Sotalol Alcohol

Decreased tremor of alcohol withdrawal decreased propranolol blood levels Increased sotalol blood levels... 

Clinically important, potentially hazardous interactions with alcohol, amiodarone, amphotericin B, cisapride, clonidine, digitalis, diltiazem, disopyramide, erythromycin, glucocorticoids, halofantrine, haloperidol, hypokalemic diruretics, imipramine antidepressants, levodopa, lithium, pentamidine, pimozide, quinidine, sotalol, stimulant laxatives, tetracosactides, thioridazine... 

The synthesis of several sulfonamidophenethanolamines, including sotalol, has been described previously (3). The synthesis of the sulfonamidophenethanolamine compounds relied upon firstly obtaining a 2-aminoacyIsulfonanilide precursor. The alcohol formed from the ketone precursor is via either palladium-catalyzed low-pressure hydrogenation or sodium borohydride chemical reduction (3). 

The infrared spectrum of sotalol hydrochloride is depicted in Figure 4. The spectrum was obtained on a KBr disk using a Nicolet 20 SX Fourier Transform infrared spectrometer. Diagnostic peaks were observed at 3570 cm (secondary alcohol, free) 3410 cm l (secondary alcohol, H-bonded) 2700-2800 cm l and 2950-3200 cm l (hydrochloride) 1325 cm (S=0 asymmetric stretch) 1154 cm l (S=0 symmetric stretch). The peaks are presented in Table I. 

The haemodynamic and pharmacokinetic effects of atenolol and metoprolol in heaithy subjects do not appear to be changed by al-cohoi. There is some evidence that alcohol modestly reduces the haemodynamic effects of propranolol, and some of the effects of sotalol may also be changed by alcohol. Some evidence suggests that the effects of alcohol and atenolol/chlortalidone or propranolol are additive on the performance of some psychomotor tests, but the importance of this is uncertain. 

A further study in 6 healthy subjects found that although the blood pressure lowering effects of sotdol 160 mg were increased by alcohol, sotalol did not cancel out the alcohol-induced rise in heart rate. ... 

A 63-year-old woman with a non-ischemic dilated cardiomyopathy possibly caused by alcohol had paroxysmal atrial fibrillation for which she took sotalol 80 mg bd. She took oseltamivir 75 mg bd for presumed influenza and after 4 days developed ventricular fibrillation. Sinus rhythm was restored with multiple shocks and intravenous magnesium. The serum potassium was normal at 4.1 mmol/1. Electrocardiography showed a QT, interval of 521 ms. The QT interval gradually shortened after withdrawal of both sotalol and oseltamivir. 

In 1997, chemists from the Process Exploration Labs at Bristol-Myers Squibb Company reported their development of a simple asymmetric synthesis of d-sotalol 105, a Class III antiarrythmia compound, utilising a CBS reduction as the key step (Scheme 14.34). ° Previous efforts towards synthesis of d-sotalol had utilised techniques such as mandelic acid resolution, chiral chromatography and use of chiral homogeneous hydrogenation. The synthesis of d-sotalol via a CBS reduction is of interest as the molecule contains a methanesulfonamide NH proton, which clearly does not interfere with the yield or enantioselectivity of the process despite the acidic nature of this substituent. The authors discuss the various elements of the reduction process that they investigated and conclude that the optimal procedure involves addition of 1 M BH3 THE over a few minutes to a mixture of the (5 )-2-MeCBS catalyst and substrate ketone 102 in MTBE held at room temperature. Under these reaction conditions (on a 1.8 mmol scale), alcohol 103 was obtained in 92% yield with 96% ee. In this instance, the enantiomeric excess was calculated by conversion of the alcohol product to... 

Clonidine may potentiate the effects of alcohol, sedatives and CNS depressants (102 ). High doses of clonidine combined with high doses of propranolol were in several cases associated with the development of nightmares, delusion and marked drowsiness (8 ). The combination of clonidine with the 3-adrenergic blocker Sotalol gave rise to an antagonistic effect, comprising a marked rise of blood pressure in 3 out of 6 cases so treated (103 ). 

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