Calcium channel blocker angina treatment

Other agents are also used for the treatment of manic-depressive disorders based on preliminary clinical results (177). The antiepileptic carbamazepine [298-46-4] has been reported in some clinical studies to be therapeutically beneficial in mild-to-moderate manic depression. Carbamazepine treatment is used especially in bipolar patients intolerant to lithium or nonresponders. A majority of Hthium-resistant, rapidly cycling manic-depressive patients were reported in one study to improve on carbamazepine (178). Carbamazepine blocks noradrenaline reuptake and inhibits noradrenaline exocytosis. The main adverse events are those found commonly with antiepileptics, ie, vigilance problems, nystagmus, ataxia, and anemia, in addition to nausea, diarrhea, or constipation. Carbamazepine can be used in combination with lithium. Several clinical studies report that the calcium channel blocker verapamil [52-53-9] registered for angina pectoris and supraventricular arrhythmias, may also be effective in the treatment of acute mania. Its use as a mood stabilizer may be unrelated to its calcium-blocking properties. Verapamil also decreases the activity of several neurotransmitters. Severe manic depression is often treated with antipsychotics or benzodiazepine anxiolytics. 

The so-called calcium channel blockers constitute a class of cardiovascular agents that have gained prominence in the past few years. These drugs, which obtund contraction of arterial vessels by preventing the movement of calcium ions needed for those contractions, have proved especially useful in the treatment of angina and hypertension. Dihydropyridines such as nifedipine (30) are par-... 

Calcium-channel blockers such as amlodipine can be used in patients receiving angiotensin-receptor blockers such as valsartan for the treatment of hypertension and angina. Side-effects common to both drugs include dizziness and hypotension. 

Propranolol and nadolol also have been used successfully in combination with certain calcium entry blockers, particularly nifedipine, for the treatment of secondary angina. Caution should be used, however, when combining a p-blocker and a calcium channel blocker, such as verapamil or diltiazem, since the negative inotropic and chronotropic effects of this combination may lead to severe bradycardia, arteriovenous nodal block, or decompensated congestive heart failure. 

Calcium channel blockers depress the contractility of the myocardium and decrease the cardiac work and the requirement of oxygen. This effect proves to be beneficial in the treatment of angina pectoris. 

Spaulding C, Cabanes L, Weber S. Pharmacological and therapeutic basis for combined administration of beta blockers and calcium channel blockers in the treatment of stable chronic angina. BrJ Clin Pract Suppl. 1997 88 17-22. 

In addition to their antianginal (see Chapter 12 Vasodilators the Treatment of Angina Pectoris) and antiarrhythmic effects (see Chapter 14 Agents Used in Cardiac Arrhythmias), calcium channel blockers also dilate peripheral arterioles and reduce blood pressure. The mechanism of action in hypertension (and, in part, in angina) is inhibition of calcium influx into arterial smooth muscle cells. 

The amount of trigger calcium that enters the cell depends on the availability of calcium channels (primarily the L type) and the duration of their opening. As described in Chapter 6 Introduction to Autonomic Pharmacology and Chapter 9 Adrenoceptor-Activating Other Sympathomimetic Drugs, sympathomimetics cause an increase in calcium influx through an action on these channels. Conversely, the calcium channel blockers (see Chapter 12 Vasodilators the Treatment of Angina Pectoris) reduce this influx and depress contractility. 

Activation of platelets is considered an essential process for arterial thrombosis. Thus, treatment with platelet-inhibiting drugs such as aspirin and ticlopidine or clopidogrel is indicated in patients with transient ischemic attacks and strokes or unstable angina and acute myocardial infarction. In angina and infarction, these drugs are often used in conjunction with -blockers, calcium channel blockers, and fibrinolytic drugs. 

Calcium antagonists can cause serious toxicity or death with relatively small overdoses. These channel blockers depress sinus node automaticity and slow AV node conduction (see Chapter 12 Vasodilators the Treatment of Angina Pectoris). They also reduce cardiac output and blood pressure. Serious hypotension is mainly seen with nifedipine and related dihydropyridines, but in severe overdose all of the listed cardiovascular effects can occur with any of the calcium channel blockers. 

Depolarization of vascular smooth muscle activates the L-type calcium channels, which results in increased cytosolic concentrations of calcium and hence increased tone. Calcium channel blockers (e.g., verapamil and diltiazem) block the influx of calcium through the L-type voltage-dependent channels located on vascular smooth muscle and cardiac muscle cells as well as cardiac nodal cells. Therefore, they are used in the treatment of angina, hypertension, and certain arrhythmias. 

Calcium channel blockers have an intrinsic natriuretic effect therefore, they do not usually require the addition of a diuretic. These agents are useful in the treatment of hypertensive patients who also have asthma, diabetes, angina, and/or peripheral vascular disease. 

Q13 A third type of agent available for the treatment of angina is a calcium channel blocker. Explain the pharmacological action of calcium channel blockers. 

Q13 Calcium channel blockers decrease the opening of L-type calcium channels in the plasma membrane of vascular smooth muscle cells, and so reduce intracellular calcium concentration and contractile activity. The blood vessels therefore dilate. Calcium channel blockers act mainly on the arterial side of the circulation, and the dihydropyridines, such as nifedipine, are useful coronary arteriolar dilator agents. These agents are usually the treatment of choice for Prinzmetal angina. 

Two groups of drugs, p-adrenergic blockers and calcium channel blockers, are used in both hypertension and angina. Several drugs for hypertension are used also in the treatment of heart failure. 

Dihydropyridine calcium channel blockers (CCBs) have been used for many years in the treatment of angina pectoris and hypertension (81). Their mechanism of action is based on inhibition of the smooth muscle L-type calcium current, thereby... 

Verapamil, proprietaiy name Calan, is a calcium channel blocker that is effective in the treatment of various cardiovascular disorders, including angina (classical and variant), arrhythmias (paroxysmal supraventricular tachycardia), atrial flutter, atrial fibrillation, hypertrophic cardiomyopathy (idiopathic hypertrophic subaortic stenosis), hypertension, congestive heart failure, and Raynaud s phenomenon, along with the preservation of ischemic myocardium and the treatment of migraine headaches. 

There are approximately a dozen calcium channel antagonists marketed in the United States for the treatment of hypertension, certain dysrhythmias, and some forms of angina (see Chaps. 13,15, and 17). The calcium channel blockers are classified by their chemical structure as phenylalkylamines (e.g., verapamil), benzothiapines (e.g., diltiazem), and dihydropyridines (e.g., amlodipine, felodipine, nicardipine, and nifedipine). Several of these agents, namely, diltiazem, nicardipine, nifedipine, and verapamil, are formulated as sustained-release oral dosage forms or have a slow onset of action and longer half-life (e.g., amlodipine " ), allowing once-daily administration. 

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