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General Pharmacology - BPT II Year (Paper V) - Complete Syllabus Notes

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1. Introduction and Definitions

• Medical Pharmacology - the science of substances used to prevent, diagnose, and treat disease
• Toxicology - the branch dealing with undesirable effects of chemicals on living systems
• Drug - any chemical substance that, when taken into a living organism, modifies one or more biological functions
• Pharmacokinetics - what the BODY does to the drug (absorption, distribution, metabolism, excretion - ADME)
• Pharmacodynamics - what the DRUG does to the body (mechanism of action, dose-response relationships)

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2. Classification of Drugs

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3. Sources of Drugs

1. Plants - morphine (opium poppy), digoxin (foxglove), atropine (deadly nightshade), quinine (cinchona bark), aspirin (willow bark)
2. Animals - insulin (porcine/bovine pancreas), heparin, thyroid hormones
3. Minerals/Inorganic - iron salts, lithium carbonate, magnesium sulfate, iodine
4. Microorganisms - penicillin (Penicillium mold), streptomycin (Streptomyces bacteria), cyclosporine
5. Synthetic/Semi-synthetic - most modern drugs; e.g., chloroquine, diazepam, omeprazole
6. Recombinant DNA technology (Biotechnology) - human insulin, erythropoietin, monoclonal antibodies (e.g., adalimumab)

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4. Routes of Drug Administration

A. Enteral (via GI tract)

B. Parenteral (bypasses GI tract)

C. Topical / Inhalational

Key concept: IV is the route of choice in emergencies because it achieves therapeutic plasma levels fastest.

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5. Distribution of Drugs

• Plasma protein binding - drugs bound to albumin (acidic drugs) or alpha-1-acid glycoprotein (basic drugs) are pharmacologically inactive and cannot cross membranes; only FREE drug is active
• Lipid solubility - highly lipophilic drugs penetrate cell membranes, CNS, and fat easily
• Tissue binding - some drugs accumulate in specific tissues (e.g., chloroquine in retina, tetracycline in bone)
• Blood-brain barrier (BBB) - restricts entry of hydrophilic or protein-bound drugs into CNS
• Placental barrier - many drugs cross the placenta (teratogenic risk)

Volume of Distribution (Vd)

Vd = Dose given / Plasma concentration

• Low Vd (e.g., heparin, warfarin) - drug stays in plasma (large, protein-bound)
• High Vd (e.g., chloroquine, digoxin) - drug distributes widely into tissues

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6. Metabolism (Biotransformation) of Drugs

Phase I Reactions (Modification)

• Oxidation, reduction, hydrolysis
• Catalyzed by cytochrome P450 (CYP) enzymes in liver microsomes
• Products may be active, inactive, or toxic
• Example: codeine → morphine (active); paracetamol → NAPQI (toxic)

Phase II Reactions (Conjugation)

• Attach endogenous molecules to Phase I products: glucuronic acid, sulfate, acetate, glycine
• Products are almost always inactive and more water-soluble
• Excreted in urine or bile

First-Pass Effect (Pre-systemic metabolism)

• Oral drugs absorbed from gut pass through liver before reaching systemic circulation
• Drugs with high first-pass effect have low oral bioavailability (e.g., morphine, GTN, lidocaine)

Enzyme Induction & Inhibition

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7. Excretion of Drugs

Renal Excretion (most common)

1. Glomerular filtration - free (unbound) drug is filtered; protein-bound drug is not
2. Active tubular secretion - energy-dependent; can secrete protein-bound drugs
3. Tubular reabsorption - lipophilic/un-ionized drugs are reabsorbed; ionization manipulations (urinary pH) affect this

pH trapping: Alkalinizing urine (sodium bicarbonate) enhances excretion of weak acids (e.g., aspirin, phenobarbital). Acidifying urine enhances excretion of weak bases (e.g., amphetamine).

Other Routes of Excretion

• Bile/Feces - large molecular weight drugs; some undergo enterohepatic circulation
• Lungs - volatile anaesthetics, alcohol
• Breast milk - risk of drug exposure to nursing infants
• Saliva, sweat, tears - minor routes

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8. Pharmacokinetics - Key Parameters

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9. Pharmacodynamics

Drug-Receptor Interaction

• Most drugs act by binding to specific receptors (proteins on cell surface or intracellularly)
• Agonist - binds receptor and activates it (produces response)
• Antagonist - binds receptor but does NOT activate it (blocks agonist)
  • Competitive antagonist - reversible; can be overcome with higher agonist dose
  • Non-competitive antagonist - irreversible or allosteric; cannot be overcome
• Partial agonist - binds and activates receptor but with less maximal effect than full agonist

Dose-Response Relationship

• Graded dose-response curve - increasing dose → increasing response (up to maximum)
• ED50 - dose producing 50% of maximal effect (potency measure)
• Emax - maximal effect possible (efficacy measure)
• Therapeutic index (TI) = TD50 / ED50 - higher TI = safer drug

Mechanisms of Drug Action

1. Acting on receptors (GPCRs, ion channels, enzyme-linked receptors, nuclear receptors)
2. Enzyme inhibition (e.g., ACE inhibitors, aspirin)
3. Ion channel blockade (e.g., local anaesthetics, calcium channel blockers)
4. Physical/chemical action (e.g., antacids, osmotic diuretics)

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10. Factors Modifying Drug Response

Patient-Related Factors

Drug-Related Factors

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11. Adverse Drug Effects

Classification (Rawlins & Thompson)

Specific Types of Adverse Effects

• Side effects - unwanted but pharmacologically predictable effects at therapeutic doses (e.g., dry mouth with atropine)
• Toxic effects - dose-dependent harmful effects (hepatotoxicity, nephrotoxicity, cardiotoxicity)
• Allergic (hypersensitivity) reactions - immune-mediated; Type I (anaphylaxis), Type II (cytotoxic), Type III (immune complex), Type IV (delayed/cell-mediated)
• Idiosyncratic reactions - genetically determined abnormal drug responses
• Teratogenicity - drug-induced fetal malformation (e.g., thalidomide, isotretinoin)
• Carcinogenicity - drug-induced cancer with long-term exposure (e.g., alkylating agents)
• Drug dependence/addiction - opioids, benzodiazepines, alcohol
• Drug interactions - pharmacokinetic (CYP-mediated) or pharmacodynamic (synergism, antagonism)

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