Disopyramide effects

Further class IA drugs include the open state blockers procainamide and disopyramide with electrophysiolog-ical effects similar to those of quinidine procainamide lacks the antimuscarinic and antiadrenergic effects. Characteristic side effects of procainamide are hypotension and immunological disorders. 

Amantadine is used cautiously in patients with seizure disorders, psychiatric problems, renal impairment, and cardiac disease. Amantadine is a Pregnancy Category B drug and is used cautiously during pregnancy and lactation. Concurrent use of antihistamines, phenothiazines, tricyclic antidepressants, disopyramide, and quinidine may increase the anticholinergic effects (dry mouth, blurred vision, constipation) of amantadine... 

The antiemetics and antivertigo drug may have additive effects when used with alcohol and other CNS depressants such as sedatives, hypnotics, antianxiety drugp, opiates, and antidepressants. There may be additive anticholinergic effects (see Chap. 25) when administered with drag s that have anticholinergic activity such as the antihistamines, antidepressants, pheno-thiazines, and disopyramide The antacids decrease absorption of the antiemetics. 

All antiarrhythmic dra are used cautiously in patients with renal or hepatic disease. When renal or hepatic dysfunction is present, a dosage reduction may be necessary. All patients should be observed for renal and hepatic dysfunction. Quinidine and procainamide are used cautiously in patients with CHF. Disopyramide is used cautiously in patients with CHF, myasthenia gravis, or glaucoma, and in men with prostate enlargement. Bretylium is used cautiously in patients with digitalis toxicity because the initial release of norepinephrine with digitalis toxicity may exacerbate arrhythmias and symptoms of toxicity. Verapamil is used cautiously in patients with a history of serious ventricular arrhythmias or CHF. Electrolyte disturbances such as hypokalemia, hyperkalemia, or hypomagnesemia may alter the effects of the antiarrhythmic dru . Electrolytes are monitored frequently and imbalances corrected as soon as possible... 

When two antiarrhythmic dragp are administered concurrently the patient may experience additive effects and is at increased risk for drug toxicity. When quinidine and procainamide are administered with digitalis, tiie risk of digitalis toxicity is increased. Hiarmacologic effects of procainamide may be increased when procainamide is administered with quinidine When quinidine is administered with the barbiturates or cimetidine, quinidine serum levels may be increased. When quinidine is administered with verapamil, there is an increased risk of hypotensive effects. When quinidine is administered with disopyramide, there is an increased risk of increased disopyramide blood levels and/or decreased serum quinidine levels. 

ADMINISTERING DISOPYRAMIDE. Because of the cholinergic blocking effects of disopyramide (see Chap. 25), urinary retention may occur. The nurse monitors the urinary output closely, especially during the initial period of therapy. If the patient s intake is sufficient but the output is low, the lower abdomen is... 

The following are examples of substances that may increase the blood glucose-lowering effect and susceptibility to hypoglycemia oral antidiabetic products, ACE inhibitors, disopyramide, fibrates, fluoxetine, MAO inhibitors, pentoxifylline, propoxyphene, salicylates, and sulfonamide antibiotics. 

In the event of increased anticholinergic side effects, plasma levels of disopyramide should be monitored and the dose of the drug adjusted accordingly. A reduction of the dose by one third, from the recommended 600 mg/day to 400 mg/day, would be... 

Concomitant antiarrhythmic therapy Reserve concomitant use of disopyramide with other class lA antiarrhythmics or propranolol for life-threatening arrhythmias unresponsive to a single agent. Such use may produce serious negative inotropic effects or may excessively prolong conduction, particularly with cardiac decompensation. 

Potassium imbalance Disopyramide may be ineffective in f7ypokalemia and its toxic effects may be enhanced in /lyperkalemia. Correct any potassium deficit before instituting therapy. 

Drugs that may affect flecainide include amiodarone, cimetidine, cisapride, disopyramide, propranolol, ritonavir, urinary acidifiers/alkalinizers, and verapamil. Smoking may also have an effect. Drugs that may be affected by flecainide include cisapride, propranolol, and digoxin. 

Rifampin is known to induce the hepatic microsomal enzymes that metabolize various drugs such as acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta blockers, chloramphenicol, clofibrate, oral contraceptives, corticosteroids, cyclosporine, disopyramide, estrogens, hydantoins, mexiletine, quinidine, sulfones, sulfonylureas, theophyllines, tocainide, verapamil, digoxin, enalapril, morphine, nifedipine, ondansetron, progestins, protease inhibitors, buspirone, delavirdine, doxycycline, fluoroquinolones, losartan, macrolides, sulfonylureas, tacrolimus, thyroid hormones, TCAs, zolpidem, zidovudine, and ketoconazole. The therapeutic effects of these drugs may be decreased. 

The effects of disopyramide on the myocardium and specialized conduction tissue (Table 16.2) are a composite of its direct actions on cardiac tissue and its indirect actions mediated by competitive blockade of muscarinic cholinergic receptors. 

Abnormal atrial automaticity may be abolished at disopyramide plasma concentrations that fail to alter either conduction velocity or refractoriness. Disopyramide increases atrial refractoriness in patients pretreated with atropine, suggesting that the primary action of disopyramide is a direct one and not a consequence of its anticholinergic effect. 

Disopyramide depresses conduction velocity and increases the ERP of the A-V node through a direct action. Its anticholinergic actions, however, produce an increase in conduction velocity and a decrease in the ERP. The net effect of disopyramide on A-V nodal... 

The effect of disopyramide on conduction velocity depends on extracellular K+ concentrations. Hypokalemic patients may respond poorly to the antiar-rhythmic action of disopyramide, whereas hyperkalemia may accentuate the drug s depressant actions. 

Disopyramide directly depresses myocardial contractility. The negative inotropic effect may be detrimental in patients with compromised cardiac function. Some patients develop overt congestive heart failure. At usual therapeutic doses, depression of myocardial function is not a problem in most patients with normal ventricular function. 

The major toxic reactions to disopyramide administration include hypotension, congestive heart failure, and conduction disturbances. These effects are the result of disopyramide s ability to depress myocardial contractility and myocardial conduction. Although disopyramide initially may produce ventricular tachyarrhythmias or ventricular fibrillation in some patients, the incidence of disopyramide-induced syncope in long-term therapy is not known. Most other toxic reactions (e.g., dry mouth, blurred vision, constipation) can be attributed to the anticholinergic properties of the drug. 

In the presence of phenytoin, the metabolism of disopyramide is increased (reducing its effective concentration) and the accumulation of its metabolites is also increased, thereby increasing the probability of anticholinergic adverse effects. Rifampin also stimulates the hepatic metaboUsm of disopyramide, reducing its plasma concentration. 

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