Pharmacology: Basic Principles

• Pharmacology is the study of how drugs interact with biological systems.
• It encompasses understanding the mechanisms of drug action, drug effects, and drug fate in the body.

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, therapeutic and toxic effects).
• Drug is any substance that brings about a change in biologic function through its chemical action.
• Receptor is the component of a cell or organism that interacts with a drug and initiates the chain of events leading to the drug's observed effects.
• Agonist is a drug that binds to a receptor and activates it, producing a response.
• Antagonist is a drug that binds to a receptor but does not activate it; it blocks the action of an agonist.
• Partial agonist is a drug that binds to a receptor and activates it, but produces a smaller response than a full agonist.
• Inverse agonist is a drug that binds to a receptor and produces an effect opposite to that of an agonist.

Pharmacokinetics: Absorption

• Absorption is the process by which a drug enters the bloodstream from its site of administration.
• Factors affecting absorption:
  • Route of administration
  • Drug formulation
  • Blood flow
  • Surface area
  • Drug properties (e.g., lipophilicity, ionization)
• Routes of administration:
  • Enteral: Oral, sublingual, rectal
  • Parenteral: Intravenous, intramuscular, subcutaneous
  • Other: Inhalation, transdermal, topical

Pharmacokinetics: Distribution

• Distribution is the process by which a drug reversibly leaves the bloodstream and enters the tissues and organs.
• Factors affecting distribution:
  • Blood flow
  • Tissue permeability
  • Binding to plasma proteins
  • Binding to tissue components
  • Volume of distribution (Vd): Vd = Dose / Plasma concentration

Pharmacokinetics: Metabolism

• Metabolism (biotransformation) is the process by which the body chemically modifies a drug.
• Primarily occurs in the liver.
• Enzymes involved: Cytochrome P450 (CYP) enzymes, Phase II enzymes (conjugation reactions)
• Prodrug: An inactive drug that is metabolized to an active form.
• First-pass effect: Metabolism of a drug before it reaches systemic circulation (e.g., oral drugs metabolized in the liver).

Pharmacokinetics: Excretion

• Excretion is the process by which the body eliminates a drug.
• Primarily occurs in the kidneys.
• Other routes: Bile, feces, lungs, sweat, saliva.
• Renal excretion involves:
  • Glomerular filtration
  • Tubular secretion
  • Tubular reabsorption
• Clearance: The volume of plasma from which a drug is completely removed per unit time.

Pharmacodynamics: Mechanisms of Action

• Drugs act by:
  • Binding to receptors
  • Interacting with enzymes
  • Interacting with ion channels
  • Interacting with transporters
  • Physical or chemical effects
• Receptor types:
  • Ligand-gated ion channels
  • G protein-coupled receptors (GPCRs)
  • Enzyme-linked receptors
  • Intracellular receptors
• Dose-response relationship: The relationship between the dose of a drug and the magnitude of its effect.
• Potency: The amount of drug required to produce a given effect.
• Efficacy: The maximum effect a drug can produce.
• Therapeutic index: A measure of drug safety; TD50/ED50 (TD50 = toxic dose in 50% of the population; ED50 = effective dose in 50% of the population).

Drug Interactions

• Drug interactions occur when the effects of one drug are altered by the presence of another drug, food, or environmental chemical.
• Types of drug interactions:
  • Pharmacokinetic: Affecting absorption, distribution, metabolism, or excretion.
  • Pharmacodynamic: Affecting the drug's mechanism of action or effect.
• Mechanisms of drug interactions:
  • Enzyme induction: Increased enzyme activity, leading to decreased drug levels.
  • Enzyme inhibition: Decreased enzyme activity, leading to increased drug levels.
  • Competition for binding sites
  • Additive, synergistic, or antagonistic effects

Adverse Drug Reactions

• Adverse drug reaction (ADR) is an unwanted or harmful reaction experienced following the administration of a drug or combination of drugs under normal conditions of use.
• Types of ADRs:
  • Type A (Augmented): Predictable, dose-dependent, related to the drug's mechanism of action.
  • Type B (Bizarre): Unpredictable, not dose-dependent, often related to immune reactions or genetic factors.
  • Type C (Chronic): Occur after prolonged use.
  • Type D (Delayed): Occur remote from the time of drug administration.
  • Type E (Ending of use): Occur upon withdrawal of the drug.
  • Type F (Failure): Unexpected failure of therapy

Specificity and Selectivity

• Specificity: A drug is specific if it affects only one type of cell.
• Selectivity: A drug is selective if it affects one type of cell more than others.

Tolerance and Dependence

• Tolerance: Decreased drug effect with repeated administration, requiring higher doses to achieve the same effect.
• Dependence: Physiological or psychological need for a drug.
  • Physical dependence: Withdrawal symptoms occur upon drug cessation.
  • Psychological dependence: Craving for the drug.

Drug Development

• Preclinical testing: Laboratory and animal studies to assess safety and efficacy.
• Clinical trials: Studies in humans to evaluate safety, efficacy, and dosage.
  • Phase 1: Safety and dosage in healthy volunteers.
  • Phase 2: Efficacy and side effects in a small group of patients.
  • Phase 3: Large-scale study to confirm efficacy, monitor side effects, and compare to other treatments.
  • Phase 4: Post-marketing surveillance to monitor long-term effects and identify rare adverse reactions.