Supraventricular arrhythmias treatment

A regioselective Friedel-Crafts acylation was used to synthesize a novel derivative of amiodarone, a pharmaceutical compound used to treat ventricular and supraventricular arrhythmias. Treatment of 2-methyl-benzofuran with tin(IV) chloride in the presence of / -methoxybenzoyl chloride gave the desired product, 3-/7-methoxybenzoyl-2-methylbenzofuran, in 63% yield. 

Other agents are also used for the treatment of manic-depressive disorders based on preliminary clinical results (177). The antiepileptic carbamazepine [298-46-4] has been reported in some clinical studies to be therapeutically beneficial in mild-to-moderate manic depression. Carbamazepine treatment is used especially in bipolar patients intolerant to lithium or nonresponders. A majority of Hthium-resistant, rapidly cycling manic-depressive patients were reported in one study to improve on carbamazepine (178). Carbamazepine blocks noradrenaline reuptake and inhibits noradrenaline exocytosis. The main adverse events are those found commonly with antiepileptics, ie, vigilance problems, nystagmus, ataxia, and anemia, in addition to nausea, diarrhea, or constipation. Carbamazepine can be used in combination with lithium. Several clinical studies report that the calcium channel blocker verapamil [52-53-9] registered for angina pectoris and supraventricular arrhythmias, may also be effective in the treatment of acute mania. Its use as a mood stabilizer may be unrelated to its calcium-blocking properties. Verapamil also decreases the activity of several neurotransmitters. Severe manic depression is often treated with antipsychotics or benzodiazepine anxiolytics. 

Disopyr mide. Disopyramide phosphate, a phenylacetamide analogue, is a racemic mixture. The dmg can be adininistered po or iv and is useful in the treatment of ventricular and supraventricular arrhythmias (1,2). After po administration, absorption is rapid and nearly complete (83%). Binding to plasma protein is concentration-dependent (35—95%), but at therapeutic concentrations of 2—4 lg/mL, about 50% is protein-bound. Peak plasma concentrations are achieved in 0.5—3 h. The dmg is metabolized in the fiver to a mono-AJ-dealkylated product that has antiarrhythmic activity. The elimination half-life of the dmg is 4—10 h. About 80% of the dose is excreted by the kidneys, 50% is unchanged and 50% as metabolites 15% is excreted into the bile (1,2). 

Phenytoin. Phenytoin sodium is sodium diphenylhydantoin [630-93-3] which is stmcturally related to the barbiturates. It was originally introduced as an anticonvulsant (18) (see Hypnotics, sedatives, and anticonvulsants) and later found to have antiarrhythmic properties (19), although not approved by the PDA for any arrhythmic indications. Phenytoin is effective in the treatment of ventricular arrhythmias associated with acute MI and with digitalis toxicity (20). It is not very effective in treatment of supraventricular arrhythmias (20). 

Esmolol hydrochloride is a competitive p-adrenergic receptor antagonist it is selective for pT adrenoceptors. In contrast to pindolol, esmolol has little intrinsic sympathomimetic activity, and it differs from propranolol in that it lacks membrane stabilizing activity Of all of the p-adrenergic blocking drugs, this compound has the shortest duration of action because it is an ester, it is hydrolyzed rapidly by plasma esterases and must be used by the intravenous route Esmolol is approved only for the treatment of supraventricular arrhythmias... 

Common supraventricular tachycardias requiring drug treatment are atrial fibrillation (AF) or atrial flutter, paroxysmal supraventricular tachycardia (PSVT), and automatic atrial tachycardias. Other common supraventricular arrhythmias that usually do not require drug therapy are not discussed in this chapter (e.g., premature atrial complexes, wandering atrial pacemaker, sinus arrhythmia, sinus tachycardia). 

Phenytoin, like lidocaine, is more effective in the treatment of ventricular than supraventricular arrhythmias. It is particularly effective in treating ventricular arrhythmias associated with digitalis toxicity, acute myocardial infarction, open-heart surgery, anesthesia, cardiac catheterization, cardioversion, and angiographic studies. 

Approved indications for propafenone include treatment of supraventricular arrhythmias and life-threatening ventricular arrhythmias in the absence of structural heart disease. Propafenone has been shown to increase mortality in patients with structural heart disease, and so extreme caution must be used in this subset of patients. As with flecainide, the patient should be hospitalized for initiation of therapy. 

CCAs (channel blockers influx inhibitors) have been used primarily for the treatment of cardiovascular disorders (e.g., supraventricular arrhythmias, angina, and hypertension). Agents such as verapamil exert their effects by modulating the influx of Ca across the cell membrane, thus interfering with calcium-dependent functions. Based partly on the common effects of lithium and this class of drugs (e.g., effects on Ca "" activity), the CCAs have been studied as a potential treatment for mania. Janicak et al. (251) reported the results of a 3-week, double-blind comparison of verapamil versus placebo, which did not demonstrate a beneficial effect for verapamil (up to 480 mg/day) in 33 acutely manic hospitalized patients. 

Although disopyramide has been shown to be effective in a variety of supraventricular arrhythmias, in the USA it is approved only for the treatment of ventricular arrhythmias. 

In the USA, amiodarone is approved for oral and intravenous use to treat serious ventricular arrhythmias. However, the drug is also highly effective for the treatment of supraventricular arrhythmias such as atrial fibrillation. As a result of its broad spectrum of antiarrhythmic action, it is very extensively used for a wide variety of arrhythmias. Amiodarone has unusual pharmacokinetics and important extracardiac adverse effects. Dronedarone, an analog that lacks iodine atoms, is under investigation. 

Adenosine is the treatment of choice for diagnosis and reversal of supraventricular arrhythmias. Verapamil is an alternative for the management of narrow complex tachycardias. Amiodarone is the most effective drug at reversing atrial fibrillation, and in prevention of ventricular arrhythmias, but has several adverse effects. 

Beta blockers are used in the treatment of hypertension, angina pectoris, supraventricular arrhythmias, supraventricular tachycardia, sinus tachycardia, ventricular tachycardia, myocardial infarction, pheochro-mocytoma, migraine headache, and essential tumor. 

Procainamide, widely used in the treatment of ventricular and supraventricular arrhythmias in the past, recently had its use restricted to short-term treatments due to the induction of autoimmunity and the development of drug-induced lupus (Ayer et al., 1993 Kretz-Rommel Rubin, 1999). It has been suggested that procainamide-induced autoimmunity is characterized predominantly by an antihistone and anti-denatured DNA immune response (Rubin et al., 1986 Rubin, 1992 Mongey Hess, 2001). Mechanistic studies have revealed that procainamide is a competitive DNMT inhibitor of some, but not all, nuclear methyltransferase activity (Scheinbart et al., 1991 Richardson, 2003). 

Tetrandrine, a traditional medicinal alkaloid, has been used in China for the treatment of hypertension, cardiac arrhythmia, and angina pectoris. Recently, it has been shown that tetrandrine blocks voltage activated L-type Ca++ channels in a variety of excitable cells including cardiac tissue. The binding site of tetrandrine is located at the benzothiazepine receptor on the aj-subunit of the channel. It is clear that tetrandrine s actions in the treatment of cardiovascular diseases, including hypertension and supraventricular arrhythmia, are due primarily to its blocking of voltage activated L-type and T-type 08" + channels. 

Timolol is an effective antihypertensive agent. It improves exercise tolerance in patients with angina pectoris. It substantially reduces the long-term risk of sudden death and reinfarction in patients surviving acute myocardial infarction. It has been shown to reduce the size of an acute myocardial infarction when given intravenously within 4 hours after the onset of symptoms. Timolol is effective in the treatment of supraventricular arrhythmias and in certain cases of recurrent ventricular tachycardia. 

Patients with chronic atrial fibrillation—a common supraventricular arrhythmia—routinely receive warfarin to prevent the development of blood clots in the poorly contracting atrium and to decrease the risk of embolism of such clots to the brain or other tissues. Such patients are also often treated with anti arrhythmic drugs. The primary goals of antiarrhythmic treatment are to slow the atrial rate and, most importantly, control the ventricular rate. 

It is frequently employed in the control and management of ventricular and supraventricular arrhythmias, and also in the treatment of angina pectoris. 

Cardiac glycosides, such as digoxin and digitoxin (Fig. 20.40), are indicated for the treatment of heart failure and supraventricular arrhythmias. These two... 

Dmgs that mimic or inhibit the actions of neurotransmitters released from parasympathetic or sympathetic nerves innervating the heart may also be used to treat supraventricular bradyarrhythmias, heart block, and supraventricular tachyarrhythmias. Those used in the treatment of arrhythmias may be found in Table 1. 

These dm are primarily used in the treatment of hypertension (see the Summary Drug Table Adrenergic Blocking Drugs also see Chap. 39) and certain cardiac arrhythmias (abnormal rhythm of the heart), such as ventricular arrhythmias or supraventricular tachycardia They are used to prevent reinfarction in patients with a recent myocardial infarction (1—4 weeks after MI). Some of these dm have additional uses, such as the use of propranolol for migraine headaches and nadolol for angina pectoris. 

Amiodarone is useful in the treatment of supraventricular and ventricular arrhythmias. Amiodarone tends to hove a number of side-effects, such os photosensitivity. Patients ore advised to ovoid exposure to sunlight and apply a sun protection factor on a doily basis. Amiodarone may also cause reversible corneal microdeposits os a result of v/hich patients find night glare irritating and so patients ore advised to ovoid driving at night. 

Procainamide (Pwnestyl, Procan SR) is a derivative of the local anesthetic agent procaine. Procainamide has a longer half-life, does not cause CNS toxicity at therapeutic plasma concentrations, and is effective orally. Procainamide is a particularly useful antiarrhythmic drug, effective in the treatment of supraventricular, ventricular, and digitalis-induced arrhythmias. 

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