Drugs for Cardiac Dysrhythmia Flashcards
Sodium channel blockers - MoA
Slow phase 0 depolarization and cardiac conduction –> increases QRS duration.
Class I sodium channel blockers - MoA and subdivision
Bind to sodium channels when the channels are in the open and inactivated states, and dissociate from the channels during the resting state.
Subdivided into 3 gr based on whether they have greater affinity for the open state or the inactivated state and based on their rate of dissociation from sodium channels (rate of recovery).
Class IA drugs - MoA
Greater affinity for the open state and have slow recovery.
Block the fast sodium channel and delayed potassium channels –> they slow phase 0 depolarization and phase 3 repolarization in ventricular tissue. These actions decrease ventricular conduction velocity and prolong the ventricular action potential duration and refractory period –> increases QRS duration and prolong QT interval.
They suppress abnormal automaticity, but they usually do not affect SA node automaticity and HR.
Class IA drugs - Special consideration + Interactions
All of class IA drugs have some degree of antimuscarinic (atropine-like) activity and reduce vagal inh of SA depolarization and AV node. Conduction –> increased HR.
Alcohol
Serum level increased by: Carbonic anhydrase inhibitors, Erithromycin, Antacids, Cimetidine
Serum level decreases by Rifampin
Class IA drugs - Adverse effects
Prodysrhythmic effect
Class IA drugs + greatest to least antimuscarinic effect
Quinidine**
Procainamide*
Disopyramide***
Quinidine - Indication
Suppress supraventricular and ventricular arrhythmias
Combination with dextromethorphan for treatment of emotional lability (pseudobulbar affect) in patients with neurodegenerative disease
Quinidine - Adverse effects
Diarrhea
Excessive QT prolongation (torsade de pointes) –> syncope and decreased CO
Thrombocytopenia
Neurologic symptoms due to overdose- cinchonism; tinnitus, dizziness and blurred vision.
Procainamide - MoA
Converted to active metabolite N-acetylprocainamide –> Class III antidysrhythmic properties.
Procainamide - Indication
Terminate wide QRS complex form of acute ventricular tachycardia and convert atrial fibrillation to sinus rhythm.
Procainamide - Adverse effects + Special consideration
Reversible lupus erythematous like syndrome, with arthralgia and butterfly rash
Pt with slow-acetylator phenotype develop lupus-like syndrome more often and earlier during treatment than do rapid acetylators.
Disopyramide - Indication
Prevent life threatening ventricular dysrhythmias; sustained VT
Disopyramide - Contraindication/Caution
It should not be used to treat asymptomatic ventricular dysrhythmias because of its protentional prodysrhythmic effect. It has negative inotropic and antimuscarinic effects and should be used with caution in pat with HF and elderly persons.
Class IB drugs - MoA
Greater affinity for inactivated sodium channels and have rapid recovery.
Class IB drugs
Lidocaine
Mexiletine
Lidocaine - MoA
Local anesthetic. More pronounced effect on ischemic tissue then normal tissue. In ischemic tissue; cells are partly depolarized because they lack sufficient adenosine triphosphate to operate the sodium pump –> sodium channels in ischemic tissue spend more time in the inactivated state.
Lidocaine - Indication
Refractory ventricular tachycardia.
Ventricular arrhythmias during/after cardiac surgery
Lidocaine - Adverse effects and Interactions
CNS; nervousness, tremor, paresthesia.
Cardiac arrest
Toxic dose: slow cardiac conduction velocity –> cardiac arrest
Drugs that inhibit cyt P450; cimetidine, can increase levels and cause toxicity
Mexiletine - MoA
Greater effect on normal cardiac tissue. Slows conduction in the heart and makes it less sensitive.
Mexiletine - Indication
Suppression of symptomatic ventricular tachycardia
Class IC drugs - MoA
Have greater affinity for the open state and a very slow recovery. Block both fast sodium channels and the rate of rise of the action potential during phase 0 to a greater extent than other class I drugs --> slow conduction throughout the heart and especially in the His-Purkinje system.
Class IC drugs
Flecainide
Propafenone
Flecainide
Propafenone - MoA
Also inhibit the potassium rectifier current (IKr) in ventricular tissue –> increases QT interval, but rarely cause torsades de pointes.
Prolongation of PR interval and QRS duration.
Flecainide - Indication
Supraventricular dysrhythmias
Documented life threatening ventricular dysrhythmias.
Flecainide - Adverse effects
VT
Brochospasm, leukopenia, thrombocytopenia, seizure
Flecainide - Special consideration
Increases mortality in pt who had experienced a MI
Propafenone - Indication
Long term; suppress supraventricular tachycardia and atrial fibrillation.
Life threatening forms of ventricular dysrhythmias such as sustained ventricular tachycardia.
Propafenone - Adverse effects
Ventricular dysrhythmias, hematological abnormalities: agranulocytosis, anemia and thrombocytopenia.
Class II drugs - MoA
beta-adrenoceptor antagonists.
Antiarrhythmic effect because of their ability to inhibit sympathetic activation of cardiac automaticity and conduction. They slow the HR, decrease AV node conduction velocity and increase AV node refractory period.
Class II drugs - Indication
Prevent and treat supraventricular dysrhythmias and to reduce ventricular ectopic depolarizations and sudden death in patients with MI
Class II drugs
Esmolol
Metoprolol
Propranolol
Esmolol - Indication
Acute supraventricular tachycardia &
Ventricular arrhythmia
Hypertension during or after surgery
Metoprolol and Propranolol - Indication
Suppress supraventricular and ventricular dysrhythmias
+ In pat with MI; metoprolol is given IV during early phase of treatment
Class III drugs - MoA
They cause prolongation of the ventricular action potential duration and refractory period. Act by blocking potassium rectifier currents that repolarize the heart during phase 3 of the action potential (except Amiodarone)
Class III drugs
Amiodarone Dronedarone Dofetilide Ibutilide Sotalol
Amiodarone - MoA
Blocks potassium, sodium and calcium channels + beta-adrenoceptors.
Decreases SA node automaticity, decreases AV node conduction velocity and prolongs AV node and ventricular refractory periods.
Increases PR interval and QT interval and causes a slight prolongation of the QRS duration.
Powerful inhibitor of ectopic pacemaker automaticity, and prolongs repolarization and refractory periods throughout the heart.
Amiodarone - Indication
Suppress supraventricular and ventricular dysrhythmias, incl atrial fibrillation, atrial flutter, supraventricular tachycardia and VT
Effective adjunct to implantable cardioverter-defibrillators to reduce nr of shocks required to maintain sinus rhythm.
Amiodarone - Adverse effects
Bradycardia
Impaired AV conduction
QT interval prolongation –> torsades de pointes
Corneal microdeposits
Photosensitivity to UV light
Blue-gray skin discoloration
Hypothyroidism (managed w levothyroxine replacement therapy)
Hyperthyroidsm
Tremor, ataxia and optic or peripheral neuropathy
Pulmonary fibrosis –> may be fatal.
Amiodarone - Interactions
Elevate plasma levels of: digoxin, Flecainide, phenytoin, procainamide, warfarin –> by inh P-glycoprotein mediated drug transport.
Interacts w inhalation anesthetics and CNS depressants –> increases incidence of adverse cardiovascular effects like bradycardia
contra: pregnancy
Dronedarone - Indications
Prevention of dysrhythmia in persons w paroxysmal atrial fibrillation or flutter
Dronedarone - Adverse effects and Contraindications
Liver injury
Increase mortality pt w HF
Contraindications: permanent atrial fibrillation, pt w HF must be monitored every 6 months. Pregnancy
Dofetilide - MoA
Selectively block the rapidly activating delayed rectifier channel (IKr) responsible for repolarizing (rectifying) myocardial tissue during phase 3 of the action potential. By inh this outward potassium current –> prolongation of ventricular repolarization and increases refractory periods and QT interval of the ECG.
Dofetilide - Indications
Convert atrial fibrillation, long term suppression of dysrhythmia
Dofetilide - Adverse effects
QT-prolongation
torsades de pointes
Ibutilide - MoA
Activates the slow (late), inward sodium current –> increases sodium influx and counteracts the outward potassium current so as to slow atrial and ventricular repolarization.
Ibutilide - Indication
Rapid conversion of atrial fibrillation or flutter to normal sinus rhythm.
Before cardioversion in pt that do not respond to cardioversion alone
Ibutilide - Adverse effect + Contraindication
Can induce torsades de pointes
Contra: in pat with prolonged QT interval (QTc>440 ms) and polymorphic VT.
Sotalol - MoA
Nonselective B-antagonist, that prolong the cardiac action potential duration and QT interval by blocking the delayed potassium rectifier current during Phase 3 of ventricular action potential. Decreases HR, slows AV node conduction velocity and increase AV node refractory period without affecting the ventricular conduction and QRS duration
Modest (-) inotropic effect
Sotalol - Indication
Supraventricular dysrhythmias
Rhythm control in persons w atrial fibrillation and flutter
Adjunctive therapy in pt w implantable cardioverter-debrillator (facilitates defibrillation by lowering the defibrillation threshold and decreases nr of shock required.
Ventricular dysrhythmia
Sotalol - Lower dose VS higher dose
Lower dose: acts through beta-receptor blockade
Higher dose: Class III action and prolongation of ventricular repolarization
Sotalol - Adverse effects
Bradycardia Bronchospasm Dyspnea Pulmonary edema and heart failure Dose dependent torsades de pointes
Class IV drugs
Diltiazem
Verapamil
Class IV drugs - MoA
Decrease AV node conduction velocity and increase AV node refractory period. Smaller effect on SA node and HR
Class IV drugs - Indication
Controlling/converting supraventricular dysrhythmias
Control ventricular rate in pt w atrial fibrillation or flutter and a rapid ventricular response.
Verapamil (IV): Terminate paroxysmal supraventricular tachycardia
Class IV drugs - Adverse effects
Exacerbate wide QRS complex VT- must be diagnosed before giving the drugs
Miscellaneous drugs
Adenosine Digoxin Magnesium sulfate Ivabradine Ranolazine
Adenosine - MoA
Derived from ATP and activates specific G protein-coupled adenosine receptors. Stimulation of these receptors leads to activation of acetylcholine sensitive potassium channels and blockade of calcium influx in the SA node, atrium and AV node. Causes cell hyperpolarization, slows AV node conduction velocity and increases AV node refractory period. Av node conduction can be completely blocked for few seconds –> brief period of asystole
Adenosine - Indication
Terminate supraventricular tachycardia by preventing retrograde conduction of reentrant impulses through AV node.
Cardioversion
Terminate acute PSVT
including Wolff-Parkinson white syndrome
Adenosine - Adverse effects and Interactions
Bronchospasm
Vasodilatory effects: facial flushing, rash, diaphoresis
Metallic taste
Dipyridamole inh cellular uptake and increases its cardiac effects.
Digoxin - Indication
Slow ventricular rate in atrial fibrillation
Magnesium sulfate - Indication and Adverse effect
Suppress drug induced torsades de pointes, treat digitalis induced ventricular dysrhythmias and supraventricular dysrhythmias associated with magnesium deficiency.
Low BP
Skin flushing
Low blood calcium
Ivabradine - MoA
Blocks funny current in the SA node which is a mixed Na/K inward current that is activated by hyperpolarization, modulated by the autonomic nervous system and responsible for diastolic depolarization and cardiac impulse initiation.
Ranolazine - MoA
Blocks late sodium current in ventricular tissue
Ivabradine and Ranolazine - Indication
Angina pectoris
Heart failure
Inoperative sinus tachycardia
Ivabradine and Ranolazine - Adverse effects
Excessive bradycardia
Slow AV conduction in some patients.
