EP Drugs (Antiarrhythmics) Flashcards
relationship between cardiac action potential & EKG
*phase 0 = sodium channels open = QRS complex
-prolongation → widened QRS
*phase 3 = repolarization (potassium channels open) = T wave
-prolongation → QT interval prolongation
relationship of pacemaker action potential (SA/AV node action potential) to automaticity, conduction velocity, and repolarization/refractory period
*phase 4 = sodium influx = AUTOMATICITY (intrinsic rate of the beat; steeper slope means faster rate)
*phase 0 = calcium influx = CONDUCTION VELOCITY (how fast the signal travels through the cells after firing)
*phase 3 = potassium efflux = REPOLARIZATION/refractory period
relationship of cardiac action potential to automaticity, conduction velocity, and repolarization/refractory period
*phase 0 = sodium influx = CONDUCTION VELOCITY (you can slow conduction velocity by blocking sodium channels)
*phase 1 = early potassium efflux (sodium channels close)
*phase 2 = plateau = balance between Ca2+ influx and K+ efflux
*phase 3 = repolarization = K+ efflux = REPOLARIZATION/refractory period (you can prolong the refractory period by blocking potassium channels)
*phase 4 = resting potential = AUTOMATICITY (not really any automaticity in the myocytes)
ways to end a re-entrant pathway
*end the re-entrant pathway by:
1. increasing absolute refractory period
2. slowing down the conduction velocity
Vaughn-Williams Classification System for Antiarrhythmic drugs
*class I: sodium channel blockers
*class II: beta blockers
*class III: potassium channel blockers
*class IV: calcium channel blockers
*classes I and III target the fast response tissues (tissues with a “cardiac action potential” - specifically the ventricles)
*classes II and IV target the slow response tissues (tissues with a “pacemaker action potential” - specifically the SA and AV nodes)
class I antiarrhythmic drugs
*sodium channel blockers
sodium channel blockers (class I) - overview
*slow or block conduction velocity (especially in depolarized cells)
*mainly target fast response tissues (tissues with a cardiac action potential; ventricles)
*decrease the slope of phase 0 depolarization → increased action at FASTER HR
*shift the curve to the left, causing fewer sodium channels to be available to fire, even at lower resting potentials, slowing conduction velocity
the different states of sodium channels
*closed (resting) - able to be activated
*open (active) - open with Na+ ions passing through
*closed (inactive) - can’t be opened (in the refractory period)
heart rate influence on states of sodium channels
*at higher heart rates, the sodium channel spends more time in open & inactive states
*at lower heart rates, the sodium channel spends more time in the resting state
class IA antiarrhythmic drugs - examples
*disopyramide
*quinidine
*procainamide
“Double Quarter Pounders make you ‘slow’ and ‘fat’”
class IA antiarrhythmic drugs - MOA
*moderate Na+ channel blockade
*increase action potential duration
*increase effective refractory period (ERP) in ventricular action potential
*increase QR interval
*some K+ channel blocking effects
class IA antiarrhythmic drugs - action potential impact
*slows phase 0
*widens action potential (AP)
class IA antiarrhythmic drugs - EKG impact
*widened QRS
*prolonged QT interval
disopyramide
*class IA antiarrhythmic (SODIUM CHANNEL BLOCKER - moderately slows phase 0 and widens AP)
-reduces contractility
-historically used to treat LVOT obstruction in hypertrophic cardiomyopathy
quinidine
*class IA antiarrhythmic (SODIUM CHANNEL BLOCKER - moderately slows phase 0 and widens AP)
-anti-malarial
-ADE: GI upset
procainamide
*class IA antiarrhythmic (SODIUM CHANNEL BLOCKER - moderately slows phase 0 and widens AP)
-used for Wolff-Parkinson-White pts with Afib when cardioversion is not an option
-ADE: some patients who use it for 6+ months will develop a lupus-like syndrome and become ANA-positive
class IB antiarrhythmic drugs - examples
*lidocaine
*mexiletine
“Lettuce and Mayonnaise make you skinny”
class IB antiarrhythmic drugs - MOA
*weak Na+ channel blockade
*decrease action potential duration
class IB antiarrhythmic drugs - action potential impact
*weakly slows phase 0
*shortens action potential
class IB antiarrhythmic drugs - EKG impact
*normal/baseline QRS
*shortened QT interval!
lidocaine
*class IB antiarrhythmic (SODIUM CHANNEL BLOCKER - weakly slows phase 0 and shortens AP)
-ADE: at high levels, pts experience confusion, paresthesias, and seizures (monitor levels)
mexiletine
*class IB antiarrhythmic (SODIUM CHANNEL BLOCKER - weakly slows phase 0 and shortens AP)
*ADE: may also cause dizziness, slurred speech, and GI upset
class IC antiarrhythmic drugs - examples
*flecainide
*propafenone
“Fries Please!” - makes you slow but not fat
class IC antiarrhythmic drugs - MOA
*strong Na+ channel blockade
*strongly slows phase 0
*significantly prolongs effective refractory period (ERP)
class IC antiarrhythmic drugs - action potential impact
*strongly slows phase 0
class IC antiarrhythmic drugs - EKG impact
*widened QRS
*no impact on QT interval
flecainide
*class IC antiarrhythmic (SODIUM CHANNEL BLOCKER - strongly slows phase 0)
-avoid in patients with LV dysfunction or coronary artery disease
propafenone
*class IC antiarrhythmic (SODIUM CHANNEL BLOCKER - strongly slows phase 0)
-avoid in patients with LV dysfunction or coronary artery disease
summary of class I antiarrhythmic drug effects
*strength of sodium blockade: class IC > IA > IB
*IA: widened QRS, QT interval prolongation
*IB: normal QRS, QT interval shortens
*IC: profound QRS widening
class II antiarrhythmic drugs
beta blockers
beta blockers (class II antiarrhythmics) - MOA
*decrease SA & AV node activity by decreasing cAMP → decreased Ca2+ currents
*suppress abnormal pacemakers by decreasing the slope of phase 4
beta blockers (class II antiarrhythmics) - indications
*supraventricular tachycardia (SVT)
*ventricular tachycardia
beta blockers (class II antiarrhythmics) - action potential impact
*strongly slows phase 4 (of the pacemaker cells - SA and AV node) to slow down heart rate
beta blockers (class II antiarrhythmics) - overview
*work by blocking the effect of beta-1 stimulation by epi/norepi
*mainly target slow response tissues (tissues with a pacemaker action potential - SA and AV nodes)
beta blockers (class II antiarrhythmics) - EKG impact
*decrease heart rate
*no impact on QRS or QT interval
*may prolong PR interval (b/c they slow conduction at the AV node)
beta blockers (class II antiarrhythmics) - ADEs
*those that also block beta2 may cause bronchospasm
*may cause AV block or sinus bradycardia
*may precipitate arterial vasospasm in Raynaud’s
*slows conversion of thyroid hormone
*prevent symptoms associated with low blood sugar (be cautious in diabetic patients)
beta blockers (class II antiarrhythmics) - examples
*metoprolol
*propranolol
*esmolol
*atenolol
*timolol
*carvedilol
class III antiarrhythmic drugs
potassium channel blockers
potassium channel blockers (class III antiarrhythmics) - examples
*amiodarone
*ibutilide
*dofetilide
*dronedarone
*sotalol
potassium channel blockers (class III antiarrhythmics) - overview
*work by blocking the potassium channels
*mainly target fast response tissues (tissues with a cardiac action potential - ventricles)
potassium channel blockers (class III antiarrhythmics) - action potential impact
*prolongs phase 3 (of ventricular cells) to increase absolute refractory period
potassium channel blockers (class III antiarrhythmics) - EKG impact
*QRS unchanged
*WIDENING OF QT INTERVAL
ibutilide
*class III antiarrhythmic (POTASSIUM CHANNEL BLOCKER - prolongs phase 3/refractory period)
-used for acute conversion of Afib
-high risk of Torsades (give Magnesium first)
dofetilide
*class III antiarrhythmic (POTASSIUM CHANNEL BLOCKER - prolongs phase 3/refractory period)
-admit to hospital for first 5 doses due to risk of Torsades
sotalol
*class III antiarrhythmic (POTASSIUM CHANNEL BLOCKER - prolongs phase 3/refractory period)
-admit to hospital for first 5 doses due to risk of Torsades
dronedarone
*class III antiarrhythmic (POTASSIUM CHANNEL BLOCKER - prolongs phase 3/refractory period)
-amiodarone without the iodine
-increases mortality in those with heart failure
amiodarone
*class III antiarrhythmic (POTASSIUM CHANNEL BLOCKER - prolongs phase 3/refractory period)
-many different effects
-drug of choice for VT/VF in setting of cardiac arrest
-significant ADEs: PULMONARY FIBROSIS, thyroid issues, liver issues (monitor PFTs, TFTs, and LFTs)
-note: amiodarone-induced pulmonary fibrosis is very bad
QT prolongation increases risk for ?
QT prolongation increases risk for Torsades de Pointes
class IV antiarrhythmic drugs
calcium channel blockers
calcium channel blockers (class IV antiarrhythmics) - overview
*decrease conduction velocity by prolonging phase 0 of pacemaker cells
*mainly acts on slow response tissues (tissues with a pacemaker action potential - SA and AV nodes)
calcium channel blockers (class IV antiarrhythmics) - MOA
*decrease conduction velocity
*increase effective refractory period (ERP)
*increase PR interval
*decrease HR
calcium channel blockers (class IV antiarrhythmics) - action potential impact
*prolongs phase 0
calcium channel blockers (class IV antiarrhythmics) - EKG impact
*INCREASE IN PR INTERVAL
*QRS unchanged
*QT interval unchanged
calcium channel blockers (class IV antiarrhythmics) - examples
*verapamil
*diltiazem
note - dihydropyridine calcium channel blockers (amlodipine, other -dipines) do not act on the heart, just the blood vessels
calcium channel blockers (class IV antiarrhythmics) - ADEs
*constipation
verapimil
*class IV antiarrhythmic (CALCIUM CHANNEL BLOCKER - prolongs phase 0 of pacemaker cells, increases PR interval)
diltiazem
*class IV antiarrhythmic (CALCIUM CHANNEL BLOCKER - prolongs phase 0 of pacemaker cells, increases PR interval)
digoxin - overview
*derived from the Digitalis purpurea (Foxglove)
*SLOWS CONDUCTION THROUGH AV NODE BY INCREASING VAGAL ACTIVITY
*regarded as a positive inotropic agent because it increases contractility by increasing intracellular calcium
digoxin - MOA
*direct inhibition of Na+/K+-ATPase → indirect inhibition of Na+/Ca2+ exchanger
*increased intracellular calcium → positive inotropy (increased contracility
*increases vagal tone → slow conduction through AV node → decrease HR
digoxin - toxic rhythm effects
*can cause:
-sinus bradycardia
-AV block
-accelerated junctional rhythm
-premature ventricular beats
digoxin - ADE: hyperkalemia
*due to inhibition of Na+/K+ ATPase, it is difficult to get potassium back into the intra-cellular environment
digoxin - acute toxicities
*GI: N/V, abdominal pain
*CV: dysrhythmias
*CNS: lethargy, confusion, weakness
digoxin & vision
*causes BLURRY YELLOW VISION
digoxin ADEs - summary
*hyperkalemia
*blurry yellow vision
*toxic heart rhythms
*N/V, abdominal pain
adenosine - overview
*adenosine has a VERY short half-life
*slows conduction through mechanisms by binding A2 receptor:
-hyperpolarizes cell by opening K+ channel
-blocks adenylate cyclase (decreased funny current & decreased calcium influx)
*by BLOCKING AV NODE, it gets people OUT OF SVT
atropine - MOA
*atropine blocks the acetylcholine receptor
*takes away parasympathetic influence on heart rate:
-increases the slope of phase 4 in SA and AV node
-heart rate should increase
*if someone is bradycardia, often put atropine to bedside in case they become symptomatic
ivabradine - MOA & info
*inhibitor of If (“funny current”
*used for rate control in heart failure if HR > 70 bpm
*side effects: bradycardia, AF
*interactions: metabolized by CYP3A4
what is the real risk of Afib/Aflutter?
*thromboembolism (most likely from the left atrial appendace)
*if someone has Afib/flutter > 48h, we need a TEE (transesophageal echo) to assess for thrombus in left atrial appendage
anticoagulation in Afib/Aflutter
*score 0 = no anticoagulation
*score 1+ = need anticoagulation wtih a direct oral anticoagulant or vitamin K antagonist
*things that contribute to CHADS2-VASc score:
-CHF, HTN, age 75+ (2 pts), diabetes, prior TIA or stroke (2 pts), vascular disease (MI, aortic plaque), age 65-74, female (1 pt)
rate control in Afib/Aflutter
*aim for rate < 110 bpm for most of the day
1st. either metoprolol or diltiazem
2nd. digoxin
3rd. AV nodal ablation
note - do NOT use calcium channel blockers (ex. diltiazem) in heart failure
emergency medication therapy for ventricular tachycardia
1st. amiodarone
2nd. lidocaine
3rd. ventricular tachycardia ablation
long-term/outpatient medication therapy for ventricular tachycardia
1st. amiodarone
2nd. mexiletine
3rd. ventricular tachycardia ablation
