Pharmacokinetics I Quiz

Pharmacokinetics I

• Pharmacokinetics is the study of how the body processes drugs.
• The principles of ADME: Absorption, Distribution, Metabolism, and Excretion.
• Absorption: How a drug enters the body.
• Distribution: How a drug moves throughout the body.
• Metabolism: How a drug is broken down.
• Excretion: How a drug leaves the body.
• ADME/LADME: Absorption, Distribution, Metabolism, and Excretion (also Liberation and Dosage form).

Drug Administration Routes

• Local: Applied directly to the area of need.
  • Examples: topical application (skin, eyes, nasal), rectal, inhalation.
• Systemic: Enters the bloodstream and exerts effects throughout the body.
  • Examples: oral, sublingual, buccal/cheek, rectal, inhalation. parenteral (injection - IV, IM, subcutaneous, transdermal).
• Parenteral routes: Involves skin puncture.
  • Examples: Intravenous (IV), Intramuscular (IM), Subcutaneous (SC), etc.
• Enteral routes: The drug enters the body through the digestive system.
  • Examples: oral, sublingual, buccal,rectal, gastric feeding.

Drug Permeation

• Movement of drug molecules across biological membranes.
• Key for ADME process.
• Factors like lipid solubility, degree of ionization, and concentration gradients influence permeation.
• Drug permeation occurs via pathways like diffusion through lipid bilayers, aqueous channels, and carrier-mediated transport.

Drug Absorption

• Process of drug movement from administration site into systemic circulation.
• Crucial in pharmacokinetic study.
• Important factors influencing oral absorption: drug stability in the GI tract, dosage form, lipophilicity, particle size, degree of ionization, gastric emptying, intestinal motility, first-pass metabolism, disease state.
• Factors affecting absorption in the small intestine: large surface area of villi and microvilli, and active secretion.

Drug Interactions

• Drug-drug: These occur when multiple drugs interact. E.g. proton pump inhibitors raise stomach pH, reducing some drug absorption.

  • Colestyramine binds to other drugs like warfarin, affecting their absorption.

• Drug-disease: Conditions that alter absorption. E.g. Crohn's disease or ulcerative colitis affects drug absorption; and some stomach conditions also impact drug absorption.

Routes of Drug Permeation

• Sublingual/Buccal: Absorption occurs via passive diffusion; limited by molecular weight of the drug through oral mucosa.
• Intramuscular (IM): Absorption into system occurs via slow process depending on muscle blood flow. Absorbed faster from deltoid than gluteal muscle.
• Subcutaneous (SC): Passive diffusion to capillary wall - Lipophilic/lipid solvable drugs travel through capillary membranes directly. Other water solvable drugs diffuse through membrane pores.
• Rectal: Highly vascularized for passive diffusion, but absorption can be erratic - some drugs pass through the superior rectal vein, which is still subjected to first pass metabolism and absorption in the liver.
• Transdermal: Drugs pass through intercellular and intracellular routes across the skin; The skin's stratum corneum (outermost layer) is a crucial factor.
• Inhalation: Drugs in aerosols or gases can be given systemically or locally..
• Intra-arterial: For thrombolytic drugs, chemotherapy or certain types of chemo, and spinal anesthesia.
• Intra-thecal: Used for central nervous system (CNS) infections or anesthesia.
• Intra-peritoneal: For continuous ambulatory peritoneal dialysis (CAPD) or animal experiments.
• Intra-articular: Injected directly into joints, often for rheumatoid arthritis treatment.

Special Formulations

• Enteric coated: Protects drugs from stomach acid and releases them in the small intestine, suitable in cases where the drug is not stable in the acidic conditions of the stomach.
• Sustained-release: Provides continuous drug delivery over an extended period.

Degree of Ionization (pH & pKa)

• Drugs are weak acids/bases, existing as ionized or unionized forms.
• Ionization impacts the drug's ability to cross membranes. Ionized forms of drugs typically do not pass through membranes as efficiently as non-ionized (uncharged) forms; which can affect absorption.
• The pH of various body parts (e.g., stomach, small intestine, blood) influences ionization.
• The Handerson-Hasselbalch equation relates pH, pKa, and the relative concentrations of ionized and unionized forms.

Other Factors Affecting Absorption

• Factors like gastric emptying rate, intestinal motility, and presence of food influence drug absorption.
• Drug interactions (drug-drug or drug-disease interactions) can also play a role, impacting absorption.
• Drug stability in the gastrointestinal tract and physicochemical properties such as lipophilicity, particle size, and form are influential factors.
• The environment in the small intestine tends to remain consistent throughout the day., which tends to affect drug absorption.