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Class 1 Antiarrhythmic: Na+ channel blockers
- Decrease automaticity in SA node by
- -shifting the threshold to more positive potentials
- -decreasing the slope of phase 4
- Decrease the likelihood of re-entry by
- -decreasing the conduction velocity
- -increasing the refractory period (class 1A)
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Class IA Antiarrhythmic Drugs
- Quinidine
- Procainamide
- Disopyramide
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Class IA Drugs Mechanism of Action
- -A moderate block on Na+ channels
- -Also block K+ channels (increase refractory period)
- -Decrease the phase 0 upstroke velocity, which decreases conduction velocity through the myocardium
- -Have some degree of anticholinergic effects *significant clinically b/c it can increase conduction velocity through the AV node
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Quinidine
Class IA Antiarrhythmic
- Adverse Effects: diarrhea, torsade de pointes (prolonged QT), syncope (fainting) secondary to reduction in CO and BP, cinchonism, tinnitus, blurred vision
- *Quinidine-induced digoxin toxicity - increases serum levels of digoxin by inhibiting Pgp
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Quinidine Uses
Occasionally to suppress atrial flutter, atrial fibrillation, supraventricular and ventricular arrhythmias
-If patient has atrial fibrillation - first treat with drug that decreases AV node conduction (digoxin) and then give quinidine
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Class IA: Procainamide
- -Long term uses causes lupus erythematosus (is reversible)
- -Indications: atrial flutter, Afib, ventricular tachycardia, paroxysmal atrial tachycardia
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Class IA: Disopyramide
- -Orally to prevent life-threatening sustained ventricular tachycardia
- -Has greater negative inotropic and anticholinergic effects than other class IAs and therefore should be used with caution in patiens with heart failure and in the elderly
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Antiarrhythmic Drugs: Class IB
- Lidocaine
- Mexiletine
- Phenytoin
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Antiarrhythmic Drugs: Class 1B MOA
- -Preferentially bind to both open and inactivated Na+ channels (I>O)
- -Fast dissociation from Na+ channels
- -Exhibit use-dependent block
- -Increases ventricular fibrillation threshold
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Lidocaine
Used most commonly to treat ventricular arrhythmias (ventricular fibrillation & ventricular tachycardia) in emergency situations associated with myocardial ischemia
High concentrations can cause confusion, dizziness, seizure
Cimetidine (or other drugs that inhibits P450 enzymes) can precipitate lidocaine toxicity
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Mexiletine
- -Analog of lidocaine
- -Primary indication: life-threatening ventricular tachycardia
- -dose related nausea and tremo
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Phenytoin
- -Considered an antiepileptic med
- -Supresses digoxin-induced delayed after depolatization
- -ventricular tachycardia
- -Induces hepatic enzymes (P450 3A4)
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Antiarrhythmic Drugs: Class 1C
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Class 1C drugs MOA
- -Preferentially bind to both open and inactivated Na+ channels (I=O)
- -Most potent Na+ channel blockers
- Little/no effect on AP duration
- -Prevent paroxysmal supraventricular tachycardia and atrial fibrillation
- -Depressive effects on cardiac function
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Flecainide
- -Various Atrial and ventricular arrhythmias, except those associated with MI (increased mortalitiy rate)
- Adverse effects: bronchospasm, leukopenia, thrombocytopenia, seizures
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Propafenone
- -Treat various atrial and ventricular arrhythmia
- -Potential ventricular arrhythmias and several hemotologic abnormalities, including agranulocytosis, anemia, and thrombocytopenia
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Antiarrhythmic Drugs: Class II drugs
- Esmolol
- Metoprolol
- Propranolol
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Antiarrhythmic Drugs: Class II drugs MOA
- -Decrease automaticity by decreasing the slope of phase 4
- -Decreases the incidence of re-entry by slowing electrical conduction at the AV node
- -The AV node is more sensitive than the SA node to the effects of B-blockers
- -The most frequently used agents in the treatment of supraventricular and ventricular arrhythmias precipitate by sympathetic stimulation
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Antiarrhythmias: Class III Drugs
- Amiodarone
- Dofetilide
- Ibutilide
- Sotalol
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Class III Drugs MOA
- -Block K+ channels
- -Prolongs AP
- +Decreases the incidence of re-entry by increasing the effective refractory period
- -Increase the likelihood of developing early afterdepolarization and torsade de pointes
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Amiodarone
- -Mainly class III
- -Also Class I, II, IV
- -Alters lipid membrane in which ion channels and receptors are located
- -decreases re-entry by prolonging AP duration
- -decreases the rate of firing in pacemarke cells as class I
- -Class II activity by noncomp. antatgonizing B-receptors
- -Cna cause significant AV block and bradycardia
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Amiodarone continued
Adverse effects: hypotension, AV block, various arrhythmias, blue-gray skin discoloration, thyroid abnormalities, fatal pulmonary fibrosis
Also corneal deposits, blurred vision, photosensitivity, and GI disturbances
Inhibits metabolism of digoxin, flecainide, phenytoin, procainamide, warfarin
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Ibutilide and Dofetilide
- Used to terminate AFib and atrial flutter
- -Adverse effects: torsades de points, may requrie electrical cardioversion
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Sotalol
- Mixed Class II and III
- -Used for patients that cannot tolerate amiodarone
- -Prevents recurrent atrial flutter/fib
- -Causes fatigue, bradycardia, and can induce torsades de pointes
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Antiarrhythmic Drugs: Class IV Drugs
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Class IV MOA
- -Block cardiac Ca channels
- -Act preferentially on SA and AV nodal tissues
- -Slows AP upstroke in AV node, leading to slowed conduction velocity through the AV node
- -Use to treat re-entrant paroxysmal sypraventricular tachycardia that involves AV node
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Misc: Adenosine
- -opens a G protein-coupled K+ channel
- -inhibits SA nodal, atrial, and
- AV nodal conduction
- -also inhibits the potentiation of Ca2+ channel
- activity by cAMP
- -has a plasma half-life of less than 10 sec
- -often used as the first-line agent for
- converting narrow-complex paroxysmal supraventricular tachycardia
- -adverse effects include headache,
- flushing, chest pain, and excessive AV or SA nodal inhibition
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Misc: Digoxin
- -Indirectly increase vagal tone and slows AV node conduction and increases AV node refractory period
- -Use to slow the ventricular rate in patients with AFib (b-blockers and CCB are usually preferred b/c of their more rapid onset of action and greater degree of AV node blockade)
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Misc: Magnesium sulfate
- -Mg is second most common intracellular cation
- -deficiency can cause arrhythmias, CHF, and GI/renal disorders
- -Mag sulfate IV suppresses drug-induced torsades de pointes to treat digitalis-induced ventricular arrhythmias
- -Also treats supraventricular arrhythmias associated with Mag deficiency
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