Pharmacology Chapter on Drug Absorption

Drug Absorption

• Absorption involves the transfer of drugs from the administration site to blood circulation.
• Rate and efficiency of absorption depend on the route of administration and dosage form.
• Oral administration requires drug dissolution in gastrointestinal fluid and penetration of intestinal epithelial cells, primarily in the duodenum.
• Understanding absorption rates is crucial for predicting the onset of drug action and response magnitude.

Bioavailability

• Bioavailability is the fraction of the administered drug that reaches systemic circulation unchanged.
• Example: If 100 mg of a drug is administered orally and 70 mg is absorbed, bioavailability is 70%.

Factors Influencing Drug Absorption

• First Pass Metabolism:

  • Drugs absorbed through the GI tract may be partially metabolized by the liver before reaching systemic circulation, reducing unchanged drug availability.

• Solubility of the Drug:

  • Poor absorption occurs in very hydrophilic or extremely hydrophobic drugs, as they cannot easily cross cell membranes.

• Chemical Instability:

  • Some drugs are unstable in gastric pH, leading to reduced absorption.

• Active Transport:

  • Requires specific chemical structures to utilize carrier molecules for drug absorption, as seen with anticancer drugs utilizing uracil transport systems.

• Pinocytosis:

  • Involves engulfing particles or liquids, important for certain polypeptides and immunoglobulins.

Route of Drug Administration

• Different routes require different absorption processes.

• Oral Route:

  • Safest administration route but lower bioavailability due to first pass metabolism.
  • Factors affecting absorption include gastric contents, blood flow, and GI tract differences across species.

• Parenteral Route:

  • Circumvents GI tract absorption; includes IV, IM, SC, and IP.
  • Absorption affected by blood flow and vasoconstriction can impair it.

• Skin/Intradermal Route:

  • Highly lipid-soluble drugs are mostly absorbed; skin disruptions can impair absorption.

• Respiratory Route:

  • Used for gases and volatile anesthetics; particle size is critical for absorption.

Distribution of Drugs

• Dose and Route of Administration:

  • Impacts distribution; adequate blood flow is essential.

• Blood Flow:

  • Varies widely among tissues; higher flow in organs like the brain, liver, and kidneys.

• Physicochemical Properties:

  • Lipid solubility, pH, and molecular size significantly influence drug distribution.

Binding to Plasma Proteins

• Only unbound drugs can cross cell membranes; plasma protein binding is reversible.
• Acidic drugs primarily bind to albumin; basic drugs bind to α1-acid glycoprotein.
• Binding may slow drug concentration achievement but does not prevent access to action sites.

Drug Interactions and Interspecies Differences

• Drug Interactions:

  • Occurs when two drugs compete for binding sites on plasma proteins, increasing free drug concentrations and effects.

• Interspecies Differences:

  • Variability in drug distribution is observed among different species, influenced by gastrointestinal tract mass.

Drug Redistribution

• Redistribution from high blood flow sites to low can terminate drug action, especially for highly lipid-soluble drugs.

CNS and Transplacental Distribution

• CNS Distribution:

  • Limited by the blood-brain barrier, requiring high lipid solubility to pass.
  • Active transport mechanisms exist for certain acids and bases in the choroid plexus, affecting CNS drug levels.

• Transplacental Distribution:

  • Drugs can cross the placenta via simple diffusion; the degree of transfer varies with drug properties.

• Other Barriers:

  • Tissues like the prostate and testicles possess barriers that limit drug concentration.

Explore the vital concepts of drug absorption and bioavailability in this quiz. Delve into factors that influence how drugs are absorbed into systemic circulation, including the impact of first-pass metabolism. Understanding these principles is essential for predicting drug action and efficacy.