Antiarryhthmics Dr. Roane Flashcards
Dr. Roane EXAM IV
What determines the duration of cardiac action potentials?
opening of ion channels: (Na, Cl, K)
-> followed by depolarization
Terms describing a fast heart rate
-Tachycardia
-Flutter
-Fibrillation
Which of the ions have high intracellular and extracellular concentrations?
-high extracellular concentration: Na+ and Cl-
-high intracellular concentration: K+
MOA of Lidocaine (Lidoderm)
Sodium channel blocker -> prevents action potential from occurring
-used for local and topic anesthesia by preventing nerve conduction
-also antiarrhythmic
Which channel causes the rapid depolarization phase?
voltage-gated sodium channels
depolarization: the potential becomes positive
What causes the prolonged plateau of depolarization?
slow and prolonged opening of voltage-gated (L-type) Ca2+-channels
+
closing of K+ channels
-> so the potential stays positive
What causes the repolarization phase?
Opening of the K+ channels
-> K+ moves out -> potential becomes negative again
Which phase of the action potential does the P-wave refer to?
depolarization in the atrium
Which phase of the action potential does the QRS complex refer to?
depolarization of ventricles, bc in the ventricles the greatest mass (number of cells is polarized (number of cells)
Which phase of the action potential does the T-wave refer to?
repolarization of Purkinje fibers
What initiates the action potential of the pacemaker?
Funny Na+ channels [1]
-the more Na+ channels are open the steeper the slope
What causes the Ca+ channels [2] to open?
The Ca+ channel opens once the threshold is reached
-once the potential reaches the threshold
-the potential is becoming positive due to the Na+ channel [1] opening
order:
F (Na+)
Transient (Ca2+)
Long-lasting (Ca2+)
K+
How do cardiac cells electrically affect adjacent cells?
-through Connexin channels (pores)
-mechanically through Desmosomes
What causes arrhythmias of the heart to occur?
malfunction of any (or two or three) of the 13 ion channels (Na+, Cl-, K+) -> ions will not flow as they should and when they should
most common due to:
-tissue damage due to ischemia
-pathological remodeling
-Covid-19
-diabetes
-hypertension
-stress/anxiety
Categories of arrhythmias
Tachycardia
Tachycardia
-Atrial fibrillation (Afib): chaotic -> associ. with future stroke
-Atrial flutter: more organized than Afib
-Ventricular fibrillation (Vfib): chaotic ventricles
-Ventricular tachycardia: too fast
-Supraventricular tachycardia: starts above the ventricles
Categories of arrhythmias
Bradycardia
-Sick sinus syndrome: damage around the SA node
-Conduction block at the AV node: the conduction of the depolarization slows down in the AV node (bottleneck), it can be blocked in the AV node - AV block
not Bradycardia:
-premature heartbeat: heart beats too soon before it gets filled up, an extra beat -> palpitation
What does the term functional syncytium mean?
it refers to cells (also muscle cells) being connected to adjacent cells through connexins
Automaticity in cells
if the SA node doesn’t work, some cells can spontaneously depolarize and take the function of the SA node
What is an ectopic cell?
cells with the ability to act as the SA node (pacemaker), when they should not
-impulse-conducting tissues are prone to that, especially when K+ levels are low (hypokalemia)
-damage to ventricular cells can induce automaticity
What induces the automaticity of cells in the heart?
l-ow K+ levels
-damage to ventricular cells
QTc prolongation
QTc prolongation = triggered event due to altered potassium levels
-DAD = delayed afterdepolarization
-EAD = early afterdepolarization
What causes DAD and EAD?
DAD: rapid ventricular beats, and high Ca2+
EAD: high influx of Ca2+ or Na+ or failure to get K+ out
-so too many positive ions
Conduction abnormalities
-Heart block (AV block): impulse doesn’t travel through the AV node as quickly as normal
-Re-entry phenomena: the signal from the SA node travles to the AV node and moves through the outer lining of the heart back to the AV node
atrioventricular re-entry tachycardia
patients with slow (fast refraction) and fast (slow refraction) pathways of conduction
refraction = time where no impulse is possible
the fast pathway goes down and excites cells of the bundle of his but also cells of the slow pathway -> the fast impulse cancels out the slow impulse
-the next impulse will travel along the slow path first bc the refraction is shorter -> it will excite cells of the bundle of his and also cells of the fast pathway retrograde up to the atrium, but also re-enters the slow pathway again -> continuous circuit, causing simultaneous ventricular and atrial contraction
How is the re-entry phenomenon treated?
Blocking K+ receptors -> Repolarization phase is delayed (comes down later) -> thereby extending the effective refractory period ERP (it takes longer for the short pathway to start?)
Goal of pharmacotherapy
-reduce ectopic pacemaker activity
-modify conduction or refractoriness in reentry circuits to disable circus movement
mechanism:
1. sodium channel blockade
2. calcium channel blockade
3. blockade of sympathetic autonomic effects in the heart
4. prolongation of the effective refractory period
Class 1A drugs MOA
-Block Na+ channels: decreases the slope of Phase 0 which slows impulse propagation
-Block some K+ channels: increases the duration of the action potentials
Quinidine
Procainamide
Disopyramide
Class 1B drugs MOA
-Block Na+ channels and effectively raise the
depolarization threshold. Treat ventricular
arrhythmias
Lidocaine
Mexiletine
Phenytoin
Class 1C drugs MOA
-Flecainide
Blocks Na+ channels and some K+ channels and blocks Ca++ release from the smooth endoplasmic reticulum
-Propafenone
Block Na+ channels
Blocks b-receptors
Slows impulse conduction and raises depolarization
threshold
What do all Class 1 antiarrhythmic drugs have in common, and practical benefits?
-all block Na+ channels
-in practice, the drugs’ efficacy increases as the
frequency of depolarizations increases
Class 2 drugs MOA
-Beta-blocker (preventing adrenaline, noradrenaline from increase heart rate and force of contraction)
-Blocking b receptors: slows heart rate, slows conduction velocity
Propranolol
Metoprolol
Esmolol (Breviblock) - half-life of minutes, emergency drug IV
Sotalol (this is a class 3 drug) - blocks K channel
Class 3 drugs MOA
-Block Na+ channels and K+ channels (mostly): this prolongs action potential duration APD
Amiodarone: effective but toxic, analog of thyroid hormone that blocks the conversion of T4 to T3
Dronedarone: safer but less effective
Dofetilide (mostly K-channel activity)
Ibutilide MOA is similar to dofetilide (mostly K-channel activity)
Sotalol (mostly K+ channel)
Class 4 drugs
Calcium channel blocker
Non dihydropyridines NDH
Verapamil
Diltiazem
Other antiarrhythmics
-Ivabradine
-Digoxin
-Magnesium sulfate
-autonomic drugs: atropine, isoproterenol
Which drug blocks funny Na+ channels?
Ivabradine
What promotes toxicity in Digoxin therapy?
-low bioavailability of digoxin due to microbes in the intestine -> antimicrobes may kill microbes -> higher plasma levels -> TOXIC
Digoxin: use in re-entry conditions
Which drug can reverse “Torsade de pointes”?
Magnesium sulfate
-blocks Ca++ channels
-Torsade de pointes: ventricular tachycardia caused by prolonged QT
Adverse effects of Amiodarone
-Extremely lipophilic with a t1/2 of weeks to months
-Can cause fatal pulmonary fibrosis
-Hypothyroidism
-Many others
