Untitled Quiz

Pharmacokinetics

• Pharmacology is the study of the actions, mechanisms, uses, and adverse effects of drugs.
• A drug is any natural or synthetic substance that alters the physiological state of a living organism.
• Pharmacology can be divided into two disciplines: pharmacokinetics and pharmacodynamics.

Pharmacokinetics

• Pharmacokinetics is the branch of pharmacology that studies the movement and disposition of drugs within and by the body.
• It includes:
  • Drug absorption
  • Distribution
  • Metabolism
  • Excretion

Drug Absorption

• Definition: passage of drug molecules from the site of administration to the systemic circulation.
• Applies to all routes of administration, except for topical and intravenous routes.
• Requires the drug to cross one or more layers of plasma membranes.
• Factors affecting absorption:
  • Molecular size: small molecules are absorbed faster than large molecules.
  • Dose and concentration of the drug: absorption increases with increasing dose (up to a limit).
  • Lipid solubility: ionization of the drug affects its ability to cross biological membranes.
  • Route of administration: IM route is faster than oral route.
  • Integrity of the absorbing surface: ischemia decreases absorption.
  • Vascularity at the site of absorption: affects the rate of absorption.

pKa and Drug Ionization

• Most drugs are weak acids or bases that exist in both ionized and nonionized forms.
• Only nonionized form (nonpolar) of the drug is lipid soluble and can cross biological membranes.
• Ionized form (polar) of the drug is non-lipid soluble (water soluble) and cannot cross biological membranes.
• The pKa of a drug determines the ratio between the two forms and affects the rate of drug absorption.
• Clinical significance of pKa:
  • Site of drug absorption from the GIT: aspirin is a weak acid that becomes nonionized and more absorbable in the stomach (pH = 1.5).
  • Drug excretion by the kidney: aspirin toxicity can be treated by alkalinization of urine, and amphetamine toxicity can be treated by acidification of urine.

Bioavailability

• Definition: the fraction of the administered dose of a drug that reaches the systemic circulation.
• Intravenously administered drug has 100% bioavailability.
• Oral bioavailability of a drug can be calculated using the formula: (total amount of drug reaching circulation / total amount of drug administered) × 100.

Apparent Volume of Distribution (Vd)

• Definition: the volume of fluid that would be required to contain the total amount of drug in the body at the same concentration as found in the plasma.
• Drugs are distributed to organs and tissues via the circulation, diffusing from the blood to the interstitial fluid and into the cells.

Elimination Half-Life (t1/2)

• Definition: the time required for the plasma concentration of a drug to decrease by one-half.
• Steady-state plasma concentration (Cpss) is reached after 5 t1/2.
• Cpss is the steady level of drug in plasma achieved when the rate of drug administration equals the rate of drug elimination.