digoxin and 1-4-dihydropyridine

Atrial fibrillation (AF), the most common form of sustained arrhythmia, is associated with a frightening risk of embolic complications, tachycardia-related ventricular dysfunction, and often disabling symptoms. Pharmacologic therapy is the treatment used most commonly to restore and maintain sinus rhythm, to prevent recurrences, or to control ventricular response rate.. This article reviews published data on pharmacologic treatment and discusses alternative systems to classify AF and to choose appropriate pharmacologic therapy.. AF is either paroxysmal or chronic. Attacks of paroxysmal AF can differ in duration, frequency, and functional tolerance. In the new classification system described, 3 clinical aspects of paroxysmal AF are distinguished on the basis of their implications for therapy. Chronic AF usually occurs in association with clinical conditions that cause atrial distention. The risk of chronic AF is significantly increased by the presence of congestive heart failure or rheumatic heart disease. Mortality rate is greater among patients with chronic AF regardless of the presence of coexisting cardiac disease. The various options available for the treatment of chronic AF include restoration of sinus rhythm or control of ventricular rate. Cardioversion may be accomplished with pharmacologic or electrical treatment. For patients in whom cardioversion is not indicated or who have not responded to this therapy, antiarrhythmic agents used to control ventricular response rate include nondihydropyridine calcium antagonists, digoxin, or beta-blockers. For patients who are successfully cardioverted, sodium channel blockers or potassium channel blockers such as sotalol, amiodarone, or a pure class III agent such as dofetilide, a selective potassium channel blocker, may be used to prevent recurrent AF to maintain normal sinus rhythm.. The ultimate choice of the antiarrhythmic drug will depend on the presence or absence of structural heart disease. An additional concern with chronic AF is the risk of arterial embolization resulting from atrial stasis and the formation of thrombi. In patients with chronic AF the risk of embolic stroke is increased 6-fold. Therefore anticoagulant therapy should be considered in patients at high risk for embolization. Selection of the appropriate treatment should be based on the concepts recently developed by the Sicilian Gambit Group (based on the specific channels blocked by the antiarrhythmic agent) and on clinical experience gained over the years with antiarrhythmic agents. For example, termination of AF is best accomplished with either a sodium channel blocker (class I agent) or a potassium channel blocker (class III agent). In contrast, ventricular response rate is readily controlled by a beta-blocker (propranolol) or a calcium channel blocker (verapamil). Alternatively, antiarrhythmic drug therapy may be chosen based on the Vaughan-Williams classification, which identifies the cellular electrophysiologic effects of the drug.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Chronic Disease; Digoxin; Dihydropyridines; Drug Administration Routes; Electrocardiography; Embolism; Heart Rate; Humans; Practice Guidelines as Topic; Prognosis; Propranolol; Secondary Prevention; Tachycardia, Paroxysmal; Verapamil

Treatment with the angiotensin-converting enzyme inhibitor, quinapril, has been shown to normalize increased dihydropyridine sensitivity and impaired potassium relaxation, characteristic features of arterial smooth muscle in spontaneously hypertensive rats, and also reduce the concentration of plasma digoxin-like immunoreactivity in these animals. However, whether angiotensin II receptor blocker therapy can beneficially influence these variables is not known. Therefore, we compared the effects of 10-week losartan and enalapril treatments (15 and 4 mg/kg/day, respectively) on functional responses of mesenteric arterial rings in spontaneously hypertensive rats and Wistar-Kyoto rats. Both losartan and enalapril normalized blood pressure, cardiac mass, and media to lumen ratio without significantly changing the media cross-sectional area in the mesenteric artery of spontaneously hypertensive rats (i.e. induced outward remodelling). The inhibitory effect of the calcium entry blocker nifedipine on calcium-evoked contractions was similar and less marked in arterial preparations from Wistar-Kyoto rats and losartan- and enalapril-treated spontaneously hypertensive rats than in those from untreated spontaneously hypertensive rats. Furthermore, the relaxations of arterial rings induced by the return of potassium to the organ bath (upon precontractions elicited by potassium-free solution) were used to evaluate the function of vascular Na+,K+-ATPase. The rate of potassium relaxation was faster in losartan- and enalapril-treated spontaneously hypertensive rats and all Wistar-Kyoto groups than in untreated spontaneously hypertensive rats, and the response was effectively inhibited by the sodium pump inhibitor ouabain. Both treatments especially augmented the ouabain-sensitive part of the potassium-relaxation in spontaneously hypertensive rats, indicating the involvement of the sodium pump in this response. However, no significant changes in plasma digoxin-like immunoreactivity were observed. In conclusion, the outward remodelling following long-term AT1-receptor blockade and angiotensin-converting enzyme inhibition in spontaneously hypertensive rats was associated with normalization of the increased dihydropyridine sensitivity of arteries. Both losartan and enalapril treatments also augmented arterial potassium relaxation in spontaneously hypertensive rats, suggesting enhanced function of Na+,K+-ATPase, but this effect could not be attributed to changes in circulating s

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Blood Pressure; Body Weight; Cardiomegaly; Digoxin; Dihydropyridines; Enalapril; Heart; Hypertension; Losartan; Male; Mesenteric Arteries; Muscle, Smooth, Vascular; Nifedipine; Organ Size; Potassium Chloride; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Sodium-Potassium-Exchanging ATPase; Tunica Media

The binding of nitrendipine to transverse (T) tubules isolated from skeletal muscle triads is inhibited by dithiothreitol (KI approximately 0.05 mM) and glutathione (KI approximately 3 mM). The t 1/2's of inhibition (18.3 and 11.5 min, respectively) suggest that these hydrophylic reagents act upon the exposed surface of the vesicles. Dithiothreitol shifts the apparent KD for nitrendipine from 8.5 nM to 30 nM without altering the Bmax extrapolated by Scatchard analysis. That T-tubules isolated by disruption of triad junctions are constrained to have the protoplasmic (P) face uniformly exposed was experimentally confirmed. These studies show that a sulfhydryl residue on the P-face of the T-tubule influences the affinity of the receptor for dihydropyridines.

Topics: Animals; Digoxin; Dihydropyridines; Dithiothreitol; Glutathione; Glutathione Disulfide; Muscles; Nifedipine; Nitrendipine; Ouabain; Pyridines; Rabbits; Sulfhydryl Compounds