JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY HYDERABAD Pharm. D II Year PHARMACOTHERAPEUTICS-I Previous Question Paper (April/May - 2019 - R08)

Hypertension is defined as a persistent elevation of systolic blood pressure (SBP) ≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg. It is a chronic medical condition where the force of blood against the artery walls is consistently too high.

Antihypertensive drugs are classified as follows:

• Diuretics: Thiazides (Hydrochlorothiazide), Loop diuretics (Furosemide), Potassium-sparing (Spironolactone).
• Sympatholytics: Beta-blockers (Atenolol, Propranolol), Alpha-blockers (Prazosin), Centrally acting agents (Clonidine).
• Calcium Channel Blockers (CCBs): Dihydropyridines (Amlodipine, Nifedipine), Non-dihydropyridines (Verapamil, Diltiazem).
• RAAS Inhibitors: ACE inhibitors (Enalapril, Lisinopril), ARBs (Losartan, Telmisartan).
• Vasodilators: Hydralazine, Minoxidil.

Calcium Channel Blockers (CCBs) are a group of drugs that inhibit the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle cells. By reducing intracellular calcium concentration, they prevent the activation of the contractile apparatus, leading to vasodilation and reduced cardiac contractility.

The mechanism of action involves:

1. Binding to L-type Calcium Channels: CCBs bind specifically to the alpha-1 subunit of L-type voltage-gated calcium channels in the cell membrane.
2. Inhibition of Calcium Influx: This binding blocks the entry of extracellular calcium into the cells during depolarization.
3. Vasodilation: In vascular smooth muscle, decreased calcium levels prevent the formation of the calcium-calmodulin complex, inhibiting myosin light-chain kinase. This results in smooth muscle relaxation, peripheral vasodilation, and a decrease in total peripheral resistance (afterload).
4. Cardiac Effects: Non-dihydropyridines (Verapamil and Diltiazem) also act on the SA and AV nodes, reducing heart rate (negative chronotropy) and myocardial contractility (negative inotropy), which decreases oxygen demand.

Dihydropyridines like Amlodipine are more selective for vascular smooth muscle, whereas non-dihydropyridines have significant effects on both the heart and blood vessels.