Mod 1 Lecture 2: anti-arrhythmic therapies Flashcards
what node produces an electrical impulse at regular internals that allows for cardiac contractions
SA Node
what is an arrhythmia
electrical activity that deviates from the previous description as a result of an abnormality in impulse initiation and/or impulse propagation
what are the treatment options for arrhythmias
pharmacotherapy, pacemakers, cardioversion, catheter ablation and surgery can be pursued
what are the mechanisms of arrhythmias
disturbances in impulse formation
disturbances in impulse conduction
what is depolarization
when the cells of the heart are activated
what is repolarization
when the cells of the heart are at rest
when should treatment of arrhythmias be avoided in general
asymptomatic or minimally symptomatic arrhythmias
How do arrhythmias arise?
ischemia ( as well as scarred or diseased tissue)
hypoxia
acidosis or alkalosis
electrolyte disturbances (potassium, calcium and chloride)
excessive catecholamine exposure (illicit drugs or excess adrenaline, cortisol, etc)
autonomic influences
Drug toxicities
what is the P wave
atrial depolarization
what is the T wave
ventricular repolarization
what is depolarized during the QRS complex
ventricular depolarization
what ions are involved during cardiac action potential
Na+
K+
Ca+
what is cardiac action potential
change in voltage across myocardial cells
involves movement of ions across cell membranes
what occurs at phase zero of the fast AP
Influx of Na+ and a spike from negative voltage to positive
what occurs at phase one of the fast AP
K+ and Cl- out
what occurs at phase 2 of the fast AP
Ca2+ in and K+ out
what occurs at phase 3 of the fast AP
K+ outward and decrease in voltage back to negative
what occurs at phase 4 of the fast AP
K+ with a net negative change of -96mV
what regulates the pacemaking activity
both parasymathetic and sympathetic activity
what are latent pacemaker cells
purkinje cells that demonstrate slow phase 4 depolarization
cells that take control of packing of the heart when SA node conduction/impulse generation is impaired - leads to disturbed impulses
when do Early Afterdepolarizations (EADs) occur
during phase 3 of action potential
when do delayed afterdepolarizations (DADs) occur
during phase 4 of action potential
what usually triggers EADs
factors that prolong action potential duration in the ventcile -> leads to QT prolongation -> torsades de pointes, tachycardia and other arrhythmias
what is QT prolongaction
caused by a blockage of rapidly activating delayed rectifier potassium channels
can be intrinsic (congenital) or extrinsic (some drugs can cause)
slow HR and hypokalemia can exacerbate states of long QT syndrome which is life threatening
when does DADs occur
when there is excess accumulation of intracellular calcium - especially at fast heart rates and can lead to ventricular tachycardia
what are possible triggers of DADs
digital toxicity
excess catecholamines
myocardial ischemia
what are disturbances of impulse conduction
most common form affecting AV note - results in various degrees of heart block
AV node is under tonic influence of PNS to slow conduction - anti-muscarinic agent like atropine can sometimes relieve heart block
what are the varied responses of impulse conduction disturbances
from slowing impulse prolongation to complete heart block (no conduction from atria to ventricles)
in complete heart black - latent purkinje pacemaker cells dictate ventricular rate
what is re-entry of impulse conduction disturbances
a serious form of conduction abnormality
one impulse re-enters and excites area of the heart more than once
paths of re-entry can be very small or involve large portions of atria or ventricles
arrhythmia from re-entry can be from a few extra beats to sustained tachycardia
what is Wolff-Parkinson-White Syndrome
re-entry circuit of atrial tissue, AV node, ventricular tissue, accessory AV connection
what can generate “daughter impulses”
re-enty arrhythmia -> VT or Afib
what is the clinical presentation of enhanced automaticity
(impulse formation)
acceleration of AP thru normal or abnormal cardiac tissue (ST, AT)
what is the presentation of triggered activity
abnormal AP triggered by preceding AP (early or delayed afterdepolarization)
AF, VT
what is the presentation of re-entry
impulse fails to die out after normal activation (usually related to an obstacle and availability of another circuit - bypass to normal conduction)
AVNRT (atrial ventricular nodal re-entry tachy) or Wolff-parkinsons-white (WPW)
what are types of arrhythmias
atrial fibrillation
atrial flutter
AV nodal re-entry (SVT)
Ventricular fibrillation
Ventricular tachycardia
What are the classes of anti-arrhythmic agents
Class 0
Class 1: action is sodium channel blockade
Class 2: action is sympatholytic
Class 3 : action manifests as prolongation of AP duration.
Class 4: action is blockade of the cardiac calcium current.
what is the action of class 1 anti-arrhythmic agents
action is sodium channel blockade. these drugs have effects on the action potential duration
what is the action of class 2 anti-arrhythmic agents
action is sympatholytic. drugs with this action reduce beta-adrenergic activity in the heart.
what is the action of class 3 anti-arrhythmic agents
action manifests as prolongation of the action potential duration. most drugs with this action block the rapid component of the delayed rectifier potassium current, I Kr
what is the action of class 4 anti-arrhythmic agents
action is blockade of the cardiac calcium current. the action slows conduction in regions where the action potential upstroke is calcium dependent, SA and AV nodes
What is class 1a drugs
sodium channel blockade, prolonged refractoriness
Quinidine
Disopyramide
Procainamide
what is class 1b drugs
sodium channel blockade, little effect on refractoriness
Lidocaine
phenytoin
mexilitine
what is class 1c drugs
sodium channel blockade, slight prolongation of refractoriness
flecainide
proprafenone
what are class 0 drugs
blocks HCN4 (hyper-polarization - activated cyclic nucleotide - gated) the If (funny channel)
Ivabradine (corlanor)
What is ARP
absolute refractory period
time during which another stimulus will not lead to another AP
what is RRP
relative refractory period
interval following ARP in which a 2nd stimulus is inhibited, but not impossible
what is ERP
Effective refractory period (ERP)
time in which a cell does not produce a new AP (phase 0,1,2,3)
What class of drugs are used to treat sinus tachycardia
Class II, IV
other underlying causes may need treatment
what class of drugs are used to treat afib/flutter
Class IA, IC, II, III, IV digitalis
ventricular rate control is important goal; anticoagulation is required
what class of drugs are used to treat paroxysmal supraventricular tachycardia
class IA, IC, II, IIII, IV adenosine
what class of drugs are used to treat AV block
Atropine
acture reversal
what class of drugs are used to treat ventricular tachycardia
Class I, II, III
what class of drugs are used to treat premature ventricular complexes (PVC)
Class II, IV
magnesium sulfate
PVS are often benign and do not require treatment
what class of drugs is used to treat digitalis toxicity
class IB
magnesium sulfate
What are the two primary class 1A agents
Quinidine
Procainamide
what is Quinidine
class 1A drug
uncommon med
primarily used in Atrial, AV junction and ventricular tachyarrhythmias
Oral
what are the adverse effects of Quinidine
blurry vision, tinnitus, headache and psychosis
what was Quinidine previously used for
treatment of malaria
what is procainamide
class 1A drug
IV ONLY
atrial/ventricular arrhythmias
not in common use
can be used in tx of hemodynamically stable, sustained monomorphic ventricular tachycardia
what is the adverse effects of procainamide
hypotension
what are the affects of class 1A agents
sodium channel blockade
what are the affects of class 1B agents
block activated and inactivated sodium channels with rapid kinetics
additionally shorten phase 3 depolarization and decrease the duration of the action potential
have greater effect on cells with long AP compared to atrial cells
what are the two class 1B agents commonly used
Lidocaine
mexiletine
what is lidocaine
class 1B agent
IV only
can be used to terminate ventricular tachycardia/fibrillation and prevention of Vfib after cardioversion in setting of acute ischemia
little to no affect on atrial or AV junction arrhythmias
what is mexiletine
class 1b agent
used in chronic (preventive) treatment of ventricular arrhythmias (in pts prone to VT)
what are the adverse effects of Lidocaine
mostly CNS changes (nystagmus, drowsiness, slurred speech)
what are the adverse effects of mexiletine
N/V; has narrow Therapeutic Index
what are the effects of class 1C agents
slowly dissociate from resting sodium channel in Purkinje and myocardial fibers causing marked slowing of PHase 0 depolarization
considered contraindicated in pts with structural heart disease
what are the two class 1C agents
Flecainide
Propafenone
what is flecainide
class 1C agent
potent blocks of sodium and potassium cahnnels with slow unblocking kinetics
can be effective in suppressing premature ventricular contractions
oral only
“pill-in-pocket” for pts with paroxysmal afib; rarely used as primary prevention against SVT, PVCs given its toxicity
what can Flecainide cause
severe exacerbation of arrhythmias in pts with pre-existing ventricular tachyarrhythmias and those with previous MI and ventricular ectopy
what is propafenone
class 1C agent
what is propafenone
class 1C agent
used primarily to control rhythm in atrial arrhythmia including flutter and afib)
also used to prevent paroxysmal SVT in pts with AV re-entrant tachycardia (AVRT)
what are the adverse effects of Propafenone
beta-blocking effects, so can cause bronchospasm; beware of use in asthmatics
what are the adverse effects of flecainide
blurry vision and nausea
what are class 2 agents
beta-blockers
diminish phase 4 depolarization to prolong AP
decrease impulse automaticity, chronotrophy, dromotropy, and inotropy
useful primarily in treating tachyarrhythmias caused my increase sympathetic activity
what are class 2 agents less effective at treating
ventricular ectopy than sodium channel blockers (class 1 agents), but can be used to prevent recurrent infarction and sudden death due to ventricular arrhythmias in pts recovering from acute MI
what are the different class 2 agents used
Metropolol
Propranolol
Esmolol
what is metropolol
class 2 agent
cardioselective beta-blocker, most widely used in tx of cardiac arrhythmias
Oral, IV preparations available
what is propranolol
non-selective beta blocker
IV, Oral available
what is esmolol
very short acting, fast onset beta-blocker used to abort acute arrhythmias
IV only
what are the effects of class 3 agents
prolong AP primarily by blocking potassium channels in cardiac muscles (results in a prolonged effective refractory period)
need to be used with extreme care; can increase risk of torsades de pointes
most drugs in this class cause QT prologation
what are common class 3 agents
amiodarone
Dronedarone
Sotalol
what is amiodarone
class 3 agent
many effects; including prolongation of AP, sodium channel-blockade, adrenergic and calcium channel antagonism
oral or IV
used to treat hemodynamically stable sustained monomorphic ventricular tachy as well as pulseless VT/VF
highly effective for treating or preventing SVT, esp Afib
what is amiodarone toxicity
symptomatic bradycardia and heart block in pts with known sinus or AV nodal disease
causes peripheral vasodilation - > hypotension
pulmonary fibrosis
thyrotoxicity and hepatotoxicity
often avoided as long-term agent in YOUNGER patients
what is dronedarone
class 3 agent
oral medciation; only clinical use is to maintain NSR in pts with atrial arrhythmias
less effective than amiodarone
what patients is dronedarone contraindicated in
patients with symptomatic HF
what is sotalol
nonselective beta blocker
used to treat life-threatening ventricular arrhythmias (ACLS algorithm)
used for cardioversion to and maintenance of sinus rhythm in patient with Afib
what are the effects of class 4 agents
non-dihydropyridine calcium cannel blockers
their activity slows phase 4 spontaneous depolarization and slows conduction in tissues dependent on calcium currents (AV and SA nodes)
major effect of these agents is on vascular smooth muscles and heart
useful in treating atrial more than ventricular arrhythmias and reentrant SVT
what are the class IV agents
verapamil and diltiazem
what is verapamil
class 4 agent
used to terminate supraventicular tachycardia (IV)
also used for rate control in Afib and flutter (IV, oral forms) but rarely is able to convert from atrial flutter/fibrillation to NSR
what is diltiazem
class 4 agent
similar in efficacy to verapamil for managing supraventricular arrhythmia
works well to control Afib; similar efficacy for converting AF to NSR
IV and oral forms available
what are other non-categorized agents for arrhytmias
Digoxin
Adenosine
atropine
what is digoxin
inhibits sodium/potassium - ATPase pump which shortens refractory period in atrial and ventricular myocardial cells or prolongs the refractory period and diminishes conduction velocity in the AV node
control ventricular response rate in Afib/flutter
narrow therapeutic index
need to be “loaded”, either IV or orally prior to maintenance dosing
what is adenosine
used to inhibit AV nodal conduction and increase AV nodal refractory period
IV
drug of choice for prompt conversion of paroxysmal SVT to sinus rhythm
Flushing, SOB, chest pain are not uncommon side effects
what is atropine
anti-muscarinic agent can be used IV form to abort life-threatening bradycardia including: symptomatic bradycardia due to medication toxicity/overdose, second degree heart block, complete heart block)
what is the goal of treating Afib
relieve patient symptoms and prevent complications of thromboembolism and tachycardia - induced heart failure
what are the objectives of treating Afib
initial treatment is objective= control of ventricular rate
- first line: CCB alone or in combination with adrenergic blocker
Second objective = restoration and maintenance of normal sinus rhythm
in the US what is the first choice therapy for rhythm control
DC cardioversion (shock)
what is the first line agent for patients with heart failure with low ejection fraction(EF) and/or hypertension
amiodarone to maintain NSR
what is the first line treatment for a patient with CAD
Sotalol
what are the mainstay treatments for patients with mild heart disease that do not revert to NSR with cardiac ablation and/or have established persistent Afib
Flecainide or Sotalol are mainstay
amiodarone is used if these fail
