JNTU Pharm. D II Year PHARMACOLOGY-I Previous Question Paper (July/August - 2021 - R08)

G-Protein Coupled Receptors (GPCRs), also known as seven-transmembrane domain receptors, constitute the largest family of cell surface receptors. They consist of a single polypeptide chain that threads across the plasma membrane seven times, creating an extracellular N-terminus for ligand binding and an intracellular C-terminus that interacts with G-proteins.

The signaling mechanism involves three key components: the receptor, a heterotrimeric G-protein (composed of alpha, beta, and gamma subunits), and an effector enzyme or ion channel. When an agonist binds to the receptor, it induces a conformational change that promotes the exchange of GDP for GTP on the alpha subunit. This causes the G-protein to dissociate into an alpha-GTP complex and a beta-gamma dimer, both of which can modulate downstream effectors such as adenylyl cyclase, phospholipase C, or ion channels. The signaling is terminated when the intrinsic GTPase activity of the alpha subunit hydrolyzes GTP back to GDP, allowing the heterotrimer to reassemble.

The oral route is the most common and convenient method of drug administration. Its merits and demerits are as follows:

Merits:

• It is the safest, most convenient, and painless route, requiring no specialized equipment.
• It is highly economical as it does not require sterile preparations.
• It allows for self-administration, improving patient compliance.
• The systemic absorption is generally predictable, and the risk of systemic infection is minimal compared to parenteral routes.

Demerits:

• The onset of action is relatively slow, making it unsuitable for emergency situations.
• Drugs may undergo significant first-pass metabolism in the liver, reducing bioavailability.
• It is ineffective for drugs that are poorly absorbed, highly polar, or destroyed by gastric acid/digestive enzymes (e.g., insulin).
• It can cause local irritation to the gastrointestinal mucosa, leading to nausea or vomiting.
• Absorption can be significantly influenced by the presence of food, gastric pH, or gastrointestinal motility.