Class IV antiarrhythmics

Class IV antiarrhythmic drugs are Ca2+ channel blockers, which predominantly slow sinus rate and atrioventricular conduction and thus are used in the treatment of supraventricular tachyarrhythmias. These drugs exert a pronounced negative inotropic effect. 

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. 

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 class IV-antiarrhythmics are the calcium antagonists, but remain limited to verapamil and possibly also diltiazem. The dihydropyridines (nifedipine and related compounds) are unsuitable for antiarrhythmic therapy. The antiarrhythmic activity of verapamil and diltiazem is based upon the impairment of AV conduction and heart rate. A few compounds may be considered to act as antiarrhyth-mics, but they are not included in the Vaughan-Williams classification. 

Another very successful apphcation of nonlinear dynamics to the heart is through mathematical modehng. An example in which a simple model based on coupled oscillators describes the dynamics of agonist induced vasomotion is in the work of de Brouwer et al. [586], where the route to chaos in the presence of verapamil, a class IV antiarrhythmic drug, is studied. 

Ca+ + Antiangina drugs Antihypertensive drugs Class IV antiarrhythmics Amlodipine, diltiazem, felodipine, nifedipine, verapamil Amlodipine, diltiazem, felodipine, isradipine, nifedipine, verapamil Diltiazem, verapamil... 

Class IV antiarrhythmic drugs can slow or block phase 0 in slow-response fibers. 

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... 

Inhibits L-type Ca" channels in cardiac and vascular smooth muscle cells more selective for the myocardium with minimal vasodilatory effects compared with dihydropyridines class IV antiarrhythmic agents Inhibits L-type Ca " " channels in cardiac and vascular smooth muscle cells by modulating ion channel gating mechanisms decreases systemic blood pressure and heart contractility Binds with high affinity to the alpha2-delta subunit of voltagegated Ca " " channels in CNS anticonvulsant drug Inhibits neuronal fast Nay channels, and thus blocks the action potential inhibits also cardiac Nay channels... 

Diltiazem malate MK-793. Calcium channel blocker with coronary vasodilating xtivity. Class IV antiarrhythmic. Antianginal antihypertensive class IV antiarrhythmic. Bristol Myers Squibb Pharm. Ltd. Forest Pharm. Inc. Fldchst AG (USA) Lemmon Co. Rhdne-Poulenc Rarer Pharm. Inc. 

Describe the effect of class IV antiarrhythmics on the cardiac action potential. 

Would class IV antiarrhythmics be useful in ventricular arrhythmias arising from ectopic foci in the Purkinje fibers ... 

I Depolarization (phase 0) is due to Na influx in fast fibers and due to Ca influx in SA and AV nodal i cells. Class I antiarrhythmic drugs block Na influx and class IV antiarrhythmics block Ca " influx. 

---