General Pharmaceutical Council Registration Assessment (GPhC Assessment) Clinical Pharmacology and Pharmaceutical Science Syllabus

Clinical Pharmacology and Pharmaceutical Science syllabus — full chapter and topic list

Expand any chapter to see its topics and sub-topics. This is the whole examinable outline for Clinical Pharmacology and Pharmaceutical Science in General Pharmaceutical Council Registration Assessment (GPhC Assessment), not a summary of it.

1. 1

   Pharmacokinetics

   4 topics

   • Absorption
     • Bioavailability and first-pass metabolism
     • Factors affecting absorption
   • Distribution
     • Volume of distribution and protein binding
   • Metabolism
     • Cytochrome P450 enzymes
     • Inducers and inhibitors
   • Excretion and Clearance
     • Renal and biliary elimination
     • Half-life and steady state
2. 2

   Pharmacodynamics

   3 topics

   • Drug-Receptor Interactions
     • Agonists, antagonists and partial agonists
     • Affinity, efficacy and potency
   • Dose-Response Relationships
     • Therapeutic index and dose-response curves
   • Mechanisms of Drug Action
     • Enzyme inhibition and ion-channel effects
3. 3

   Drug Interactions and Adverse Reactions

   4 topics

   • Pharmacokinetic Interactions
     • Enzyme-mediated interactions
     • Transporter and absorption interactions
   • Pharmacodynamic Interactions
     • Additive and antagonistic effects
   • Adverse Drug Reactions
     • Type A and Type B reactions
     • Yellow Card scheme reporting
   • High-Risk Drugs and Monitoring
     • Therapeutic drug monitoring principles
4. 4

   Pharmaceutics and Drug Delivery

   4 topics

   • Dosage Forms
     • Solid, liquid and semi-solid forms
     • Modified-release formulations
   • Routes of Administration
     • Oral, parenteral, topical and inhaled routes
   • Stability and Storage
     • Expiry, shelf life and storage conditions
     • Cold chain requirements
   • Excipients and Bioavailability
     • Role of excipients in formulation

Clinical Pharmacology and Pharmaceutical Science flashcards for General Pharmaceutical Council Registration Assessment (GPhC Assessment)

24 of 51 cards from the Clinical Pharmacology and Pharmaceutical Science deck — real questions with worked answers.

1. Define pharmacokinetics and pharmacodynamics, and state the simple distinction between them.

   Pharmacokinetics is what the body does to the drug (Absorption, Distribution, Metabolism, Excretion — ADME). Pharmacodynamics is what the drug does to the body (its biochemical/physiological effects and mechanism of action). Mnemonic: PK = body affects drug; PD = drug affects body.

2. What are the four processes that make up ADME in pharmacokinetics?

   Absorption, Distribution, Metabolism, and Excretion. These describe the movement of a drug into, around, and out of the body over time.

3. Define bioavailability ($F$) and give the equation for absolute bioavailability.

   Bioavailability is the fraction of an administered dose of unchanged drug that reaches the systemic circulation. Absolute bioavailability compares an extravascular route to IV: $$F = \frac{AUC_{oral} \times Dose_{IV}}{AUC_{IV} \times Dose_{oral}}$$ By definition $F = 1$ (100%) for intravenous administration.

4. What is the first-pass effect (first-pass metabolism)?

   The phenomenon whereby an orally absorbed drug is metabolised in the gut wall and especially the liver (via the hepatic portal vein) before reaching the systemic circulation, reducing the fraction of active drug that becomes bioavailable. Drugs with high first-pass metabolism (e.g. GTN, propranolol, lidocaine) have low oral bioavailability.

5. Which routes of administration bypass first-pass hepatic metabolism?

   Intravenous, intramuscular, subcutaneous, sublingual/buccal, transdermal, inhaled, and (largely) rectal administration. They deliver drug to the systemic circulation without first passing through the liver via the portal vein.

6. According to the pH-partition hypothesis, in what state must a drug be to cross lipid membranes, and how does pH affect absorption of weak acids and bases?

   A drug crosses lipid membranes best in its non-ionised (uncharged, lipid-soluble) form. Weak acids are non-ionised and better absorbed in acidic environments (e.g. stomach); weak bases are non-ionised and better absorbed in alkaline environments (e.g. small intestine). Despite this, most absorption occurs in the small intestine due to its huge surface area.

7. State the Henderson–Hasselbalch equations for a weak acid and a weak base.

   For a weak acid: $$pH = pK_a + \log\frac{[A^-]}{[HA]}$$ For a weak base: $$pH = pK_a + \log\frac{[B]}{[BH^+]}$$ These relate the ratio of ionised to non-ionised drug to the pH and $pK_a$.

8. Define the apparent volume of distribution ($V_d$) and give its formula.

   $V_d$ is the theoretical volume into which the total amount of drug would need to be uniformly distributed to give the observed plasma concentration. $$V_d = \frac{\text{Amount of drug in body}}{C_p}$$ where $C_p$ is plasma concentration. A large $V_d$ implies extensive tissue distribution rather than confinement to plasma.

9. What does a large versus small volume of distribution indicate about where a drug resides?

   A small $V_d$ (e.g. ~5 L, plasma volume; or ~15 L, extracellular fluid) suggests the drug is largely confined to plasma/ECF, often due to high plasma protein binding. A large $V_d$ (can exceed total body water, >42 L, even hundreds of litres, e.g. digoxin, amiodarone) indicates extensive distribution into and binding within tissues.

10. How does plasma protein binding affect drug distribution and activity? Name the main binding proteins.

    Only the free (unbound) drug is pharmacologically active and able to distribute to tissues, be metabolised and excreted. Protein-bound drug acts as a reservoir. Acidic drugs mainly bind albumin; basic drugs bind $\alpha_1$-acid glycoprotein. Displacement from binding sites can transiently increase free drug concentration.

11. What is the difference between Phase I and Phase II metabolism?

    Phase I reactions (oxidation, reduction, hydrolysis — largely by cytochrome P450) introduce or expose a functional group, often making the drug more polar and sometimes producing active or toxic metabolites. Phase II reactions are conjugation (e.g. glucuronidation, sulfation, acetylation, glutathione conjugation), adding an endogenous molecule to greatly increase water solubility for excretion.

12. What is the cytochrome P450 (CYP450) system and which isoenzyme metabolises the most drugs?

    CYP450 is a superfamily of hepatic (and gut) haem-containing enzymes responsible for most Phase I oxidative drug metabolism. CYP3A4 metabolises the largest proportion of drugs; other important isoenzymes include CYP2D6, CYP2C9, CYP2C19, and CYP1A2.

13. Distinguish enzyme inducers from enzyme inhibitors and give the effect on a substrate drug's plasma level.

    Enzyme inducers increase CYP450 activity (over days–weeks), accelerating substrate metabolism and lowering its plasma concentration/effect. Enzyme inhibitors reduce CYP450 activity (often rapidly), slowing substrate metabolism and raising its plasma concentration, risking toxicity.

14. List common CYP450 enzyme inducers (use the PC BRAS mnemonic).

    PC BRAS: Phenytoin, Carbamazepine, Barbiturates, Rifampicin, Alcohol (chronic), Sulphonylureas/St John's Wort. Also griseofulvin and smoking (CYP1A2). These lower plasma levels of co-administered substrate drugs (e.g. reduced warfarin and contraceptive efficacy).

15. List common CYP450 enzyme inhibitors (use the AO DEVICES / SICKFACES.COM mnemonic).

    Common inhibitors: Sodium valproate, Isoniazid, Cimetidine, Ketoconazole (and other -azoles), Fluconazole/Fluoxetine, Alcohol (acute/binge), Chloramphenicol, Erythromycin/clarithromycin (macrolides), Sulphonamides, Ciprofloxacin, Omeprazole, Metronidazole, and grapefruit juice. They raise plasma levels of substrate drugs.

16. Define clearance ($CL$) and give the relationship between clearance, volume of distribution, and elimination rate constant.

    Clearance is the volume of plasma completely cleared of drug per unit time (e.g. mL/min). $$CL = k_e \times V_d$$ where $k_e$ is the elimination rate constant. Total body clearance is the sum of hepatic, renal and other organ clearances: $CL_{total} = CL_{hepatic} + CL_{renal} + \ldots$

17. Distinguish zero-order from first-order elimination kinetics.

    First-order: a constant fraction of drug is eliminated per unit time; rate is proportional to concentration; half-life is constant. Zero-order (saturation/Michaelis–Menten): a constant amount is eliminated per unit time because enzymes are saturated; rate is independent of concentration; half-life is not constant. Examples of zero-order: ethanol, phenytoin (at therapeutic doses), high-dose aspirin.

18. Define elimination half-life ($t_{1/2}$) and give its relationship to $k_e$ and to $V_d$ and $CL$.

    The half-life is the time for plasma concentration to fall by 50%. $$t_{1/2} = \frac{0.693}{k_e} = \frac{0.693 \times V_d}{CL}$$ where $0.693 = \ln 2$. It applies to first-order kinetics.

19. How many half-lives are needed to reach steady state and to eliminate a drug from the body?

    Approximately 4–5 half-lives are needed to reach steady state on regular dosing (94–97% of steady state) and likewise ~4–5 half-lives for a drug to be essentially eliminated after stopping. A loading dose can achieve therapeutic levels faster.

20. Give the formula for a loading dose and for a maintenance dose at steady state.

    Loading dose: $$LD = \frac{C_{target} \times V_d}{F}$$ Maintenance dose rate: $$MD = \frac{C_{ss} \times CL}{F}$$ where $C_{target}/C_{ss}$ is the desired (steady-state) plasma concentration, $V_d$ volume of distribution, $CL$ clearance and $F$ bioavailability.

21. What is the structure of renal drug excretion (the three processes)?

    Renal handling involves: (1) glomerular filtration of free drug; (2) active tubular secretion (e.g. via OAT/OCT transporters in the proximal tubule); and (3) passive tubular reabsorption (favoured for non-ionised, lipid-soluble drug). Net renal excretion = filtration + secretion − reabsorption.

22. How can urinary pH be manipulated to enhance elimination of acidic versus basic drugs in overdose?

    Ion trapping: alkalinising the urine (e.g. with sodium bicarbonate) ionises weak acids, reducing their reabsorption and enhancing excretion — used for aspirin/salicylate overdose. Acidifying the urine would similarly trap weak bases. The ionised, water-soluble form cannot be reabsorbed and is excreted.

23. Define an agonist and an antagonist in drug–receptor interactions.

    An agonist binds a receptor and activates it to produce a biological response (it has affinity and intrinsic efficacy). An antagonist binds the receptor but produces no response itself (affinity but no efficacy); it blocks the action of agonists. A partial agonist produces a submaximal response even at full receptor occupancy.

24. Distinguish competitive from non-competitive (irreversible) antagonism, including effect on the agonist dose–response curve.

    Competitive antagonist binds reversibly to the same (orthosteric) site as the agonist; it shifts the agonist dose–response curve to the right (increased $EC_{50}$) but $E_{max}$ is unchanged and surmountable by more agonist. Non-competitive/irreversible antagonist binds irreversibly or to a separate site; it reduces $E_{max}$ and cannot be overcome by increasing agonist.

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