Procainamide

Procainamide was approved by the US FDA on June 2, 1950 under the brand name Pronestyl Due to the loss of Indonesia in World War II , a source for the quin alkaloid , the precursor of quinidine , the drug intake was greatly reduced. This led to the study of new antiarrhythmic drugs. As a result, procaine was found to have similar cardiac effects, like quinidine. ^[1] In 1936, it was investigated by Mautz that, applying it directly to the myocardium, the ventricular threshold for electrical stimulation was changed

An antiarrhythmic drug of class Ia, has a membrane-stabilizing effect. It inhibits the incoming fast current Na ⁺ , reduces the rate of depolarization to phase 0. It inhibits conduction, slows down repolarization. Reduces the excitability of the myocardium of the atria and ventricles . It increases the duration of the effective refractory period of the action potential (to a greater extent in the affected myocardium). The deceleration of conductivity, which is observed regardless of the magnitude of the resting potential, is more pronounced in the atria and ventricles, less in the AV node . The indirect m-anticholinergic effect, in comparison with quinidine and disopyramide , is less pronounced, therefore, a paradoxical improvement in AV conductivity is usually not observed. It affects depolarization phase 4, reduces the automatism of the intact and affected myocardium, inhibits the function of the sinus node and ectopic pacemakers in some patients. The active metabolite - N-acetylprocainamide (N-APA) has a pronounced activity of class III antiarrhythmic drugs, lengthens the duration of the action potential. It has a weak negative inotropic effect (without a significant effect on the minute volume of blood circulation ). It has vagolytic and vasodilating properties, which causes tachycardia and a decrease in blood pressure , general peripheral vascular resistance . Electrophysiological effects are manifested in the broadening of the QRS complex and the lengthening of the PQ and QT intervals. The time to achieve the maximum effect when taken orally is 60-90 minutes, with intravenous administration - immediately, with intramuscular - 15-60 minutes.

Absorption - up to 95%, fast. Bioavailability - 85%, communication with plasma proteins - 15-20%. TCmax for oral administration - 1-2 hours, Cmax in plasma - 10 μg / ml. Penetrates through the blood-brain barrier and the placental barrier , is secreted with breast milk . It has a “first pass” effect, is metabolized in the liver with the formation of an active metabolite - N-APA. About 25% of the injected procainamide is converted to the indicated metabolite, however, with rapid acetylation or with chronic renal failure , 40% of the dose is converted. In chronic renal failure or chronic heart failure, the metabolite rapidly accumulates in the blood to toxic concentrations, while the procainamide concentration remains within acceptable limits. T _1/2 - 2.5-4.5 h; in chronic renal failure - 11-20 hours; N-APA - about 6 hours. It is excreted by the kidneys (50-60% unchanged), with bile . Procainamide and N-APA are excreted during hemodialysis , but not during peritoneal dialysis .

Supraventricular arrhythmias: atrial fibrillation and / or flutter (including paroxysmal), tachycardia (including WPW syndrome ), atrial extrasystole , ventricular arrhythmias (tachycardia, ventricular extrasystole).

Hypersensitivity , AV block II – III Art. (except for the use of a pacemaker ), ventricular flutter or fibrillation, arrhythmias due to intoxication with cardiac glycosides , leukopenia .

Caution

Myocardial infarction , bundle branch block , myasthenia gravis , liver and / or kidney failure , systemic lupus erythematosus (including a history of ), bronchial asthma , decompensated chronic heart failure, ventricular tachycardia with coronary artery occlusion , surgical interventions (including surgery dentistry), prolongation of the QT interval, arterial hypotension, severe atherosclerosis , myasthenia gravis , advanced age.

Procainamide is administered intravenously, intramuscularly or orally. For adults. For intravenous administration, 5 ml ampoules with a solution of 100 mg / ml are released. The contents of the ampoule are diluted in a 0.9% NaCl solution or 5% dextrose solution and slowly administered at a rate of not more than 50 mg / min under the control of blood pressure and ECG. If necessary, repeat the administration in the same dose every 5 minutes, until the effect is achieved or to a total dose of 1000 mg. To prevent re-development of arrhythmias, infusion can be performed at a rate of 2-6 mg / min After stopping the arrhythmia, intramuscular administration is possible - 0.5-1 g (up to 2-3 g / day) to maintain the effect, however, the oral or intravenous routes are preferable.

For oral administration, 250 mg tablets are available. For atrial arrhythmias that do not require emergency treatment, the loading dose is 1.25 g, then 0.75 g every 1-2 hours if necessary and taking into account tolerance of 0.5-1 g every 2-3 hours. Maintenance dose is 0.5-1 g, depending on the effectiveness and tolerability, every 4-6 hours. For ventricular arrhythmias that do not require emergency treatment, the loading dose is 50 mg / kg / day in 8 divided doses (every 3 hours), if necessary, adjust the dose. Sustained-release tablets - maintenance dose for supraventricular arrhythmias: by mouth, 1 g every 6 hours; with ventricular arrhythmia - 50 mg / kg / day in 4 divided doses (every 6 hours), if necessary, adjust the dose. When switching to the oral route of administration after the termination of intravenous infusion, the first dose is prescribed after 3-4 hours. The maximum maintenance dose for adults is 6 g / day. Children. Inside, 12.5 mg / kg or 375 mg / m ^{2 of} the body surface 4 times a day. In chronic renal failure, the interval between doses is 4 hours ( CC (creatinine clearance) more than 50 ml / min), 6-12 hours (CC 10-50 ml / min), 12-24 hours (CC less than 10 ml / min). In chronic heart failure II — III Art. the daily dose is reduced by 25%. If a dose is missed, it should be taken as soon as possible within 2 hours (4 hours for long-acting tablets); do not accept if discovered later; do not double the dose.

From the nervous system: hallucinations , depression , myasthenia gravis , dizziness , headache , cramps , psychotic reactions with productive symptoms, ataxia .
From the digestive system: bitterness in the mouth.
Hematopoietic organs and hemostasis: with prolonged use - inhibition of bone marrow hematopoiesis ( leukopenia , thrombocytopenia , neutropenia , agranulocytosis , hypoplastic anemia ), hemolytic anemia with a positive Coombs test .
From the sensory organs: taste disturbances.
From the cardiovascular system: lowering blood pressure, ventricular paroxysmal tachycardia. With rapid intravenous administration, collapse , violation of atrial or intraventricular conduction, asystole are possible.
Allergic reactions: skin rash.
Other: with prolonged use - medicinal lupus erythematosus (in 30% of patients with a duration of therapy more than 6 months). Microbial infections, delayed healing processes and bleeding gums are likely due to the risk of leukopenia and thrombocytopenia.

Overdose

Symptoms: confusion, oliguria , fainting, drowsiness, severe dizziness (especially in elderly patients), rapid or irregular heartbeat , nausea , vomiting , diarrhea , loss of appetite , decreased amplitude of the QRS complex and T wave , decreased blood pressure, collapse, AV block, ventricular paroxysmal tachycardia, asystole.
Treatment: if taken recently - gastric lavage , the use of drugs that acidify urine ; hemodialysis; with a decrease in blood pressure - the introduction of norepinephrine or phenylephrine .

Take on an “empty” stomach (1 hour before meals or 2 hours after meals) with a glass of water for faster absorption or with food or milk to prevent irritation of the gastric mucosa ; for extended-release tablets, swallow whole, do not break, do not crush, do not chew. Before intravenous administration, it is necessary to dilute, inject at a rate of not higher than 50 mg / min; should be taken only in a hospital setting. When conducting therapy, it is necessary to monitor blood pressure, ECG , peripheral blood formulas , especially the number of leukocytes (every 2 weeks during the first 3 months of therapy, then at longer intervals). After prolonged maintenance therapy, approximately 80% of patients have an increase in the titer of antinuclear antibodies, most often 1-12 months after the start of therapy (in connection with the appearance of symptoms similar to systemic lupus erythematosus, it is necessary to periodically determine the titer of antinuclear antibodies). Leukopenia is more likely when prolonged-release dosage forms are used, especially after surgery on the heart or blood vessels . It is usually noted in the first 3 months of therapy (the blood formula is restored a few weeks after withdrawal). When used in children, higher doses may be required to maintain therapeutic concentrations; in the elderly, hypotension is more likely to develop. Care must be taken when interpreting laboratory results (possible effect on test results). When prescribed during pregnancy, there is a potential risk of maternal arterial hypotension, which can lead to uteroplacental insufficiency . During the treatment period, care must be taken when driving vehicles and engaging in other potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Enhances the effect of antiarrhythmic, antihypertensive, anticholinergic and cytostatic drugs, muscle relaxants , side effects of bretilium tosylate . With simultaneous use with antihistamines, atropine-like effects may increase; with pimozod - lengthening of the QT interval. Reduces the activity of anti-myasthenic drugs. Cimetidine reduces the renal clearance of procainamide and lengthens T _1/2 . With combination therapy with antiarrhythmic drugs of class III, the risk of developing an arrhythmogenic effect increases. Medicines that inhibit bone marrow hematopoiesis increase the risk of myelosuppression .