7 Antiarrhythmia drugs Flashcards
Describe the Vaughan Williams classification of antiarrhythmic drugs
- I= Na channel blockers
- IA=moderate potency
- IB= least potent
- IC= most potent
- II= Beta adrenergic blockers
- III= K channel blockers
- IV= Ca channel blockers
What are the direct effects of class IA drugs? What are the indirect effects?
- Direct: Primarily block Na channels:
- Increase AP threshold
- Decrease Vmax
- Increase ERP= increase AP duration
- Indirect:
- blocks K channels -> EADs
- vagolytic effect (“brakes” on the PNS -> faster signal from atria to ventricles/through AV node)
What are 3 main class IA drugs?
Na channel blockers:
quinidine, procainamide, disopyramide
What are some side effects of IA drugs?
- severe GI effects (quinidine)
- vagolytic effect on heart
- proarrhythmic (prolongs QT)
- metabolized in the liver (quinidine… ok for pts with renal failure)
What are some drug interactions for class IA drugs?
- inhibit CYP2D6 (decreased metabolism of narcotics)
- reduced renal clearance of digitalis
What are 2 class IB drugs?
Lidocaine and mexiletine
What are the direct effects of class IB drugs?
- increase AP threshold
- block Na channels (decrease Vmax)
- at high HR **use dependent
- and in depolarized cells (high affinity for inactivated Na channel; can target diseased/ischemic cells well)
- decreases AP duration/ERP
What are some side effects of class IB drugs?
- CNS toxicity (neurons rely on Na!); dizziness, drowsiness, seizures
- GI toxicity; nausea, vomiting
When are class IB drugs used?
- V tach
- digitalis induced arrhythmias
**safe for patients with long QT syndrome (shortens AP)
What are some drug interactions for class IB drugs?
- drugs that interfere with CYP3A4 (e.g. cimetidine)
- drugs metabolized by CYP1A2 (Mexiletine potently inhibits 1A2)
What are 2 class IC drugs?
Flecainide and propafenone
What are the direct effects of class IC drugs?
- increased AP threshold
- few/variable effects on AP duration/ERP
- decreased Vmax (conduction velocity)
What are some side effects of class IC drugs?
- pro-arrhythmic (increased incidence of malignant arrhythmias and mortality)
- negative inotropic effect (can worsen heart failure)
- dizziness, nausea
- bradycardia (propafenone inhibits Ca channel and beta receptors)
When are class IC drugs used?
Only approved in life threatening situations when SVT/ventricular arrhythmias are resistant to other drugs (because of pro-arrhythmic side effects)
What are some drug interactions for class IC drugs?
- drugs that inhibit CYP2D6… e.g:
- bupropion (antidepressant)
- ritonavir (antiretroviral)
- terbinafine (antifungal)
- cimetidine (H2 antagonist)
- amiodarone (antiarrhythmic drug)
What are 3 class II drugs?
Propranolol, esmolol, metoprolol
What are the direct effects of class II drugs?
**Beta blockers
- bind beta adrenergic receptors on cardiac cell membranes to competitively inhibit epi/NE binding
- antagonize effects of sympathetic stimulation (slow rate of diastolic/phase 4 depolarization)
When are class II drugs used?
- all atrial arrhythmias
- ventricular tachycardia and fibrillation
**B blockers are currently the most useful antiarrhythmic drugs available due to their safety (don’t prolong AP; safe in long QT syndrome) and wide clinical applications
What are some side effects of class II drugs?
- negative inotropic effect
- heart block
- bradycardia
- bronchospasm
What are 3 class III drugs?
Amiodarone, sotalol, and dofetilide
What are the direct effects of class III drugs?
- main common property= K channel blockers
- prolongs repolarization
- most common target= IKr (hERG channel)… can result in aquired long QT syndrome
- reverse use-dependent (more effective at a slower heart rate)
- ultimately increase ERP
What are the effects of amiodarone? What is it commonly used for?
- Major action= K channel blocker (both IKr and IKs)
- modest Na channel blocker
- modest Ca channel blocker
- modest beta-adrenoreceptor blocker
**effective against v tach/fib and to prevent recurrent atrial fib/flutter
What are some common side effects of amiodarone?
- triggered arrhythmias (from EADs) **Rarely associated with Torsades!
- hypothyroidism
- pulmonary fibrosis
- hepatotoxicity
What are some drug interactions with amiodarone?
Inhibits P450s, dectreasing clearance of:
- warfarin
- digoxin
- quinidine
- flecainide
- sildenafil (PDE5 inh)
- simvastatin
What are the effects of sotalol? What is it commonly used for?
- major action= K channel blocker (IKr)
- secondary action= beta blocker
**effective against V tach/fib, SVTs, and atrial fibrillation
What are some common side effects of sotalol?
- most serious= triggered arrhythmias with Torsades de pointes
- fatigue
- bradycardia
What are some drug interactions with sotalol?
**Use with caution in conjunction with other drugs that prolong QT (e.g. class IA antiarrthmics, tricyclic antidepressants, and quinolong antibiotics)
What are the effects of dofetilide? What is it commonly used for?
- major action= K channel blocker (IKr)
**effective against atrial fibrillation and flutter (not hepatotoxic like amiodarone and safe for patients with L ventricular dysfunction)
What are some common side effects of dofetilide?
- most serious= triggered arrhythmias (torsades de pointes!)…. requires careful monitoring
- headache
- dizziness
- chest pain
What are some drug interactions with dofetilide?
- drugs that interfere with renal secretion (dofetilide is eliminated via the kidney)
- drugs that inhibit CYP3A4 (e.g. cimetidine)
What are 2 class IV drugs?
Diltiazem (benzothiazepines) and Verapamil (phenylalkylamines)
**Dihydropyridines NOT used for arrhythmias (they mainly target the vasculature, used for angina)
What are the effects of class IV drugs? What are they commonly used for?
- Ca channel blockers **act primarily on slow response cells (SA/AV node) which are dependent on Ca influx for AP depolarization
- increase AP threshold
- increase nodal cell refractory period
- depress conduction velocity in the SA and AV nodes
**commonly used for SVT (rarely for v tach!)
What are some common side effects of class IV drugs?
- negative chronotropic effect (decreases automaticity of SA node)
- negative inotropic effect (decreases Ca influx during plateau phase of ventricular AP)
- hypotension (decreased Ca inlfux into vascular smooth mucle)
- nifedipine= peripheral edema
- verapamil= constipation
- verapamil and diltiazem=
- interacts with digitalis -> slowed AV conduction -> heart block
- increase plasma digitalis (competes for renal excretion)
What are some drug interactions with class IV drugs?
Diltiazem and verapamil are moderate inhibitors of CYP3A4, reducing clearance of quinidine, digoxin, simvastatin
Describe the effects of adenosine
- very rapidly activates K channels to slow depolarization at the AV node
- blocks cAMP enhanced Ca channel activity
- indicated for SVT (slows AV conduction and HR)
Describe the effects of digoxin
- aka digitalis glycoside
- enhances vagal parasympathetic activity to slow conduction at the AV node
- indicated for A fib and SVT to control ventricular response rate
Describe the effects of ranolazine
- blocks persistent Na channel current (reducing excitability) and IKr
- prolongs QT interval
- used for treatment of chronic angina
Describe the effects of ivabradine
- inhibits the pacemaker funny current If
- prolongs diastolic depolarization and slows SA node firing -> reduces HR
Summarize when you would use different antiarrhythmic drugs
- IA for all arrhythmias (SVT, premature ventricular contraction, V tach, some effect on A fib)
- quinidine, procainamide, disopyramide
- IB for premature ventricular contractions and V tach
- lidocaine and mexiletine
- IC for premature ventricular contractions and V tach (some effect on SVT)
- flecainide, propagenone
- II and III for all arrhythmias
- propranolol, amiodarone, sotalol
- IV for SVT (some effect on A fib) **nodal effects, don’t help ventricular arrhythmias
- Digitalis for SVT and A fib
- Adenosine for SVT
