Pharmacology Chapter on Drug Excretion

Pharmacokinetics and Pharmacodynamics

• Pharmacokinetics studies the rate and concentration of a drug in the body, including onset, peak action time, and duration of action. This also determines the route and frequency of drug administration.
• Absorption is the drug's entry into the bloodstream via the biological membrane from the site of administration.
• Biopharmaceutics studies factors that influence the extent and rate of drug absorption and release from dosage forms.
• Factors affecting drug absorption include biological factors (passage through body membranes, site of absorption, presence of food and salts, and routes of administration) and physicochemical factors (lipid solubility, dissociation constant, pH, dissolution rate, viscosity, crystal form, and drug complexes/ionization).
• Pharmaceutical factors involve the various dosage forms and their physical nature (like aqueous solutions, suspensions, powders, tablets, and capsules).
• Bioavailability describes the rate and extent of a drug's absorption, calculated through amounts in various bodily fluids (blood, urine, etc.).
• Calculations like loading dose (Vd x TC / F) help determine drug dosage, where Vd is volume of distribution, TC is target plasma concentration, and F is bioavailability.
• Distribution involves the movement of the drug into various body fluids (intestinal fluid, transcellular fluids, fluids in the gastrointestinal tract, CSF, etc.)
• Distribution factors include plasma protein binding, redistribution, blood-brain barrier, and placental barrier.
• Metabolism, mainly in the liver, chemically alters the drug within the body. Other metabolic sites include the intestine, kidney, lung, and plasma.
• Drug metabolism involves phases 1 (like oxidation, reduction, and hydrolysis) and 2 (conjugation to form more excretable products). The pathways often include enzymes like CYP3A4/5, CYP2C19,2CYP2D6, CYP2C8/9, CYP2E1, and CYP1A1/2
• Factors affecting drug metabolism include age, sex, nutrition, disease conditions, and pregnancies. They are affected by the intestine and liver microflora.
• Excretion mainly occurs via the kidneys, skin, lungs, and the alimentary tract. Volatile drugs like chloroform are excreted through the lungs. Renal excretion involves glomerular filtration, tubular secretion (the process removing bound drugs), and passive diffusion. Factors like pH can impact these processes.
• Clearance is the rate of urinary excretion divided by the average plasma concentration. Biological half-life (t½) is the time taken for drug concentration to decrease by 50%.

Pharmacodynamics

• Pharmacodynamics studies the effects of drugs (biochemical and physiological) and their mechanisms of action.
• Drug action types include stimulation, irritation, depression, replacement, and bactericidal/cytotoxic effects.
• Sites of drug action can involve localized regions (e.g., topical anesthetics like lignocaine and procaine) or systemic effects after absorption (e.g., general anesthetics).
• Drug action modifications due to factors like age, sex, body size, species/racial differences, genetics, routes and time of administration, pathological conditions (renal, hepatic, gastrointestinal, head injury, congestive heart failure, hyperthyroidism), tolerance, drug resistance, and medications.
• Tolerance is when dosages need to be increased to get a response. Drug resistance is similar but applied to microorganisms. Tachyphylaxis is rapid tolerance development
• Types of drug combination effects include additive (when effects are in the same direction), synergistic (one drug enhances the action of another), and supraadditive (overall effect is greater than the sum of individual effects).
• Antagonism occurs when one drug diminishes another's effect, either through physical or chemical interactions. Used to treat drug poisoning in some situations
• Important concepts include relating drug structure (SAR) to its activity, dose-response relationships, mechanisms of drug action, receptors, receptor classifications (like ligand-gated ion channels and G-protein coupled receptors), affinity (drug binding to receptors), and intrinsic activity (pharmacological response from receptor interaction).