Calcium channel blockers heart failure with

ACE inhibitors can be administered with diuretics (qv), cardiac glycosides, -adrenoceptor blockers, and calcium channel blockers. Clinical trials indicate they are generally free from serious side effects. The effectiveness of enalapril, another ACE inhibitor, in preventing patient mortaUty in severe (Class IV) heart failure was investigated. In combination with conventional dmgs such as vasodilators and diuretics, a 40% reduction in mortaUty was observed after six months of treatment using 2.5—40 mg/d of enalapril (141). However, patients complain of cough, and occasionally rash and taste disturbances can occur. 

Patients with asymptomatic left ventricular systolic dysfunction and hypertension should be treated with P-blockers and ACE inhibitors. Those with heart failure secondary to left ventricular dysfunction and hypertension should be treated with drugs proven to also reduce the morbidity and mortality of heart failure, including P-blockers, ACE inhibitors, ARBs, aldosterone antagonists, and diuretics for symptom control as well as antihypertensive effect. In African-Americans with heart failure and left ventricular systolic dysfunction, combination therapy with nitrates and hydralazine not only affords a morbidity and mortality benefit, but may also be useful as antihypertensive therapy if needed.66 The dihydropyridine calcium channel blockers amlodipine or felodipine may also be used in patients with heart failure and left ventricular systolic dysfunction for uncontrolled blood pressure, although they have no effect on heart failure morbidity and mortality in these patients.49 For patients with heart failure and preserved ejection fraction, antihypertensive therapies that should be considered include P-blockers, ACE inhibitors, ARBs, calcium channel blockers (including nondihydropyridine agents), diuretics, and others as needed to control blood pressure.2,49... 

Adverse effects and contraindications of calcium channel blockers are described in Table 5-2. Verapamil, diltiazem, and first-generation dihydropyridines should also be avoided in patients with acute decompensated heart failure or left... 

As described in the previous section, calcium channel blockers should not be administered to most patients with ACS. Their role is a second-line treatment for patients with certain contraindications to P-blockers and those with continued ischemia despite P-blocker and nitrate therapy. Administration of either amlodipine, diltiazem, or verapamil is preferred.2 Agent selection is based on heart rate and left ventricular dysfunction (diltiazem and verapamil are contraindicated in patients with bradycardia, heart block, or systolic heart failure). Dosing and contraindications are described in Table 5-2. 

Although P-blockers should be avoided in patients with decompensated heart failure from left ventricular systolic dysfunction complicating an MI, clinical trial data suggest that it is safe to initiate P-blockers prior to hospital discharge in these patients once heart failure symptoms have resolved.64 These patients may actually benefit more than those without left ventricular dysfunction.65 In patients who cannot tolerate or have a contraindication to a P-blocker, a calcium channel blocker can be used to prevent anginal symptoms, but should not be used routinely in the absence of such symptoms.2,3,62... 

Intravenous diltiazem can be used cautiously for up to 24 hours in patients with non-decompensated heart failure, bpm, beats per minute CCB, calcium channel blocker (diltiazem or verapamil) HF, heart failure LV, left ventricular LVEF, left ventricular ejection fraction. 

FIGURE 6-6. Decision algorithm for long-term ventricular rate control with oral drug therapy for patients with paroxysmal or permanent atrial fibrillation, bpm, beats per minute CCB, calcium channel blocker (diltiazem or verapamil) HF, heart failure LV, left ventricular function LVEF, left ventricular ejection fraction. (Algorithm adapted with permission from Tisdale JE, Moser LR. Tachyarrhythmias. In Mueller BA, Bertch KE, Dunsworth TS, et al. (eds.) Pharmacotherapy Self-Assessment Program, 4th ed. Kansas City American College of Clinical Pharmacy 2001 ... 

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. 

The pharmacokinetic properties of these drugs are set forth in Table 12-5. The choice of a particular calcium channel-blocking agent should be made with knowledge of its specific potential adverse effects as well as its pharmacologic properties. Nifedipine does not decrease atrioventricular conduction and therefore can be used more safely than verapamil or diltiazem in the presence of atrioventricular conduction abnormalities. A combination of verapamil or diltiazem with 3 blockers may produce atrioventricular block and depression of ventricular function. In the presence of overt heart failure, all calcium channel blockers can cause further worsening of heart failure as a result of their negative inotropic effect. Amlodipine, however, does not increase the mortality of patients with heart failure due to nonischemic left ventricular systolic dysfunction and can be used safely in these patients. 

Chronic heart failure is typically managed by reduction in physical activity, low dietary intake of sodium (less than 1500 mg sodium per day), and treatment with vasodilators, diuretics and inotropic agents. Drugs that may precipitate or exacerbate CHF—nonsteroidal antiinflammatory drugs (NSAIDs), alcohol, (3-blockers, calcium channel-blockers and some antiarrhythmic drugs—should be avoided if possible. Patients with CHF complain of dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea, fatigue, and dependent edema. 

Dilation of venous blood vessels leads to a decrease in cardiac preload by increasing venous capacitance arterial dilators reduce systemic arteriolar resistance and decrease afterload. Nitrates (see p. 175) are commonly employed venous dilators for patients with congestive heart failure. If the patient is intolerant of ACE inhibitors, the combination of hydralazine and isosorbide dinitrate is most commonly used. Amlodipine and felodipine (see p. 188) have less negative inotropic effect than other calcium channel blockers, and seem to decrease sympathetic nervous activity. 

Medications such as P-blockers, calcium channel blockers, digoxin, and amiodarone can be used to control cardiac conduction abnormalities (arrhythmias), and a pacemaker may be inserted to combat heart failure. The general supportive care measures used in acute stroke syndromes also should be followed. Death in patients with MELAS is usually the result of cardiac failure, pulmonary embolus, or renal failure. 

Thiazide diuretics are ineffective once the GFR becomes less than 25 mL/min, and loop diuretics are often used at high doses (e.g. furosemide 500 mg to 1 g daily) to gain an effect. Metolazone is effective when combined with a loop diuretic. Potassium-sparing diuretics such as amiloride are not recommended. Spironolactone is not generally used, but is beneficial in low dose for the treatment of heart failure even in patients on dialysis. Beta-blockers and calcium channel blockers are generally well tolerated. Any ankle swelling with calcium channel blockers must not be confused with fluid overload. 

AMIODARONE CALCIUM CHANNEL BLOCKERS Risk of bradycardia, AV block and 1 BP when amiodarone coadministered with diltiazem or verapamil Additive negative inotropic and chronotropic effect. Also, amiodarone inhibits intestinal P-gp, which t the bioavailability of diltiazem and verapamil Monitor PR, BP and ECG closely watch for heart failure... 

CALCIUM CHANNEL BLOCKERS DISOPYRAMIDE Risk of myocardial depression and asystole when disopyramide is co-administered with verapamil, particularly in the presence of heart failure Disopyramide is a myocardial depressant like verapamil and can cause ventricular tachycardia, ventricular fibrillation or torsades de pointes Avoid co-administering verapamil with disopyramide if possible. If single-agent therapy is ineffective, monitor PR, BP and ECG closely watch for heart failure... 

CALCIUM CHANNEL BLOCKERS DOXORUBICIN t serum concentrations and efficacy of doxorubicin when co-administered with verapamil, nicardipine and possibly diltiazem and nifedipine however, no cases of doxorubicin toxicity have been reported Uncertain however, verapamil is known to inhibit intestinal P-gp, which may t the bioavailability of doxorubicin Watch for symptoms/signs of toxicity (tachycardia, heart failure and hand-foot syndrome)... 

CALCIUM CHANNEL BLOCKERS FAMOTIDINE Reports of heart failure and l BP when famotidine is given with nifedipine Additive negative inotropic effects Caution when co-administering famotidine with calcium channel blockers, especially in elderly people... 

BACLOFEN, TIZANIDINE 1. ANAESTHETICS - general 2. ANTICANCER AND IMMUNOMODULATING DRUGS - IL-2 3. ANTIDEPRESSANTS - MAOIs 4. ANTI HYPERTENSIVES AND HEART FAILURE DRUGS 5. ANTI-PSYCHOTICS 6. ANXIOLYTICS AND HYPNOTICS 7. BETA-BLOCKERS 8. CALCIUM CHANNEL BLOCKERS 9. DIURETICS 10. NITRATES 11. PERIPHERAL VASODILATORS-moxisylyte (thymoxamine) 12. POTASSIUM CHANNEL ACTIVATORS t hypotensive effect Additive hypotensive effect. Tizanidine also has a negative chronotropic effect and may cause additive bradycardia with beta-blockers and calcium channel blockers Monitor BP at least weekly until stable. Warn patients to report symptoms of hypotension (light-headedness, dizziness on standing, etc.)... 

FLUCONAZOLE, ITRACONAZOLE, KETOCONAZOLE, POSACONAZOLE, VORICONAZOLE CALCIUM CHANNEL BLOCKERS Plasma concentrations of dihydropyridine calcium channel blockers are t by fluconazole, itraconazole and ketoconazole. Risk of t verapamil levels with ketoconazole and itraconazole. Itraconazole and possibly posaconazole may t diltiazem levels The azoles are potent inhibitors of CYP3A4 isoenzymes, which metabolize calcium channel blockers. They also inhibit CYP2C9-mediated metabolism of verapamil. Ketoconazole and itraconazole both inhibit intestinal P-gp, which may t bioavailability of verapamil. Diltiazem is mainly a substrate of CYP3A5 and CYP3A5P1, which are inhibited by itraconazole. 75% of the metabolism of diltiazem occurs in the liver and the rest in the intestine. Diltiazem is a substrate of P-gp (also an inhibitor but unlikely to be significant at therapeutic doses), which is inhibited by itraconazole, resulting in t bioavailability of diltiazem Monitor PR, BP and ECG, and warn patents to watch for symptoms/signs of heart failure... 

OESTROGENS 1. ANTIHYPERTENSIVES AND HEART FAILURE DRUGS 2. BETA-BLOCKERS 3. CALCIUM CHANNEL BLOCKERS 4. NITRATES f hypotensive effect Oestrogens cause sodium and fluid retention Monitor BP at least weekly until stable the routine prescription of oestrogens in patients with t BP is not advisable... 

Amlodipine is a long-acting dihydropyridine calcium channel blocker. It has an adverse effects profile similar to those of other dihydropyridines, but at a lower frequency (1). Along with felodipine (2), but unlike other calcium channel blockers, it may also be safer in severe chronic heart failure when there is concurrent angina or hypertension (3). 

Vasodilatory calcium channel blockers have been reported to improve exercise tolerance in some preliminary studies. A multicenter, randomized, placebo-con-trolled trial was therefore performed in 437 patients with mild to moderate heart failure to assess the effects of amlodipine 10 mg/day in addition to standard therapy (5). Over 12 weeks amlodipine did not improve exercise time and did not increase the incidence of adverse events. 

It has been argued that dihydropyridine calcium channel blockers, which increase heart rate, can all increase the risk of death and reinfarction (35,36). Early beneficial results with diltiazem in patients with non-Q-wave infarction (37) were not confirmed in the Multicenter Diltiazem Postinfarction Trial (38). In patients with pulmonary congestion, diltiazem was associated with an increase in cardiac events, and there was a similar result in patients with low ejection fractions. However, verapamil does appear to reduce reinfarction (39), a benefit that is more marked in those without heart failure (40). Nifedipine may also have a detrimental effect in unstable angina it certainly appears to offer no benefit (41). 

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