Verapamil contraindications

As described above, 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 /S-blockers and those with continued ischemia despite /S-blocker and nitrate therapy. They are a first-line therapy in patients with Prinzmetal s vasospastic angina and those with cocaine-associated ACS. Administration of either am-lodipine, diltiazem, or verapamil is preferred. Agent selection based on heart rate and LV dysfunction (diltiazem and verapamil contraindicated in patients with bradycardia, heart block, or systolic heart failure) is described in more detail in the section Early Pharmacotherapy for ST-Segment-Elevation ACS above. Dosing and contraindications are described in Table 16-4. 

Calcium is contraindicated in patients with hypercalcemia or ventricular fibrillation and in patients taking digitalis. Calcium is used cautiously in patients with cardiac disease. Hypercalcemia may occur when calcium is administered with the thiazide diuretics. When calcium is administered with atenolol there is a decrease in Hie effect of atenolol, possibly resulting in decreased beta blockade. There is an increased risk of digitalis toxicity when digitalis preparations are administered with calcium. The clinical effect of verapamil may be decreased when the drug is administered with calcium. Concurrent ingestion of spinach or cereal may decrease file absorption of calcium supplements. 

Blockers are contraindicated in patients with severe bradycardia (heart rate less than 50 beats per minute) or AV conduction defects in the absence of a pacemaker. (3-Blockers should be used with particular caution in combination with other agents that depress AV conduction (e.g., digoxin, verapamil, and diltiazem) because of increased risk for bradycardia and heart block. Relative contraindications include asthma, bronchospastic disease, severe depression, and peripheral vascular disease. (3,-Selective blockers are preferred in patients with asthma or chronic obstructive pulmonary... 

In randomized, controlled, clinical trials, calcium channel blockers were as effective as p-blockers at preventing ischemic symptoms. Calcium channel blockers are recommended as initial treatment in IHD when /3-blockers are contraindicated or not tolerated. In addition, CCBs may be used in combination with /3-blockers when initial treatment is unsuccessful. However, the combination of a (1-blocker with either verapamil or diltiazem should be used with extreme caution since all of these drugs decrease AV nodal conduction, increasing the risk for severe bradycardia or AV block when used together. If combination therapy is warranted, a long-acting dihydropyridine CCB is preferred. (3-Blockers will prevent reflex increases in sympathetic tone and heart rate with the use of calcium channel blockers with potent vasodilatory effects. 

STE ACS class lla recommendation and NSTE ACS class I recommendation for patients with ongoing ischemia who are already taking adequate doses of nitrates and P-blockers or in patients with contraindications to or intolerance to P-blockers (diltiazem or verapamil for STE ACS and diltiazem, verapamil, or amlodipine for NSTE ACS). 

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... 

Dihydropyridine channel blockers (e.g., nifedipine) have little benefit on clinical outcomes beyond symptom relief. The role of verapamil and diltiazem appears to be limited to symptom relief or control of heart rate in patients with supraventricular arrhythmias in whom /l-blockers are contraindicated or ineffective. 

In symptomatic patients, medical therapy can be tailored either to control ventricular response or to restore sinus rhythm. Nondihydropyridine calcium antagonists (e.g., verapamil) are considered first-line drug therapy for decreasing ventricular response. Type I agents (e.g., procainamide, quinidine) are only occasionally effective in restoring sinus rhythm. DCC is ineffective, and /3-blockers are usually contraindicated because of coexisting severe pulmonary disease or uncompensated HF. 

Good candidates for calcium channel antagonists include patients with contraindications or intolerance to /3-blockers, coexisting conduction system disease (excluding the use of verapamil and possibly diltiazem), Prinzmetal angina, peripheral vascular disease, severe ventricular dysfunction, and concurrent hypertension. Amlodipine is probably the agent of choice in severe ventricular dysfunction, and the other dihydropyridines should be used with caution if the EF is less than 40%. 

QT prolongation common. Concurrent use with cimetidine, verapamil, ketoconazole contraindicated. 

Beta-blocker AND ACE-I (ARB if ACE-I intolerant). Verapamil if beta-blockers contraindicated. If heart failure, see below... 

Contraindications include baseline prolongation of the QT interval, use of other QT-prolonging drugs history of torsades de pointes a creatinine clearance of less than 20 mL/minute simultaneous use of verapamil, cimetidine, or ketoconazole uncorrected hypokalemia or hypomagnesemia and pregnancy or breast-feeding. 

Contraindications Concurrent use of drugs that prolong the QT interval concurrent use of amiodarone, megestrol, prochlorperazine, or verapamil congenital or acquired prolonged QT syndrome paroxysmal atrial fibrillation severe renal impairment... 

As noted earlier, lithium is contraindicated in patients with unstable congestive heart failure or the sick sinus node syndrome ( 307, 328). In older patients or those with prior cardiac histories, a pretreatment ECG should be obtained. Except for the potential adverse interactions with diuretics, the concomitant use of other cardiac drugs is generally safe. Because verapamil may lower serum levels of lithium, however, more careful monitoring may be required to assure continued therapeutic effects (329). Some data also indicate that verapamil may predispose to lithium neurotoxicity. Conversely, increased lithium levels leading to toxicity has occurred with methyidopa and enalapril. When antihypertensive therapy is necessary, b-blockers are a reasonable choice when lithium is coadministered. 

Dofetilide is 100% bioavailable. Verapamil increases peak plasma dofetilide concentration by increasing intestinal blood flow. Eighty percent of an oral dose is eliminated by the kidneys unchanged the remainder is eliminated by the kidneys as inactive metabolites. Inhibitors of the renal cation secretion mechanism, eg, cimetidine, prolong the half-life of dofetilide. Since the QT-prolonging effects and risks of ventricular proarrhythmia are directly related to plasma concentration, dofetilide dose must be based on the estimated creatinine clearance. Treatment with dofetilide should be initiated in hospital after baseline measurement of the QTc and serum electrolytes. A baseline QTC of > 450 ms (500 ms in the presence of an intraventricular conduction delay), bradycardia of < 50 beats/min, and hypokalemia are relative contraindications to its use. 

Approximately 25% of all patients with hypertrophic cardiomyopathy (HCM) have latent left ventricular outflow obstruction with an intraventricular gradient (I). Pathophysiologic features are asymmetric hypertrophy of the septum and a systolic anterior movement of the anterior leaflet. Medical treatment includes betablockers, and calcium antagonists of the verapamil type. Approximately 5— 10% of the patients with outflow obstruction are refractory to such negative inotropic therapy (2). Positive inotropic drugs such as digitalis or sympathomimetics are strictly contraindicated. In the presence of atrial fibrillation, anticoagulation therapy should be started. Since endocarditis is more common in patients with HCM because of turbulence in the left ventricle, prophylactic antibiotics should be administered for periods of potential bacteraemia. 

Verapamil and diltiazem are prototypic calcium channel blockers. As indicated previously, these drugs influence cardiac function by blocking inward calcium movement through L channels. In so doing they block conduction velocity in SA and AV node cells. They are used therapeutically to treat reentry arrhythmias through the AV node as well as paroxysmal supraventricular tachycardias. In fact, verapamil has been reported to terminate 60-80 percent of paroxysmal supraventricular tachycardias within several minutes. However, because of their potent effect on AV conduction, these drugs are contraindicated in patients with preexisting conduction problems since they may produce complete AV block. 

Adverse effects Verapamil and diltiazem have negative inotropic properties and therefore may be contraindicated in patients with preexisting depressed cardiac function. Both drugs can also cause a decrease in blood pressure caused by peripheral vasodilation. 

Verapamil [ver AP a mill] slows cardiac conduction directly and thus decreases heart rate and oxygen demand. Verapamil causes greater negative inotropic effects than does nifedipine, but it is a weaker vasodilator. Verapamil is contraindicated in patients with preexisting depressed cardiac function or AV conduction abnormalities. It also causes constipation. Verapamil should be used with caution in digitalized patients, since it increases digoxin levels (see p. 160). 

There is some anecdotal evidence that atrioventricular nodal blockade with verapamil or a beta-blocker can also be effective. However, in two cases the addition of a beta-blocker (either atenolol or metoprolol) to treatment with class I antidysrhythmic drugs (cibenzoline in one case and flecainide in the other) did not prevent the occurrence of atrial flutter with a 1 1 response (47). However, the author suggested that in these cases, although the beta-blockers had not suppressed the dysrhythmia, they had at least improved the patient s tolerance of it. In both cases the uses of class I antidysrhythmic drugs was contraindicated by virtue of structural damage, in the first case due to mitral valvular disease and in the second due to an ischemic cardiomyopathy. 

Good candidates for calcium channel blockers in angina include patients with contraindications to or intolerance of /3-blockers, those with coexisting conduction system disease (except for verapamil and diltiazem), those with Prinzmetal s angina (vasospastic or variable-threshold angina), those with peripheral vascular disease, those with severe ventricular dysfunction (amlopidine is probably the calcium channel blocker of choice, and others need to be used with caution if the ejection fraction is less than 40%), and those with concurrent hypertension. 

Although earlier trials suggested that verapamil and diltiazem may provide improved benefit in selected patients, the large Incomplete Infarction Trial of European Research Collaborators Evaluating Prognosis post-Thrombolysis (INTERCEPT) has dampened the interest for the use of diltiazem in patients receiving fibrinolytics. In this trial, the use of extended-release diltiazem had no effect on the 6-month risk of cardiac death, MI, or recurrent ischemia. Therefore, the role of verapamil or diltiazem appears to be limited to relief of ischemia-related symptoms or control of heart rate in patients with supraventricular arrhythmias for whom /8-blockers are contraindicated or ineffective. ... 

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. ... 

Heart block is a contraindication for the nondihydropyridines. The most common side effects are bradycardia and heart block (for the nondihydropyridines). Peripheral edema and headache are also common. Nondihydropyridines exacerbate bradycardic effects of /S-blockers, and verapamil raises digoxin serum concentrations by 70%. Diltiazem raises cyclosporine serum concentrations. Intravenous calcium salts inhibit the pharmacologic effect of CCBs. Generic formulations or similar products, but not necessarily generic equivalents to the original brand names, are available for verapamil, nifedipine, and diltiazem. 

The goal of treatment of patients with HCM is primarily to reduce their symptoms of dyspnea and exercise intolerance. Either /3-blockers or CCBs may be used. If a /3-blocker is chosen, it is best to use an agent that does not have intrinsic sympathomimetic activity. The dose should be maximized. If the patient does not tolerate a -blocker or has a contraindication to the use of a /3-blocker, then verapamil may be tried. Patients should be monitored for resolution of symptoms and an increase in exercise tolerance. Resolution of symptoms may take months to occur. In addition, both 8-bIockers and CCBs may cause hypotension and conduction abnormalities. -Blockers may worsen pulmonary function. If dyspnea continues with maximal doses of a /3-blocker or CCB, a diuretic agent or a nitrate may be added with caution. Patients who are at high risk for sudden cardiac death should be considered candidates for an ICD. 

The calcium channel blockers generally are considered seconder third-line options for preventive treatment when other drugs with established clinical benefit are ineffective or contraindicated. Verapamil is the most widely used calcium chaimel blocker for preventive treatment, but it provided only modest benefit in decreasing the frequency of attacks in two placebo-controlled studies." The therapeutic effect of verapamil may not be noted for up to 8 weeks after initiation of therapy. Side effects of verapamil may include constipation, hypotension, bradycardia, atrioventricular block, and exacerbation of congestive heart failure. Evaluations of nifedipine, nimodipine, diltiazem, and nicardipine have yielded equivocal results. ... 

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