What Is Propafenone?

Propafenone is a broad-spectrum, highly effective membrane-inhibiting antiarrhythmic drug. It has membrane stabilization and competitive beta receptor blocking. Can reduce myocardial excitability, prolong action potential duration and effective refractory period, and extend conduction. It can be used clinically to prevent and treat ventricular and supraventricular ectopic beats, ventricular or supraventricular tachycardia, pre-excitation syndrome, and ventricular fibrillation after electrocardioversion. It has the characteristics of quick onset and long lasting effect.

Drug Name: Propafenone
Alias: Amphetamine, heart rate
Foreign name: Propafenone

Main indications: Arrhythmia due to coronary heart disease and hypertension
Adverse reactions: Dry mouth, headache, dizziness, gastrointestinal discomfort
Dosage form: tablet

Introduction to Propafenone Compounds

Propafenone Basic Information

Chinese name: Propafenone

Chinese alias: 1- [2- [2-hydroxy-3- (propylamino) -propoxy] phenyl] -3-phenyl-1-propanone; acetone; heart rate level; amphetamine acetone; hydroxypropyl Phenylacetone; Phenylacetone; Phenone; Phenylpropionol; Letomonol; Ritalin; Propofolone Hydrochloride

English name: propafenone

English alias: 5-OH-Propafenone-D5; PROPAFENONE HCL USP; WZ-884-642; WZ-884-643; Propafenone; Propafenonc; Berarytmon; Rytmonorm

CAS number: 54063-53-5

Molecular formula: C ₂₁ H ₂₇ NO ₃

Molecular weight: 341.44400

Exact mass: 341.19900

PSA: 58.56000

LogP: 3.63230

Physical and chemical properties of propafenone

Appearance and properties: white crystalline powder

Density: 1.096 g / cm ³

Melting point: 171-174ºC

Flash point: 268ºC

Refractive index: 1.557

Storage conditions: 2-8ºC

Propafenone Safety Information

Danger category code: R46

Safety instructions: 53-36 / 37 / 39-45 ^[1]

Propafenone Drug Description

Application of propafenone

Effects on the cardiovascular system

It is a new class of antiarrhythmic drugs. It belongs to the first class (ie, those that act directly on the cell membrane) of antiarrhythmic drugs. Experimental results in isolated animal myocardium indicate that 0.5 to 1 g / ml can reduce the depolarization effect of the systolic phase, thereby prolonging the conduction, the duration of the action potential and the effective refractory period are also slightly extended, and can increase myocardial cells The threshold potential significantly reduces the spontaneous excitability of the myocardium. It not only affects the atrium and ventricle (mainly affects Pujinye fibers, but has less effect on the heart muscle), and it also affects the formation and transmission of excitement. Clinical data show that the therapeutic dose (300 mg orally and 30 mg intravenously) can reduce myocardial stress, with long-lasting effects, increased PQ and QRS, and prolong the effective refractory period of atria and atrioventricular nodes. It is antagonistic to various types of experimental arrhythmias.

The antiarrhythmic effect is related to its membrane stabilization and competitive -blocking effect. It also has weak calcitonin resistance (100 times weaker than verapamil) and can interfere with the sodium fast channel.

There are still mild myocardial inhibitory effects, increasing end-stage diastolic blood pressure, and reducing stroke volume, and their effects are directly proportional to the dose of medication.

It also has mild antihypertensive and slow heart rate effects.

Bronchial smooth muscle

In vitro experiments show that propafenone can relax coronary arteries and bronchial smooth muscle.

Local anesthetic effect

After oral administration, it is well absorbed from the gastrointestinal tract, and the anti-arrhythmic effect reaches the peak effect 2 to 3 hours after taking it. The effect can last for more than 8 hours, and its t1 / 2 is 3.5 to 4 hours.

Pharmacological effects of propafenone

This product is a class Ic antiarrhythmic drug. Its electrophysiological effect is to inhibit the inflow of fast sodium ions, slow down the contraction and depolarization speed, reduce the conduction speed, and mildly

Propafenone hydrochloride tablets Prolonging the action potential interval and effective refractory period mainly affect the atrial and myocardial conductive fibers, so it may be effective for atrial arrhythmia. It also has a prolonged effect on the forward and reverse conduction velocity of the atrioventricular bypass. Can increase myocardial cell threshold potential. Therefore, this product has the effects of reducing conduction velocity, prolonging the effective refractory period, reducing excitability and eliminating reentrant arrhythmia. In addition, this product also has mild beta receptor blockade and slow calcium ion channel blockade, and mild to moderate inhibition of myocardial contractility, the degree of which is related to the dose.

Pharmacokinetics of propafenone

Oral absorption of 95%, the first pass effect (first pass effect) of the initial medication is obvious, bioavailability is 4.8% to 23.5%, long-term administration, the dose is increased to a certain degree, the first pass effect of the liver (first pass effect) reaches saturation, The bioavailability is significantly increased. It takes effect about 30 minutes after taking the drug. The blood concentration reaches a peak in 2 to 3 hours. The effect lasts for 6 to 8 hours. The effective blood concentration is 0.2 to 3.0 g / ml. The effective blood concentration varies greatly among individuals. Steady-state concentration has a non-linear relationship with dose, and a three-fold increase in the dose can increase the blood concentration by a factor of ten. The drug-plasma protein binding rate was 95%, and the half-life was 3 to 6 hours. Mainly metabolized by the liver, the metabolite 5-hydroxy-propafenone has pharmacological activity, 90% of metabolites are excreted from the kidney, and about 1% of the original drug is excreted by the kidney.

Propafenone indications

It is a sodium channel blocker and has a rapid antiarrhythmic effect. Directly stabilize the cell membrane, reduce the maximum rise rate of myocardial conductive fibers and the phase 0 of myocardial cell action potential, slow down the conduction, prolong the action potential duration and effective refractory period, and prolong or block bypass forward and reverse conduction. Increase the myocardial excitement threshold, reduce the spontaneous excitability of myocardial cells, block the reentry pathway, and eliminate reentry excitement. There are also mild inhibition of myocardial contraction and similarities to procaine

Propafenone hydrochloride tablets Hemp effect ^[2] .

Oral is suitable for premature ventricular contractions and paroxysmal ventricular tachycardia. Followed by supraventricular arrhythmias, including atrial premature beats, paroxysmal supraventricular tachycardia, and preexcitation syndrome with supraventricular tachycardia, atrial flutter, or atrial fibrillation, but correcting atrial fibrillation or atrial flutter poor effect.

Intravenous injection is suitable for paroxysmal ventricular tachycardia and supraventricular tachycardia (including those with preexcitation syndrome). Oral is suitable for atrial premature beat and ventricular premature beat to prevent the onset of supraventricular tachycardia. It has poor effect on atrial fibrillation and atrial flutter. Intravenous injection is suitable for discontinuing paroxysmal supraventricular tachycardia, ventricular tachycardia and pre-excitation syndrome with supraventricular tachycardia and slowing the ventricular rate of atrial fibrillation or atrial flutter. This product is mainly used for pre-excitation syndrome with supraventricular arrhythmia and reentrant supraventricular tachycardia via atrioventricular node.

Dosage of propafenone

Oral: 100 to 200 mg once, 3 to 4 times a day. The amount of treatment is 300 to 900 mg per day, divided into 4 to 6 times. dimension

Holding amount, 300-600mg per day, divided into 2 to 4 times. Due to its local anesthetic effect, it should be swallowed with a drink or food after a meal without chewing. Extreme daily amount: 0.9g. In children, 5 to 7 mg / kg each time, 3 times a day, the dosage should be halved after the effect to maintain the effect.

If necessary, slow intravenous injection or intravenous drip under intensive supervision, once 70mg, once every 8 hours. The total amount per day does not exceed 350mg.

Intravenous injection or intravenous drip: 70mg / time, 1 time / 8 hour, daily maximum: 0.35g. Or each time l ~ 1.5mg / kg, diluted with 20ml of glucose injection slowly and intravenously for more than 5 minutes, if necessary, it can be repeated once after 20 minutes, and then maintained at a drip rate of 0.5-lmg / minute. Pediatric lmg / kg each time, diluted with 20ml of glucose injection slowly and intravenously for more than 5 minutes, if necessary, can be repeated once after 20 minutes.

Propafenone precautions

(1) There are fewer adverse reactions, the main ones are dry mouth and numbness of tongue and lips, which may be caused by its local anesthetic effect. In addition, early adverse reactions include headaches, dizziness, and sparkling; gastrointestinal disorders such as nausea, vomiting, and constipation can occur later. Elderly patients may experience a drop in blood pressure after administration. There are also symptoms of atrioventricular block. Two cases of cholestatic liver injury have been reported after two consecutive weeks of administration, and the enzyme activities returned to normal 2 to 4 weeks after discontinuation. It is believed that this pathological change is an allergic reaction and individual factors.

(2) During the trial period, no damage to the lung, liver and hematopoietic system was seen. A few patients showed the above-mentioned minor reactions such as dry mouth, headache, dizziness, and gastrointestinal discomfort. Generally, the symptoms disappeared after drug withdrawal or reduction . There are reports of atrioventricular block in some patients, QT interval prolonged, PR interval slightly extended, and QRS time extended.

(3) Use with caution in severely damaged myocardium.

(4) Sinus node dysfunction, severe atrial block, double bundle branch block, and cardiogenic shock disabled; severe bradycardia, liver and kidney dysfunction, and caution in patients with significant hypotension.

(5) If there is a high degree of sinus or atrioventricular block, sodium lactate, atropine, isoproterenol, or meta-adrenaline can be given by injection.

Prostatone banned with caution

(1) Allergic to this product, severe heart failure, cardiogenic shock, severe bradycardia, sick sinus node syndrome, obvious electrolyte imbalance, patients with severe chronic obstructive pulmonary disease, emphysema, and sinoatrial, atrioventricular and Ventricular block is disabled in patients.

(2) The elderly may cause blood pressure drop after medication, and should be observed carefully.

Propafenone hydrochloride tablets (3) The following conditions should be disabled: sinus node dysfunction; or degree atrioventricular block, double bundle branch block (unless a pacemaker); cardiogenic shock.

(4) The following cases should be used with caution: severe sinus bradycardia; degree AV block; hypotension; liver or kidney dysfunction.

(5) Elderly people have decreased blood pressure, severe heart failure, cardiogenic shock, severe bradycardia, sinoatrial, atrioventricular block, sick sinus syndrome, significant electrolyte imbalance, and severe obstructive pulmonary disease And obvious hypotension are disabled. Use with caution in early pregnancy, lactating women or those with impaired liver and kidney function.

(6) Patients with liver and kidney function impairment must take medications. Due to the effects of in vivo metabolism and excretion, plasma free fraction and bioavailability increase. Therefore, it is required to use under strict ECG monitoring, and the dose should be halved.

(7) The plasma drug concentration of this product increases disproportionately with the dose. Care should be taken when increasing the dose, and it is best to monitor the blood drug concentration. During intravenous injection, blood pressure and electrocardiogram should be closely monitored. When you need to switch to other antiarrhythmic drugs, you should stop using this product for 1 day; on the contrary, you should stop using at least 1 half-life of various antiarrhythmic drugs. For patients with severe acute arrhythmia, the withdrawal time can be shortened as appropriate, but intensive monitoring is required.

Adverse reactions to propafenone

Adverse reactions include dry mouth, numb lips, headache, dizziness, eye flashes, drowsiness, nausea, vomiting, constipation, etc., which disappear after reduction or withdrawal. In large doses, very few patients experience finger tremor, bradycardia, sinus rest, sinoatrial or atrioventricular block, mental disorders or hypotension, elevated serum alanine aminotransferase, and cholestatic hepatitis. The most common cardiovascular system is to induce or exacerbate ventricular arrhythmias, atrioventricular or bundle branch block, induce or exacerbate congestive heart failure, and increase the incidence of angina pectoris. Sinus node dysfunction can also occur, such as severe sinus bradycardia, sinus arrest, and more severe hypotension. More severe cases are reported. Adverse reactions are dose-dependent.

(1) Cardiovascular: Can produce bradycardia, cardiac arrest and conduction block, especially those with original sinus node or atrioventricular node dysfunction, should stop drug and intravenous atropine or isoproterenol. Pacing treatment if necessary.

Propafenone hydrochloride tablets Arrhythmogenic effect. 4.4% had hypotension, especially in patients with original cardiac insufficiency. Booster drugs, isoproterenol, etc. can be used, which can also aggravate or induce heart failure. Therefore, patients with original heart failure should be combined with strong heart and diuretics.

(2) Gastrointestinal: loss of appetite, nausea, vomiting and constipation, can also produce dry mouth and numbness of tongue and lips. Reduction or withdrawal can disappear.

(3) Nerves: dizziness and dizziness. Reduction or withdrawal can disappear.

(4) Others: Liver transaminase is elevated, and it returns to normal 2-4 weeks after discontinuation.

The nervous system is often dizzy or dizzy, headache, sweating, drowsiness, facial flushing, sensory disturbances, changes in mental state, visual disturbances, ataxia and convulsions.

The digestive system is often anorexia, dry mouth, nausea, vomiting, taste disorders, constipation and indigestion or abdominal discomfort. Occasionally hepatic impairment occurs, and cholestatic hepatitis occurs in individual patients. Visible hematopoietic system

Leukopenia and hemolytic response. Occasion of acne, rash, or hives on the skin.

Propafenone drug interactions

1. Other antiarrhythmic drugs, including verapamil, propranolol, amiodarone, and quinidine, may increase the adverse reactions of this product.

2. Combined with antihypertensive drugs, it can enhance the antihypertensive effect.

Propafenone hydrochloride tablets

3 Combination with local anesthetic may increase the adverse effects of the central nervous system of this product.

4 Combination with digoxin may increase blood concentration of digoxin.

5. Combined with warfarin, it can increase the blood concentration of warfarin and prolong the prothrombin time.

6. Combined with cimetidine, it can increase the blood concentration of this product by 20%, but there is no change in ECG parameters.

7. Used with phenobarbital to reduce the blood concentration of this product.

8. Equivalent to tricyclic antidepressants, cyclosporine, theophylline, digoxin, warfarin, can enhance the effect and toxicity of this product.

9. With diltiazem, the blood level of both is increased.

Propafenone poisoning

Propafenone (amphetamine, arrhythmione, acetone) is a sodium channel blocker, which has a rapid antiarrhythmic effect, and is suitable for a variety of arrhythmias, atrioventricular block, and atrial fibrillation.

Oral: 0.1 0.2g each time, 3 4 / d, maintenance amount is 0.3 0.6g / d, daily maximum amount 0.9g; intravenous injection or intravenous drip 70mg each time, 1 / 8h, daily maximum amount 350mg.

Human poisoning blood drug concentration> 1000ng / ml. LD50 rats were orally administered at 760 to 876 mg / kg, and intravenously injected at 18.8 to 22.8 mg / kg. This medicine mainly damages the heart, central nervous system, liver and kidneys.

Clinical manifestation

1. Adverse reactions such as bradycardia, atrioventricular block, dizziness, headache, sweating, anorexia, dry mouth, nausea, vomiting, rash, etc.

2. Poisoning performance

(1) Cardiovascular system performance: induce or exacerbate ventricular arrhythmias, congestive heart failure, angina pectoris; high AV block, sinus arrest, hypotension, shock, etc. may occur.

(2) Nervous system performance: drowsiness, paresthesia, altered mental state, ataxia, and convulsions. (3) Digestive system performance: constipation, abdominal discomfort, occasional liver damage, and cholestatic jaundice.

(4) Blood system performance: granulocytopenia, hemolytic response, and hemoglobinuria. (5) Respiratory system performance: bronchial asthma, respiratory depression, respiratory arrest.

treatment

The main points of treatment for propafenone poisoning are:

1. The medicinal amount is too large, and gastric lavage, catharsis, and intravenous infusion should be performed immediately to accelerate the excretion of drugs in the body.

2. When sinus arrest and conduction block occur, atropine or isoprenaline can be given intravenously, and a pacemaker can be placed for treatment if necessary.

3. Patients with hypotension and cardiac insufficiency should be treated with booster drugs and cardiotonic drugs.

4. Antihistamines or glucocorticoids for allergic reactions.

5. Patients with increased heart failure after treatment can be treated with heart-strengthening and diuretic drugs.

6. Other symptomatic treatments ^[3] .

Propafenone Expert Reviews

According to comprehensive literature reports, propafenone is indeed a drug with high efficacy and less toxic and side effects. It can be used as a first-line drug for ventricular arrhythmias. In view of its class Ic drugs, patients with myocardial infarction should be used with caution ^[4] .