Antiarrhythmatics part 2 Flashcards Preview

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Flashcards in Antiarrhythmatics part 2 Deck (58):

What is the resting membrane potential of pacemaking cells?

-40 to -65


What is the resting membrane potential of non-pacemaking cells?

-80 to -95


What is an arrhythmia?

any rhythm that is not a normal sinus rhythm with normal atrioventricular (AV) conduction


What are the different arrhythmia patterns?

- irregular
- tachycardia
- bradycardia
- problems related to abnormal conduction and/or muscle depolarization


What is considered bradycardia?

HR < 50-60 bpm
- sinus sick syndrome
- atrio-ventricular conduction block


What is considered a tachycardia?

HR > 100 bpm


What is considered a paroxysmal tachycardia?

HR of 150-250 bpm


What is considered an atrial flutter?

atria beat at 250-350 bp, regular heart rhythm


What is considered atrial fibrillation?

atria beat up to 500 bpm, irregular rhythm, uncoordinated contraction


What is considered a ventricular tachycardia?

over 120 bpm, regular heart rhythm


What is considered a ventricular fibrillation?

irregular rhythm with uncoordinated contraction, immediate cause of death


What is a tornado de points?

Long QT syndrome


What is an arrhythmia caused by?

- alteration in the movement of ions responsible for the action potentials int he pacemaker calls, conduction system and/or muscle


What are the 2 important ions in the action potential?

1. pacemaking (slow) cells (SA node, AV node)
- Ca and K are most important
- this is in the atria
2. Conduction and muscle (fast) cells (atria, parking fibres, ventricles)
- Na, Ca and K are the most important


What are some common causes of cardiac arrhythmias?

- insufficient oxygen to myocardial cells
- acidosis or accumulation of waste products
- electrolyte disturbances
- structural damage of the conduction pathway (can be patients with heart failure and patients with the previous MI)
- drugs (antipsychotic and anti-arrythmias. Drugs can also participate an MI)


What are the 2 mechanisms of cardiac arrhythmias?

1. Abnormal impulse formation
(abnormal automaticity and triggered activity)
2. Abnormal conduction
(impaired AV node leads to bradyarrhythmias, re-entry conduction leads to tachyarrhythmias)


What is triggered activity?

slow and poorly conducted action potential in the atria or the ventricles


Describe abnormal automaticity

- altered SA node firing rate through changes in autonomic activity
- enhanced activity of spontaneous pacemakers (ie. AV node, purkinje fibres) - ectopic pacemakers
---- decrease in phase 4 K conductance (hypokalemia) - increases spontaneous depolarization
----- inactivation of Na channels in depolarized cells (schema)- converts fast cells into ectopic pacemakers
---- localized supersensitivity to catecholamines following ischemia


What happens when you increase the rate of depolarization? When you decrease the rate of depolarization?

Increase: increased HR
Decrease: decreased HR


What happens when you make the RMP more depolarized? More hyper polarized?

depolarized: increased HR
more hyperpolarized: decreased HR


What happens when there is a more negative threshold? What happens with a more positive threshold?

negative: inreased HR
more positive threshold: decreased HR


What is the action of the NT acetylcholine?

- released from parasympathetic nerve
- acts on the muscarininc receptors
- phase 4- slows depolarization rate
- decreases automaticity (SA node), slowed conduction (AV node)


What is the action NT norepinephrine and epinephrine?

- released from the sympathetic nerves
- acts on B-adrenergic receptors
- phase 4 - increases depolarization rate and reduces AP firing threshold
- increases automaticity (SA node), increased conduction (AV node)


What is the triggered activity?

- cells depolarize before complete depolarization has occurred
- non-automatic myocardial cells (atria, ventricles)
--- repolarization is required to change Na channels from inactive to resting
--- Ca channel availability is based on time
--- may be caused by prolonged duration of the action potential- prolonged QT interval? (i.e.. blockade of K channels by class 1 and 3 anti arrhythmic drugs)
--- with increased action potential duration (QT interval) calcium channels may be ready before the sodium channels


What happens when EAD is sub threshold?

prolonged action potential leads to early after depolarization


What happens when EAD reaches threshold?

prolonged action potential leads to a run of spontaneous activity


What can EADs trigger?

Torsade de pointes


Conditions/drugs which prolong the QT interval may precipitate _____

Torsades de Pointes


What is a torsades de pointes?

- it is characterized by twisting of isoelectric points on ECG and prolonged QT interval
- inherited and/or drug induced (increased QT interval)
- can lead to ventricular fibrillation and sudden death
- responds to magnesium


What drugs can increase the QT interval?

- antiarrhythmics
- antihistamines
- anti-psychotics
- antibiotics (e.g. erythromycin)
- can cause sudden death - hERG assays now routine during drug development


What is the mechanism of cardiac arrythmias that lead to abnormal conduction reentry?

- local differences in conduction velocity and membrane characteristics lead to development of electrical circuits (circus conduction)
- re-reouting of the normal electrical circuitry results in multiple beats before the next sinus beat is generated, resulting in tachycardia


What does normal conduction reentry involve?

- reentry requires an available circuit (closed conduction loop)
- unidirectional block
- different conduction speed in limbs of circuit: conduction time (CT) > effective refractory period (ERP)


What does unidirectional block re-entry involve?

- available circuit (closed conduction loop)
- unidirectional block
- different conduction speed in limbs of circuit: conduction time (CT) > effective refractory period (ERP)


What are the main causes of re-entry?

- ischemia
- congenital


What parts of the heart can re-entry occur in?

- AV node
- between the SA node and the atria
- between atria and ventricles
- accounts for most tachyarrhythmias in cardiac patients


How can re-entry be stopped?

can be stopped by converting the unidirectional block tissue to bi-directional block
- in non-pacemaker (fast) cells, this can be done with drugs that block Na channels directly (class 1 drugs )


What is paroxysmal supra ventricular tachycardia?

- its a special case of reentry in the AV node
- the cause is not clear and is often short lasting


What can a paroxysmal supra ventricular tachycardia?

- controlled by drugs that depress AV conduction, causing bidirectional block
- calcium channel blockers (Class 4)
- B-adrenergic receptor blockers (class 2)
- adenosine (class 5)


What is it called when there is an an abnormal electrical pathway in the paroxysmal supra ventricular tachycardia?

Wolff-Parkinson-White syndrome (conducts from the ventricles to atria - bundle of Kent)


What is the treatment options of Wolff-Parkinson-White syndrome?

- treated by catheter ablation of abnormal electrical pathway
- amiodarone first choice agent used to stabilize heart rate


Should void AV node blockers if _________ or _______. What drugs do these include?

atrial fibrillation

B-adrenergic receptor blocker, calcium antagonist, adenosine or digoxin


What are the three mechanisms of action of anti-arrhythmic drugs?

1. reducing automaticity
2. blocking re-entry mechanisms
3. normalize ventricular rate (supra-ventriular tachycardia)


Blocking inactivated Na+ or Ca++ channels depolarizing tissues (preventing conversion to "resting" state) lead stop reduced ________

triggered activity


Hyperpolarizing resting membrane potential (more negative RMP) leads to reduced _______ activity



When you have an increasing membrane threshold potential for activation of Na+ (fast cells) or Ca++ channels (slow cells) leads to what?

reduced pacemaker activity


What is 1 way that you can block re-rentry mechanisms via anti-arrythmic drugs?

reduce phase 0 depolarization -> slows conduction in ischemia area -> converts region of unidirectional block of bidirectional block


What is another mechanism of blocking re-entry mechanisms?

prolong the action potential depolarization -> increases the effective refractory period (ERP) -> conduction time < ERP = re-entry blocked


How to antiarrhythmic drugs work to normalize ventricular rates in supra-ventricular tachycardia?

slowing AV nodal conduction (beta blockers, calcium channel blockers and digoxin) -> reduces ventricular rate -> increasing time for ventricular filling from atrium -> improves stroke volume -> increase cardiac output (CO =HRx increases SV) -> improved hemodynamics


What are examples of class 1 antiarrhythmic drugs and what is their action in the cell?

- procainamide, lidocaine, flecainide
- primarily block Na channels


What are the examples of class 2 antiarrythmic drugs and what is their action inside the cell?

- propanolol, metoprolol, esmolol
- primarily blocks B-adrenergic receptors


What are the examples of class 3 antiarrythmic drugs and what is their action inside of the cell?

- amiodarone, sotalol
- primarily blocks K channels


What are the example of class 4 antiarrythmic drugs and what is their action inside of the cell?

- verapamil
- primarily blocks Ca channels


What are the examples of class 5 antiarrythmic drugs and what is their action inside of the cell?

- magnesium, adenosine and digoxin
- block calcium gated channels - K blockers target on pacemaking cells


Describe IA sodium channel blockers. What is an example of this?

- moderate phase 0 depression and slow conduction; usually prolong repolarization
- procainamide


Describe IB sodium channel blockers. What is an example of this?

- minimal phase 0 depression and slow conduction; usually shorten repolarization (lidocaine)


Describe IC sodium channel blockers. What is an example of this?

- shows marked depression and slow conduction; little effect on repolarization


Class 1A Na channel blockers primarily block _______, especially in depolarized cells

Na channels


What are the two things that cane seen on an ECG after giving a class 1A drug that corresponds to the bloc?

slowing of the phase 0 depolarization
- slowing conduction velocity (widening of the QRD complex of the ECG)