Pharmacology for Medical Graduates

1. Pharmacokinetics: What the Body Does to Drugs

Pharmacokinetics: It means the movement of drug within the body; it includes the processes of absorption (A), distribution (D), metabolism (M) and excretion (E).

Drug movement. Pharmacokinetics describes how a drug moves through the body from administration to elimination. It involves four key processes: absorption from the site of administration into the bloodstream, distribution to various tissues and organs, metabolism (biotransformation) into metabolites, and excretion from the body, primarily via the kidneys or liver. These processes determine the drug concentration at its site of action over time.

Crossing membranes. Drugs must cross biological membranes, primarily lipid bilayers, via mechanisms like passive diffusion (for lipid-soluble drugs), active transport (requiring energy), facilitated diffusion (carrier-mediated), filtration (size-dependent), or endocytosis. Factors like drug solubility, ionization state (pH-dependent), particle size, and formulation influence absorption and distribution. Bioavailability, the fraction reaching systemic circulation, is crucial, especially considering first-pass metabolism in the gut wall and liver.

Elimination pathways. Metabolism, mainly in the liver by microsomal (e.g., cytochrome P450 enzymes) and nonmicrosomal enzymes, converts drugs into more water-soluble forms for easier excretion. This process can be affected by age, diet, disease, genetics (pharmacogenetics), and drug interactions (enzyme induction/inhibition). Excretion primarily occurs via the kidneys (glomerular filtration, tubular secretion/reabsorption), but also through lungs, bile, feces, sweat, saliva, and milk. Plasma half-life and clearance are key parameters determining dosing frequency and duration of action.

2. Pharmacodynamics: How Drugs Act on the Body

Pharmacodynamics: It is the study of drugs – their mechanism of action, pharmacological actions and their adverse effects.

Drug-receptor interaction. Pharmacodynamics explores how drugs exert their effects on the body, focusing on their mechanism of action. Most drugs act by binding to specific receptors, which are macromolecules on cell surfaces or intracellularly. This binding initiates a cascade of events leading to a cellular response. Key concepts include affinity (drug's ability to bind) and intrinsic activity (drug's ability to produce an effect after binding).

Agonists and antagonists. Drugs can be agonists (bind and activate receptors, having both affinity and intrinsic activity), antagonists (bind but do not activate, blocking agonist action, having affinity but no intrinsic activity), partial agonists (bind and partially activate), or inverse agonists (bind and produce opposite effects). Receptors belong to families like ligand-gated ion channels (fastest response), G protein-coupled receptors (using second messengers), enzyme-linked receptors, and nuclear receptors (regulating gene expression).

Dose-response relationship. The magnitude of a drug's effect is related to its concentration at the site of action, described by dose-response curves. Potency refers to the amount of drug needed for a given effect, while efficacy is the maximum effect a drug can produce. Drug effects can be stimulation, depression, irritation, cytotoxic, or replacement. Combined drug effects can be additive, synergistic (greater than sum), or antagonistic (reduced effect). Factors like age, weight, sex, genetics, and disease states can modify drug action.

3. Drug Safety: Understanding Adverse Effects & Interactions

Adverse effect is defined as any undesirable or unwanted effect of a drug.

Predictable vs. unpredictable. Adverse drug reactions (ADRs) are harmful responses occurring at normal doses. They are classified as predictable (Type A), related to the drug's pharmacology (side effects, secondary effects, toxic effects from overdose/chronic use), or unpredictable (Type B), not dose-related (allergy, idiosyncrasy). Drug allergy is an immune-mediated abnormal response, categorized into four types (I-IV hypersensitivity reactions), ranging from urticaria to anaphylactic shock. Idiosyncrasy is a genetically determined abnormal reaction.

Serious adverse events. Beyond common side effects, drugs can cause serious issues.

• Teratogenicity: Causing birth defects if taken during pregnancy.
• Carcinogenicity/Mutagenicity: Inducing cancer or genetic damage.
• Organ Toxicity: Damaging specific organs (e.g., hepatotoxicity, nephrotoxicity, ototoxicity).
• Drug Dependence: Leading to psychological or physical dependence with withdrawal symptoms upon cessation.
• Iatrogenic Diseases: Physician-induced conditions resulting from drug therapy.

Drug interactions. When multiple drugs are used, their effects can be altered. Interactions can be pharmaceutical (incompatibility outside the body), pharmacokinetic (one drug alters another's ADME), or pharmacodynamic (drugs interact at receptors or physiological systems). Pharmacokinetic interactions include altered absorption (e.g., antacids reducing tetracycline uptake), distribution (e.g., warfarin displacement from protein binding), metabolism (enzyme induction/inhibition), or excretion (e.g., probenecid delaying penicillin excretion). Pharmacodynamic interactions can be beneficial (synergy) or harmful (antagonism, increased toxicity).

4. Autonomic Drugs: Controlling the Body's Automatic Functions

Acetylcholine (ACh) is the neurotransmitter in the cholinergic system.

Autonomic nervous system. The autonomic nervous system (ANS) regulates involuntary functions like heart rate, digestion, and respiration, divided into sympathetic (fight-or-flight) and parasympathetic (rest-and-digest) divisions. Drugs targeting the ANS mimic or block the actions of its neurotransmitters, primarily acetylcholine (ACh) and noradrenaline (NA). Cholinergic drugs affect ACh signaling, while adrenergic drugs affect NA signaling.

Cholinergic agents. Cholinergic agonists (cholinomimetics) either directly stimulate muscarinic (M1-M5) or nicotinic (NN, NM) receptors (e.g., pilocarpine) or indirectly increase ACh levels by inhibiting cholinesterase enzymes (anticholinesterases like neostigmine).

• Muscarinic effects: Decreased heart rate, increased GI/urinary motility, increased secretions, miosis.
• Nicotinic effects: Ganglionic stimulation, skeletal muscle contraction.
  Anticholinesterases are used in myasthenia gravis, glaucoma, and to reverse neuromuscular blockade. Anticholinergic agents (antimuscarinics like atropine) block ACh at muscarinic receptors, causing opposite effects (e.g., increased heart rate, decreased secretions, mydriasis).

Adrenergic agents. Adrenergic agonists (sympathomimetics) stimulate adrenergic receptors (alpha-1, alpha-2, beta-1, beta-2, beta-3). Direct agonists (e.g., adrenaline, salbutamol) bind directly to receptors. Indirect agonists (e.g., amphetamine) release NA. Mixed agonists (e.g., ephedrine) do both.

• Alpha-1: Vasoconstriction, mydriasis.
• Alpha-2: Inhibits NA release (presynaptic), vasoconstriction (postsynaptic).
• Beta-1: Increased heart rate/contractility, renin release.
• Beta-2: Bronchodilation, vasodilation, uterine relaxation.
  Adrenergic agonists are used in anaphylaxis, asthma, shock, and nasal congestion. Adrenergic receptor blockers (alpha-blockers like prazosin, beta-blockers like propranolol) block these effects, used in hypertension, angina, arrhythmias, and benign prostatic hyperplasia.

5. Cardiovascular Drugs: Managing Heart & Blood Vessel Conditions

Hypertension is a common cardiovascular disease affecting worldwide population.

Hypertension management. Antihypertensive drugs lower elevated blood pressure, reducing the risk of damage to vital organs. Major classes include:

• Diuretics (thiazides, loop diuretics): Reduce blood volume and peripheral resistance.
• ACE inhibitors/ARBs: Block the renin-angiotensin system, causing vasodilation and reduced aldosterone.
• Calcium Channel Blockers (CCBs): Cause vasodilation and reduce cardiac contractility/rate.
• Beta-blockers: Reduce heart rate, contractility, and renin release.
• Alpha-blockers: Cause vasodilation.
• Central sympatholytics (clonidine): Reduce sympathetic outflow.
• Vasodilators (nitrates, hydralazine): Directly relax blood vessels.
  Combination therapy is often needed, tailored to patient factors and comorbidities (e.g., ACEIs/ARBs in diabetes, beta-blockers in angina/post-MI). Hypertensive emergencies require rapid-acting intravenous agents.

Angina and MI. Antianginal drugs restore the balance between myocardial oxygen supply and demand.

• Nitrates (nitroglycerin): Primarily venodilators, reducing preload and coronary vasospasm.
• Beta-blockers: Reduce heart rate and contractility, decreasing oxygen demand.
• CCBs: Cause vasodilation, reducing afterload and coronary spasm, some reduce heart rate.
  Acute MI management involves antiplatelets (aspirin, clopidogrel), analgesics (morphine), nitrates, beta-blockers, ACEIs/ARBs, statins, and reperfusion therapy (fibrinolytics or PCI).

Congestive cardiac failure. Drugs for CHF improve cardiac function and reduce symptoms.

• Diuretics: Reduce fluid overload (preload).
• Vasodilators (ACEIs, ARBs, nitrates, hydralazine): Reduce preload and/or afterload.
• Beta-blockers (carvedilol, metoprolol): Improve long-term outcomes by blocking sympathetic overactivity.
• Cardiac glycosides (digoxin): Increase contractility (positive inotropic effect), slow heart rate in atrial fibrillation.
• Sympathomimetics (dobutamine, dopamine): Increase contractility in acute failure.
• Aldosterone antagonists (spironolactone): Reduce fluid retention and improve survival.

6. CNS Drugs: Modulating Brain & Nerve Activity

Analgesics are drugs that relieve pain without significantly altering consciousness.

Pain management. Analgesics are classified as opioid (narcotic) or nonopioid (NSAIDs). Opioid analgesics (e.g., morphine) act on opioid receptors in the CNS and periphery, providing potent pain relief but carrying risks of respiratory depression, dependence, and other side effects. They are used for moderate to severe pain. NSAIDs (e.g., aspirin, ibuprofen) inhibit prostaglandin synthesis, effective for mild to moderate pain, inflammation, and fever, but can cause GI, renal, and cardiovascular issues.

Sedation and sleep. Sedatives reduce excitement, while hypnotics induce sleep. Benzodiazepines (BZDs) enhance GABA activity, used for anxiety, insomnia, seizures, and muscle spasms, with a wider safety margin than older barbiturates. Nonbenzodiazepine hypnotics (e.g., zolpidem) are more selective for sleep induction.

Epilepsy treatment. Antiepileptic drugs control seizures by various mechanisms: blocking sodium channels (phenytoin, carbamazepine), enhancing GABA activity (phenobarbitone, BZDs, valproate), blocking calcium channels (ethosuximide, valproate), or other mechanisms (lamotrigine, topiramate). Selection depends on seizure type and patient factors. Status epilepticus is a medical emergency treated with intravenous BZDs, phenytoin, or phenobarbitone.

Other CNS conditions. Drugs also target specific neurological and psychiatric disorders.

• Parkinsonism: Treated with levodopa (dopamine precursor), dopamine agonists, MAO/COMT inhibitors (enhancing dopamine), or anticholinergics (reducing cholinergic overactivity).
• Psychoses (schizophrenia, mania): Managed with antipsychotics (neuroleptics) that block dopamine and/or serotonin receptors, classified as conventional or atypical.
• Anxiety: Treated with BZDs (acute) or SSRIs/SNRIs (chronic), buspirone, or beta-blockers.
• Depression: Treated with antidepressants like TCAs, SSRIs, SNRIs, or atypical agents, primarily by increasing monoamine levels (serotonin, norepinephrine, dopamine).

7. Endocrine Drugs: Regulating Hormonal Balance

Hormone is a substance produced by specialized cells in specific glands and transported to a distance where it acts on target tissues.

Hormone replacement. Endocrine pharmacology involves using hormones or their analogues for replacement therapy when endogenous production is deficient (e.g., insulin in type 1 diabetes, levothyroxine in hypothyroidism, testosterone in hypogonadism, hydrocortisone in adrenal insufficiency). Hormones act via cell surface, cytoplasmic, or nuclear receptors, regulating cellular processes and protein synthesis.

Modulating hormone action. Drugs can also modulate hormone activity.

• Antagonists: Block hormone receptors (e.g., antiandrogens, antioestrogens, mifepristone blocking progesterone/glucocorticoid receptors).
• Synthesis Inhibitors: Block hormone production (e.g., antithyroid drugs like thioamides, aromatase inhibitors blocking oestrogen synthesis, ketoconazole blocking steroid synthesis).
• Receptor Modulators: Have tissue-selective agonist/antagonist effects (e.g., SERMs like tamoxifen).
• Analogues: Synthetic versions with altered properties (e.g., GnRH analogues, long-acting insulin analogues).

Key endocrine conditions.

• Diabetes Mellitus: Type 1 requires insulin. Type 2 is managed with oral antidiabetics (sulfonylureas, biguanides, incretins, SGLT-2 inhibitors) or insulin, aiming to control blood glucose.
• Thyroid Disorders: Hypothyroidism treated with levothyroxine. Hyperthyroidism managed with antithyroid drugs (thioamides, iodine, radioactive iodine) or surgery.
• Adrenal Disorders: Adrenal insufficiency treated with hydrocortisone/fludrocortisone. Hypercortisolism (Cushing's) managed with surgery, radiation, or synthesis inhibitors/antagonists.
• Sex Hormone Disorders: Managed with sex hormones, antagonists, or modulators for conditions like infertility, contraception, HRT, prostate/breast cancer, and benign prostatic hyperplasia.
• Calcium Disorders: Regulated by PTH, vitamin D, calcitonin. Managed with calcium salts, vitamin D analogues, bisphosphonates, or calcimimetics for conditions like hypocalcemia, osteoporosis, Paget's disease, and hypercalcemia.

8. Antimicrobials: Fighting Infections Effectively

Chemotherapy is the treatment of infectious diseases or malignancy with drugs which destroy microorganisms or cancer cells preferentially with minimal damage to host tissues.

Selective toxicity. Antimicrobial agents (AMAs) target specific features of microorganisms not present in host cells, achieving selective toxicity. They are classified by action (bactericidal/bacteriostatic), spectrum (narrow/broad), or mechanism (inhibiting cell wall synthesis, protein synthesis, nucleic acid function, or acting as antimetabolites).

Mechanisms of action.

• Cell Wall Synthesis Inhibitors: Beta-lactams (penicillins, cephalosporins, carbapenems, monobactams) and glycopeptides (vancomycin) weaken the bacterial cell wall, leading to lysis.
• Protein Synthesis Inhibitors: Aminoglycosides (bactericidal) and others like tetracyclines, macrolides,
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Last updated: May 16, 2025