Veterinary Pharmacology and Toxicology- ICAR JRF/SRF 2024

• Physiological Properties of the Blood-Brain Barrier (BBB):
• The BBB is constituted by continuous, non-fenestrated capillary endothelial cells joined by complex tight junctions (zonula occludens), enveloped by a thick basal lamina and astrocyte end-feet (perivascular glial endfeet).
• Regulatory Direction: The BBB primarily restricts and regulates the influx of substances from the systemic circulation (blood) into the brain extracellular fluid, NOT the passage of substances from brain into blood [Statement 4 is incorrect/FALSE]. (Efflux transporters like P-glycoprotein pump drugs out of endothelial cells back into the capillary lumen).

Correct option: (4) It regulates passage of substances from brain into blood

• Fundamental Objective of Biotransformation: The primary biological purpose of enzymatic drug metabolism (Phase I functionalization and Phase II conjugation) is to convert non-polar, lipid-soluble xenobiotics into polar, water-soluble (non-lipid soluble) metabolites.
• Elimination Rationale: Lipophilic molecules are passively reabsorbed across renal tubular epithelial membranes and cannot be excreted. Biotransformation generates hydrophilic ionized metabolites that are readily eliminated in urine and bile.

Correct option: (1) Convert lipid soluble drugs into nonlipid soluble metabolites

• Identification of Prodrug: Sulfasalazine is a classic prodrug.
• Activation Mechanism: Sulfasalazine is an azo-linked conjugate of 5-aminosalicylic acid (5-ASA / mesalamine) and sulfapyridine. It is poorly absorbed from the upper GIT; upon reaching the colon, bacterial azo-reductase enzymes cleave the azo bond, releasing active 5-ASA to exert local anti-inflammatory effects in the colonic mucosa.
• Active Drugs: Clonidine, hydralazine, and captopril (active sulfhydryl ACE inhibitor, unlike enalapril) are pharmacologically active in their administered forms.

Correct option: (1) Sulfasalazine