Calcium channel blockers arrhythmias class

Sodium and potassium are not the only ions which can participate in pumps and channels. Calcium is also pumped, channeled, exhanged,and stored. See Figure 23. Calcium concentration within the cell cytoplasm is very low. This allows the calcium to play a pivotal role in cellular activity. The cytoplasmic protein calmodulin binds and stores calcium ion. Various intracellular structures and organelles such as the mitochondria and sarcoplasmic reticulum also store calcium. Calcium is vital to such functions as the release of neurotransmitters from nerve cells. There are at least seven known modes of biochemical action for this ion, one of the most important of which involves stimulation of cardiac muscle protein (actin-myosin). Certain types of angina (heart pain) are believed to be caused by abnormal stimulation of cardiac arteries and muscle (coronary spasm) A relatively new class of drugs, known as the calcium channel blockers, has brought relief from pain and arrhythmias (irregular heart beats). 

B Because this patient has asthma and is wheezing, calcium channel blockers are the drug class of choice. Unlike beta-blockers and adenosine, they do not cause bronchospasm. Beta-blockers and adenosine should be used cautiously in patients with obstructive lung disease, and use should be avoided in patients with asthma. Digoxin is not contraindicated, but it is not the drug of choice due to its slow onset. Amiodarone is indicated for ventricular arrhythmias, but not PSVT. 

Class I calcium channel blockers work preferentially on calcium ion channels in cardiac muscle cells. This results in a delay in electrical conduction in cardiac muscle, reduced contractility and reduction in the heart rate. Because of these effects, class I calcium channel blockers are used to treat ischaemic heart disease and atrial arrhythmia. An example is verapamil. 

While class 1 calcium channel blockers are used to treat atrial arrhythmia, class II and class 111 calcium channel blockers are now considered first-line therapy for many patients with hypertension. Resistant hypertension can be treated with add-on drugs ai-antagonists, centrally acting antihypertensives and adrenergic neurone blockers. 

Amiodarone (Cordarone) is an iodine-containing benzo-furan derivative identified as a class III agent because it predominantly prolongs action potentials. Amiodarone also blocks sodium and calcium channels and is a noncompetitive p-receptor blocker. Amiodarone is effective for the treatment of most arrhythmias. Toxicity associated with amiodarone has led the U. S. Food and Drug Administration (FDA) to recommend that it be reserved for use in patients with life-threatening arrhythmias. 

CCAs (channel blockers influx inhibitors) have been used primarily for the treatment of cardiovascular disorders (e.g., supraventricular arrhythmias, angina, and hypertension). Agents such as verapamil exert their effects by modulating the influx of Ca across the cell membrane, thus interfering with calcium-dependent functions. Based partly on the common effects of lithium and this class of drugs (e.g., effects on Ca "" activity), the CCAs have been studied as a potential treatment for mania. Janicak et al. (251) reported the results of a 3-week, double-blind comparison of verapamil versus placebo, which did not demonstrate a beneficial effect for verapamil (up to 480 mg/day) in 33 acutely manic hospitalized patients. 

Endogenous norepinephrine stimulates cardiac beta receptors. Receptor-linked cAMP-dependent protein kinases phosphorylate calcium channels to increase intracellular calcium. Elevated intracellular calcium increases conduction velocity (phase 0) and decreases the threshold potential in normal SA and AV node cells (see Figure 12.13). Beta blockers slow spontaneous conduction velocity in the SA node by approximately 10-20 percent. In addition, beta blockers can slow conduction velocity while increasing the refractory period of the AV node. These effects control the ventricular rate in atrial fibrillation or flutter and terminate paroxysmal supraventricular tachycardias. They are also safer, although somewhat less effective, than other drugs for suppression of premature ventricular complexes (PVCs). Drugs in this class approved by the FDA for treatment of various arrhythmias include propranolol, acebutolol, and esmolol. Problems with the beta blockers include drowsiness, fatigue, impotence, and depressed ventricular performance. 

A. Prototypes, Mechanisms, and Effects Beta-blockers are discussed in more detail in Chapter 10. Propranolol and esmolol are the prototype antiarrhythmic beta-blockers. Their mechanism in arrhythmias is primarily cardiac beta blockade and reduction in cAMP, which results in the reduction of both sodium and calcium currents and the suppression of abnormal pacemakers. The AV node is particularly sensitive to beta-blockers the PR interval is usually prolonged by class II drugs (Table 14-2). Under some conditions, these dmgs may have some direct local anesthetic (sodium channel-blocking) effect in the heart, but this is probably rare at the concentrations achieved clinically. 

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