JNTU B.Pharmacy III Year PHARMACOLOGY-II Previous Question Paper (October/November-2020 - R17)

Anti-hypertensive drugs are classified based on their mechanism of action as follows:

• Diuretics: Thiazides (Hydrochlorothiazide), Loop diuretics (Furosemide), Potassium-sparing diuretics (Spironolactone).
• Sympatholytics: Beta-blockers (Propranolol, Atenolol), Alpha-blockers (Prazosin), Centrally acting agents (Clonidine, Methyldopa).
• Calcium Channel Blockers (CCBs): Dihydropyridines (Amlodipine, Nifedipine), Phenylalkylamines (Verapamil), Benzothiazepines (Diltiazem).
• RAAS Inhibitors: ACE inhibitors (Enalapril, Lisinopril), Angiotensin Receptor Blockers (Losartan, Telmisartan), Direct Renin Inhibitors (Aliskiren).
• Vasodilators: Hydralazine, Minoxidil, Sodium nitroprusside.

Pharmacology of Calcium Channel Blockers (CCBs):

CCBs inhibit the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle cells by blocking L-type voltage-gated calcium channels. This reduction in intracellular calcium prevents the activation of the contractile apparatus, leading to vasodilation and reduced cardiac contractility.

Mechanism of Action: By preventing calcium entry, CCBs decrease peripheral vascular resistance (afterload), which lowers blood pressure. In the heart, they decrease myocardial oxygen demand by reducing contractility and heart rate (specifically non-dihydropyridines).

Classification and Pharmacological Profile:

• Dihydropyridines (e.g., Amlodipine): These are potent peripheral vasodilators with minimal direct effect on the heart. They are preferred for hypertension due to their long duration of action and efficacy in reducing systemic vascular resistance.
• Phenylalkylamines (e.g., Verapamil): These have significant effects on both the heart and blood vessels. They exert negative inotropic and chronotropic effects, making them useful in treating hypertension accompanied by angina or supraventricular tachyarrhythmias.
• Benzothiazepines (e.g., Diltiazem): These possess intermediate effects on the heart and vasculature, providing both vasodilation and a reduction in heart rate.

Clinical Uses: CCBs are first-line agents for hypertension, particularly in elderly patients and those with low-renin hypertension. They are also used in stable angina, variant (Prinzmetal's) angina, and certain arrhythmias.

Adverse Effects: Common side effects include peripheral edema (especially with dihydropyridines), dizziness, flushing, headache, and constipation (notably with Verapamil). Reflex tachycardia may occur with short-acting dihydropyridines.

Anti-arrhythmic drugs are classified based on the Vaughan Williams classification system, which categorizes them according to their primary mechanism of action on cardiac ion channels:

• Class I: Sodium channel blockers: Divided into IA (e.g., Quinidine, Procainamide), IB (e.g., Lidocaine, Mexiletine), and IC (e.g., Flecainide, Propafenone).
• Class II: Beta-adrenergic receptor antagonists: (e.g., Propranolol, Metoprolol, Esmolol).
• Class III: Potassium channel blockers: (e.g., Amiodarone, Sotalol, Dofetilide).
• Class IV: Calcium channel blockers: (e.g., Verapamil, Diltiazem).
• Miscellaneous: (e.g., Adenosine, Digoxin, Magnesium sulfate).

Pharmacology of Class II Drugs (Beta-blockers):

Class II agents act by competitively blocking beta-1 adrenergic receptors in the heart. By inhibiting the action of catecholamines (epinephrine and norepinephrine), they reduce sympathetic nervous system stimulation of the myocardium.

Mechanism of Action:

Key Pharmacological Effects:

• Negative Chronotropic Effect: Decreased heart rate by slowing the firing rate of the SA node.
• Negative Dromotropic Effect: Decreased conduction velocity through the AV node, which is particularly useful in controlling ventricular rate during atrial fibrillation or flutter.
• Negative Inotropic Effect: Reduced myocardial contractility, which helps decrease myocardial oxygen demand.
• Anti-ischemic effect: By reducing heart rate and contractility, they improve the balance between oxygen supply and demand.

Clinical Utility: These drugs are primarily used for tachyarrhythmias caused by increased sympathetic activity, supraventricular tachycardias, and for secondary prevention of sudden cardiac death following myocardial infarction. Esmolol is preferred in acute settings due to its ultra-short half-life, while propranolol and metoprolol are commonly used for chronic management.