Calcium channel blockers

These drugs include a heterogeneous class of compounds which act by preventing the entry of slow calcium ions into the cellos which are required for the contraction of muscles. These drugs act on the calcium channel receptors and cause blockade of the calcium channels.

1. [email protected] Lecture-2 Medicinal Chemistry-II Surendra Kumar Assistant Professor KNIMT, Faculty of Pharmacy, Sultanpur CALCIUM CHANNEL BLOCKERS

2. Calcium channel blockers lower your blood pressure by preventing calcium from entering the cells of your heart and arteries. Calcium causes the heart and arteries to contract more strongly. By blocking calcium, calcium channel blockers allow blood vessels to relax and open. Some calcium channel blockers have the added benefit of slowing your heart rate, which can further lower your blood pressure, relieve chest pain (angina) and control an irregular heartbeat. Calcium channel blockers are also called calcium antagonists. Calcium channel blockers are available in short-acting and long-acting forms. Short-acting medications work quickly, but their effects last only a few hours. Long-acting medications are slowly released to provide a longer lasting effect. CALCIUM CHANNEL BLOCKERS

3. Examples of calcium channel blockers include : Amlodipine ( Norvasc ) Diltiazem ( Cardizem , Tiazac , others) Felodipine Isradipine Nicardipine Nifedipine ( Adalat CC, Procardia ) Nisoldipine ( Sular ) Verapamil ( Calan , Verelan ) Calcium channel blockers: Calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as medications to decrease blood pressure in patients with hypertension .

4. VERAPAMIL IUPAC Name: 2-(3, 4-dimethoxyphenyl)-5-[2-(3, 4-dimethoxyphenyl)ethyl- methylamino ]- 2-propan-2-ylpentanenitrile

5. Inhibition of calcium influx prevents the contraction of vascular smooth muscle, causing relaxation/dilation of blood vessels throughout the peripheral circulation - this lowers systemic vascular resistance (i.e. afterload ) and thus blood pressure . This reduction in vascular resistance also reduces the force against which the heart must push, decreasing myocardial energy consumption and oxygen requirements and thus alleviating angina. Electrical activity through the AV node is responsible for determining heart rate, and this activity is dependent upon calcium influx through L-type calcium channels . By inhibiting these channels and decreasing the influx of calcium, verapamil prolongs the refractory period of the AV node and slows conduction, thereby slowing and controlling the heart rate in patients with arrhythmia. MECHANISM OF ACTION

6. USES Verapamil is used to treat  high blood pressure  and to control  angina  ( chest pain ). It is also used to treatment cerebral vasospasm and in cluster headache . BEPRIDIL HYDROCHLORIDE IUPAC Name: N-benzyl-N-[3-(2-methylpropoxy)-2-pyrrolidin-1-ylpropyl] aniline; hydrochloride

7. Bepridil has inhibitory effects on both the slow calcium (L-type) and fast sodium inward currents in myocardial and vascular smooth muscle, interferes with calcium binding to calmodulin , and blocks both voltage and receptor operated calcium channels . Bepridil inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth muscle. This has been demonstrated in isolated myocardial and vascular smooth muscle preparations in which both the slope of the calcium dose response curve and the maximum calcium-induced inotropic response were significantly reduced by bepridil . MECHANISM OF ACTION

8. USES Bepridil (trade name Vascor ) is an amine calcium channel blocker once used to treat angina . DILTIAZEM HYDROCHLORIDE IUPAC Name: [(2S, 3S)-5-[2-( dimethylamino )ethyl]-2-(4-methoxyphenyl)-4-oxo-2,3-dihydro-1,5-benzothiazepin-3-yl] acetate; hydrochloride

9. Diltiazem inhibits the inflow of calcium ions into the cardiac smooth muscle during depolarization. Reduced intracellular calcium concentrations equate to increased smooth muscle relaxation resulting in arterial vasodilation and, therefore, decreased blood pressure. Diltiazem is a potent coronary artery vasodilator and is consequently used for chronic angina and in those patients with coronary vasospasm. Vasospasm of the coronary arteries can lead to debilitating conditions such as myocardial infarction. MECHANISM OF ACTION USES Diltiazem is used to treat hypertension (high blood pressure), angina (chest pain), and certain heart rhythm disorders .

10. NIFEDIPINE IUPAC Name: dimethyl 2, 6-dimethyl-4-(2-nitrophenyl)-1, 4-dihydropyridine-3, 5-dicarboxylate

11. Nifedipine blocks voltage gated L-type calcium channels in vascular smooth muscle and myocardial cells . This blockage prevents the entry of calcium ions into cells during depolarization, reducing peripheral arterial vascular resistance and dilating coronary arteries. These actions reduce blood pressure and increase the supply of oxygen to the heart, alleviating angina .

12. USES It is used in management of hypertension. It has no antiarrhythmic activity. This medication is used to prevent certain types of chest pain (angina). It may allow you to exercise more and decrease the frequency of angina attacks. AMLODIPINE

13. MECHANISM OF ACTION Amlodipine is an angioselective calcium channel blocker and inhibits the movement of calcium ions into vascular smooth muscle cells and cardiac muscle cells which inhibits the contraction of cardiac muscle and vascular smooth muscle cells .

14. USES Amlodipine is used to treat chest pain (angina) and other conditions caused by coronary artery disease. Amlodipine is also used to treat high blood pressure (hypertension ). FELODIPINE IUPAC Name: 5-O-ethyl 3-O-methyl 4-(2,3-dichlorophenyl)- 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate

15. MECHANISM OF ACTION It acts primarily on vascular smooth muscle cells by stabilizing voltage-gated L-type calcium channels in their inactive conformation . By inhibiting the influx of calcium in smooth muscle cells, felodipine prevents calcium-dependent myocyte contraction and vasoconstriction . USES Felodipine is used to treat high blood pressure and stable angina . It should not be used for people who are pregnant, have acute heart failure, and are having a heart attack, have an obstructed heart valve, or have obstructions that block bloodflow out of the heart .

16. NICARDDIPINE IUPAC Name: 5-O-[2-[benzyl (methyl) amino] ethyl] 3-O-methyl 2, 6-dimethyl-4-(3-nitrophenyl)-1, 4-dihydropyridine-3, 5-dicarboxylate; hydrochloride MECHANISM OF ACTION Nicardipine hydrochloride capsules are a calcium entry blocker (slow channel blocker or calcium ion antagonist) that inhibits the transmembrane influx of calcium ions into cardiac muscle and smooth muscle without changing serum calcium concentrations.

17. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels . The effects of Nicardipine hydrochloride capsules are more selective to vascular smooth muscle than cardiac muscle. USES Nicardipine is used to treat hypertension (high blood pressure) and angina (chest pain).

18. NIMODIPINE IUPAC Name: 3-O-(2-methoxyethyl) 5-O-propan-2-yl 2,6-dimethyl-4-(3-nitrophenyl)- 1,4-dihydropyridine-3,5-dicarboxylate

19. MECHANISM OF ACTION During the depolarization of smooth muscle cells of blood vessels, there is an influx of calcium ions. The primary function of nimodipine is to block voltage-gated L-type calcium channels in their inactive conformation, avoiding this influx, to prevent vasoconstriction . It has a preference to act on cerebral blood vessels since it is lipophilic and can cross the blood-brain barrier .

20. USES Nimodipine is used to decrease problems due to a certain type of bleeding in the brain (subarachnoid hemorrhage-SAH ). Nimodipine is called a calcium channel blocker. The body naturally responds to bleeding by narrowing the blood vessel to slow blood flow. However, when the bleeding is in the brain, stopping blood flow causes more brain damage. Nimodipine is thought to work by relaxing narrowed blood vessels in the brain near the area of bleeding so blood can flow more easily.

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