Arrhythmia and Pharmacotherapy Flashcards
phase 2 “plateau” of ventricular depolarization
L-type calcium channel, predominant channel in heart
conduction velocity is the function of ____
Na channel (function of the inward current magnitude and related to the rate in rise in phase 0 of AP)
Note how SA and AV nodal cells’ AP differ than ventricular action potentials (5)
- relatively depolarized (-60), due to l ack of IK1 channel (ventricular AP rests at -85)
- T-type calcium channel
- If channel: pacemaker current
- L-type calcium channel current mediates the AP upstroke (in ventricle its the fast Na channel)
- rich autonomic innervation
Two examples of bradyarrhythmias
- sinus node arrest or exit block
- usually due to fibrosis from idiopathic degerantion, inflammmation, infiltration, drugs, autonimc influences - AV conduction problems
- first, second, third AV block
- level of AV node: first degree and Mobitz I second degree(wnekebach)
- level of His-bundle: Second degree Mobitz II or third degree
describe the EKG in sinoatrial exit block
sinus rate is regular before and after, and the pause is exactly twice the sinue cycle length
see a little blip-sinus P wave failed to get out of the SA nodal area, so no conduction to the AV node, to the ventricle, and thus no QRS
next interval still comes on time
describe EKG in a sinus pause
sinus activation = P wave
in EKG< you would see no initiation of sinus activity at all
third degree block
no atrial impulse is propagated to the ventricle
Tachycardia-bradycardia syndrome: describe EKG
supraventricular tachycardia, HR is very fast, followed by 6-sec pause that causes dizziness (bradycardia <60), then normalizes
two principle mechanisms of tachyarrhythmias
- disorder of impulse propgation: reentry
- disorder of impulse formation: enhanced automaticity and triggered activity
Explain the 4 features of reentry in tachyarrhythmias
- difference in conduction or refractoriness in two or more regions connected by a closed loop
- unidirectional block in one pathway
- slow conduction over the other pathway
- re-excitation of the first, blocked path
Describe enhanced automaticity and triggered activity
automaticity typically arises from SA node or AV junction, specialized atrial fibers and purkinje fibers
triggered activity may be early (from prolonged AP), or delayed (digitalis toxicity, VT induced by exercise or reperfusion) after depolarization
due to increased calcium inside cell
What’s the difference between Early After Depolarization (EAD) and Delayed After Deplarization (DAD)?
EAD: reactivation of L-type Ca current
DAD: intracellular calcium overload
Explain what’s going on at each dot in this EKG
and interpret the bottom EKG
- no real P wave
- wider QRS –appears to come earlier than when it should = Ventricular Premature Complex (VPC)
- inverted-some coming from RV, some from LV
- two VPCs in a row = couplet
VPC = automatic focus (abnormal pacemaker that has an If current or T channel) comes from the ventricle
bottom EKG: 8 wide complexes in a row, tachycardia
This type of tachycardia is a secondary arrhythmia, ie, secondary to stress or high catecholamines
Sinus tachycardia (when you see this, always think of underlying cause: too much thyroid, fever, sepsis, dehydration, blood loos, hypovolemia)
Atrial flutter is due to ____
atrial reentry in the right atrium
Paroxysmal supraventricular tachycardia (PSVT) is usually due to _____
2 common examples
reentry
examples: AV nodal reentry tachycardia and AV reentry tachycardia
AV reentrant tachycardia involves _____
bypass tract (different path from ventricles to atria)
usually presents as a delta wave on QRS
WPW results when pre-excitation of the ventricles
Susatained V tach is usually associated with ____
Sustained uniform VT is due to ____
____ is a terminal rhythm, requiring immediate defibrillation
- decreased BP
- due to rentry around an old infarct
- V flutter and/or fibrillation
K channel mutatione ffect on QRS
- less K coming out of cell, less repolarization, longer AP, longer QT interval
- these mutations are most common cause of congenital QT elongation (long QT = LQT)
What can cause an elevated ST segment, that can mimic an MI on EKG?
mutation with a short QT
What’s wrong with this pt
Patient in complete heart block - depolarization initiated by the AV node or bundle, pace at a very slow HR
What are the three mechanisms for arrhythmia
- abnormal automaticity
- triggered activity
- reentry
Abnormal Automaticity and 3 clinical examples
- cells outside conduction system acquire automaticity
- injury causes membranes to “leak” ions
- creation of ectopic beats
- myocyte depolarization on its own (when they’re sick)
- premature atrial contractions (PAC)
- atrial tachycardia
- some forms of ventricular tachycardia
Triggered activity and 5 clinical examples
- abnormal conditions cause afterdepolarizations
- can become self-perpetuating
- early vs. late (EAD vs. LAD)
- digitalis toxic rhythms
- torsades de points (long QT)
- some forms of ventricular tachycardia
- electrolyte arrhythmias
- drug-related arrhythmias: antiarrhytmic agents, tri-cyclic antidepressants
Re-entry and 3 clinical examples
- injury –> mosaic of conducting cells (occurs after people have had an MI) = abnormal impulse conduction
- need two things:
- unidirectional block
- slow retrograde conduction
- ventricular tachycardia
- AV nodal reentry tachycardia (AVNRT)
- AV reentry tachycardia (AVRT)
Describe the EKG
- no P waves before QRS
- narrow QRS
- fast rhythm: 150 bpm
- bumps in ST segment = retrograde p waves
= AV nodal reentrant tachycardia (AVNRT)
Describe AVNRT
- dual pathways in the AV node
- 2 roadways: 1 conducts slowly, 1 conducts fast
- you HAVE to have dual pathways present AND a premature atrial contraction to start the arrhythmia (PAC will send electricity down slow pathway since it has a short refractory pathway, and when it reaches bottom, fast pathway has recovered and it can go up the fast, and then down the slow etc.
- if you have a sinus rhythm, you wont notice it
what causes the retrograde P wave in an AVNRT?
- there are no P waves because the rhythm is being generated by the AV node, which will send electricity down to the His Bundle and generate the QRS
- when electrical activity comes back to the AV node, it sends a retrograde signal up to the atria from the AV node, creating this retrograde P wave
- circle goes again, sends another heartbeat down to His bundle, then another retrograde P wave
- still normal QRS because still using His bundle system
common symptom in PTs with AVNRT
recurrent episodes of palpitations
How do you break the arrhythmia in AVNRT?
- decrease conduction slow pathway
- carotid massage (massage on neck stretches fibers, tricks carotid sinus into thinking theres high BP, brain increases PNS and slows conduction through the heart and AV node, usually blocks the AVNRT)
- vagal manuevers (hold breath)
- adenosine (vasodilator, medicin that slows conduction through AV node)
AVNRT chronic treatment
- many pt need no therapy
- beta blockers, verapamil/diltiazem (slows conduction in slow pathway + AV node)
- surgical ablation of slow pathway
If you had to develop an antiarrhythmic drug, what do you think would make the drug ideal?
- drug works on selective ion channels only in specific pathophsyiologic states (i.e. tachycardia)
- converting **unidrectional block **into birdirectional block to get rid of reentrant teachycardias
-suppression of abnormal automaticity
What are some of the main ideas behind the mechanism of lidocaine as use of an antiarrhythmic drug
Modulated Receptor hypothesis:
- voltage, time, and use dependence of receptor occupancy by the drug
- effect on the channel kinetics including channel availability, effects on the action potential
Antiarrhythmic drugs that prolong the AP duration
- side effects
- exception
- class III and some class IA drugs
- can cause torsades de pointes tachycardias
- exception: amiodarone: likely related to this form of arrhythmia due to blocking action on multiple channels blockade (ICaL, and Ina, and K channel)
use and side effects of amiodarone
- atrial fibrillation - only works in 60% of cases
- pulmonary fibrosis, liver and thyroid toxicity
use of internal cardioverter-defibrillator (ICD) use
patients after myocardial infarction whose heart function remains depressed significantly. Created after failure of flecanide to reduce high risk of ventricular arrhythmias and sudden cardiac death.
Antiarrhythmic Drugs:
Class I - drugs and action
Ia - disopiramide, quinidine, procainamide
Ib - lidocaine, mexiletine, tocainamide
Ic - flecainide, propafenone
all block Na channels in the heart in phase 0
Class II antiarrhythmic drugs mechanism
beta blockers
Class III aniarrhythmic drugs: drug list and mechanism
- amiodarone, sotalol, dofetilide, ibutilide
- K channel blockers (slows rate at which K leaves during phase 3)
Class IV antiarrhythmic drugs: drugs and mechanism
- verapamil/diltiazem
- Ca-channel blockers
Class II and IV antiarrhythmic drugs work on which types of cell?
- beta blockers and calcium channel blockers work on pacemaker cells
- they don’t affect APs of atria or ventricular cells
Review the phases of the atrial/ventricular action potential
see figure
effect on QRS, QT, AP and effective refractory period (ERP) for class Ia, Ib, and Ic drugs
see figure
(blue line is Ib)
effect on QRS, QT, AP, and ERP with Class III drugs
see figure
When do you see torsade de pointes occur? What is the result? Which drugs cause this?
- possible outcome when QT gets prolonged
- results in cardiac arrest
-Class IA and III drugs prolong QT
what do beta blockers (class II drugs) affect? Describe what they do to: HR, conduction velocity, phase 4 of AP, and PR interval
- beta blockers affect pacemaker AP, not myocytes
- decrease HR, decrease conduction velocity, decrease slope of phase 4, and increase PR interval
recall the AP phases for SA-AV nodal cells
If = nonselective cation channel
explain effects of Class IV CCB on HR, conduction veloctiy, and PR interval
decreaes HR, decrease conduction velocity, and increase PR interval
-decreases slope, so you see a slower rise
Amiodarone
- drug type, target, effect
- other effects
- what is it good for
- potential side effects? who is at greatest risk?
- class III drug- K channel blocker, prolongs QT
- also has effects on the other class drugs (I, II, IV) - prolongs QRS
- suppresses atrial fib and ventricular tachycardia
-lots of potential side effects: less likely at lower dosages, risk accumulates over time, young patients on indefinite therapy at greater risk
What are the specific side effects with amiodarone (4)
- hyper and hypo thyroidism
- pulmonary fibrosis
- skin sensitivity to sun
- increased liver function tests
- note: when starting amiodarone: check CXR, PFT< TFT (thyroid), annd LFT*
Lidocaine
- class, target,
- preferential impact
- oral version
- class Ib- Na channel blocker
- preferentially impacts ischemic tissue
i. e. ventricular tachycardiia in ischemia, pateient having MI develops VT and cardiac arrest - mexilitine = oral lidocaine
Propafenone/Flecainide:
- class drug, target
- use
- action
- alarm
- class Ic - Na channel blocker
- suppresses paroxysmal atrial fibrillation
- prolongs refractory period in AV node which is a special property since most drugs affect atria or ventricile
- must have structurally normal hearts (no LVH, Heart failure history, coronary disease)
Propafenone/Flecainide
“use dependent”
- more effect at faster heart rates - good for tachyarrhthmia suppression
- normal QRS at rest –> prolonged QRS during exercise
- more risk of arrhythmia at lower heart rates
note: class III drugs have “reverse use dependence”
Drugs that cause drug-induced lupus (3) and key finding
- procainamide (class Ia), hydralazine (blood pressure pill), izoniazide
- anti-histone antibodies
procainamide use
- A fib with WPW
- suppresses conduction over the bypass tract
(class Ia drug, Na channel blocker)
adenosine
- mechanism of action
- effects (2 main ones)
- drives K+ out of cells
- hyperpolarizes cells (makes it harder to depolarize)
- slows down conduction through AV node
- vasodilator: flushing, hypotension (body thinks there’s increased metabolic activity so it will dilate)
- supraventricular tach will break or reveal etiology
An acute management of torsades. What is its mechanism of action and effect
- magnesium
- blocks influx of Ca into cells
(recall Ca influx leads to early afterdepoliarzations)
Atropine
- what is it
- what does it do
- what’s it used for
- muscarinic receptor antagonist
- BLOCKS parasympathetic system
- speeds conduction through AV node
- used for bradycardia
Digoxin
- what does it do
- what is it used for
- its effects are similar to what other drugs?
- suppresses AV node conduction, increases contractility, activates parasympathetic
- can be used to slow heart rate in rapid A fib
- effects similar to BB and CCB in AV node: prolong refractory period, increases PR interval
Digoxin toxicity
- what does it target,
- effect
- blocks Na-K-ATPase in ventricular cells
- raises resting potential atrial/vent cells
- increasd automaticity/afterdepolarizations
- dig toxic rhythms: atrial, junctional, vent tach (often with evidence of AV node block)
- watch for PACs, PVCs, or Heart block
see figure: dashed line is someone on dig-resting potential has gone up, phase 3 is not so flat anymore
for class 1 drugs, compare how each affects the action potential duration (APD) and type of kinetics required to dissociate from the channel
Ia- prolongs APD, dissociates with intermediate kinetics
Ib- shortens APD in some heart tissues; dissociates with rapid kinetics
Ic - minimal effects on APD, dissociate from channel with slow kinetics
The resting potential is mainly determined by ____
The resting potential greatly influences the ____ channel availability, with more channels at (less/more) negative potentials
Potassium
Na channel; more channels at less negative potentials
relatively minor changes in K+ concentration can have major effects on resting potential:
hyperkalemia leads to _____ potentials
hypokalemia leads to _____
hyperkalemia = less negative potentials
hypokalemia = hyperpolarization
(hyperpolarization occurs when K leaves the cell, so if theres low K outside cell, you will be more likely to hyperpolarize)
What happens when you have fewer available Na channels?
Leads to slower conduction and conduction block
sodium channels are dependent on these two factors
- voltage dependent (activated when membrane gets depolarized, Na further depolarizes the cell and rushes in)
- time dependent (gets inactivated very quickly)
When myocytes due to ischemia, what is one important thing they release that has a big domino effect?
Myocytes release K+ when they die –> local hyperkalemia –> decreased AP and less negative resting membrane potential –> results in partially inactivated Na+ channel with conduction slowing and unidirectional block
lidocaine binds preferentially in the ____ state with ____ kinetics
lidocaine has bigger effect in _____ cells
lidocaine works wel in ventricular ____ caused by ____ by converting ____ into _____
- inactivated or open state with rapid kinetics
- bigger effect in partially depolarized cells (less Na channels available and cells with long AP [purkinje fibers])
- ventricular tachycardia, ischemia, converts unidirectional block into bi-directional block
- flecanide effect on ventricular arryhthmias and mortality
- amiodarone effects on arrhythmias and mortaility
- ICD therapy effect on sudden death
- flecanide: does NOT prevent ventricular arrhythmias after MI, increases mortality
- amiodarone prevents arrhythmias after MI, no effect on mortality
- ICD therapy prevents suddent deaths after pts with MI
what causes EAD, what causes DAD
EAD:
- occurs at slow heart rates
- cells with long APs more susceptible
- due to Ca-influx during phase 2 and 3
- LQT, Class II antiarrhythmias
DAD:
- occurs at fast heart rates
- associated with digoxin intoxication
- Ca release and membrane oscillation from SR (comes from INSIDE, not outside)
Rate of automaticity can be changed by the following 3
- changing slope of diastolic depolarization
- changing the threshold
- changing the resting potential
(If and Ica channels)
Some antiarrhythmics can change the voltage threshold such as ____ and ____ to more positive levels
Quinidine and procainamide (class Ia)
- which type of myocytes have a very low tendency to develop automaticity?
- which type of myocytes have the potential to show normal AND abnormal automaticity?
- abnormal automaticity of ___ can occur when the ___ is reduced
- normal atrial and ventricular myocytes
- purkinje fibers
- purkinje fibers can show abnormal automaticity when the diastolic potential is reduced
when do you consider ablation of atrial fibrillation?
symptomatic patients who failed antiarrhythmic therapy
