JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY HYDERABAD B. Pharmacy III MEDICINAL CHEMISTRY-I Previous Question Paper (July/August - 2023 - R17)

The history of medicinal chemistry began with the use of natural products from plants and animals in ancient civilizations like the Egyptians, Chinese, and Indians. The field evolved significantly in the 19th century with the isolation of pure active principles, such as morphine from opium by Friedrich Sertürner in 1804. The development of synthetic chemistry in the late 19th and early 20th centuries, marked by the synthesis of aspirin and the discovery of sulfa drugs and antibiotics like penicillin, transformed medicinal chemistry into a systematic science focused on the rational design and optimization of synthetic therapeutic agents.

Drug metabolism occurs primarily in the liver, which contains the highest concentration of drug-metabolizing enzymes, particularly the cytochrome P450 system. While the liver is the principal site, metabolism also takes place in several extrahepatic tissues:

• Gastrointestinal tract: The intestinal mucosa and gut microflora play a significant role in the first-pass metabolism of orally administered drugs.
• Kidneys: These organs possess significant metabolic capacity, contributing to the biotransformation of various xenobiotics.
• Lungs: The pulmonary tissue contains enzymes capable of metabolizing drugs, especially those administered via inhalation.
• Blood plasma: Contains various esterases and amidases that rapidly hydrolyze certain drugs in systemic circulation.
• Skin and Placenta: These tissues possess localized enzymatic activity that can influence the systemic availability of drugs applied topically or during pregnancy.