Do calcium channel blockers affect cardiac muscle?

Uses

Calcium channel blockers are used in the management of angina pectoris, hypertension, supraventricular arrhythmias, subarachnoid hemorrhage, and pulmonary hypertension, and for the prevention of migraine. They are recommended for the treatment of angina in patients with certain coexisting medical conditions such as asthma, chronic obstructive pulmonary disease, mild peripheral vascular disease, and severe peripheral vascular disease with rest ischemia. Calcium channel blockers may be used to inhibit uterine contractions to delay delivery during preterm labor (tocolytic therapy). They are sometimes used in the treatment of Raynaud's disease.

Hematologic

Calcium channel blockers rarely cause hematological effects. A hemorrhagic diathesis, including impaired platelet function, develops in chronic renal insufficiency, in which calcium channel blockers are used widely as antihypertensive agents. In 156 patients with moderate to severe chronic renal insufficiency not on hemodialysis calcium channel blockers prolonged the bleeding time (OR = 3.52; 95% CI = 1.01, 12.3) [84]. However, despite this effect, there were no clinically serious hemorrhagic events during the study. Among those taking calcium channel blockers, 21 patients with prolonged bleeding times were randomly assigned to two groups; in one group treatment was withdrawn and bleeding time shortened; in those who continued to take the treatment the bleeding time was unchanged.

Nifedipine has been reported to cause agranulocytosis [85] and leukopenia was attributed to diltiazem; the latter patient had scleroderma, active rheumatoid disease, and pulmonary fibrosis, but the white cell count fell after 3 weeks of diltiazem, recovered on withdrawal, and fell on rechallenge [86]. Diltiazem has also been reported to cause immune thrombocytopenia in a 68-year-old man with angina [87].

Acute and Short-Term Toxicity (or Exposure)

Calcium channel blockers

Calcium channel blockers are not useful in the therapy of complex VA. Although verapamil can terminate a left septal VT, hemodynamic collapse can occur if intravenous verapamil is given to persons with the more common forms of VT. An analysis was made of randomized, controlled clinical trials including 20,342 patients that investigated the use of calcium channel blockers after MI.45 Mortality was insignificantly increased in persons receiving calcium channel blockers than in persons receiving no antiarrhythmic drugs (odds ratio = 1.04).45

On the basis of the available data, none of the calcium channel blockers should be used to treat VT or complex VA in elderly or younger persons with heart disease.

Calcium-Channel Blockers

Calcium-channel blockers decrease peripheral vascular resistance and, therefore, are theoretically ideal antihypertensive agents in the elderly. Long-acting dihydropyridine agents have been beneficial in the treatment of isolated systolic hypertension.28,88 Because calcium channel blockers have no adverse effects on serum lipids and are less likely than β -blockers to cause fatigue, they are generally well tolerated. Most preparations of calcium channel blockers are available in sustained-release formulations, which can be taken once a day.

Calcium channel blockers do have side effects that are important for some patients. Verapamil and diltiazem can cause cardiac conduction defects and may impair myocardial contractility; thus, they should be avoided if a patient has an impaired ejection fraction. Nifedipine and amlodipine may cause peripheral edema. Calcium channel blockers are also associated with gingival hyperplasia (which may lead to problems with denture fit) and with constipation.

Mouth and Teeth

Calcium channel blockers

Calcium channel blockers are used to treat hypertension and cardiac disease, including angina and arrhythmias. Verapamil is a calcium channel blocker that may, rarely, cause extrapyramidal symptoms, including chorea and dystonia. In one report, a 28-year old woman developed an acute dystonic reaction after three doses of verapamil over a 3-day period (Pina et al., 1998). Her symptoms included oral-lingual dystonia, retrotorticollis, and oculogyric crisis (Pina et al., 1998). After treatment with 10 mg diazepam, her symptoms resolved within 24 hours. Another calcium channel blocker, nifedipine, has also been linked to myoclonic dystonia (de Medina et al., 1986). Although the exact mechanism of action for this effect is unknown, calcium channel blockers may alter the central production of dopamine through N-type calcium channels (Pina et al., 1998).

5.4 Calcium channel blockers

Calcium channel blockers (CCBs) prevent calcium entry to the PASMCs by inhibiting L-type voltage-dependent calcium channels to cause relaxation of SMCs and vasodilatation. CCBs are useful in the 5–15% of idiopathic PAH patients with a positive response to vasoreactivity testing. This test is done by inhaled nitric oxide, intravenous PGI2, or intravenous adenosine together with a reduction in mean PAP between 10 and 40 mmHg with preserving cardiac output (Sitbon et al., 2005). Prolonged survival, persistent functional and hemodynamic improvements can be obtained by CCB therapy in vasoreactive patients (Hemnes et al., 2015). Long-acting nifedipine, diltiazem or amlodipine are CCBs that are frequently used for the management of PAH (Zolty, 2020). The daily doses of CCB drugs in patients with IPAH are relatively high (amlodipine 20 mg, nifedipine 120–240 mg, or diltiazem 240–720 mg) (Thenappan et al., 2018; Yaghi et al., 2020). Verapamil is not suggested due to its negative inotropic effects. Although diltiazem can show negative inotropic effects, too, it is used preferably compared to amlodipine or nifedipine in patients with sinus or atrial tachycardia. Close monitoring should be done in patients receiving CCBs for adequate response and used specific treatments of PAH when symptoms progress (Table 2) (Thenappan et al., 2018).

Clinical applications

Calcium channel blockers are highly effective for treating paroxysmal supraventricular tachycardia. Diltiazem is particularly useful for slowing ventricular rate in patients with atrial fibrillation. Experimentally, calcium channel blockers are effective for suppressing accelerated idioventricular rhythms in dogs following shock-induced myocardial injury and myocardial infarction. They have also been effective at suppressing digitalis-induced ventricular arrhythmias in conscious experimental dogs. To our knowledge, however, no reports exist in the veterinary literature concerning the use of calcium channel blockers to suppress ventricular arrhythmias in canine patients.

The dihydropyridines are not useful for treating arrhythmias. Instead, they are used to treat heart failure secondary to mitral regurgitation as well as systemic hypertension in dogs and cats.

Calcium Channel Blockers.

Calcium channel blockers, which block norepinephrine-mediated calcium transport into vascular smooth muscle, have been used successfully at several medical centers to preoperatively prepare patients with pheochromocytoma.114 Nicardipine is the most commonly used calcium channel blocker in this setting; the starting dose is 30 mg twice daily of the sustained-release preparation (see Table 16-8).115,116 Nicardipine is given orally to control blood pressure preoperatively and if needed is given as an intravenous infusion intraoperatively (Table 16-9). Although there is less collective experience with calcium channel blockers than with α- and β-adrenergic blockers, when calcium channel blockers are used as the primary mode of antihypertensive therapy, they may be just as effective.116,117 Clearly, the exclusive use of calcium channel blockers for the perioperative management of patients with catecholamine-secreting tumors does not prevent all hemodynamic changes; however, its use has been associated with low morbidity and mortality rates.117 The main role for this class of drugs may be either to supplement the combined α- and β-adrenergic blockade protocol when blood pressure control is inadequate or to replace the adrenergic blockade protocol in patients with intolerable side effects.