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