100814 antiarrthymic drugs Flashcards
what inhibitors depolarization of fast response cells in the myocardium?
class I antiarrhythmics
inhibitors of depolariztion for slow response cells of myocardium?
calcium entry blockers (verapamil, diltiazem)
diff btwn fast and slow response cells
diastolic depolarization-in slow response cells usually
fast response cells-their level of resting membrane potential determines maximum upstroke or conduction velocity of the action potential
effective refractory period (minimum interval btwn two propagating impulses): slow response cells have delayed recovery
3 mechanisms of arrhythmias
increased automaticity
triggered automaticity (normal AP is interrupted or followed by an abnormal depoliariztion; afterdepolarizations)
reentry (abnormal impulse conduction)
what is early afterdepolarization exacerbated by?
long QT syndrome-Torsades de Pointes results
what is delayed afterdepolarization exacerbated by?
fast rates, high intracellular calcium, digitalis toxicity, catecholamines, ischemia
delayed afterdepolarizations occur AFTER repolarization
two types of reentry
functionally defined reentry (tissue with ischemia, hypoxia)
anatomic reentry (reentry in AV node)
four ways in which antiarrhyth drugs work
decrease phase 4 slope
increase threshold
increase maximum diastolic potential (making it more negative)
increase action potential duration
class IA drugs action
sodium channel blocker
moderate phase 0 depression and slowed conduction; prolong repolarization
examples of class IA drugs
quinidine
procainamide
disopyramide
class IB drugs action
sodium channel blocker
minimal phase 0 depression and slow conduction; shorten reploarization
ex of class IB drug
lidocaine
class IC drugs action
sodium channel blocker
marked phase 0 depression and slow conduction
little effect on repolarization
ex of class IC drug
flecainide
class II drug action
beta adrenergic blocker
ex of class II drugs
proproanolol, esmolol
class III drug action
K+ channel blocker-prolong repolarization
ex of class III drug
amiodarone
sotalol
dofetilide
class IV drug action
calcium channel blocker
ex of class IV drug
verapamil
diltiazem
MOA of class I
reduce membrane responsiveness
increase threshold of AP firing
reduce Vmax (depress conduction velocity)
prolong effective refractive period
what kind of cells do class I drugs act on
fast response cells
uses of class IA drugs
atrial flutter or fibrillation
prevent ventricular tachycardia and fibrillation
side effects of class IA drugs
block K channels so can get early afterdepolarizations
vagolytic effect (if used on atrial fibrillation, can decrease atrial firing but this may increase AV nodal firing due to giving AV node enough time to surpass refractory period)
severe GI
inhibits P450
proarrhythmic
reduces renal clearance of digitalis
metabolized by liver actually
SO MANY SIDE EFFECTS OVERALL
class IB MOA
increase AP threshold
block Na+ channels at high HR (greater than 120, so it’s use dependent) and in depolarized cells (so could target disease ischemic cells)… binds preferably in Na+ inactivated channel state
decrease AP duration and ERP
use of class IB
ventricular tachycardia
digitalis induced arrhythmias
safe for patients with long QT syndrome
class IC MOA
increase AP threshold decrease Vmax (conduction velocity)
dissociates from Na channel slowly
side effects of class IC
pro arrhythmic
use of class IC
life threatening situations when supraventricular and ventricular arrhythmias are resistant to other drugs
class II drugs act on what phase of AP?
phase 4–prolongs it in the slow response cells
uses of beta blockers
all atrial arrhythmias, ventricular tachycardia and fibrillation
most useful antiarrhytmic drugs due to safety record and wide clinical applications
side effects of beta blockers
negative inotropic effect
heart block
bradycardia
bronchospasm
MOA of class III
prolong AP repolarization
uses of amiodarone
ventricular tachyarrhytmias and fibrillation
prevention of recurrent paroxysmal atrial fibrillation or flutter
side effects of amiodarone
triggered arrhthmias, but rarely associated with Torsades de Pointes
altered thyroid fxn
pulmonary fibrosis
most serious side effect of sotalol
triggered arrhytmias, with Torsades de Pointes
uses of sotalol
ventricular tachyarrhtmias and fibrillation
supraventricular tachycardias, atrial fibrillation
class IV drugs act most on what type of cells
slow response cells
MOA of calcium channel blockers
increase threhold for AP firing in nodal cells
increase nodal cell refractory period
depress conduction velocity in SA and AV nodes
uses of calcium channel blockers
paroxysmal supraventricular tachycardia
note: rarely used for ventricular tachycardia
side effects of calcium ch blockers
negative chronotropic effect (decreases automaticity of SA node, bradycardia)
negative inotropic effect (decreases calcium influx during plateau phase of ventricular AP)
hypotension (decreases calcium influx into vascular sm muscle cells)
constipation (verapamil)
interacts with digitalis to slow conduction velocity in AV node, leading to heart block (verapamil and diltiazem)
increase plasma digitalis levels for competing for renal excretion (verapamil and diltiazem)
adenosine MOA
VERY RAPIDLY activates K channels to slow phase 4 depolarization AV node (half life of 10 seconds)
blocks cAMP enhanced Calcium channel activity at AV node
uses of adenosine
supraventricular tachycardia-slows AV conduction and heart rate
digoxin MOA
enhances vagal parasympathetic activity to slow conduction at the AV node
uses of digoxin
atrial fibrillation and supraventircular tachycardia to control ventricular response rate
what should you be careful of with flecainide?
increases risk of death in pts with CAD
adenosine may be better than diltiazem and metoprolol for AV nodal reentrant tachycardia b/c
adenosine targets directly the AV node
although all three could be used
what has been shown to be most effective for long QT syndrome?
propranolol
