Verapamil, antiarrhythmic action

Verapamil possesses antiarrhythmic, antianginal, and hypotensive activity. It reduces the myocardial need for oxygen by reducing contractility of the myocardium and slowing the frequency of cardiac contractions. It causes dilation of coronary arteries and increased coronary blood flow. It reduces tonicity of smooth musculature, peripheral arteries, and overall peripheral vascular resistance. It provides antiarrhythmic action in supraventricular arrhythmia. 

Fig. 6. Influences of different types of antiarrhythmic agents (Vaughan-William s classification) on the shape of cardiac action potentials. First row Class I-agents action potentials of ventricular myocardial cells. Second row (from left to right) Action potential of SA-node cells influence of a )0-hlocker (class II). Action potential of ventricular myocardial cells influence of a class Ill-antiarrhythmic. Action potential of AV nodal cells influence of a class IV-antiarrhythmic (verapamil, diltiazem).

The antiarrhythmic actions and uses of diltiazem (Cardizem see Chapter 19) are similar to those of verapamil. Diltiazem is effective in controlling the ventricular rate in patients with atrial flutter or atrial fibrillation. The pharmacology of diltiazem is discussed in detail in Chapter 19. 

Rowland E, McKenna WJ, Krikler DM. Electrophysiologic and antiarrhythmic actions of bepridil. Comparison with verapamil and ajmaline for atrioventricular reentrant tachycardia. Am J Cardiol 1985 55(13 Pt 1) 1513-19. 

Verapamil. Verapamil hydrochloride (see Table 1) is a synthetic papaverine [58-74-2] C2qH2 N04, derivative that was originally studied as a smooth muscle relaxant. It was later found to have properties of a new class of dmgs that inhibited transmembrane calcium movements. It is a (+),(—) racemic mixture. The (+)-isomer has local anesthetic properties and may exert effects on the fast sodium channel and slow phase 0 depolarization of the action potential. The (—)-isomer affects the slow calcium channel. Verapamil is an effective antiarrhythmic agent for supraventricular AV nodal reentrant arrhythmias (V1-2) and for controlling the ventricular response to atrial fibrillation (1,2,71—73). 

Verapamil (Class IV antiarrhythmic drug) is an effective agent for atrial or supraventricular tachycardia. A Ca++ channel blocker, it is most potent in tissues where the action potentials depend on calcium currents, including slow-response tissues such as the SA node and the AV node. The effects of verapamil include a decrease in heart rate and in conduction velocity of the electrical impulse through the AV node. The resulting increase in duration of the AV nodal delay, which is illustrated by a lengthening of the PR segment in the ECG, reduces the number of impulses permitted to penetrate to the ventricles to cause contraction. 

Verapamil (Isoptin, Covera), in addition to its use as an antiarrhythmic agent, has been employed extensively in the management of variant (Prinzmetal s) angina and effort-induced angina pectoris (see Chapters 17 and 19). It selectively inhibits the voltage-gated calcium channel that is vital for action potential genesis in slow-response myocytes, such as those found in the sinoatrial and A-V nodes. 

As noted above, the antiarrhythmic drugs can modify impulse generation and conduction. More than a dozen such drugs that are potentially useful in treating arrhythmias are currently available. However, only a limited number of these agents are clinically beneficial in the treatment of selected arrhythmias. For example, the acute termination of ventricular tachycardia by lidocaine or supraventricular tachycardia by adenosine or verapamil are examples in which antiarrhythmic therapy results in decreased morbidity. In contrast, many of the antiarrhythmic agents are now known to have lethal proarrhythmic actions, that is, to cause arrhythmias. 

Therapeutic uses. Because of their narrow therapeutic margin, antiarrhythmics are only employed when rhythm disturbances are of such severity as to impair the pumping action of the heart, or when there is a threat of other complications. Combinations of different antiarrhythmics are not recommended (e.g., quinidine plus verapamil). Some agents, such as amiodarone, are reserved for special cases. This iodine-containing substance has unusual properties its elimination half-life is 50-70 days depending on its electrical charge, it is bound to apolar and polar lipids, stored in tissues (corneal opacification, pulmonary fibrosis) and it interferes with thyroid function. 

Calcium channel blockers inhibit the passage of calcium through the membrane charmels the result in myocardial cells is to depress contractility, and in pacemaker cells to suppress their automatic activity. Members of the group therefore may have negative cardiac inotropic and chronotropic actions. These actions can be separated nifedipine, at therapeutic concentrations, acts almost exclusively on noncardiac ion charmels and has no clinically useful anti-arrhythmic activity whilst verapamil is a useful antiarrhythmic. 

The roule (raveled by a Ca channel blocker, such as verapamil, (o its receptor site parallels (hat observed with many local aneslhetic-like antiarrhythmic agents. It i.s believed that verapamil, like mo.sl of (he Ca channel blockers. crosses the cell membrane in an uncharged form to gain access to its site of action on the intracellular side of the membrane. Data show a greater affinity of verapamil and other Ca- channel hlockers to the inactivated. state of the channel. ... 

IV) ANTIARRHYTHMIC. It is a SMOOTH MUSCLE RELAXANT and coronary VASODILATOR. It can be used as an antihypertensive and antianginal. and in antimigraine prophylaxis, verapamil hydrochloride verapamil, veratridine is an alkaloid from Schoenocaulon officinale (Liliaceae), and is a neurotoxin and sodium-Channel ACTIVATOR that binds to Na -channels, leading to depolarization. It has similar but weaker actions to batrachotoxin. Vercyte pipobroman. 

Class IV antiarrhythmic drugs are Ca2+ channel blockers that decrease the SA and AV nodal activity and the slope of phase 4 of the action potential in pacemakers. The uses and adverse effects of verapamil... 

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