Methods of Drug Elimination

Methods of Drug Elimination include renal excretion, biliary excretion, pulmonary excretion, and metabolism for drug clearance.

Methods of Drug Elimination

• Elimination is the process by which drugs are removed from the body. It primarily occurs through metabolism and excretion, ensuring that the drug’s effects do not persist indefinitely.
• Various pathways contribute to drug elimination, each with unique mechanisms and physiological relevance.

1. Metabolism (Biotransformation)

   • Definition: Chemical modification of drugs into more polar, water-soluble metabolites to facilitate excretion.
   • Primary site: Liver
   • Enzymatic involvement: Mainly catalyzed by the cytochrome P450 (CYP450) enzyme system.

   • Phases of Metabolism:

     • Phase I reactions: Oxidation, reduction, hydrolysis (introduce or expose functional groups).
     • Phase II reactions: Conjugation with molecules like glucuronic acid, sulfate, or glutathione (increase water solubility).

2. Renal Excretion

   • Primary organ: Kidneys
   • Major route for elimination of unchanged drugs and polar metabolites.

   • Processes Involved:

     • Glomerular Filtration: Passive filtration of small, unbound drug molecules into the renal tubule.
     • Tubular Secretion: Active transport of drug molecules from blood into the renal tubule.
     • Tubular Reabsorption: Movement of drug molecules back into the bloodstream, especially for lipophilic
   • Note: Hydrophilic drugs are more likely to be excreted in urine; lipophilic drugs may require metabolism before elimination.

3. Biliary Excretion

   • Organ involved: Liver, with excretion into bile.
   • Bile is stored in the gallbladder and secreted into the small intestine.
   • Drugs excreted in bile may:
     • Be eliminated via feces.
     • Undergo enterohepatic recirculation (reabsorption from the intestine back into the bloodstream).

4. Pulmonary Excretion

   • Route: Exhalation through the lungs
   • Common for volatile or gaseous drugs (e.g., anesthetics like halothane).
   • Influenced by:
     • Drug solubility in blood
     • Pulmonary blood flow
     • Ventilation rate

5. Excretion via Sweat, Saliva, and Tears

   • Secondary routes of elimination.
   • Usually involves small amounts of drug or metabolites.
   • May be relevant for:
     • Drugs causing local irritation (e.g., sweat-related dermatitis).
     • Forensic or diagnostic purposes.

6. Excretion through Breast Milk

   • Drugs can pass into breast milk, potentially affecting nursing infants.
   • Degree of excretion depends on:
     • Lipophilicity
     • Molecular weight
     • Ionization and pKa
     • Plasma protein binding

   • Clinical consideration:

     • Drugs excreted in significant amounts may require caution or avoidance during breastfeeding.

7. Excretion via Hair and Nails

   • Involves incorporation of drugs/metabolites into growing tissues.
   • Not a significant elimination route for pharmacological purposes.
   • However, useful in long-term drug exposure detection (e.g., forensic toxicology).
     • patients.

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