Excretion of Drugs

Overview

• Excretion: Process of eliminating a drug from the body.
• Primary Organs involved: Kidneys, liver (bile system), lungs, and GI tract.

Main Routes of Excretion

1. Kidneys (Urine): Primary route
2. Liver (Bile): Via the GI tract and anteropatic circulation
3. Lungs: Exhalation (e.g., anesthetics)
4. GI tract (Feces): Drugs that are not absorbed

Role of Kidneys in Drug Excretion

• Kidney Function: Crucial for drug excretion. Impaired kidney function leads to drug accumulation and toxicity.
• Factors affecting kidney excretion: Filtration, Secretion, Reabsorption

Filtration

• Occurs at the glomerulus.
• Glomerular Filtration Rate (GFR): Key factor; reduced GFR = decreased drug excretion.
• Protein Binding: Highly protein-bound drugs (e.g., bound to albumin) are less likely to be filtered.

Secretion

• Occurs in peritubular capillaries.
• Solubility and Concentration Gradient: Important for passive or active transport.
  1. Polar, Water-Soluble, Large Drugs: Need transporters and ATP (e.g., organic anion and cation transporters).
  2. Non-Polar, Lipid-Soluble, Small Drugs: Passively diffuse.
• Drug Interactions: Some drugs can inhibit transporters, affecting secretion (e.g., Cimetidine, Trimethoprim).

Reabsorption

• Occurs in distal convoluted tubule.
• Dependent on drug characteristics: Non-Polar, Small, Hydrophobic Drugs easily reabsorbed.
• Can be modified by the liver to make drugs more polar and less reabsorbable.

Ion Trapping Concept (Overdose Scenario)

• Weak Acids (e.g., Phenobarbital, Aspirin): Alkalinize urine to trap the drug (use Sodium Bicarbonate).
• Weak Bases (e.g., Amphetamines): Acidify urine to trap the drug (use Ammonium Chloride).
• Objective: Shift drug equilibrium to charged form to prevent reabsorption and enhance excretion.

Summary

• Filtration: Dependent on GFR and protein binding.
• Secretion: Use of transporters, affected by solubility, gradient, and drug interactions.
• Reabsorption: Modifiable by drug characteristics and urinary pH

Next Topics

• Clearance, half-life, and enzyme kinetics.