Pharmacology: Basic Principles

• Pharmacology is the study of drugs and their effects on living systems
• Pharmacology encompasses how drugs are absorbed, distributed, metabolized, and excreted (ADME), as well as their mechanisms of action and therapeutic and toxic effects

Basic Principles

• Pharmacokinetics describes what the body does to a drug, including absorption, distribution, metabolism, and excretion
• Pharmacodynamics describes what a drug does to the body, involving mechanisms of action and the relationship between drug concentration and effect
• Drugs interact with specific molecular targets such as receptors, enzymes, ion channels, and transporters in the body to produce effects
• The binding of a drug to its target can result in a cascade of events that ultimately lead to a physiological response
• The dose-response relationship describes the relationship between the dose of a drug and the magnitude of its effect
• Affinity is the measure of how tightly a drug binds to its receptor
• Efficacy refers to the maximum effect a drug can produce, while potency refers to the amount of drug needed to produce a given effect
• Agonists activate receptors, while antagonists block receptors from being activated

Pharmacokinetics

• Absorption is the process by which a drug enters the bloodstream from its site of administration
• Factors affecting absorption include the route of administration, the drug's formulation, and physiological factors such as gastric emptying and intestinal motility
• Bioavailability refers to the fraction of an administered dose of a drug that reaches the systemic circulation unchanged
• Distribution is the process by which a drug is transported throughout the body
• Factors affecting distribution include blood flow, tissue permeability, and binding to plasma proteins
• Metabolism is the process by which a drug is chemically transformed in the body
• The liver is the primary site of drug metabolism, involving enzymes such as cytochrome P450s
• Prodrugs are inactive compounds that are metabolized into active drugs in the body
• Excretion is the process by which a drug is eliminated from the body
• The kidneys are the primary site of drug excretion, involving processes such as glomerular filtration, tubular secretion, and tubular reabsorption
• Clearance is a measure of the rate at which a drug is removed from the body
• Half-life is the time it takes for the plasma concentration of a drug to decrease by half

Pharmacodynamics

• Receptors are proteins that bind to drugs and mediate their effects
• Ligand-gated ion channels open or close in response to drug binding, altering ion flow across cell membranes
• G protein-coupled receptors (GPCRs) activate intracellular signaling pathways through G proteins
• Enzyme-linked receptors activate intracellular signaling pathways through phosphorylation
• Intracellular receptors are located in the cytoplasm or nucleus and regulate gene transcription
• Agonists bind to receptors and activate them, producing a pharmacological effect
• Antagonists bind to receptors and block them, preventing agonists from binding and producing an effect
• Competitive antagonists bind reversibly to the same site as the agonist, while noncompetitive antagonists bind irreversibly or to a different site
• Partial agonists produce a maximal effect that is less than that of a full agonist
• Inverse agonists bind to receptors and produce an effect opposite to that of an agonist
• Tolerance is a decrease in the response to a drug with repeated use
• Dependence is a state in which the body has adapted to the presence of a drug and experiences withdrawal symptoms upon discontinuation
• Additive effects occur when two drugs produce a combined effect that is equal to the sum of their individual effects
• Synergistic effects occur when two drugs produce a combined effect that is greater than the sum of their individual effects
• Antagonistic effects occur when two drugs produce a combined effect that is less than the sum of their individual effects

Drug Development

• Drug discovery involves identifying new drug targets and developing new drug candidates
• Preclinical studies involve testing drug candidates in vitro and in vivo to assess their safety and efficacy
• Clinical trials involve testing drug candidates in humans to assess their safety and efficacy
• Phase 1 clinical trials evaluate the safety and tolerability of a drug in a small number of healthy volunteers
• Phase 2 clinical trials evaluate the efficacy of a drug in a larger number of patients with the target disease
• Phase 3 clinical trials compare the efficacy and safety of a drug to existing treatments in a large number of patients with the target disease
• Phase 4 clinical trials are conducted after a drug has been approved to monitor its long-term safety and efficacy

Toxicology

• Toxicology is the study of the adverse effects of drugs and other chemicals on living systems
• Dose-response relationships are used to assess the toxicity of drugs and other chemicals
• The therapeutic index is a measure of the safety of a drug, calculated as the ratio of the toxic dose to the therapeutic dose
• Adverse drug reactions (ADRs) are unwanted or unexpected effects of drugs
• Allergic reactions are immune-mediated ADRs
• Idiosyncratic reactions are unpredictable ADRs that occur in a small percentage of patients
• Drug interactions can increase or decrease the toxicity of drugs
• Overdoses can result in serious toxicity and death