VL 3: Drug administration

1. blood flow

2. capillary permeability

   • Ionized or polar drugs generally fail to enter the CNS

3. Drug Binding to Plasma Proteins and Tissue proteins

4. Drug Hydrophobicity

Phase I: Introduces or unmasks polar functional groups (e.g., -OH, -COOH, -NH2,). The pharmacological activity of drugs may increase, decrease, or remain unchanged.

Phase II: Conjugates drugs with polar endogenous substances (e.g., glucuronic acid) to form water-soluble metabolites

= Kidney excretion into urine is the primary route of drug excretion

1. Glomerular Filtration

   • Free drug (not bound to albumin) flows through the glomerular capillary slits into Bowman’s space

   • Lipid solubility and pH do not influence the passage

   • The glomerular filtration rate (normal GFR = 125 mL/min) and plasma binding of the drugs may affect this process

2. Proximal tubular secretion

   • Drugs that escape glomerular filtration are secreted by active transport systems into the proximal tubules via:

     • Anion transport (for weak acid deprotonated forms)

     • Cation transport (for weak base protonated forms)

3. Distal tubular reabsorption

   • As drugs move to the distal tubule, uncharged drugs may re-enter systemic circulation

   • Manipulating the pH of urine to increase the ionized form of the drug in the lumen can decrease the amount of back-diffusion

• Other routes for drug excretion: Intestinal (Feces), bile, lungs, sweat, and breast milk,...

• ntestinal clearance: Involves unabsorbed drugs or those secreted in bile

Lungs: Primarily involved in the elimination of anesthetic gases (for example, halothane and isoflurane)

Breast milk: Drugs can pass to nursing infants, causing potential side effects

• Excretion of most drugs into sweat, saliva, tears, hair, and skin occurs only to a small extent

• Deposition of drugs in hair and skin has been used as a forensic tool in many criminal cases