Lecture №8: Antiarrhythmic Drugs PDF

Asian Medical Institute Memorial S.Tentishev Department of Interprofessional discipline Subject - Basic and clinical Pharmacology Teacher - Temirbekovа Gulnura Lecture:№8 Theme: Antiarrhythmic drugs  Arrhythmia is a violation of cardiac conduction, as well as the frequency and regularity...

Asian Medical Institute Memorial S.Tentishev Department of Interprofessional discipline Subject - Basic and clinical Pharmacology Teacher - Temirbekovа Gulnura Lecture:№8 Theme: Antiarrhythmic drugs  Arrhythmia is a violation of cardiac conduction, as well as the frequency and regularity of its contractions, resulting in a violation of the normal functioning of the heart and subjectively unpleasant symptoms.  Arrhythmias are understood as any changes in the work of the heart, which as a result disrupt its correct contraction - both in speed and in the synchronicity of the work of its departments.  The essence of the mechanism of action of antiarrhythmic drugs is the normalization of the conductivity of electrolytes through the ion channels of the myocardium. Each cardiomyocyte (sac cells of the heart) is permeated with a large number of ducts of different orientations, along which potassium, sodium, chlorine ions run.  This movement forms the action potential of each cell, contributes to the correct conduction of nerve impulses through the myocardium.  To restore the correct movement of ions, you need to reduce its activity, stop the circulation of the impulse. This is what antiarrhythmic drugs do, which close damaged ion channels, reducing the negative impact on the heart and sympathetic receptors of the myocardium.  The choice of antiarrhythmic depends on the type of heart rhythm disturbance. If the sinus rhythm cannot be restored, electrical pacing is used (outpatient or inpatient). CLASS I ANTIARRHYTHMIC DRUGS Class I antiarrhythmic drugs act by blocking sodium (Na+) channels. Class I drugs are divided into three groups Class IA: Quinidine Mechanism of action: Quinidine binds to open sodium channels and prevents the influx of sodium. Therapeutic use: Quinidine is used in the treatment of a wide range of arrhythmias, including atrial ones.  Pharmacokinetics: Quinidine is rapidly and almost completely absorbed after oral administration. It undergoes intensive metabolism mainly in the liver. Side effects: Large doses of quinidine can cause symptoms (such as blurred vision, tinnitus, headache, disorientation, and psychosis).  Class IB: Lidocaine and Mexiletine Class IB agents quickly bind and dissociate (dissolution or decay) to sodium channels. Pharmacokinetics: Lidocaine is administered intravenously due to extensive transformation of the first passage by the liver, which excludes oral administration. Since lidocaine is a highly extractive drug, drugs that reduce blood flow to hepatic blood (β-blockers) may require dose adjustment of lidocaine. Mexiletine is well absorbed after oral administration.  Side effects: Nausea, vomiting, and dyspepsia are the most common side effects. Class IC antiarrhythmic drugs: Flecainide and propafenone These drugs have effects even at normal heart rate. Flecainide also blocks potassium channels, resulting in an increase in the duration of the action potential, even greater than propafenone.  Therapeutic uses: Flecainide is useful for maintaining sinus rhythm (left ventricular hypertrophy, heart failure, atherosclerotic heart disease) and in the treatment of refractory ventricular arrhythmias. The use of propafenone is limited mainly to atrial arrhythmias. Pharmacokinetics: Flecainide is absorbed orally, with renal failure, dosage adjustment may be required. Side effects: Flecainide, usually well tolerated dizziness and nausea, occur most often.  CLASS II ANTIARRHYTHMIC DRUGS CLASS II agents are β-blockers. These drugs. In addition, β-blockers prevent life-threatening ventricular arrhythmias after myocardial infarction. Metoprolol [me-TOE-pro-lol] is the β-blocker most widely used in the treatment of cardiac arrhythmias. It is intensively metabolized in the liver.  Esmolol [ESS-moe-lol] is a very short- acting β-blocker used for intravenous administration in acute arrhythmias that occur during surgery or emergencies. It has a rapid onset of action and a short half-life, making it ideal for acute situations. CLASS III ANTIARRHYTHMIC DRUGS Block potassium channels. Amiodarone. Therapeutic use: Amiodarone is effective in the treatment of all refractory supraventricular and ventricular tachyarrhythmias. Amiodarone was the basis of therapy for the rhythmic control of fibrillation or atrial flutter.  Pharmacokinetics: Amiodarone is not fully absorbed after administration. The drug is unusual in that it has a long life for several weeks, and it is widely distributed in adipose tissue. Full clinical effect can be achieved only a few months after the start of treatment, if loading doses are not used. Side effects: Amiodarone exhibits a variety of toxic effects, including pulmonary fibrosis, neuropathy, and hepatotoxicity. However, low-dose use and close monitoring reduce toxicity while maintaining clinical efficacy.  Sotalol [SOE-ta-lol], although a Class III antiarrhythmic agent, also has potent non- selective β-blocker activity. Sotalol is used to maintain a normal sinus rhythm in patients with atrial fibrillation. Since sotalol has β-blocking properties, it is usually used according to preliminary indications in patients with left ventricular hypertrophy or atherosclerotic heart disease. CLASS IV ANTIARRHYTHMIC DRUGS Calcium channel blockers Although voltage-sensitive calcium channels are found in many different tissues, the main action of calcium channel blockers is on the smooth muscles of the vessels and the heart. Verapamil has a greater effect on the heart. These drugs are more effective against the atria than against ventricular arrhythmias. VII. OTHER ANTIARRHYTHMIC DRUGS. Magnesium is necessary for the transport of sodium, calcium and potassium through cell membranes. Intravenous administration of magnesium sulfate used to treat arrhythmias, since oral magnesium is not effective in conditions of arrhythmia.