Pharmacokinetics Overview Quiz

Pharmacokinetics Overview

• Pharmacokinetics is the quantitative study of drug movement in, through, and out of the body
• Intensity of effect depends on drug concentration at the site of action, which is determined by pharmacokinetic properties
• Important to determine route of administration, dose, onset of action, peak action time, duration of action, and frequency of dosing

ADME

• Absorption Absorption is transfer of a drug from its site of administration into the bloodstream
• Distribution Distribution is the passage of a drug from the circulation to the tissue and site of action
• Metabolism Metabolism is the chemical alteration of a drug in the body Aim to convert nonpolar lipid-soluble compounds to polar lipid-soluble compounds to prevent reabsorption in renal tubules
• Excretion Excretion is the elimination of drug or its metabolites from the body

Factors Affecting Drug Absorption

• Drug properties: lipid solubility, molecular weight, polarity
• Blood flow to the absorption site
• Total surface area available for absorption
• Contact time at the absorption surface
• Affinity with special tissue

Routes of Administration

• Topical: depends on lipid solubility; only lipid-soluble drugs penetrate intact skin
• Subcutaneous and intramuscular: drugs directly reach capillaries, pass through capillary endothelium, and reach circulation, faster and more predictable than oral absorption
• Oral: physical properties (physical state, lipid or water solubility), dosage forms (particle size, disintegration time and dissolution rate, formulation-biopharmaceutics), and physiological factors (ionization, pH effect, presence of food and other agents)

First Pass Metabolism

• Before drugs reach systemic circulation, they can be metabolized in the liver or intestine, reducing concentration in systemic circulation

Bioavailability (AUC)

• Bioavailability refers to the rate and extent of absorption of a drug from a dosage form. It is determined by concentration-time curve in blood or by its excretion in urine
• Measured by fraction (F) of administered dose of a drug that reaches systemic circulation unchanged
• Bioavailability of drug injected IV is 100%, but oral bioavailability may be lower due to incomplete absorption or first-pass metabolism in intestinal wall and/or liver

Volume of Distribution (Vd)

• Represents the apparent volume that would be required to contain all the drug in the body if the concentration were the same as in the plasma
• Affected by factors such as lipid solubility, pKa of the drug, affinity for different tissues, blood flow to tissues, disease states, and plasma protein binding

Redistribution

• Highly lipid-soluble drugs distribute to brain, heart, and kidney immediately, followed by muscle and fat tissues
• Redistribution happens when bound drug is released from tissues and distributes to the plasma

Blood-Brain Barrier (BBB)

• A barrier limiting the entry of non-lipid-soluble drugs into the central nervous system
• Only lipid-soluble unionized drugs penetrate and have actions on the CNS

Placental Transfer

• Only lipid-soluble drugs can penetrate the placental barrier
• Placental P-gp serves as limiting factor for hydrophillic drugs

Plasma Protein Binding

• Most drugs bind to plasma proteins (mainly albumin for acidic drugs and a1-glycoprotein for basic drugs)
• Extent of binding depends on different compounds and increasing drug concentration can saturate binding sites
• Clinically significant implications include:
  • High PPB drugs are restricted to vascular compartment, low Vd
  • PPB fraction is not available for action
  • Equilibration between PPB fraction of drug and free molecules

Tissue Storage

• Drugs can accumulate in specific organs or get bound to specific tissue constituents Examples include heart, liver, kidney, thyroid, brain, etc

Biotransformation (Metabolism)

• Chemical alteration of drugs in the body, often converting them into inactive or more polar metabolites
• Aim is to convert non-polar lipid-soluble drugs into polar lipid-soluble compounds to prevent reabsorption in renal tubules
• Required for protection of body from toxic metabolites
• Two phases (Phase I and Phase II)

Phase I Reactions

• Oxidation
• Reduction
• Hydrolysis
• Cyclization
• Decyclization

Phase II Reactions

• Conjugation - most important synthetic reaction
• Glucuronidation
• Acetylation
• Sulfation
• Methylation

Factors Affecting Biotransformation

• Concurrent drug use (induction and inhibition)
• Genetic polymorphisms
• Pollutant influences
• Age
• Pathological status

Enzyme Inhibition and Induction

• Inhibition: one drug can inhibit the metabolism of other drugs if they use the same enzyme or if a drug inhibits one isoenzyme while being a substrate of another isoenzyme
• Induction: drugs can induce the synthesis of metabolizing enzymes
• Rifampicin, phenytoin, and carbmazepine are examples of inducers

Excretion

• Elimination of drug or metabolites from the body
• Principal routes: kidney, biliary, sweat, saliva, milk, pulmonary

Renal Excretion

• Glomerular filtration: filtration of non-protein-bound drugs
• Tubular reabsorption: passive reabsorption of lipid-soluble drugs
• Tubular secretion: active secretion of drugs

Kinetics of Elimination

• First-order kinetics: rate of elimination is directly proportional to drug concentration (constant fraction of drug eliminated per unit time)
• Zero-order kinetics: rate of elimination is constant irrespective of drug concentration

Plasma Half-Life

• Time required for plasma concentration of a drug to reduce to half of its original value
• Important in determining dosing intervals

Target Level Strategy

• Maintains drug concentration within therapeutic range
• Suitable for drugs with narrow therapeutic index and short half-lives
• Uses loading and maintenance doses

Monitoring of Plasma Concentration

• Useful for drugs with a narrow therapeutic index or large individual variations

Summary

• Key concepts include drug transport, absorption, distribution, metabolism, excretion, and elimination kinetics
• Important factors include bioavailability, Vd, and half-life.

Prolongation of Drug Action

• Prolonging absorption
• Increasing plasma protein binding
• Retarding metabolism
• Retarding renal excretion.

Test your understanding of pharmacokinetics, the study of drug movement in the body. This quiz covers key concepts such as absorption, distribution, metabolism, and excretion, along with factors that influence drug absorption. Perfect for students in pharmacology or related fields.