Pharmacology Study Notes - Concepts and Terminology

Pharmacology (notes by emalyn) Pharmacology is the scientific study of drugs and their interactions with living systems, encompassing how medications affect the body and how the body processes them. This comprehensive guide covers all major areas of a standard pharmacology course.​ General Pharmacology Fundamental Concepts and Terminology Pharmacology encompasses several key terms that form the foundation of drug therapy. Clinical pharmacology refers to the application of pharmacological principles in clinical practice, whilst a drug is any substance that alters physiological function when administered to a living organism. Prodrugs are inactive compounds that require metabolic conversion to become pharmacologically active, whilst orphan drugs are medications developed for rare diseases affecting small patient populations.​ Drug addiction refers to a psychological and physical dependence on a substance, characterised by compulsive drug-seeking behaviour. Drug dependence occurs when the body adapts to a drug's presence, leading to withdrawal symptoms upon discontinuation. Toxicology is the study of adverse effects of chemicals on living organisms, including drug overdoses and poisoning.​ Drug Sources and Nomenclature Drugs are derived from various sources including plants, animals, minerals, synthetic processes, and biotechnology. Each drug typically has three names: a chemical name describing its molecular structure, a generic (non-proprietary) name assigned by official bodies, and a brand name given by pharmaceutical companies.​ Pharmacokinetics Absorption Absorption describes how drugs enter the bloodstream from their site of administration. The drug transport process involves various mechanisms including passive diffusion, active transport, facilitated diffusion, and endocytosis. Bioavailability refers to the fraction of administered drug that reaches systemic circulation unchanged, and can be absolute (comparing different routes) or relative (comparing different formulations).​ Bioequivalence occurs when two drug products release the same amount of active ingredient at the same rate under similar conditions. Factors affecting absorption include drug formulation, route of administration, blood flow at absorption site, drug lipid solubility, pH at absorption site, and gastrointestinal motility.​ Distribution Distribution describes how drugs are transported throughout the body via bloodstream to various tissues and organs. Volume of distribution indicates the extent of drug distribution in body tissues. Factors affecting distribution include blood flow to tissues, protein binding (particularly to albumin), tissue permeability, and lipid solubility.​ Metabolism Metabolism (biotransformation) converts drugs into more water-soluble compounds for easier elimination. The liver is the primary site of drug metabolism, utilising cytochrome P450 enzymes for most drug transformations. Phase I reactions involve oxidation, reduction, or hydrolysis, whilst Phase II reactions involve conjugation with endogenous substances like glucuronic acid or sulphate.​ Excretion Excretion is the process by which drugs and metabolites are eliminated from the body. The kidneys are the primary route of drug excretion through glomerular filtration, active tubular secretion, and passive tubular reabsorption. Other routes include biliary excretion, pulmonary excretion (for volatile substances), and minor routes such as sweat, saliva, and breast milk.​ Plasma half-life (t½) is the time required for drug concentration in plasma to decrease by 50%. Clearance refers to the volume of plasma from which drug is completely removed per unit time, serving as a measure of drug elimination efficiency.​ Pharmacodynamics Mechanisms of Drug Action Pharmacodynamics examines how drugs produce their effects at the molecular and cellular level. Drugs generate biological responses by interacting with target molecules, including receptors, enzymes, ion channels, and carrier proteins. Drug affinity refers to the strength of binding between a drug and its receptor, whilst intrinsic activity describes the ability of a drug to activate a receptor once bound.​ Agonists and Antagonists Agonists are drugs that bind to receptors and activate them, producing a biological response. Full agonists produce maximal receptor activation, whilst partial agonists produce submaximal responses even at full receptor occupancy. Antagonists bind to receptors without activating them, preventing agonist binding and blocking responses.​ Competitive antagonists compete with agonists for the same binding site and their effects can be overcome by increasing agonist concentration. Non-competitive antagonists bind to different sites or irreversibly, and their effects cannot be overcome by increasing agonist concentration.​ Receptors and Classification The G-protein coupled receptor (GPCR) family represents the largest group of drug targets. These receptors transmit signals across cell membranes through G-proteins, initiating intracellular signalling cascades. Other receptor types include ligand-gated ion channels, enzyme-linked receptors, and nuclear receptors.​ Dose-Response Relationships The dose-response relationship describes the correlation between drug dose and magnitude of effect. Factors influencing drug response include age, body weight, gender, genetic factors, disease states, drug interactions, tolerance, and individual variation.​ Routes of Drug Administration Classification and Factors Routes of administration are classified as local (drug acts at site of application) or systemic (drug is absorbed into circulation). Factors governing route selection include desired onset of action, drug properties (stability, solubility), patient condition, and desired duration of action.​ Common routes include oral (convenient but subject to first-pass metabolism), intravenous (rapid onset, 100% bioavailability), intramuscular (reliable absorption), subcutaneous (sustained release possible), sublingual (bypasses first-pass metabolism), transdermal (continuous delivery), and inhalation (direct delivery to lungs). Each route offers specific advantages such as convenience, rapid onset, or bypassing hepatic metabolism, but also presents disadvantages including variable absorption, pain, or requirement for sterile technique.​ Drug Dosing Loading and Maintenance Doses A loading dose is a larger initial dose given to rapidly achieve therapeutic drug concentrations. Maintenance doses are smaller, regular doses given to maintain steady-state concentrations within the therapeutic range. Fixed-dose combinations contain two or more drugs in a single formulation to improve adherence and therapeutic outcomes.​ Drug Classification Systems By Pharmacological Effect Drugs are classified according to their primary therapeutic action. Analgesics relieve pain, anti-inflammatory drugs reduce inflammation, antihypertensives lower blood pressure, and anxiolytics reduce anxiety. This classification helps clinicians select appropriate therapies based on desired therapeutic outcomes.​ By Drug Action and Mechanism This classification focuses on how drugs produce their effects at the molecular level. For example, antihypertensive medications may work through different mechanisms such as ACE inhibition, calcium channel blockade, or beta-adrenergic receptor antagonism, despite sharing the same therapeutic goal.​ By Chemical Structure Drugs with similar chemical structures often share pharmacological properties. For instance, all sulphonamides contain a common sulphonamide group, whilst beta-lactam antibiotics share a beta-lactam ring structure. Structural variations within a class can affect potency, duration of action, and side effect profiles.​ By Molecular Targets This system groups drugs based on their primary molecular targets, such as specific receptors, enzymes, or ion channels. Drugs sharing the same target typically have similar mechanisms of action and are particularly useful during clinical trials and drug development.​ Autonomic Nervous System Pharmacology Sympathetic Nervous System Drugs Sympathomimetics (adrenergic agonists) mimic the effects of sympathetic nervous system activation. Alpha-1 agonists cause vasoconstriction and are used for nasal decongestion and hypotension. Beta-1 agonists increase heart rate and contractility, whilst beta-2 agonists cause bronchodilation and are used in asthma treatment.​ Sympatholytics (adrenergic antagonists) block sympathetic effects. Alpha-blockers reduce peripheral vascular resistance and are used for hypertension and benign prostatic hyperplasia. Beta-blockers reduce heart rate and blood pressure, used for hypertension, angina, and arrhythmias.​ Parasympathetic Nervous System Drugs Parasympathomimetics (cholinergic agonists) enhance parasympathetic activity, causing effects such as increased gastrointestinal motility, miosis, and bronchial secretions. Parasympatholytics (anticholinergics) block muscarinic receptors, causing effects including mydriasis, reduced secretions, bronchodilation, and reduced gastrointestinal motility.​ Cardiovascular System Pharmacology Antihypertensive Agents Multiple drug classes treat hypertension through different mechanisms. ACE inhibitors block angiotensin-converting enzyme, reducing angiotensin II formation and aldosterone secretion. Angiotensin receptor blockers (ARBs) directly block angiotensin II receptors. Calcium channel blockers prevent calcium entry into vascular smooth muscle and cardiac cells, causing vasodilation and reduced contractility.​ Diuretics reduce blood volume by increasing sodium and water excretion. Thiazide diuretics act on the distal tubule, loop diuretics act on the loop of Henle, and potassium-sparing diuretics preserve potassium whilst promoting sodium excretion.​ Anti-Anginal Drugs Nitrates cause venous and arterial vasodilation, reducing cardiac preload and oxygen demand. Beta-blockers reduce heart rate and contractility, decreasing oxygen consumption. Calcium channel blockers reduce afterload and may decrease heart rate, improving oxygen supply-demand balance.​ Antiarrhythmic Drugs These medications are classified into four classes based on mechanism. Class I agents block sodium channels, Class II agents are beta-blockers, Class III agents prolong action potential duration, and Class IV agents are calcium channel blockers.​ Heart Failure Medications ACE inhibitors and ARBs reduce afterload and prevent ventricular remodelling. Beta-blockers (despite negative inotropic effects) improve long-term outcomes. Diuretics reduce fluid overload. Digoxin increases contractility through inhibition of Na+/K+-ATPase.​ Anticoagulants and Antiplatelets Anticoagulants prevent clot formation. Warfarin inhibits vitamin K-dependent clotting factor synthesis. Heparins activate antithrombin III. Direct oral anticoagulants (DOACs) include direct thrombin inhibitors and factor Xa inhibitors.​ Antiplatelet agents prevent platelet aggregation. Aspirin irreversibly inhibits cyclooxygenase. Clopidogrel and related drugs block ADP receptors on platelets.​ Central Nervous System Pharmacology Sedatives and Hypnotics Benzodiazepines enhance GABA activity, producing anxiolytic, sedative, muscle relaxant, and anticonvulsant effects. Common examples include diazepam, lorazepam, and alprazolam. Side effects include sedation, cognitive impairment, and risk of dependence.​ Non-benzodiazepine hypnotics (Z-drugs) like zolpidem selectively target GABA-A receptors, promoting sleep with reduced muscle relaxant and anticonvulsant effects.​ Antipsychotic Drugs First-generation (typical) antipsychotics primarily block dopamine D2 receptors, treating positive symptoms of schizophrenia but causing extrapyramidal side effects. Second-generation (atypical) antipsychotics block both dopamine and serotonin receptors, with lower risk of extrapyramidal effects but increased metabolic side effects.​ Antidepressants Selective serotonin reuptake inhibitors (SSRIs) block serotonin reuptake, increasing synaptic serotonin levels. Examples include fluoxetine, sertraline, and paroxetine. Side effects include nausea, sexual dysfunction, and serotonin syndrome when combined with other serotonergic drugs.​ Tricyclic antidepressants (TCAs) block reuptake of norepinephrine and serotonin but have more anticholinergic side effects. Monoamine oxidase inhibitors (MAOIs) prevent breakdown of monoamine neurotransmitters but require dietary restrictions.​ Anticonvulsants These medications prevent or reduce seizure activity through various mechanisms. Phenytoin and carbamazepine block sodium channels. Valproic acid enhances GABA activity and blocks sodium channels. Newer agents like levetiracetam bind to synaptic vesicle protein SV2A.​ Drugs for Parkinson's Disease Levodopa (combined with carbidopa as Sinemet) increases central dopamine levels, providing symptomatic relief. Side effects include nausea, dyskinesia (in ~80% of patients), and cardiovascular effects including arrhythmias. Dopamine agonists like bromocriptine directly stimulate dopamine receptors. MAO-B inhibitors like selegiline prevent dopamine breakdown. Anticholinergics like benztropine reduce cholinergic overactivity.​ Opioid Analgesics Opioids bind to mu, kappa, and delta receptors, producing analgesia, euphoria, and respiratory depression. Examples include morphine, fentanyl, and codeine. Naloxone is an opioid antagonist used to reverse overdoses.​ Antimicrobial Agents Beta-Lactam Antibiotics Penicillins inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins. Categories include natural penicillins (penicillin G), aminopenicillins (amoxicillin), and anti-staphylococcal penicillins (methicillin). Cephalosporins are structurally related, classified into generations with varying spectra of activity.​ Aminoglycosides These bactericidal antibiotics bind to the 30S ribosomal subunit, inhibiting protein synthesis. Examples include gentamicin, tobramycin, and amikacin. Side effects include nephrotoxicity and ototoxicity.​ Tetracyclines Tetracyclines inhibit bacterial protein synthesis by binding to the 30S ribosomal subunit. They have broad-spectrum activity but are bacteriostatic. Side effects include photosensitivity and tooth discolouration in children.​ Macrolides Macrolides like erythromycin, azithromycin, and clarithromycin inhibit protein synthesis by binding to the 50S ribosomal subunit. They're used for respiratory infections and as alternatives for penicillin-allergic patients. QT prolongation is a significant side effect, particularly when combined with fluoroquinolones.​ Fluoroquinolones These broad-spectrum antibiotics inhibit bacterial DNA gyrase and topoisomerase IV. Examples include ciprofloxacin, levofloxacin, and moxifloxacin. Ciprofloxacin and pefloxacin inhibit cytochrome P450 1A2, potentially increasing toxicity of drugs like theophylline. Combination with NSAIDs increases seizure risk.​ Antifungal Agents Azoles (fluconazole, ketoconazole) inhibit fungal ergosterol synthesis. Polyenes (nystatin, amphotericin B) bind to ergosterol, creating pores in fungal membranes. Echinocandins inhibit cell wall synthesis.​ Antiviral Agents Antivirals target various stages of viral replication. Nucleoside reverse transcriptase inhibitors block HIV reverse transcriptase. Protease inhibitors prevent viral protein processing. Neuraminidase inhibitors block influenza virus release from infected cells.​ Endocrine System Pharmacology Antidiabetic Drugs Insulin preparations vary in onset and duration, used for type 1 diabetes and advanced type 2 diabetes. Biguanides (metformin) reduce hepatic glucose production and improve insulin sensitivity. Sulphonylureas stimulate insulin release from pancreatic beta cells. DPP-4 inhibitors and GLP-1 agonists enhance incretin effects, promoting insulin release and reducing glucagon.​ Thyroid Medications Levothyroxine replaces thyroid hormone in hypothyroidism. Antithyroid drugs like methimazole inhibit thyroid hormone synthesis in hyperthyroidism.​ Corticosteroids These hormones have anti-inflammatory and immunosuppressive effects. Glucocorticoids include hydrocortisone, prednisolone, and dexamethasone. Side effects include hyperglycaemia, osteoporosis, immunosuppression, and adrenal suppression with prolonged use.​ Gastrointestinal System Pharmacology Antiulcer Drugs Proton pump inhibitors (PPIs) irreversibly inhibit the H+/K+-ATPase pump, profoundly reducing gastric acid secretion. H2-receptor antagonists competitively block histamine H2 receptors, reducing acid secretion. Antacids neutralise existing stomach acid.​ Antiemetics These medications prevent nausea and vomiting through various mechanisms. 5-HT3 antagonists like ondansetron block serotonin receptors in the chemoreceptor trigger zone. Dopamine antagonists like metoclopramide block D2 receptors. Antihistamines and anticholinergics reduce vestibular input.​ Laxatives and Antidiarrhoeals Laxatives promote bowel movements through various mechanisms including bulk formation, osmotic effects, or stimulation of intestinal motility. Antidiarrhoeals like loperamide reduce intestinal motility by acting on opioid receptors in the gut.​ Renal System Pharmacology Diuretics Diuretics increase urine production by affecting renal tubular function. Loop diuretics (furosemide) act on the thick ascending limb of the loop of Henle, producing potent diuresis. Thiazides act on the distal convoluted tubule with moderate efficacy. Potassium-sparing diuretics (spironolactone, amiloride) act on the collecting duct, preserving potassium.​ Respiratory System Pharmacology Bronchodilators Beta-2 agonists relax bronchial smooth muscle through cAMP-mediated mechanisms. Short-acting beta agonists (SABAs) like salbutamol provide quick relief. Long-acting beta agonists (LABAs) like salmeterol provide sustained bronchodilation. Anticholinergics like ipratropium block muscarinic receptors, reducing bronchoconstriction.​ Anti-Inflammatory Agents Inhaled corticosteroids reduce airway inflammation in asthma and COPD. Leukotriene modifiers block inflammatory mediators. Mast cell stabilisers prevent mediator release from mast cells.​ Cancer Chemotherapy Alkylating Agents These drugs form covalent bonds with DNA, preventing replication. Examples include cyclophosphamide and cisplatin. Side effects include bone marrow suppression and secondary malignancies.​ Antimetabolites These drugs interfere with DNA synthesis by mimicking normal metabolites. Methotrexate inhibits dihydrofolate reductase. 5-fluorouracil interferes with thymidylate synthesis.​ Natural Products Plant-derived agents include vinca alkaloids (vincristine, vinblastine) that disrupt microtubules, and taxanes (paclitaxel) that stabilise microtubules. Anthracyclines (doxorubicin) intercalate DNA and generate free radicals.​ Targeted Therapies Monoclonal antibodies target specific proteins on cancer cells. Tyrosine kinase inhibitors block signalling pathways driving cancer growth.​ Drug Interactions Pharmacokinetic Interactions These interactions affect drug absorption, distribution, metabolism, or excretion. Enzyme induction increases drug metabolism, reducing effectiveness—for example, rifampicin induces cytochrome P450 enzymes, reducing levels of many drugs including oral contraceptives. Enzyme inhibition decreases drug metabolism, potentially causing toxicity—for instance, clarithromycin inhibits CYP3A4, increasing ciclosporin levels and nephrotoxicity risk.​ Drugs competing for protein binding can displace each other, increasing free drug concentrations. Absorption interactions occur when drugs chelate (tetracyclines with calcium) or alter gastric pH.​ Pharmacodynamic Interactions These interactions occur when drugs with similar or opposing effects are combined. Synergistic interactions produce effects greater than the sum of individual effects. Additive interactions produce combined effects equal to the sum. Antagonistic interactions produce opposing effects.​ Examples include NSAIDs combined with glucocorticoids increasing gastric bleeding risk, ACE inhibitors with potassium-sparing diuretics causing dangerous hyperkalaemia, and SSRIs with triptans potentially causing serotonin syndrome. Fluoroquinolones combined with macrolides can prolong the QT interval, increasing risk of torsade de pointes arrhythmia.​ Adverse Drug Effects Types of Adverse Effects Adverse effects range from predictable, dose-dependent effects to unpredictable idiosyncratic reactions. Type A reactions are dose-dependent and predictable based on pharmacology. Type B reactions are idiosyncratic, unpredictable, and not dose-dependent.​ Risk Factors Patient factors increasing adverse effect risk include age extremes, polypharmacy (particularly in elderly patients who average 5 drugs), genetic variations, renal or hepatic impairment, and pregnancy. Drug factors include narrow therapeutic index, steep dose-response curves, and extensive protein binding.​ Pharmacogenetics Genetic variations affect drug response, metabolism, and toxicity. Cytochrome P450 polymorphisms create poor, intermediate, extensive, or ultrarapid metabolisers. CYP2D6 variations affect codeine activation to morphine and tamoxifen activation to endoxifen—CYP2D6 inhibition by SSRIs is associated with increased breast cancer mortality in tamoxifen-treated patients.​ Clinical Pharmacy Clinical pharmacy involves direct patient care to optimise medication therapy. Responsibilities include medication therapy management, monitoring for adverse effects and interactions, patient education, therapeutic drug monitoring, and participation in healthcare teams. The essential medicines list identifies drugs meeting priority healthcare needs, emphasising efficacy, safety, and cost-effectiveness.​ This comprehensive coverage addresses all major pharmacology topics essential for medical and healthcare professional training, providing a solid foundation for understanding drug therapy principles and clinical applications.