PHM 309 — Introduction to Pharmacology

• Describe the history and scope of pharmacology, the sources of drugs, and the nature and nomenclature of drugs. not yet covered
• Explain the molecular targets of drug action and the signal transduction mechanisms linked to each receptor family. not yet covered
• Analyse drug–receptor interactions quantitatively: concentration–response relationships, affinity and efficacy, types of antagonism, Schild analysis and radioligand binding. not yet covered
• Explain the mechanisms and consequences of receptor regulation, desensitisation and tolerance. not yet covered
• Describe the absorption, distribution, metabolism and excretion of drugs, and apply pharmacokinetic parameters to calculate and interpret dosing regimens. not yet covered
• Predict pharmacokinetic and pharmacodynamic drug interactions from their mechanisms. not yet covered
• Explain transmission in the somatic, autonomic and enteric nervous systems, and predict the effects of drugs acting at cholinergic, adrenergic, ganglionic, neuromuscular and NANC sites. not yet covered

Pharmacology

• Describe the history and scope of pharmacology, the sources of drugs, and the nature and nomenclature of drugs. not yet covered
• Explain the molecular targets of drug action and the signal transduction mechanisms linked to each receptor family. not yet covered
• Analyse drug–receptor interactions quantitatively: concentration–response relationships, affinity and efficacy, types of antagonism, Schild analysis and radioligand binding. not yet covered
• Explain the mechanisms and consequences of receptor regulation, desensitisation and tolerance. not yet covered
• Describe the absorption, distribution, metabolism and excretion of drugs, and apply pharmacokinetic parameters to calculate and interpret dosing regimens. not yet covered
• Predict pharmacokinetic and pharmacodynamic drug interactions from their mechanisms. not yet covered
• Explain transmission in the somatic, autonomic and enteric nervous systems, and predict the effects of drugs acting at cholinergic, adrenergic, ganglionic, neuromuscular and NANC sites. not yet covered

History and scope of pharmacology

• Outline the major milestones in the history of pharmacology, from materia medica and the isolation of active plant principles to the receptor concept (Langley, Ehrlich) and modern biologics. 14 questions
• Define pharmacology and distinguish its branches: pharmacodynamics, pharmacokinetics, pharmacotherapeutics, toxicology and pharmacogenomics. 12 questions
• Distinguish pharmacology from related disciplines (pharmaceutics, pharmacognosy, medicinal chemistry, clinical pharmacy). 10 questions

Sources, nature and nomenclature of drugs

• Identify the sources of drugs (plant, animal, mineral, microbial, synthetic and semi-synthetic, biotechnological) with at least one example of each, including medicines derived from plants used in Ghanaian traditional medicine. 16 questions
• Define drug, medicine, prodrug and placebo. 10 questions
• Describe the physical nature of drugs (state, molecular size, reactivity) and explain the significance of chirality and enantiomers for drug action. 17 questions
• Apply drug nomenclature correctly: chemical name, code name, generic (International Non-proprietary Name) and proprietary (brand) name; explain why generic prescribing is preferred. 13 questions

Overview of drug discovery, development and regulation

• Outline the stages of drug development: discovery, preclinical testing, clinical trial phases I–IV and post-marketing surveillance. 14 questions
• Describe the role of pharmacovigilance and of the national regulatory authority (Food and Drugs Authority, Ghana) in approving and monitoring medicines. 18 questions

Targets of drug action and drug–receptor interaction

• Name the four main classes of protein target (receptors, ion channels, enzymes, carriers/transporters) and give an example drug acting on each. 13 questions
• Distinguish drugs acting on specific targets from those acting by non-specific physicochemical mechanisms (e.g. antacids, osmotic diuretics, chelating agents). 15 questions
• Describe the forces involved in drug–receptor interaction (ionic, hydrogen, van der Waals, hydrophobic, covalent) and relate bond type to reversibility and duration of action. 5 questions
• Explain drug specificity, selectivity, structure–activity relationships and stereoselectivity. 12 questions

Receptor families and second-messenger effector systems

• Describe the four receptor superfamilies (ligand-gated ion channels, G protein-coupled receptors, kinase-linked receptors, nuclear receptors): structure, time scale of response and a prototype example of each. 15 questions
• Explain the G-protein cycle and the main effector pathways: Gs/Gi–adenylyl cyclase–cAMP–protein kinase A; Gq–phospholipase C–IP₃/DAG–Ca²⁺–protein kinase C; direct regulation of ion channels. 17 questions
• Describe the second messengers (cAMP, cGMP, IP₅, DAG, Ca²⁺, nitric oxide) and explain signal amplification. 14 questions

Relation between binding and response: affinity and efficacy

• Apply the law of mass action and occupancy theory (Hill–Langmuir equation) to relate drug concentration to receptor occupancy. 14 questions
• Define and distinguish affinity (KA/Kd), efficacy (intrinsic activity), potency (EC₅₀) and maximal effect (Emax). 13 questions
• Construct and interpret graded concentration–response curves (arithmetic and log scale) and quantal dose–response curves (ED₅₀, TD₅₀, LD₅₀, therapeutic index, margin of safety). 9 questions
• Distinguish full agonists, partial agonists, inverse agonists and neutral antagonists; explain constitutive receptor activity. 14 questions
• Explain spare receptors (receptor reserve) and their effect on agonist potency and on the action of irreversible antagonists. 11 questions

Agonists, antagonists and types of antagonism

• Classify antagonism: reversible competitive, irreversible (non-equilibrium) competitive, non-competitive, allosteric, chemical, pharmacokinetic and physiological (functional), with an example of each. 14 questions
• Predict the effect of each type of antagonist on an agonist concentration–response curve (parallel rightward shift versus depression of the maximum). 14 questions
• Explain the behaviour of a partial agonist given alone and in the presence of a full agonist. 9 questions

Quantitative analysis of antagonism and radioligand binding

• Define dose ratio and state the Schild equation (r – 1 = [B]/KB). 10 questions
• Construct a Schild plot, determine pA₂ and interpret a slope of unity as evidence of simple competitive antagonism. 11 questions
• Calculate dose ratio, KB or pA₂ from experimental data. 13 questions
• Describe saturation radioligand binding: total, non-specific and specific binding; derive Kd and Bmax; explain how non-specific binding is measured and why it is subtracted. 14 questions
• Describe competition binding experiments (IC₅₀) and the conversion of IC₅₀ to Ki (Cheng–Prusoff relationship). 11 questions

Receptor regulation, desensitisation and tolerance

• Define and distinguish desensitisation, tachyphylaxis and tolerance. 15 questions
• Describe the mechanisms of desensitisation: receptor uncoupling (phosphorylation by GRKs, PKA, PKC; β-arrestin binding), sequestration/internalisation, down-regulation and degradation, mediator depletion, increased drug metabolism and physiological adaptation. 14 questions
• Distinguish homologous from heterologous desensitisation, with examples. 8 questions
• Explain receptor up-regulation and supersensitivity (e.g. rebound after abrupt β-blocker withdrawal) and their clinical implications. 10 questions

Drug permeation and absorption

• Describe the mechanisms by which drugs cross membranes: passive diffusion, aqueous pores, carrier-mediated transport (SLC and ABC transporters, including P-glycoprotein) and endocytosis. 15 questions
• Apply the Henderson–Hasselbalch equation to predict the ionisation of weak acids and bases and explain ion trapping. 11 questions
• Compare the routes of drug administration (oral, sublingual, rectal, intravenous, intramuscular, subcutaneous, inhalational, topical, transdermal): advantages and limitations. 17 questions
• Explain the factors affecting oral absorption; define bioavailability, bioequivalence and first-pass metabolism. 17 questions

Drug distribution

• Describe body fluid compartments and the factors that determine drug distribution: blood flow, lipid solubility, plasma-protein and tissue binding, and barriers (blood–brain barrier, placenta). 16 questions
• Define apparent volume of distribution, calculate it (Vd = dose / C₀) and interpret large and small values. 12 questions
• Explain the clinical relevance of plasma-protein binding (albumin, α₁-acid glycoprotein) and of displacement interactions. 8 questions
• Describe redistribution as a determinant of the duration of action (e.g. thiopental). 11 questions

Drug metabolism (biotransformation)

• Describe phase I (oxidation, reduction, hydrolysis) and phase II (glucuronidation, sulfation, acetylation, glutathione conjugation, methylation) reactions and the properties of their products. 13 questions
• Explain the role of the cytochrome P450 system (CYP3A4, 2D6, 2C9, 2C19, 1A2) and name common enzyme inducers and inhibitors. 13 questions
• Explain the time course and consequences of enzyme induction and inhibition. 17 questions
• Describe prodrugs, and active and toxic metabolites (e.g. paracetamol and NAPQI). 20 questions
• Outline the effects of genetics (acetylator status, CYP2D6 polymorphism), age and liver disease on drug metabolism. 6 questions

Drug excretion

• Describe renal excretion: glomerular filtration, active tubular secretion and passive tubular reabsorption; explain the effect of urinary pH (e.g. urinary alkalinisation in salicylate poisoning). 18 questions
• Describe biliary excretion and enterohepatic circulation, and minor routes (lungs, breast milk). 15 questions
• Define renal clearance and relate it to glomerular filtration rate. 11 questions

Quantitative pharmacokinetics and dosing

• Define clearance, elimination rate constant, half-life (t½ = 0.693 × Vd / CL) and area under the curve. 14 questions
• Distinguish first-order from zero-order (saturation) kinetics, with examples (ethanol, phenytoin, high-dose aspirin). 11 questions
• Interpret plasma concentration–time curves for an intravenous bolus, an oral dose and a constant infusion using a one-compartment model. 15 questions
• Explain steady state, accumulation and the time to reach steady state (about 4–5 half-lives). 17 questions
• Calculate loading and maintenance doses from Vd, CL, target concentration, dosing interval and bioavailability. 13 questions
• Describe the principles of therapeutic drug monitoring and the significance of a narrow therapeutic index. 16 questions

Drug interactions

• Classify drug interactions as pharmaceutical, pharmacokinetic (absorption, distribution, metabolism, excretion) or pharmacodynamic (additive, synergistic, antagonistic). 12 questions
• Predict clinically important interactions from their mechanism (e.g. enzyme inducers with oral contraceptives, CYP inhibitors with warfarin, probenecid with penicillin). 14 questions

Organisation of the efferent nervous system

• Compare the somatic efferent, autonomic (sympathetic and parasympathetic) and enteric nervous systems: anatomy, transmitters and receptors at each junction. 14 questions
• Describe the effects of sympathetic and parasympathetic activation on the major effector organs (eye, heart, blood vessels, bronchi, gut, bladder, glands) and the concept of dominant tone. 22 questions
• Outline the steps of chemical neurotransmission, Dale's principle, co-transmission and presynaptic modulation. 14 questions

Ganglionic transmission and ganglion-blocking drugs

• Describe nicotinic (NN) transmission in autonomic ganglia. 9 questions
• Describe ganglion stimulants (nicotine) and blockers (hexamethonium, trimetaphan, mecamylamine), and predict their effects on each organ from its dominant autonomic tone. 19 questions

Cholinergic transmission and drugs

• Describe the synthesis (choline acetyltransferase), vesicular storage, release and hydrolysis (acetylcholinesterase, butyrylcholinesterase) of acetylcholine. 11 questions
• Identify the sites for drug action at the cholinergic synapse with an example drug for each: choline uptake (hemicholinium), vesicular storage (vesamicol), release (botulinum toxin), hydrolysis (reversible and irreversible anticholinesterases) and receptors. 11 questions
• Classify muscarinic receptors (M₁–M₅) by location, G-protein coupling, effector mechanism and function. 5 questions
• Describe muscarinic agonists (acetylcholine, methacholine, carbachol, bethanechol, pilocarpine): effects and uses. 19 questions
• Describe muscarinic antagonists (atropine, hyoscine, ipratropium, tropicamide, oxybutynin): effects, uses and adverse effects; recognise anticholinergic toxicity. 8 questions
• Describe organophosphate poisoning and its management with atropine and pralidoxime. 20 questions

Adrenergic transmission and drugs

• Describe noradrenaline synthesis (tyrosine hydroxylase as the rate-limiting step), vesicular storage (VMAT), release and inactivation (uptake 1/NET, uptake 2, MAO, COMT). 13 questions
• Identify pre- and post-junctional sites for drug action: α-methyltyrosine, reserpine, neuron-blocking drugs (guanethidine), α₂-autoreceptors, uptake inhibitors (cocaine, tricyclic antidepressants), and MAO and COMT inhibitors. 16 questions
• Explain false transmitters (methyldopa → α-methylnoradrenaline) and indirectly acting sympathomimetic amines (tyramine, amphetamine, ephedrine), including the tyramine–MAOI interaction. 18 questions
• Classify adrenoceptors (α₁, α₂, β₁, β₂, β₃) by location, G-protein coupling, second messenger and response. 17 questions
• Relate receptor selectivity to representative agonists (adrenaline, noradrenaline, isoprenaline, phenylephrine, clonidine, dobutamine, salbutamol) and antagonists (prazosin, phentolamine, propranolol, atenolol, labetalol) at an introductory level. 24 questions

Somatic efferent transmission: the neuromuscular junction

• Describe transmission at the skeletal neuromuscular junction (NM receptors, end-plate potential). 13 questions
• Distinguish non-depolarising (tubocurarine, atracurium, rocuronium) from depolarising (suxamethonium) neuromuscular blockers, including phase I and phase II block and reversal (anticholinesterases, sugammadex). 16 questions

Non-adrenergic, non-cholinergic (NANC) and purinergic transmission

• Define NANC transmission and co-transmission; give examples of NANC mediators (ATP, adenosine, nitric oxide, VIP, neuropeptide Y, substance P, CGRP) and the tissues in which they act. 12 questions
• Describe purinergic signalling: release and inactivation of ATP and adenosine; P1 (A₁, A₂A, A₂B, A₃) and P2 (P2X ionotropic, P2Y metabotropic) receptors. 13 questions
• Relate purinergic pharmacology to drugs in use: methylxanthines (caffeine, theophylline), adenosine, dipyridamole and P2Y₁₂ antagonists (clopidogrel). 17 questions
• Describe nitric oxide as a NANC transmitter (e.g. penile erection, gastrointestinal relaxation) and link it to PDE5 inhibitors. 15 questions

Integrative autonomic pharmacology and revision

• Predict the net response to autonomic drugs in organs with dual innervation, including baroreceptor reflex responses (e.g. reflex bradycardia with phenylephrine; adrenaline reversal by α-blockade). 20 questions
• Solve problem-based cases that integrate pharmacodynamic, pharmacokinetic and autonomic principles. 10 questions