Flecainide

IUPAC: (RS )-N -(2- piperidylmethyl ) - 2,5-bis - (2,2,2- trifluorethoxy ) benzamide

• C17H20F6N2O3 ( flecainide )
• C17H20F6N2O3 · C2H4O2 ( flecainide acetate · )

• 54143-55-4 ( flecainide )
• 54143-56-5 ( flecainide acetate · )

C01BC04

Antiarrhythmic

• 414.34 g · mol -1 ( flecainide )
• 474.39 g · mol -1 ( flecainide acetate · )

145-147 ° C ( flecainide acetate · )

Risk

1346 mg · kg -1 ( LD50, Rat, oral, acetate)

Template: Infobox chemical / molecular formula search available

Flecainide is a drug from the group of antiarrhythmic drugs, used to treat heart rhythm disorders. As sodium channel blockers have no effect on the duration of the action potential, it is counted to the class classification Ic (no change in the duration of the action potential ) of the Vaughan / Williams.

Representation and extraction

The synthesis of flecainide is achieved in three steps. The starting material 2,5-dihydroxybenzoic acid is completely etherified in the presence of sodium bicarbonate in the first step by means of 2,2,2- Trifluorethyltrifluormethansulfonat and esterified. The second step is the formation of an acid amide by reaction with 2- aminomethyl pyridine. The target compound arises by the hydrogenation of Pyridinfunktion in the presence of palladium on carbon. From the synthesis results, the racemate sequence.

Application

Supraventricular tachycardias ( eg AV junctional tachycardia, supraventricular tachycardia in WPW syndrome, paroxysmal atrial fibrillation), if they are symptomatic and require treatment. Life-threatening ventricular tachycardias.

Contraindications and warnings

Three months after myocardial infarction ( = heart attack), decompensated heart failure, significant electrolyte disturbance or marked hypotension may flecainide not be used in severe bradycardia, SA- blocking and high-grade AV block and sinus node syndrome, when a pacemaker is implanted. In cases of impaired cardiac pump function ( ejection fraction <35 %) it may be used only in the case of life-threatening ventricular Arrhyhtmien.

In case of hepatic or renal impairment, the dose should be adjusted. During therapy, renal function and the width of the QRS complex should be monitored in resting ECG. Flecainide has a very narrow therapeutic range between 0.2-1.0 micrograms / ml in serum. The toxic (harmful or toxic ) range starts from serum levels of 1.5 ug / ml. Overdoses - also due to reduced excretion in renal failure - must be avoided.

Possible side effects

Dizziness, headache, nausea, blurred vision, shortness of breath and indigestion. Rarely fatigue and increased perspiration. Very rarely, dry mouth, fever, muscle or joint pain, anxiety, allergic skin reactions and transient erectile dysfunction.

Especially feared are paradoxical proarrhythmic effects of flecainide, which may occur particularly in patients with coronary heart disease. This could, among other things by a beta -1 - adrenoceptor mediated additional sodium channel blockade can be explained by flecainide. Especially the polymorphism of the adrenergic beta -1 receptor at the points 389 and 49 of the amino acid chain of the receptor is an important predictor of flecainide sensitivity dar. Thus, some patients more likely to benefit by flecainide, for example, which are heterozygous at the points 389 and 49, and others ( Arg389Arg and Ser49Ser ) may be more likely at greater risk of suffering be proarrhythmogene side effects.

Trade names

Aristocor (A), Flecagamma (D), Tambocor (D, CH ), various generics (D)