Calcium channel blockers negative inotropic effects

INHALATIONAL CALCIUM CHANNEL BLOCKERS t hypotensive effects of dihydropyridines, and hypotensive/bradycardic effects of diltiazem and verapamil Additive hypotensive and negative inotropic effects. General anaesthetics tend to be myocardial depressants and vasodilators they also 1 sinus automaticity and AV conduction Monitor BP and ECG closely... 

Verapamil. Verapamil hydrochloride is a pbenyl alkyl amine and is considered the prototype of the Class I calcium channel blockers. Verapamil is also a potent inhibitor of coronary artery spasm and is useful in Prinzmetal s angina and in unstable angina at rest. Verapamil produces negative chronotropic and inotropic effects. These two actions reduce myocardial oxygen consumption and probably account for the effectiveness of verapamil in chronic stable effort angina (98,99). Moreover, verapamil is an effective antihypertensive agent. 

Treatment with nondihydropyridine calcium channel blockers (diltiazem and verapamil) may worsen HF and increase the risk of death in patients with advanced LV dysfunction due to their negative inotropic effects. Conversely, dihydropyridine calcium channel blockers, although negative inotropes in vitro, do not appear to decrease contractility in vivo. Amlodipine and felodipine are the two most extensively studied dihydropyridine calcium channel blockers for systolic H F.39 4() These two agents have not been shown to affect patient survival, either positively or negatively. As such, they are not routinely recommended as part of a standard HF regimen however, amlodipine and felodipine can safely be used... 

Current data suggest little benefit on clinical outcomes beyond symptom relief for calcium channel blockers in the setting of ACS.43 Moreover, the use of first-generation shortacting dihydropyridines, such as nifedipine, should be avoided because they appear to worsen outcomes through their negative inotropic effects, induction of reflex sympathetic activation, tachycardia, and increased myocardial ischemia.43 Therefore, calcium channel blockers should be avoided in the acute management of MI unless there is a clear symptomatic need or a contraindication to p-blockers. 

Calcium-channel blockers interfere with the inward movement of calcium ions through the cell membrane channels. This results in reduction of myocardial contractility (hence negative inotropes), reduction of cardiac output and arteriolar vasodilatation. The dihydropyridine group, such as nifedipine and amlodipine, which may be used in the management of hypertension, are very effective as arterial vasodilators, whereas diltiazem and verapamil are very effective in reducing atrioventricular conduction. 

Amlodipine is a calcium-channel blocker that blocks the intracellular movement of calcium ions and hence slows the contractility of the myocardium and relaxes the vascular smooth muscle. The negative inotropic effects are rarely seen at therapeutic doses since amlodipine has a greater selectivity for vascular smooth muscle than for the myocardium. 

Verapamil and diltiazem have negative inotropic effects. These calcium channel blockers may be harmful in asymptomatic patients with a low LVEF and in post-MI patients without HF symptoms. Digoxin will not be good to use in patients with low FF, with sinus rhythm and no history of HF symptoms, because the benefits will not exceed the risk. 

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. 

Volatile anaesthetics, calcium channel-entry blockers, and some anti-arrhythmic drugs may potentiate the negative inotropic effect of the 3-adrenoceptor antagonists. Concomitant digoxin therapy may cause AV dissociation. Potentiation of the hypoglycaemic effects of insulin and oral antidiabetic drugs may occur. 

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. 

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. 

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 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... 

CALCIUM CHANNEL BLOCKERS BACLOFEN AND TIZANIDINE t hypotensive effect with baclofen of tizanidine. Risk of bradycardia with tizanidine Additive hypotensive effect. Tizanidine has a negative inotropic and chronotropic effect Monitor BP at least weekly until stable. Warn patients to report symptoms of hypotension (light-headedness, dizziness on standing, etc.)... 

Calcium channel blockers in combination with bupivacaine produce significant negative inotropic effects on the heart in animals, possibly due to reduced protein... 

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. ... 

Calcium-channel blockers potentiate the negative inotropic effects of type la antiarrhythmic agents. 

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