JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY HYDERABAD Pharm. D IV Year BIOPHARMACEUTICS AND PHARMACOKINETICS Previous Question Paper (January/February - 2021 - R08)

Active transport is a carrier-mediated process that moves drug molecules across biological membranes against a concentration gradient. Its salient features include:

• Energy Requirement: It requires metabolic energy, typically in the form of ATP, to transport drugs against the electrochemical gradient.
• Carrier Mediation: The process involves specific membrane-bound carrier proteins that bind to the drug molecule to facilitate its translocation.
• Saturation Kinetics: Because the number of carrier proteins is finite, the rate of transport increases with drug concentration until all carriers are occupied, reaching a maximum velocity (Vmax).
• Structural Specificity: Carriers often exhibit high selectivity for drugs with specific chemical structures or functional groups.
• Competitive Inhibition: Structurally similar compounds or analogs can compete for the same carrier protein, leading to inhibition of the drug's transport.
• Directionality: It is a unidirectional process, typically moving substances from a region of low concentration to high concentration.

Phase II reactions, also known as conjugation reactions, involve the attachment of an endogenous polar group to a drug or its Phase I metabolite to increase water solubility and facilitate excretion. These reactions are typically catalyzed by transferase enzymes.

• Glucuronidation: The most common pathway, involving the transfer of glucuronic acid from UDP-glucuronic acid to the drug by the enzyme UDP-glucuronosyltransferase (UGT). Example: Morphine is conjugated to morphine-3-glucuronide.
• Sulfation: The transfer of a sulfate group from 3'-phosphoadenosine-5'-phosphosulfate (PAPS) by sulfotransferases. Example: Acetaminophen (paracetamol) undergoes sulfation.
• Acetylation: The transfer of an acetyl group from Acetyl-CoA by N-acetyltransferases. Example: Isoniazid is metabolized to N-acetylisoniazid.
• Glutathione Conjugation: Involves the conjugation of electrophilic drugs with glutathione (GSH) via glutathione S-transferases, often serving as a detoxification mechanism. Example: Reactive metabolites of acetaminophen are neutralized by glutathione.
• Methylation: The transfer of a methyl group from S-adenosylmethionine (SAM) by methyltransferases. Example: Catecholamines like epinephrine are methylated by COMT.
• Amino Acid Conjugation: Conjugation with amino acids like glycine. Example: Salicylic acid is conjugated with glycine to form salicyluric acid.