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CVS Pharmacology

Cardiovascular system pharmacology- Anti Arrhythmic Drugs

Very important fact about anti-arrhythmic drugs? Very toxic
Classes of anti-arrhythmic drugs? 1,2,3, and 4
Class 1 drugs are what type of drugs? Sodium channel blockers
Class 2 drugs are what type of drugs? Beta blockers
Class 3 drugs are what type of drugs? Potassium channel blockers
Class 4 drugs are what type of drugs? Calcium channel blockers
Mechanism of anti-arrhythmic drugs: Readily bind to activated channels or inactivated channels, but bind poorly to rested channels, so normal cells release the drugs quickly
Increased dosage of anti-arrhythmic drugs can cause? Loss of selectivity, leading to drug induced arrhythmia
In what other cases can these anti-arrhythmic drugs cause arrhythmia? 1) Fast heart rates, 2) Acidosis 3) Hyperkalemia 4) Ischemia
What other therapies can we try before using drugs? 1) Surgery 2) Radiofrequency Catheter Ablation 3) Implantable Cardioverter- Defibrillator (ICD) 4) Gene therapy
What are the risk factors of Torsade de Pointes? 1) Bradycardia. 2) Hypokalemia. 3) Decreased Triggered upstrokes. 4) Drugs which increase APD.
Treatment of Torsade de Pointes? 1) K+ 2) Triggered upstrokes (B-Blockers or Mg++) 3) APD (Pacemaker or isoproterenol).
TdP is also known as: Polymorphic Ventricular Fibrillation
Causes of TdP: 1) Familial long QT interval 2) Drug - Induced (drugs which prolong APD)
Cardiac Causes of arrhythmia: 1) Ischemic heart disease. 2) Inflammation. 3) Trauma, most commonly after heart surgery 4) Congestive heart failure 5) Hypotension
Non-cardiac of arrhythmia: 1) Electrolyte imbalance. 2) Acid-Base imbalance. 3) Hypoxia. 4) Drugs: Digitalis, Anesthetics, Tricyclic, Diuretics, Bronchodilators. 5) G.I. reflexes. 6) Neural reflexes
Example of Class 1A drug: Disopyramide
Example of a Class 1B drug: Lidocaine
Example of a Class 2 drug: Propanolol Atenolol
Example of a Class 3 drug: Amiodarone Sotalol
Example of a Class 4 drug: Verapamil
Which substances increase potassium channel activation? Adenosine Digoxin
Which substance causes Calcium channel block? Magnesium chloride
Electrophysiological actions of Class 1 drugs? Reduced rate of depolarization of action potential Increased ERP (refractory period) Decrease AV conduction
Electrophysiological actions of Class 2 drugs? Slowed pacemaker activity Increased AV refactory period
Electrophysiological actions of Class 3 drugs? Increase action potential duration Increased ERP
Electrophysiological actions of Class 4 drugs? Decrease APD (Action potential duration) Slowed AV conduction
Potassium channel activators have which physiological action? Slowed AV conduction
Clinical use of Class 1 drugs: Ventricular Fibrillation associated with MI
Clinical use of Class 2 drugs: Dysrhythmia prevention in MI Paroxysmal A-Fib due to sympathetic activity
Clinical use of Class 3 drugs: A-fib Ventricular fibrillation
Clinical use of Class 4 drugs: Supraventricular tachycardias A-fib
Clinical use of adenosine? IV for supraventricular tachycardias
Clinical use of digoxin? A-fib
Clinical use of Magnesium chloride: Ventricular fibrillation Digoxin toxicity
Phase 2 of APD can be activated by sympathetic activity inhibited by Calcium-channel blockers beta blockers
Phase 3 can be inhibited by Class 3 drugs
Phase 4 can be inhibited by class 2 drugs
Phase 0 inhibited by: Class 1 drugs
Class 1A drugs: Double Quarter Pounder Disopyramide Quinidine Procainamide
Which Class 1A drugs is the prototype? Quinidine is the prototype, derived from Quinine which is an antimalarial, from cinchona tree
Side effects of Quinidine: Cinchonism, characterised by headache, dizziness, tinnitus Diarrhea in 33% of patients Thrombocytopenia TdP symptoms Increases serum digoxin and Warfarin effects
What does Quinidine do? Inhibits a and muscarinic receptors, prolongs action potential duration and QRS
Clinical use of Quinidine: used with patients with atrial/ventricular arrythmias but NORMAL HEART
Characteristics of Procainamide: Oral Short half life Lupus- like symptoms
Characteristics of Dispyramide: More anticholinergic effects but less diarrhea than quinidine
Class 1B drugs: Lettuce, Mayo, Tomato, Potato Lidocaine, Mexiletine, Tocainide, Phenytoin
Lidocaine is A widely used local anesthetic agent
When is Lidocaine used? When the patient is NOT hypokalemic Ventricular arrythmias in Post MI patients to prevents V-A (Used to be the drug of choice) Not effective in atrial arrhythmias
Lidocaine is given: Intravenously
Side effects of Lidocaine: CNS Hypotension with large doses Least cardiotoxic as side-effects not cardiac, no sudden death
What are Tocainide and Mexilitine? Oral analogs of lidocaine
Side effects of Tocainide and Mexilitine GI and neurologic side-effects
Phenytoin is: Anti-epileptic drug, for special conditions of cardiac arrhythmias: digitalis or congenital heart surgery, or congenital prologned QT interval
Class 1c drugs are usually used as A last resort
Class 1C drugs are: Fries Please Flecainide Propafenone
Function of Flecainide: Blocks K channels
Uses of Flecainide: Proarrhythmic Effective in supra ventricular tachycardia in normal hearts
Consequence of Flecainide use: Sudden death
Propafenone has what function? Beta-blocking and channel blocking activity NO effect on QT Same use and milder effects from Flecainide
Class 2 drugs end with: -olol
What is the prototype of this class of drugs? Propranolol
What is the use of Propranolol? Used to treat hypertension, but found to be very effective to treat arrhythmias from post-MI
In all doses, propranolol is: Anti-arrhythmic
What other class 2 drugs are used? 1) Esmolol IV injection 2) Acebutolol
What are the characteristics of Esmolol? 1) Very short acting, so used in surgeries or acute arrhythmias, 2) B1 selective 3) NO membrane stablizaition effect (unlike propranolol)
What are some general characteristics of class 3 drugs? combined activity of class 1,2,4, wide-spectrum of activity
When is Amidarone given? For life-threatening atrial and ventricular arrhythmias Given IV to induce peripheral vasodilation
Even though Amidarone prolongs QT, what does not occur? TdP
Because Amidarone is slow acting, it needs: A loading dose (given IV) and maintained orally
What is the half life of Amidarone? 25-110 days
Side effects of Amidarone: Cardiac Toxicity Lung fibrosis (most common) Liver toxicity Increases digoxin and anticoagulants levels as it is metabolized by CYP34A4
What is Sotalol? beta blocker with class 3 action
What is Bretylium tosylate? Anti-Hypertensive
When is was Bretylium tosylate used? life-threatening condition of VF after failure of cardiversion or lidocaine
Class 4 drugs: Verapamil and Diltiazem
Function of class 4 drugs? Block activated and inactivated L-type Ca channels, for Paroxysmal Supraventricular Tachycardia
Class 4 drugs were the drugs of choice in: Paroxysmal Supraventricular Tachycardia
Now, the DOC of Paroxysmal Supraventricular Tachycardia is Adenosine
Calcium Channel blockers are being investigated for: Treatment in cancer
Digoxin is used for treatment of Heart failure Atrial arrhythmias
Side Effects of digoxin: Ventricular arrhythmias Toxicity Potential Heart block due to inceased AV
Magnesium works to: Block multiple channels Hypertensive agent (when there is toxemia of pregnancy)
Clinical uses of Magnesium: Effective in refractory digitalis only in hypomagnesemic patients (IV) and Tdp with hypomagnesemic patients Hypertensive agent (when there is toxemia of pregnancy)
Potassium is used for: Digitalis induced arrhythmia with hypokalemia
DOA for adenosine is: Max 15 seconds
Adenosine used for: supraventricular tacchyardia - DOC
Which substances reduce the activity of adenosine? 1) Theophylline 2) Caffeine
Most important side effect of adenosine: Transient flushing
Created by: Ulaisl



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