Diltiazem heart failure

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. 

Diltiazem Hypotension, sinus bradycardia, heart failure exacerbation, AV block... 

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 ... 

Verapamil decreases heart rate, slows atrioventricular (AV) nodal conduction, and produces a negative inotropic effect that may precipitate heart failure in patients with borderline cardiac reserve. Diltiazem decreases AV conduction and heart rate to a lesser extent than verapamil. 

Diltiazem and verapamil can cause cardiac conduction abnormalities such as bradycardia, AV block, and heart failure. Both can cause anorexia, nausea, peripheral edema, and hypotension. Verapamil causes constipation in about 7% of patients. 

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. 

Headache, flush, dizziness, hypotension, ankle oedema (mostly dihydropyridines), bradycardia, and impaired atrioventricular conduction (verapamil and, to a lesser extent, diltiazem), constipation (verapamil), heart failure (verapamil, rare), oesophageal reflux. 

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. 

Verapamil, diltiazem Nonselective block of L-type calcium channels in vessels and heart Reduced vascular resistance, cardiac rate, and cardiac force results in decreased oxygen demand Prophylaxis of angina, hypertension, others Oral, IV, duration 4-8 h Toxicity Atrioventricular block, acute heart failure constipation, edema Interactions Additive with other cardiac depressants and hypotensive drugs... 

Goldstein RE, Boccuzzi SJ, Cruess D, Nattel S. Diltiazem increases late-onset congestive heart failure in postinfarction patients with early reduction in ejection fraction. The Adverse Experience Committee and the Multicenter Diltiazem Postinfarction Research Group. Circulation 1991 83 52-60,... 

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... 

BETA-BLOCKERS DILTIAZEM t hypotensive and bradycardic effects cases of severe bradycardia and AV block when both drugs are administered concurrently in the presence of pre-existing heart failure or conduction abnormalities Additive effects on conduction diltiazem causes bradycardia, sinoatrial block and AV block. Also, diltiazem inhibits CYP1A2-mediated metabolism of propanolol Monitor PR, BP and ECG at least weekly until stable. Warn patients to report symptoms of hypotension (light-headedness, dizziness on standing, etc.)... 

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)... 

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... 

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). 

Similarly, verapamil should be used with caution in patients with heart failure, and both diltiazem and nifedipine can cause problems in patients with poor cardiac reserve. However, the PRAISE study (18) suggested that amlodipine may be used safely, even in the presence of severe heart failure optimally treated with diuretics. 

Mahgoub AA, El-Medany AH, Abdnlatif AS. A comparison between the effects of diltiazem and isosorbide dinitrate on digoxin pharmacodynamics and kinetics in the treatment of patients with chronic ischemic heart failure. Saudi Med J 2002 23(6) 725-31. 

The nondihydropyridine calcium channel blockers, such as verapamil and diltiazem, have efficacy rates similar to that of adenosine, but are considered second line. Intravenous calcium channel blockers have a few disadvantages. In contrast to adenosine, caution should be taken in hypotensive patients. Adenosine may cause hypotension, but appears to be safe in patients who present with hypotension due to the short half-life. In addition, calcium channel blockers also should be used with caution in patients with systolic heart failure, patients receiving concurrent beta-blocker therapy, and in those with accessory pathways. 

Diltiazem and verapamil can canse cardiac condnction abnor-mahties snch as bradycardia or atrioventricnlar block, bnt this occurs mostly with high doses. Heart failure has been reported in otherwise... 

Adverse effects and contraindications of calcium channel blockers are described in Table 16. Verapamil, diltiazem, and first-generation dihydropyridines also should be avoided in patients with acute decompensated heart failure or LV dysfunction because they can worsen heart failure and potentially increase mortality secondary to their negative inotropic effects. In patients with heart failure requiring treatment with a calcium channel blocker, amlodipine is the preferred agent. ... 

Diltiazem/verapamil Hypotension, bradycardia, heart block, heart failure, gingival hyperplasia BP and HR every 8 hours during oral administration during hospitalization then every 6 months following hospital discharge dental exam and teeth cleaning every 6 months... 

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