What Factors Affect Sotalol Dosage?

The chemical name of sotalol is 4 '-(1-hydroxy-2-isopropylamineethyl) methanesulfonylaniline, white crystal, molecular formula is C ₁₂ H ₂₀ N ₂ O ₃ S, molecular weight is 272.36400, density It is 1.239 g / cm3, boiling point is 443.3ºC at 760 mmHg, flash point is 221.9ºC, refractive index: 1.57.

Chinese name: Sotalol
Foreign name: sotalol

CAS: 3930-20-9
Molecular formula: C12H20N2O3S
Molecular weight: 272.3638

Sotalol compound profile

Sotalol Basic Information

Chinese name Sotalol

Chinese alias: sotalol hydrochloride; 4 '-(1-hydroxy-2-isopropylaminoethyl) methanesulfonylanilide; (RS) -4'-(1-hydroxy-2-isopropylaminoethyl) methyl Sulfanilide;

English name: sotalol

English alias: Sotalol; N- (4- (1-Hydroxy-2- (isopropylamino) ethyl) phenyl) methanesulfonamide;

CAS number: 3930-20-9

Molecular formula: C ₁₂ H ₂₀ N ₂ O ₃ S

Molecular weight: 272.36400

Structural formula:

Exact mass: 272.11900

PSA: 86.81000 ^[1]

Physical properties of sotalol

Appearance and properties: white crystal

Density: 1.239 g / cm3

Boiling point: 443.3ºC at 760 mmHg

Flash point: 221.9ºC

Refractive index: 1.57 ^[1]

Sotalol molecular structure data

1. Molar refractive index: 72.13

2. Molar volume (cm / mol): 219.7

3. Isotonic specific volume (90.2K): 586.0

4. Surface tension (dyne / cm): 50.6

5. Polarizability (10-24cm3): 28.59 ^[2]

Sotalol production method

Methanesulfonyl chloride was added dropwise to a solution of aniline, triethylamine, and ethanol in an ice bath with stirring, and then stirred at room temperature. It was filtered and the filtrate was concentrated. After crystallization, it was recrystallized from ethanol and dried to obtain mesylanilide. In an ice bath and with stirring, in a solution of mesylanilide, bromoacetyl bromide and carbon disulfide, add anhydrous aluminum trichloride and reflux. After filtration and recrystallization, the obtained compound was added to a methanol solution of isopropylamine and reacted. Concentrate under reduced pressure, add acetone, pass hydrogen chloride to pH 2. The reaction solution is treated, the compound obtained is dissolved in methanol, Pd-C is added, and hydrogen is reacted. After the reaction is completed, it is filtered and the filtrate is concentrated to dryness. Methanol is heated to complete dissolution, and the activated carbon is decolorized. Cool and filter to give white sotalol hydrochloride. ^[1]

Sotalol uses

Beta-blockers. Used for paroxysmal supraventricular tachycardia, atrial fibrillation, atrial flutter and other arrhythmias, as well as angina pectoris and hypertension. ^[1]

Sotalol Compound Related Drugs

Sotalol drug name:

[Common name] Sotalol hydrochloride tablets

[Product Name] Sotacor

[English name] Sotalol Hydrochloride Tablets

[Chinese Pinyin] Yan Suan Suo Ta Luo Er Pian ^[3]

Sotalol belongs to category:

Chemicals & Biological Products >> Circulatory System Drugs >> Antihypertensive Drugs >> Sympathetic Inhibitors

Chemicals and biological products >> Circulatory system drugs >> Antiarrhythmic drugs >> Antitachycardia drugs ^[3]

Sotalol traits:

This medicine is a white, round flat tablet with SOTACOR 80 printed on one side. In addition to the active ingredients, it also contains the following inactive ingredients: lactose, magnesium stearate, starch and talc. ^[3]

Sotalol indications:

Various life-threatening ventricular tachyarrhythmias. ^[3]

Sotalol Specifications:

80mg x 28 tablets ^[3]

Sotalol Usage and Dosage:

The first dose is 160 mg / day, taken orally in two divided doses, about 12 hr apart, taken 1-2 hr before meals. The usual dose is 160-320 mg / day. ^[3]

Sotalol adverse reactions:

Temporary dyspnea, fatigue, dizziness, headache, fever, bradycardia and / or hypotension, if any, usually disappear after the dose is reduced. The most serious adverse reactions were arrhythmias, including apical torsional ventricular tachycardia. In addition, chest pain, palpitations, edema, syncope, pre-syncope syndrome, and heart failure can occur. rash. Nausea / vomiting, diarrhea, indigestion, abdominal pain, flatulence. Muscle cramps. Sleep disorders, depression, paresthesia, mood changes, anxiety, sexual dysfunction. Vision impairment, abnormal taste, and hearing impairment. ^[3]

Sotalol Taboo:

Patients with a history of allergies to this drug, bronchial asthma or chronic obstructive airway disease, cardiogenic shock, use of anesthesia that produces myocardial depression, sinus bradycardia, sick sinus syndrome, grade II and III atrioventricular block (Unless a pacemaker is installed), uncontrolled congestive heart failure, renal failure, and QT interval prolongation syndrome are contraindicated. ^[3]

Sotalol warns:

Drugs that prolong the QT interval can cause apical torsional ventricular tachycardia, a type of ventricular tachycardia associated with prolongation of the QT interval, which appears on the electrocardiogram in multiple forms. The danger of torsional VT is related to the following factors:
-QT interval extended.
-Slow heart rate.
-Decreased serum potassium and magnesium concentrations (as caused by the use of diuretics).
-High plasma drug concentrations (for example, due to overdose or renal dysfunction).
-Sotalol and other drugs that are prone to apical torsional ventricular tachycardia, such as antidepressants or class I antiarrhythmics.
-Women are at greater risk of developing a twisted tip.
ECG monitoring usually shows that the QT interval and QTc interval are significantly prolonged immediately before or after the onset of torsional ventricular tachycardia. This drug is generally not used in patients whose QTc is more than 450 milliseconds before treatment. Caution should be exercised in patients with prolonged QT intervals.
Apical torsional VT is dose-dependent. Most patients usually occur early in the beginning of treatment or when the dose is gradually increasing. In most patients, torsional VT is self-limiting or symptomatic (such as syncope). But may develop to ventricular fibrillation. Other risk factors for apical torsional ventricular tachycardia are excessive QTc prolongation and a history of cardiac hypertrophy or congestive heart failure. Patients with persistent ventricular tachycardia and congestive heart failure are at highest risk for severe arrhythmias after administration. Patients who discontinue beta-blocker therapy are highly sensitive to catecholamines. Sudden discontinuation of beta-blocker treatment occasionally exacerbates angina pectoris and arrhythmias, and in some cases even myocardial infarction. Therefore, discontinuation after long-term treatment should be careful, especially for patients with ischemic heart disease. Monitor, if possible, the dose should be gradually reduced within 1-2 weeks.
-blocking effect will further inhibit myocardial contractility and exacerbate heart failure. Patients with left ventricular dysfunction need to be cautious at the beginning of treatment. It is advisable to start with small doses and carefully adjust the dose. Patients with left ventricular dysfunction must be weighed against the pros and cons of administering this drug after infarction, and patients must be carefully monitored and dose adjusted. Patients with a left ventricular ejection fraction (smaller than or equal to) 40%, but without severe ventricular arrhythmias, should avoid this medicine. Use a fixed dose of 320 mg / day after infarction and high-dose (640 mg / day) treatment for high-risk post-infarction patients with a left ventricular ejection fraction (smaller than or equal to) 40%, all suggesting that Increase the likelihood of early sudden death.
Patients with hypokalemia or hypomagnesemia should not use this medicine until the disorder is corrected, because this condition will increase the prolongation of QT and increase the possibility of tip torsional ventricular tachycardia. Special attention should be paid to the electrolyte and acid-base balance of patients with severe or long-term diarrhea or patients taking drugs that release magnesium or potassium at the same time. The QT interval is excessively extended, and> 550 milliseconds can be used as an indicator of poisoning and should be avoided. For patients with a history of allergic reactions to various allergens, the reaction will be aggravated after taking beta-blockers multiple times. For such patients, the usual dose of epinephrine for allergic reactions may not respond. ^[3]

Sotalol Notes:

Patients should use caution during surgery and use of anesthetics that inhibit myocardium, such as cyclopropane or trichloroethylene. Use with caution in patients with renal insufficiency, patients with diabetes or patients with a history of spontaneous hypoglycemia. Beta-blocking effects can mask certain clinical symptoms of hyperthyroidism and hypoglycemia. Patients suspected of having progressive hyperthyroidism should avoid the sudden interruption of beta-blocker administration. ECG QT interval (greater than or equal to) 500 ms should be reduced or discontinued. ^[3]

Sotalol medication for pregnant and lactating women:

Rats and rabbits were given 100 times and 22 times the maximum recommended doses of this drug, respectively. No signs of fetal damage were seen, but studies on animal reproduction have not always been able to predict human responses. Fully effective studies have not been conducted on pregnant women, but it has been confirmed that this drug can pass through the placenta and exists in amniotic fluid, so it can be used only during pregnancy when the advantages outweigh the disadvantages. This drug is secreted in breast milk, so the potential adverse effects of this drug on lactating babies and the importance of the drug to the mother should be considered in order to weigh whether to stop breastfeeding or stop using the drug. ^[3]

Sotalol medication for children:

This drug has not been proven to be safe and effective for children under 18 years of age. ^[3]

Sotalol Drug Interactions:

Do not use in combination with class Ia antiarrhythmic drugs such as propiramine, quinidine and procainamide, and other class III drugs (such as amiodarone) as they may prolong the refractory period. Combination of this drug with other beta-blockers can cause cumulative effects of class II.
Combined with potassium excretion diuretics, hypokalemia or hypomagnesemia can occur, increasing the possibility of tip-torsional ventricular tachycardia.
Extreme caution should be used with drugs known to prolong the QT interval, such as Class I antiarrhythmics, phenothiazines, tricyclic antidepressants, terfenadine, and astemizole.
Simultaneous administration of beta-blockers and calcium channel blockers can cause hypotension, bradycardia, conduction disorders, and heart failure. Beta-blockers should be avoided in combination with heart-suppressing calcium channel blockers such as verapamil and azathione because they have an additive effect on atrioventricular conduction and ventricular function.
Combination with depleting catecholamines such as reserpine, guanethidine, and -blockers can cause excessive reduction in resting sympathetic tone. Close monitoring of hypotension and / or masking bradycardia that may cause syncope in patients Signs are happening.
This medicine can cause hyperglycemia, and the dose of hypoglycemic drugs needs to be adjusted.
Beta2-agonists such as salbutamol, terbutaline and isoprenaline should be dosed in combination with this drug.
Reflex hypertension is sometimes observed after clonidine is discontinued, and beta-blockers enhance this effect. Therefore, -blockers should be discontinued slowly a few days before gradual removal of clonidine.
Spectrophotometric determination of adrenaline levels in urine can cause false elevations due to the presence of the drug in urine. For patients suspected of having pheochromocytoma and treating with sotalol, solid-phase extraction and high-performance liquid method must be used. The urine was analyzed. ^[3]

Sotalol Overdose:

Symptoms Bradycardia, congestive heart failure, hypotension, bronchospasm, hypoglycemia, prolonged QT interval, ventricular premature beats, ventricular tachycardia, and torsional ventricular tachycardia.
Treatment should be stopped immediately, and the patient's condition should be closely monitored.
If bradycardia occurs, give atropine, a beta-adrenergic receptor agonist or transvenous cardiac pacing.
In the presence of cardiac block (degrees II and III), venous cardiac pacing can be given.
If hypotension occurs, use epinephrine instead of isoproterenol or norepinephrine.
In case of bronchospasm, an aerosol of aminophylline or a 2-receptor agonist is administered. In case of apical torsional ventricular tachycardia, direct cardioversion, venous cardiac pacing, epinephrine and / or magnesium sulfate are given. ^[3]

Sotalol Pharmacology and Toxicology:

Pharmacological effects This drug is a racemic mixture of d-type and l-type sotalol hydrochloride. It is a non-selective -adrenergic receptor blocker. It acts on 1 and 2 receptors without intrinsic sympathomimetic activity and membrane stability. effect. Can inhibit the release of renin. The effects of renin are obvious at rest and during exercise. Its -adrenergic receptor blockade causes slow heart rate (negative frequency effect) and limited weakening of contractile force (negative Sexual muscle effect), these changes reduce myocardial oxygen consumption and work.
This drug has both anti-arrhythmic features of -adrenergic receptor blockade and prolonged cardiac action potential duration, has no effect on the rate of action potential rise (except for the polarization period), and uniformly prolongs the heart tissue only by extending the repolarization phase Action potential duration. Its main role is to extend the effective refractory period of the atrium, ventricle, and bypass. Class II and III features are reflected on the electrocardiogram as PR, QT and QTc (QT corrected by heart rate) intervals are extended, and there is no significant change in QRS time.
The d and l isomers of sotalol hydrochloride have similar class III antiarrhythmic effects, and the entire -blocking effect is actually caused by the l isomer. 25 mg orally can cause obvious -blocking effect, but usually a daily dose greater than 160 mg produces a class III effect. After oral administration of this drug in adults, heart rate and cardiac output are reduced, while stroke volume is unchanged. Oral administration of 160-640 mg / day resulted in a 21-24% reduction in heart rate and an 8% reduction in systolic and diastolic blood pressure. In some patients, tachycardia caused by exercise and isoproterenol can be antagonized by this drug, with a small increase in total peripheral resistance, little or no change in blood pressure, systemic blood pressure in normal patients, and no significant change in pulmonary vascular pressure. This medicine significantly reduces systolic and diastolic blood pressure in patients with hypertension.
The class II (-blocking) electrophysiological effects of this drug are manifested by an increase in the length of the sinus node cycle (slower heart rate) and an increase in the atrioventricular node refractory period. Class III electrophysiological effects include prolonged atrial and ventricular uniphasic action potentials, and prolong the effective refractory period of forward and reverse conduction of atrial muscles, ventricular muscles, and atrioventricular bypass (if present). Oral 160-640 mg / day, ECG showed an average increase in QT of 40-100 milliseconds and an increase in QTc of 10-40 milliseconds. This change is dose-dependent. No significant change in the QRS wave was seen.
Toxicology study: In 24 months, rats were given 30 times the maximum recommended oral sotalol dose (137-275 mg / kg body weight / day) or mice were given about 450-750 times the oral dose. Talorol (4.141-7.122 g / kg body weight / day), no evidence of carcinogenicity was observed. The rats were taken orally at 1 g / kg / day (about 100 times the maximum human recommended dose) before mating, and no significant decrease in fertility was observed, but the number of litters per litter was slightly reduced. ^[3]

Sotalol pharmacokinetics:

The bioavailability of this drug is basically complete (more than 90%), peak concentration is reached 2.5-4 hours after oral administration, and steady-state blood concentration is reached 2-3 days. Taking it while eating will reduce drug absorption by about 20%. At doses ranging from 40-640 mg / day, plasma concentrations increase proportionally with dose. The drug is distributed in the central (plasma) and peripheral compartments, with a elimination half-life of 10-20 hours. Does not bind to plasma proteins and has no metabolic processes. Individual differences in plasma concentrations are minimal. The drug does not easily cross the blood-brain barrier, and its concentration in the cerebrospinal fluid is only 10% of the plasma concentration.
The main route of elimination is renal excretion, about 80-90% of which is excreted by the urine as a prototype, and the rest is excreted by feces. Dosage must be reduced when renal function declines. Age does not significantly change the pharmacokinetics, but the decline of renal function in the elderly slows the rate of excretion, leading to an increase in drug accumulation. ^[3]

Sotalol Expert Reviews

This product was originally thought to be a -receptor blocker. Recent studies have shown that it also has the characteristics of class II and III antiarrhythmic drugs. It has a weak inhibitory effect on myocardium, does not affect stroke volume, and does not increase left ventricular end-diastolic pressure. Clinically used as antiarrhythmic drugs, antianginal drugs and antihypertensive drugs. In addition, this product can reduce the frequency of angina pectoris and the amount of nitroglycerin. In patients with acute myocardial infarction, this product reduces the incidence of sudden death compared with placebo, and the incidence of reinfarction is significantly reduced. ^[4]