Atrioventricular block verapamil

CCB non- Angina pectoris Atrioventricular block Constipation (verapamil)... 

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... 

Verapamil can induce atrioventricular block when used in large doses or in patients with atrioventricular nodal disease. This block can be treated with atropine and 3-receptor stimulants. 

Verapamil s cardiotoxic effects are dose-related and usually avoidable. A common error has been to administer intravenous verapamil to a patient with ventricular tachycardia misdiagnosed as supraventricular tachycardia. In this setting, hypotension and ventricular fibrillation can occur. Verapamil s negative inotropic effects may limit its clinical usefulness in diseased hearts (see Chapter 12 Vasodilators the Treatment of Angina Pectoris). Verapamil can lead to atrioventricular block when used in large doses or in patients with atrio-ventricular nodal disease. This block can be treated with atropine and -receptor stimulants. In patients with sinus node disease, verapamil can precipitate sinus arrest. 

The incidence of atrioventricular block has been reported in 600 consecutive patients who underwent stress myocardial perfusion imaging with adenosine (140 micrograms/kg/minute for 6 minutes), and of whom 43 had first-degree heart block before adenosine and 557 had a baseline PR interval less than 200 ms (Table 1) (31). The heart block in all cases was of short duration, was not associated with any specific symptoms, and in no case required specific treatment. The risk of atrioventricular block during adenosine infusion was not increased by the presence of other drugs that might have caused atrioventricular block (digitalis, beta-blockers, diltiazem, verapamil). 

A serious bradydysrhythmia with complete atrioventricular block occurred after some months of conventional verapamil at normal doses and dose-adjusted digoxin in a 72-year-old woman with chronic renal insufficiency of unknown cause the atrioventricular block resolved after 2 hours of hemodialysis (8). 

A 79-year-old white woman developed extreme fatigue and dizziness (34). Her heart rate was 40/minute and her blood pressure 80/40 mmHg. An electrocardiogram showed complete atrioventricular block, an escape rhythm at 50/minute, and QT interval prolongation to 583 milliseconds. This event was attributed to concomitant treatment with verapamil 480 mg/day and erythromycin 2000 mg/day, which had been prescribed 1 week before admission. 

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. ... 

Another report describes atrioventricular block in a patient with a pacemaker when treated with digoxin, flecainide and verapamil. ... 

A patient given quinidine gluconate 648 mg every 6 hours had an increase in serum quinidine levels iiom 2.6 to 5.7 mierograms/mL when given verapamil 80 mg every 8 hours for a week. He became dizzy and had blurred vision and was found to have atrioventricular block (heart rate 38 bpm) and a systolic blood pressure of 50 mmHg. In a subsequent study in this patient it was found that the verapamil halved the quinidine clearanee and almost doubled the serum half-life. ... 

Important differences between the available calcium channel blockers arise from the details of their interactions with cardiac ion channels and, as noted above, differences in their relative smooth muscle versus cardiac effects. Sodium channel block is modest with verapamil, and still less marked with diltiazem. It is negligible with nifedipine and other dihydropyridines. Verapamil and diltiazem interact kinetically with the calcium channel receptor in a different manner than the dihydropyridines they block tachycardias in calcium-dependent cells, eg, the atrioventricular node, more selectively than do the dihydropyridines. (See Chapter 14 for additional details.) On the other hand, the dihydropyridines appear to block smooth muscle calcium channels at concentrations below those required for significant cardiac effects they are therefore less depressant on the heart than verapamil or diltiazem. 

Verapamil blocks both activated and inactivated L-type calcium channels. Thus, its effect is more marked in tissues that fire frequently, those that are less completely polarized at rest, and those in which activation depends exclusively on the calcium current, such as the sinoatrial and atrioventricular nodes. Atrioventricular nodal conduction time and effective refractory period are invariably prolonged by therapeutic concentrations. Verapamil usually slows the sinoatrial node by its direct action, but its hypotensive action may occasionally result in a small reflex increase of sinoatrial nodal rate. 

The major toxicities are extensions of their therapeutic effects. Frequent or severe adverse effects include dizziness, headache, edema, constipation (especially verapamil), atrioventricular (AV) block, bradycardia, heart failure, and lupus-like rash with... 

Patients with impaired function of the sinus node or impaired atrioventricular conduction can develop sinus bradycardia, sinus arrest, heart block, hypotension and shock, and even asystole, with verapamil (139) or diltiazem. These drugs should not be given to patients with aberrant conduction pathways associated with broad-complex tachydysrhythmias, and they can cause severe conduction disturbances in hypertrophic cardiomyopathy. 

ADVERSE EEEECTS AND PRECAUTIONS The /3 adrenergic blocking agents should be avoided in patients with asthma, with sinoatrial or atrioventricular (AV) nodal dysfunction, or in combination with other drugs that inhibit AV conduction, such as verapamil. Patients with type 1 diabetes mellitus also are better treated with other drugs e.g., ACE inhibitors). 

C. Clinical Use and Toxicities Calcium channel blockers are effective for converting atrioventricular nodal reentry (also known as nodal tachycardia) to normal sinus rhythm. Their major use is in the prevention of these nodal arrhythmias in patients prone to recurrence. These drugs are orally active verapamil is also available for parenteral use (Table 14—2). The most important toxicity of verapamil is excessive pharmacologic effect, since cardiac contractility, AV conduction, and blood pressure can be significantly depressed. See Chapter 12 for additional discussion of toxicity. Amiodarone has moderate calcium channel-blocking activity. 

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