Pharmacology: Basic Principles and Pharmacokinetics

• Pharmacology is the study of drugs and their effects on the body

Basic Principles

• Pharmacokinetics describes what the body does to a drug
• Pharmacodynamics describes what a drug does to the body
• Drugs can be derived from natural sources (e.g., plants, minerals) or synthesized
• Drugs produce effects by interacting with biological targets, such as receptors, enzymes, and ion channels

Pharmacokinetics

• Absorption is the process by which a drug enters the bloodstream
• Distribution is the process by which a drug spreads throughout the body
• Metabolism (or biotransformation) is the process by which the body chemically modifies a drug
• Excretion is the process by which the body eliminates a drug
• The main routes are oral, intravenous, intramuscular, subcutaneous, transdermal, and inhalation
• Bioavailability refers to the fraction of an administered dose of unchanged drug that reaches the systemic circulation
• Factors affecting absorption include: route of administration, drug formulation, and physiological factors (e.g., gastric emptying, intestinal motility)
• The blood-brain barrier (BBB) restricts the passage of many drugs into the central nervous system (CNS)
• The volume of distribution (Vd) relates the amount of drug in the body to the plasma concentration
• Drug metabolism primarily occurs in the liver, involving Phase I (e.g., oxidation, reduction, hydrolysis) and Phase II (conjugation) reactions
• Cytochrome P450 (CYP) enzymes are a major family of enzymes involved in drug metabolism
• Drug excretion primarily occurs through the kidneys, involving glomerular filtration, tubular secretion, and tubular reabsorption
• Half-life (t1/2) is the time required for the plasma concentration of a drug to decrease by 50%
• Clearance (CL) is the rate of drug elimination from the body relative to the drug concentration in plasma

Pharmacodynamics

• Receptors are proteins that bind drugs and mediate their effects
• Agonists activate receptors, producing a response
• Antagonists block receptors, preventing activation by agonists
• Affinity is the measure of how tightly a drug binds to a receptor
• Efficacy is the measure of a drug's ability to produce a response once bound to a receptor
• Potency refers to the amount of drug needed to produce a certain effect
• Dose-response curves illustrate the relationship between drug dose and effect
• The therapeutic index (TI) is the ratio of the toxic dose to the therapeutic dose, indicating drug safety
• Drug interactions can occur through pharmacokinetic or pharmacodynamic mechanisms
• Additive effects occur when the combined effect of two drugs equals the sum of their individual effects
• Synergistic effects occur when the combined effect of two drugs is greater than the sum of their individual effects
• Tolerance is the decreased response to a drug after repeated administration
• Dependence is the physiological or psychological need for a drug
• Withdrawal symptoms occur when a drug is discontinued after prolonged use

Autonomic Nervous System Pharmacology

• The autonomic nervous system (ANS) regulates involuntary functions
• The ANS has two main divisions: the sympathetic and parasympathetic nervous systems
• The sympathetic nervous system is responsible for the "fight or flight" response
• The parasympathetic nervous system is responsible for "rest and digest" functions
• Neurotransmitters: Acetylcholine (ACh), Norepinephrine (NE), Epinephrine (EPI)
• Cholinergic receptors bind acetylcholine and include nicotinic and muscarinic receptors
• Adrenergic receptors bind norepinephrine and epinephrine and include alpha (α) and beta (β) receptors
• Sympathomimetic drugs (adrenergic agonists) mimic the effects of sympathetic stimulation
• Sympatholytic drugs (adrenergic antagonists) block the effects of sympathetic stimulation
• Parasympathomimetic drugs (cholinergic agonists) mimic the effects of parasympathetic stimulation
• Parasympatholytic drugs (cholinergic antagonists) block the effects of parasympathetic stimulation

Central Nervous System Pharmacology

• The CNS includes the brain and spinal cord
• Neurotransmitters: Dopamine, Serotonin, GABA, Glutamate
• Dopamine is involved in reward, motivation, and motor control
• Serotonin is involved in mood, sleep, and appetite
• GABA is the primary inhibitory neurotransmitter in the brain
• Glutamate is the primary excitatory neurotransmitter in the brain
• Antidepressants: Selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs)
• Antipsychotics block dopamine receptors and are used to treat schizophrenia
• Anxiolytics reduce anxiety (e.g., benzodiazepines, SSRIs)
• Sedative-hypnotics promote relaxation and sleep (e.g., benzodiazepines, barbiturates)
• Opioid analgesics relieve pain by activating opioid receptors (e.g., morphine, codeine)
• General anesthetics induce a state of unconsciousness for surgical procedures

Cardiovascular Pharmacology

• Antihypertensives lower blood pressure (e.g., diuretics, ACE inhibitors, beta-blockers, calcium channel blockers)
• Antiarrhythmics regulate heart rhythm (e.g., sodium channel blockers, beta-blockers, potassium channel blockers, calcium channel blockers)
• Antianginals relieve chest pain (angina) by improving blood flow to the heart (e.g., nitrates, beta-blockers, calcium channel blockers)
• Heart failure medications improve heart function (e.g., ACE inhibitors, beta-blockers, diuretics, digoxin)
• Anticoagulants prevent blood clot formation (e.g., warfarin, heparin)
• Antiplatelet drugs inhibit platelet aggregation (e.g., aspirin, clopidogrel)
• Thrombolytics dissolve blood clots (e.g., tissue plasminogen activator (tPA))
• Lipid-lowering drugs reduce cholesterol levels (e.g., statins)

Endocrine Pharmacology

• Insulin lowers blood glucose levels and is used to treat diabetes
• Oral hypoglycemic agents (e.g., metformin, sulfonylureas) also lower blood glucose levels in type 2 diabetes
• Thyroid hormones (e.g., levothyroxine) replace or supplement thyroid hormone in hypothyroidism
• Glucocorticoids (e.g., prednisone) have anti-inflammatory and immunosuppressant effects
• Estrogens and progestins are used in hormone replacement therapy and contraception
• Androgens (e.g., testosterone) are used in hormone replacement therapy and to treat certain conditions

Anti-inflammatory and Immunopharmacology

• Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce inflammation, pain, and fever (e.g., ibuprofen, naproxen)
• Glucocorticoids (e.g., prednisone) are potent anti-inflammatory and immunosuppressant drugs
• Disease-modifying antirheumatic drugs (DMARDs) are used to treat autoimmune diseases (e.g., methotrexate)
• Immunosuppressants suppress the immune system to prevent organ rejection or treat autoimmune diseases (e.g., cyclosporine, azathioprine)

Antimicrobial Pharmacology

• Antibiotics kill or inhibit the growth of bacteria (e.g., penicillins, tetracyclines, macrolides)
• Antivirals inhibit the replication of viruses (e.g., acyclovir, oseltamivir)
• Antifungals kill or inhibit the growth of fungi (e.g., fluconazole, amphotericin B)
• Antiparasitics kill or inhibit the growth of parasites (e.g., metronidazole, chloroquine)

Toxicology

• Toxicology is the study of the adverse effects of chemicals on living organisms
• Dose-response relationship: The effect of a toxicant is related to the dose
• Exposure routes: Ingestion, inhalation, dermal absorption, injection
• Factors influencing toxicity: Dose, duration, route of exposure, individual susceptibility
• Mechanisms of toxicity: Cellular damage, enzyme inhibition, receptor interactions
• Treatment of poisoning: Activated charcoal, antidotes, supportive care

Explore the fundamental aspects of pharmacology, including pharmacokinetics and pharmacodynamics. Learn about drug sources, mechanisms of action, and how the body processes drugs through absorption, distribution, metabolism, and excretion. Discover routes of administration and bioavailability.