Verapamil antiarrhythmic activity

After po dosing, verapamil s absorption is rapid and almost complete (>90%). There is extensive first-pass hepatic metabolism and only 10—35% of the po dose is bioavahable. About 90% of the dmg is bound to plasma proteins. Peak plasma concentrations are achieved in 1—2 h, although effects on AV nodal conduction may be apparent in 30 min (1—2 min after iv adrninistration). Therapeutic plasma concentrations are 0.125—0.400 p.g/mL. Verapamil is metabolized in the liver and 12 metabolites have been identified. The principal metabolite, norverapamil, has about 20% of the antiarrhythmic activity of verapamil (3). The plasma half-life after iv infusion is 2—5 h whereas after repeated po doses it is 4.5—12 h. In patients with liver disease the elimination half-life may be increased to 13 h. Approximately 50% of a po dose is excreted as metabolites in the urine in 24 h and 70% within five days. About 16% is excreted in the feces and about 3—4% is excreted as unchanged dmg (1,2). 

Antiarrhythmic activity (verapamil, possibly also diltiazem) impairment of AV conduction and to a lesser degree also that of sinus node activity. 

Reduction of the left ventricular outflow obstruction and antiarrhythmic activity underlying the beneficial effect of verapamil. 

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. 

It is noteworthy that calcium inhibitory compounds with the ability to inhibit %a+ possess the most potent antiarrhythmic activity against both experimental and clinical arrhythmias (126). For example, nifedipine exerts minimal, if any, antiarrhythmic effect against ischemic induced arrhythmias in intact animals (6, 87, 131). Diltiazem and perhexiline, on the other hand, demonstrate variable antiarrhythmic effects dependent upon their dose and the mechanism responsible for arrhythmia production (ischemia, hypoxia, digitalis, aconitine) (102, 126, 151, 152). Only verapamil, which has been investigated in the largest number of experimental and clinical trials, has demonstrated consistent antiarrhythmic activity against cardiac arrhythmias regardless of cause (155) ... 

Verapamil possesses antiarrhythmic, antianginal, and hypotensive activity. It reduces the myocardial need of oxygen by reducing contractibility of the myocardium and slowing the freqnency of cardiac contractions. It canses dilation of coronary arteries and increases... 

During the last decades several drugs and compounds have been identified that to different degrees are able to overcome MDR so that the cells resemble sensitive cells in their chemosensitivity. These drugs mainly include catamphiphilic, membrane-active compounds and belong to various classes of drugs such as calcium channel blockers (verapamil), neuroleptics (flupentixol), anesthetics, antimalarial drugs (quinidine), antiarrhythmics (amiodarone), and many other compounds. Reviews were recently published [61, 157]. 

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. 

Raschack, M. Relationship of antiarrhythmic to inotropic activity and antiarrhythmic qualities of the optical isomers of verapamil. Arch. Pharmacol. 1976, 294 (3), 285-291. 

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. 

Tamargo et al gave a very recent review.139 They point out that KATP channels are inhibited by ATP and activated by Mg ADP, so that the channel activity is influenced by the ATP/ADP ratio. They also draw attention to the fact that mitochondrial KATp channel is responsible for ischemic preconditioning. They suggest that these channels are not blocked only by sulfonylureas, but also by many antiarrhythmic drugs, such as bretylium, disopyramide, flecainide and propafenone, and also by diltiazem and verapamil, but not by amiodarone or dronedarone, which will be addressed later. 

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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