Pharmacology: Basic Principles

• Pharmacology is the study of drugs and their effects on living systems.
• It encompasses how drugs interact with biological systems, their mechanisms of action, therapeutic uses, and adverse effects.

Basic Principles

• Pharmacokinetics describes what the body does to the drug (absorption, distribution, metabolism, excretion).
• Pharmacodynamics describes what the drug does to the body (mechanism of action and effects).

Pharmacokinetics

• Absorption is the process by which a drug enters the bloodstream.
• Distribution refers to the movement of a drug from the bloodstream to various tissues and organs in the body.
• Metabolism (or biotransformation) is the process by which the body chemically modifies a drug.
• Excretion is the process by which a drug is removed from the body.

Absorption

• Routes of administration include oral, intravenous, intramuscular, subcutaneous, transdermal, and inhalation.
• Oral administration involves absorption from the gastrointestinal tract, subject to first-pass metabolism in the liver.
• Intravenous administration bypasses absorption, providing immediate and complete bioavailability.
• Bioavailability refers to the fraction of an administered dose of drug that reaches the systemic circulation.

Distribution

• Factors affecting distribution include blood flow, tissue permeability, protein binding, and tissue binding.
• The blood-brain barrier restricts the passage of many drugs into the central nervous system.
• Volume of distribution (Vd) is a theoretical volume representing the extent to which a drug distributes in the body.
• Plasma protein binding affects the distribution of a drug, as only unbound drugs can exert their effects.

Metabolism

• The liver is the primary site of drug metabolism.
• Phase I reactions (e.g., oxidation, reduction, hydrolysis) introduce or expose a functional group on the drug molecule.
• Phase II reactions (e.g., glucuronidation, sulfation, acetylation) conjugate the drug molecule with a polar molecule, increasing its water solubility and facilitating excretion.
• Cytochrome P450 (CYP) enzymes are a major family of enzymes involved in drug metabolism.
• Some drugs can induce (increase the activity of) or inhibit CYP enzymes, leading to drug interactions.

Excretion

• The kidneys are the primary site of drug excretion.
• Drugs can be excreted in the urine via glomerular filtration, tubular secretion, or tubular reabsorption.
• Biliary excretion involves the elimination of drugs in the feces.
• Clearance is a measure of the rate at which a drug is removed from the body.
• Half-life (t1/2) is the time it takes for the plasma concentration of a drug to decrease by 50%.

Pharmacodynamics

• Receptors are proteins that bind to drugs, initiating a biological response.
• Ligand-gated ion channels open or close in response to drug binding, altering ion flux across cell membranes.
• G protein-coupled receptors (GPCRs) activate intracellular signaling pathways via G proteins.
• Enzyme-linked receptors activate intracellular enzymes upon drug binding.
• Intracellular receptors regulate gene transcription.
• Agonists are drugs that bind to receptors and activate them, producing a biological effect.
• Antagonists are drugs that bind to receptors but do not activate them, blocking the effects of agonists.
• Potency refers to the amount of drug needed to produce a given effect.
• Efficacy refers to the maximum effect a drug can produce.
• The dose-response relationship describes the relationship between the dose of a drug and the magnitude of its effect.

Drug Safety

• Adverse drug reactions (ADRs) are unwanted or harmful effects of drugs.
• Side effects are predictable, dose-related effects that are not the primary therapeutic effect.
• Toxicity refers to severe ADRs that can be life-threatening.
• Allergic reactions are immune-mediated responses to drugs.
• Drug interactions occur when one drug affects the activity of another drug.
• Contraindications are situations in which a drug should not be used.
• Tolerance is a decreased response to a drug with repeated use.
• Dependence is a state in which the body has adapted to a drug, leading to withdrawal symptoms upon discontinuation.

Drug Development

• Preclinical studies involve in vitro and in vivo testing to assess drug safety and efficacy.
• Clinical trials involve testing drugs in humans to evaluate their safety and effectiveness.
• Phase I trials assess the safety and tolerability of a drug in a small number of healthy volunteers.
• Phase II trials evaluate the efficacy of a drug in patients with the target disease.
• Phase III trials are large, randomized controlled trials that compare the drug to standard treatments.
• Phase IV trials are post-marketing studies that monitor the long-term safety and effectiveness of a drug.