Sotalol

MECHANISM OF ACTION

Sotalol has a dual mechanism of action. As a non-selective beta-adrenergic blocker (Class II antiarrhythmic), it inhibits both β1 and β2 receptors, reducing sympathetic stimulation of the heart. This leads to decreased heart rate, reduced myocardial contractility, and slower conduction through the atrioventricular (AV) node. Additionally, sotalol has Class III antiarrhythmic activity by blocking potassium channels, which prolongs the cardiac action potential and refractory period in atrial and ventricular myocytes. This combination of beta-blockade and potassium channel inhibition helps control both ventricular and supraventricular arrhythmias, reducing the likelihood of abnormal electrical impulses and re-entry circuits in the heart.

PHARMACOKINETICS

Absorption

Sotalol has excellent absorption after oral administration, with a bioavailability of 90–100%. The absorption is rapid, with peak plasma concentrations typically achieved within 2 to 4 hours. 

Distribution

The volume of distribution of sotalol ranges from approximately 1.2 to 2.4 L/kg, reflecting the extent to which the drug disperses throughout the body relative to its plasma concentration.

Metabolism 

Sotalol is not metabolized by the liver and is primarily excreted unchanged via the kidneys. It does not produce active metabolites and is not processed by the cytochrome P450 enzyme system, reducing the risk of drug-drug interactions related to liver metabolism. However, because its elimination depends on renal function, dose adjustments may be necessary in patients with impaired kidney function.

Excretion

Sotalol is predominantly excreted unchanged in the urine by the kidneys, with minimal metabolism in the liver. Its elimination is closely linked to renal function, meaning that in patients with reduced kidney function, the drug can accumulate and increase the risk of toxicity. Because sotalol is not metabolized by the liver, it has a low potential for drug interactions involving hepatic pathways, and its clearance relies almost entirely on renal excretion.

PHARMACODYNAMICS

Sotalol’s pharmacodynamics are based on its dual action as a non-selective beta-adrenergic blocker and a Class III antiarrhythmic agent. As a beta-blocker, it reduces sympathetic stimulation of the heart, leading to decreased heart rate, reduced myocardial contractility, and slower conduction through the atrioventricular (AV) node. Concurrently, its Class III activity involves potassium channel blockade, which prolongs the action potential duration and refractory period in atrial and ventricular cardiac cells. This combination suppresses abnormal electrical activity, reduces the likelihood of re-entry circuits, and stabilizes the cardiac rhythm, making sotalol effective in treating both ventricular and supraventricular arrhythmias.

DOSAGE AND ADMINISTRATION

Sotalol is administered orally, usually in the form of tablets or capsules. The exact dose depends on the species, size, and clinical condition of the patient, as well as renal function. In veterinary medicine, sotalol is commonly prescribed for dogs and cats with ventricular or supraventricular arrhythmias, and the typical dosage ranges from 1 to 2 mg/kg given every 8 to 12 hours, though dosing must be individualized and adjusted based on response and tolerance. Because sotalol is primarily excreted by the kidneys, dose adjustments are essential in patients with impaired renal function to avoid accumulation and toxicity. The drug should be administered consistently at the same times each day, and abrupt discontinuation should be avoided to prevent rebound arrhythmias. Regular cardiac monitoring and electrocardiograms (ECGs) are recommended to assess efficacy and detect potential proarrhythmic effects, particularly in patients with structural heart disease or compromised renal function.

DRUG INTERACTIONS

Sotalol has a relatively low potential for drug interactions because it is not metabolized by the liver and does not involve the cytochrome P450 enzyme system. However, interactions can occur with other medications that affect cardiac conduction or potassium levels, increasing the risk of arrhythmias. Drugs such as digoxin, calcium channel blockers (like verapamil or diltiazem), amiodarone, or other antiarrhythmics can potentiate its effects on heart rate or rhythm. Additionally, medications that alter renal function or electrolyte balance for example, diuretics causing hypokalemia or hyperkalemia may increase the risk of sotalol-induced proarrhythmia, including torsades de pointes. Careful monitoring and dose adjustments are recommended when sotalol is used in combination with these drugs.

FOOD INTERACTIONS

Sotalol has no significant food interactions, meaning it can generally be administered with or without food. Food does not affect its absorption or therapeutic efficacy. However, consistent administration either always with or always without food may help maintain predictable plasma concentrations and reduce the risk of gastrointestinal upset in some patients.

CONTRAINDICATIONS

Sotalol is contraindicated in patients with known hypersensitivity to the drug or any of its components. It should not be used in animals or humans with significant bradycardia, atrioventricular (AV) block, or sick sinus syndrome unless a pacemaker is in place. The drug is also contraindicated in patients with severe heart failure or cardiogenic shock, as its negative inotropic effects can worsen cardiac output. Because sotalol can prolong the QT interval, it should be avoided in individuals with congenital or acquired long QT syndrome or a history of torsades de pointes. Caution is also advised in patients with impaired renal function, as reduced clearance can lead to accumulation and increased risk of proarrhythmia.

SIDE EFFECTS

• Fatigue or unusual tiredness.

• Dizziness or lightheadedness.

• Weakness.

• Headache.

• Nausea, vomiting, diarrhea, or upset stomach.

• Blurred vision.

• Shortness of breath.

• Sleep disturbances.

• Liver issues.

• Severe allergic reactions.

• Severely slow heart rate.

• Worsening heart failure.

• Dangerous heart rhythm changes. 

OVERDOSE

• Marked bradycardia (slow heart rate)

• Hypotension (low blood pressure)

• Dizziness and fatigue

• Syncope (fainting)

• Atrioventricular (AV) block

• Heart failure

• Ventricular arrhythmias, including torsades de pointes

• Cardiac arrest in severe cases

• Nausea, vomiting, and diarrhea

• Seizures in extreme overdose

TOXICITY

Sotalol toxicity results from excessive beta-blockade and potassium channel blockade, leading to severe bradycardia, hypotension, AV block, ventricular arrhythmias (including torsades de pointes), heart failure, and potentially cardiac arrest. Non-cardiac signs may include fatigue, dizziness, nausea, vomiting, diarrhea, and seizures. It is more likely in patients with renal impairment or those on other QT-prolonging drugs. Management is supportive, as there is no specific antidote.