Overview
This lecture provides a comprehensive introduction to pharmacology, covering general principles (pharmacokinetics and pharmacodynamics), drug absorption, distribution, metabolism, elimination, various systems pharmacology, drug interactions, and key drug classes.
General Pharmacology: Pharmacokinetics and Pharmacodynamics
- Pharmacokinetics is what the body does to a drug: absorption, distribution, metabolism, and elimination (ADME).
- Absorption is drug passage through a membrane into the blood, e.g., gut, lung, mouth, skin, rectum.
- Distribution moves the drug from blood to tissues; free drug is active, protein-bound is inactive.
- Metabolism (biotransformation) changes drugs to active, inactive, or toxic forms, often in the liver.
- Elimination removes drugs through urine, bile, feces, sweat, or breath, mainly via the kidneys.
- Pharmacodynamics is what the drug does to the body, including binding to receptors (internal for lipid-soluble drugs, external for water-soluble drugs).
- Agonists activate receptors; antagonists block receptors with no effect; inverse agonists cause the opposite effect.
Drug Solubility and Administration
- Lipid-soluble drugs cross cell membranes easily but require protein carriers in blood; water-soluble drugs move freely in plasma but need membrane receptors.
- The route of administration depends on drug solubility, polarity, size, and charge.
- IV drugs do not require absorption; inhalation offers rapid absorption.
Factors Affecting Drug Action
- Small, lipid-soluble, and uncharged drugs diffuse faster through membranes.
- Absorption and diffusion increase with higher concentration gradients, surface area, and temperature, but decrease with larger size and thicker membranes.
- Passive transport (diffusion) requires no energy; active transport requires ATP.
- Carrier-mediated transport shows specificity, competition, and saturation (reaches Vmax).
Systemic Pharmacology Overview
Autonomic Pharmacology
- The autonomic nervous system includes sympathetic (fight/flight), parasympathetic (rest/digest), and enteric (gut) divisions.
- Sympathetic stimulates heart, dilates pupils, increases blood flow to muscles; parasympathetic promotes digestion and relaxation.
- Neurotransmitters: acetylcholine (cholinergic), norepinephrine (adrenergic).
Neuropharmacology
- Excitatory neurotransmitters: glutamate, aspartate; inhibitory: GABA, glycine.
- Sedatives (benzodiazepines, barbiturates) enhance GABA, causing neural inhibition.
- Opioids (e.g., morphine) inhibit neurons via potassium outflow, reducing pain.
Cardiac Pharmacology
- Cardiac drugs include anti-arrhythmics, antihypertensives, diuretics, anti-anginals, lipid-lowering agents, and inotropes.
- Example: Digoxin increases heart contractility by increasing intracellular calcium.
Endocrine Pharmacology
- Endocrine organs release hormones into blood or lymph; the hypothalamus and pituitary regulate endocrine glands.
- Hormone replacement therapy compensates for hormone deficiencies.
Chemotherapy
- Chemotherapeutic drugs can be cell cycle-specific (target S, G2, M phases) or non-specific.
- Side effects include hair loss, GI disturbances, and bone marrow suppression.
Toxicology
- Toxicology studies drug and toxin overdose, side effects, and management.
- Drugs with a narrow therapeutic window (e.g., digoxin, lithium, warfarin) are easy to overdose.
- Emergency management emphasizes Airway, Breathing, Circulation.
Ooids, Eicosanoids, and Autacoids
- Ooids and eicosanoids are local signaling molecules (paracrine/autocrine) derived from arachidonic acid (prostaglandins, leukotrienes).
- They regulate inflammation, coagulation, and other local processes.
Antimicrobials
- Antimicrobials include antibacterials, antifungals, antivirals, and antiparasitics.
- Antibiotics can be bactericidal (kill bacteria) or bacteriostatic (inhibit growth).
- Drug combinations can be synergistic, additive, or antagonistic.
Key Terms & Definitions
- Pharmacokinetics — study of drug movement through the body (ADME).
- Pharmacodynamics — study of drug effects on the body.
- Agonist — drug that activates a receptor to produce an effect.
- Antagonist — drug that blocks a receptor with no effect.
- Inverse agonist — drug that causes the opposite effect of an agonist.
- Lipid-soluble — dissolves in fats, crosses membranes easily.
- Water-soluble — dissolves in water, circulates freely in plasma.
- Therapeutic window — range between effective and toxic drug doses.
- Synergy — combined drug effect greater than the sum of individual effects.
Action Items / Next Steps
- Review pharmacokinetics and pharmacodynamics principles.
- Learn systemic pharmacology by organ system (autonomic, neuro, cardiac, endocrine, etc.).
- Study drug classes, mechanisms, and side effects for each system.
- Practice identifying drugs with a narrow therapeutic window and understand their management.
- Prepare for upcoming lectures by reviewing the physiology of relevant organ systems.