Mexiletine, Structure, Mechanism of action, Drug Interactions, Therapeutic Uses, Adverse effects and Contraindications

                                                Mexiletine

Mexiletine is a medication primarily used to treat certain heart rhythm disorders, specifically ventricular arrhythmias. It belongs to a class of drugs known as antiarrhythmics. Mexiletine works by blocking sodium channels in the heart, which helps to stabilize the heart's electrical activity and prevent abnormal heart rhythms.

One of the common brand names for Mexiletine is "Mexitil." It is essential to note that brand names may vary depending on the country and the manufacturer.

Mechanism Of Action

The MOA (Mechanism of Action) of Mexiletine involves its activity as a class Ib antiarrhythmic medication. It primarily affects the electrical properties of cardiac cells, specifically by blocking sodium channels.

• Sodium Channel Blockade: Mexiletine inhibits the fast inward sodium current in cardiac cells during the depolarization phase of the action potential. By doing so, it reduces the rate of rise of the action potential, leading to a decrease in the conduction velocity and excitability of cardiac tissues, especially in the ventricles.
• Antiarrhythmic Effects: The blockade of sodium channels helps stabilize the electrical activity of the heart, preventing the occurrence of certain types of abnormal heart rhythms or arrhythmias, particularly ventricular arrhythmias.
• Prolonged Refractory Period: Mexiletine also increases the duration of the cardiac refractory period, which is the time during which the cardiac cells are unresponsive to new electrical stimuli. This effect contributes to preventing reentrant arrhythmias, where electrical signals can loop around in the heart and cause irregular rhythms.

By modulating sodium channels and the refractory period, Mexiletine reduces the likelihood of dangerous ventricular arrhythmias, potentially improving the overall electrical stability of the heart and reducing the risk of life-threatening cardiac events in certain individuals. It is important to remember that the use of Mexiletine should be closely monitored by a healthcare professional due to potential side effects and interactions with other medications or medical conditions.

Drug Interactions

Mexiletine can interact with other medications, potentially affecting their effectiveness or increasing the risk of side effects. Some significant drug interactions with Mexiletine include:

• Beta-blockers: Concurrent use of Mexiletine with beta-blockers (e.g., propranolol, metoprolol) may lead to an additive effect on the heart, causing excessive slowing of the heart rate (bradycardia) or other heart rhythm disturbances.
• Cimetidine: Cimetidine, a medication used to treat stomach ulcers and acid reflux, may increase the concentration of Mexiletine in the blood, potentially leading to higher levels of the drug and an increased risk of side effects.
• Phenytoin: The combination of Mexiletine with phenytoin, an anticonvulsant drug, may reduce the effectiveness of both medications. Additionally, phenytoin can decrease Mexiletine levels, leading to reduced antiarrhythmic effects.
• Flecainide: Combining Mexiletine with flecainide (another antiarrhythmic drug) may increase the risk of serious heart rhythm disturbances and should be avoided unless under close medical supervision.
• Fluvoxamine: Fluvoxamine, an antidepressant, can increase the concentration of Mexiletine in the blood, potentially leading to an increased risk of side effects.
• CYP2D6 Inhibitors: Mexiletine is primarily metabolized by the liver enzyme CYP2D6. Drugs that inhibit this enzyme, such as certain antidepressants (e.g., fluoxetine, paroxetine) and antipsychotics, can increase Mexiletine levels and may require dosage adjustments.
• CYP1A2 Inducers/Inhibitors: Some drugs that induce or inhibit the CYP1A2 enzyme (e.g., rifampicin, ciprofloxacin) can affect Mexiletine metabolism and concentrations in the blood.

Therapeutic Uses

Mexiletine is primarily used for the treatment of certain heart rhythm disorders, specifically ventricular arrhythmias. Its therapeutic use is focused on preventing and managing abnormal heart rhythms originating from the ventricles, the lower chambers of the heart. Some of the therapeutic uses of Mexiletine include:

• Ventricular Arrhythmias: Mexiletine is effective in treating various types of ventricular arrhythmias, including premature ventricular contractions (PVCs), ventricular tachycardia (VT), and ventricular fibrillation (VF). These arrhythmias can be life-threatening and may lead to cardiac arrest if not managed properly.
• Long QT Syndrome: Mexiletine may be used in certain cases of Long QT syndrome, a congenital or acquired condition characterized by a prolonged QT interval on an electrocardiogram (ECG). Prolonged QT intervals can predispose individuals to serious ventricular arrhythmias.
• Arrhythmias in Specific Conditions: It can be used in patients with arrhythmias associated with other underlying heart conditions, such as hypertrophic cardiomyopathy or Brugada syndrome.
• Unstable Angina: In some cases, Mexiletine may be used as an adjunctive treatment for patients with unstable angina (chest pain) when other treatments are not well-tolerated or contraindicated.

Side Effects

Mexiletine, like all medications, can cause side effects in some individuals. Not everyone will experience these side effects, and their severity can vary from mild to more serious. Common side effects of Mexiletine may include:

• Nausea and Vomiting: Gastrointestinal disturbances, such as nausea and vomiting, are relatively common side effects of Mexiletine use.
• Dizziness and Lightheadedness: Some people may experience dizziness or feel lightheaded while taking Mexiletine.
• Tremors: Hand tremors or shakiness may occur as a side effect of the medication.
• Headache: Headaches are reported by some individuals taking Mexiletine.
• Blurred Vision: Mexiletine can cause temporary blurred vision or other visual disturbances.
• Loss of Appetite: Some people may experience a decreased appetite while on Mexiletine.
• Fatigue: Feeling tired or fatigued is another possible side effect.
• Constipation: Mexiletine may lead to constipation in some individuals.
• Heart Rhythm Changes: In some cases, Mexiletine can cause or worsen heart rhythm disturbances, including QT interval prolongation or ventricular arrhythmias.
• Allergic Reactions: Although rare, some individuals may experience allergic reactions to Mexiletine, leading to symptoms such as rash, itching, swelling, severe dizziness, or difficulty breathing.

Contraindications

Mexiletine has certain contraindications, meaning there are specific situations or medical conditions in which its use is not recommended or should be avoided. Some of the contraindications for Mexiletine include:

• Known Allergy: Mexiletine should not be used in individuals who have a known hypersensitivity or allergy to the drug or any of its components.
• Cardiogenic Shock: Mexiletine is contraindicated in patients with cardiogenic shock, a severe condition where the heart is unable to pump enough blood to meet the body's needs.
• Second or Third Degree Atrioventricular (AV) Block: Mexiletine is not recommended in individuals with certain types of heart block, specifically second or third-degree AV block, as it may worsen the condition or lead to serious heart rhythm disturbances.
• Pre-existing Prolonged QT Interval: The medication should be avoided in patients with a pre-existing prolonged QT interval on their electrocardiogram (ECG), as it may further prolong the QT interval and increase the risk of life-threatening arrhythmias.
• Hypersensitivity to Local Anesthetics: Mexiletine may cross-react with local anesthetics, so it should be used with caution or avoided in individuals with known hypersensitivity to local anesthetics (e.g., lidocaine).
• Myasthenia Gravis: Mexiletine may exacerbate symptoms in patients with myasthenia gravis, a neuromuscular disorder characterized by muscle weakness and fatigue.
• Liver Impairment: Mexiletine is primarily metabolized by the liver, so it should be used cautiously and with close monitoring in patients with significant liver impairment.
• Use with Certain Medications: Mexiletine may interact with other medications, such as certain antiarrhythmics (e.g., flecainide) or drugs that inhibit or induce liver enzymes (e.g., cimetidine, fluvoxamine). Therefore, caution or avoidance may be necessary when using Mexiletine in combination with these medications.