyperkalemia is worsened by ACE inhibitors, ARBs, and potassium-sparing diuretics.

Biologics: monoclonal antibodies (~150 kDa) have long half-lives via FcRn recycling; they are degraded to amino acids, not renally cleared intact.

Immunogenicity: anti-drug antibodies can reduce efficacy and cause infusion reactions; risk depends on product origin, aggregation, and route of administration.

Biosimilars: require analytical similarity, functional assays, and comparative clinical studies; they are not identical to the reference product and require distinct naming.

Protein stability: aggregation, deamidation (Asn), oxidation (Met), and hydrolysis are common degradation pathways; formulation controls pH, buffer, and excipients.

Biopharmaceutics: for BCS Class II drugs, dissolution is rate-limiting; food can increase absorption of lipophilic drugs (positive food effect) or delay it.

First-pass metabolism reduces oral bioavailability; routes avoiding it (IV, sublingual, transdermal, rectal partially) improve systemic exposure.

Protein binding: only free drug is pharmacologically active; high protein binding (e.g., warfarin ~99%) means displacement can raise free fraction and toxicity.

Therapeutic proteins require cold chain (2–8 °C) and avoidance of vigorous shaking to prevent aggregation.

Beer–Lambert law: A = ε·b·c; absorbance is linear with concentration at fixed path length and wavelength; deviations occur at high concentration or with polychromatic light.

HPLC: retention depends on stationary/mobile phase interaction; resolution Rs = 2(t2 − t1)/(w1 + w2); Rs ≥ 1.5 is baseline separation.

Validation parameters: accuracy, precision, specificity, linearity, range, detection limit, quantitation limit, robustness (ICH Q2).

System suitability: tailing factor ≤ 2, theoretical plates adequate, %RSD of replicate injections ≤ 2% for assay methods.

Titration: equivalence point from the inflection of the titration curve; indicators or potentiometric endpoints determine the result.

Limit tests: heavy metals (sulfide precipitation), chloride (opalescence with AgNO3), sulfate (turbidity with BaCl2); results are pass/fail against a standard.

Stability studies: accelerated conditions 40 °C/75% RH for 6 months, long-term at 25 °C/60% RH or 30 °C/65% RH; shelf life derived from degradation kinetics.

Dissolution testing: USP Apparatus I (basket, 100 rpm) and II (paddle, 50–75 rpm); Q value typically 80% in 30–45 min for immediate-release products.