Intro to Antiarrhythmic Drugs Flashcards
Arrhythmias consist of cardiac depolarizations that deviate from normal in what three potential ways?
rate of impulse
impulse site of origin
conduction of impulse
In the atrial, purkinje and ventricular cells, what ion current leads to depolarization?
NA+
In the SA and AV ndoal cells, depolarizaion depends on what ion current/
Ca2+
What are the three potential states for the Na+ channel?
resting = no Na passes thorugh
activated = Na enters the cell
Inactivated - inactivation gate is closed, no Na passes thorugh
Although most Ca2+ channels become activated and inactivated in the same manner as Na+ channels, how do they differ?
the transition between activated and inactivated occurs more slowly and at more positive membrane potentials
For both cell types, final repolarization (phase 3) results from permeability to what ion?
K+
What two currents are collectively called the Ik?
rapidly activating potassium current
slowly activating potassium current
Why does the resting potential of a cell affect the number of action potentials that can be evoked?
Membrane potential determines how many channels are open - via activation/inactivation gates
So…If Na+ channels inactivate between 75 and -55mV, will more Na+ channels be available for diffusion at -60 mV or -80 mV.
-80 mV - fewer channels will be in the inactivated state
During the positive membrane potential during plateau (phase 2), are any Na+ channels available?
none
What happens to the Na+ channels during repolarization?
they recover from inactivation and become available
What period spans the time when all Na+ channels are inactivated to when enough are open again?
the refractory period
What happens if you add a drug that blocks Na+ channels?
the total number of Na+ channels available at optimal conditions will be decreased
at suboptimal conditions, the Na+ channels will be uanvailable dur to both inactivation gate closure AND drug blockade
Na+ channel recovery time increases with depolarization or hyperpolarization of the membrane potnetial?
depolarization - they stay inactivated longer
this means depolarized cells recover more slowly and the refractory period increases
Depolarization to what membrane potential will abolish Na+ currents
-55 mV - they’re all inactivated
What are the potential factors that lead to arrhythmia?
Ischemia Drug Toxicity Hypoxia Acidosis / Alkalosis Electrolyte Abnormalities Overstretching of Cardiac Fibers Excessive Catecholamine Exposure Autonomic Influences Scarred or Diseased Tissue
Pacemaker cell impulse formation is split into the diastolic interval and the action potential. Which is more important for increasing heart rate?
the diastolic - increase Na+ permeability
What are the two ways you can slow the diastolic interval?
flatten the slope of the diastolic interval - make it take more time
hyperpolarize the diastolic interval, make it need to go further
Drugs blocking what receptor will act to slow the pacemaker?
beta-adrenoceptor (inhibits NE sympathetics)
What are some things - conditions or drugs that will increase the slope of diastolic interval speeding up the pacemaker?
hypokalemia beta adrenoceptor stimulants positive chronotropic drugs fiber stretch acidosis
What are afterdepolarizations?
they’re membrane voltage oscillations that result in transient, abnormal depolarizations of cardiac myocytes during phase 2, 3, or 4 of the cardiac AP (either early afterdepolarization or delayed afterdepolarization)
When do early afterdepolarizations occur?
DURING the action potential and interrupt orderly repolarization of the myocyte
What causes early afterdepolarizations during late phase 2?
opening more Ca2+ channels
What causes early afterdepolarizations in early pase 3?
opening of Na+ channels
Inhibition of K+ channels will cause early afterdepolarizations in what phase?
both phase2 and 3
Are early afterdepolarizations exacerbated at slow or rapid heart rates?
slow
When do delayed afterdeplarizations occur?
occur after the AP when the membrane is nearly or fully repolarized, but before another AP would normally occur
What are DADs caused by>
elevated cytosolic Ca2+ levels - overload of the SR causes spotnaneous release of Ca2+ and leads to depolarizing current
Are delayed afterdepolarizations exacerbated at slow or fast heart rates?
fast
Afterdepolarizations can lead to arrhythmias more likely when the AP duration is abnormally short or long?
long
What are the two general types of heart blocks?
partial or complete
Where can blocks occur?
SA node, AB node, bundle of his (infra-hisian block), bundle branch block, fascicles (hemiblocks)
What is reentry?
when the impulse reenters and excites areas of the heart more than once - also called “circus movement”
What are the required conditions for reentry to occur?
- there must be an obstacle to homogenous conduction
- there must be a unidirectional block at some point
- conduction time must exceed the effective refractory period
What is an example of reentry that is strictly anatomical?
Wolff-Parkinson-White syndrome, where you get the bundle of kent - an abnormal electrical accessory connection between atria and ventricle, allowing the impulse to conduct
Why is timing everything for reentry to occur?
If conduction is too slow, you end up with a bidirectional block and you can’t get reentry
If conduction is too fast (which would be close to normal, 1. you end up with a bidirectional block and 2. the impulse travels around the unidirectional block too quicky, reaching tissue that is still refractory
What are the Class I antiarrhythmics?
Na+ channel blockers - alter AP duration and kinetics of Na+ channel blockage
What are the Class II antiarrhytmics?
beta-adrenoceptor blockade - block sympathetic nervous system effects on the heart
What are the Class III antiarrhtymics?
K+ channel blockers - prolongation of the effective refractory period
What are class IV antitarhytmics?
Ca2+ channel blockade
slows conduction where depolarization is Ca2+ dependent
What do all the antiarrhythmics have in common?
They are all “use” or “state dependent” drugs, meaning they bind readily to activated or inactivated channels so they only work in areas where depolarization is abnormal
Antiarhyrthmics block electrical activity during what situations?
fast tachycardia (when there are many channel activation and inactivations per unit time)
significant loss of resting potential (many inactivated channel during rest)
What is the goal for an antiarrhythmic in a reentry arrhythmia that depends on depressed conduction? (hint - it’s counterintuitive)
you want to slow conduction speed which will change the block from unidirectional to bidirectional – no more reentry
Is channel specificity directly or inversely related to dose of antiarrhytmic drugs?
inversely - higher dose, more spillover to secondary channels
especially with the Class I Na+ blockers affected K+ channels
How do we classify cardiac arrhythmias based on heart rate? heart rhythm? site of origin?
tachycardia vs bradycardia
regular v sirregular
supraventircular vs ventricular
What would you see on EKG with premature atrial contractions?
early extra beats that originate in the atria, so you’ll see a p wave riding right on the tail of a T wave - everything is otherwise normal, it’s just the timing
What would you see on EKG with paroxysmal supraventricular tachycardia?
It’s a rapid, usually regular rhythm originating from above the ventricles - begins and ends suddenly.
What would you see on EKG with accessory pathway tachycardias? (bypass tract tachycardias)
It’s a rapid heart rhythm due to an extra abnormal pathway or connection between the atria and ventricles (Like WPS syndrome) - you get a delta wave or “slurred” upstroke in the QRS somplex
What are the three variants of AV nodal reentrant tachydardia? What is the general cause?
it’s a rapid heart rate due to more than one pathway thorugh the AV ndoe
atrial tachycardia, atrial fibrilllation, atrial flutter
What is atrial fibrillation?
irregular heart rhythm where many impulses begin and spread in the atria competing for a chance to travel through the AV node. the result is a disorganized, rapid, irregular rhythm. You get less coordinated atrial contraction as well.
What is atrial flutter and how doe it differ from fibrillation?
There are many impulses that are vying to travel to the AV node, but they occur in a mroe organized loop. This means it’s different from fibrillation because it’s more regular.
What will you see on EKG with PVCs?
they’re extra early beats beginning in the ventricles. You see a big QRS spike that’s occuring right after a T wave without the usual P wave in between
What is ventricular tachycardia?
It’s a rapid rhythm originating form the ventricles - this prevents the heart from filling with blood and less is pumped thorugh the body.
What is ventricular fibrillation and why is it an emergency?
It’s erratic, disorganized firing impulses from the ventricles - like a quiver. the ventricles can’t contract or pump any blood. On EKG you’ll be unable to discern where any of the waves are.
What’s the treatment for v-fib?
CPR and defibrillation
What will long QT syndrome look like on EKG?
If the time between the Q wave and the end of the T wave is over 450 ms, that’s long QT
Long QT syndrome increases the risk for what life-threatening form of V-tach?
torsade de pointes
What will sinus node dusfunction look like on EKG?
a slow hear rhythm where you get nothing for 3+ seconds with no SA node activity
What will a heart block look like on EKG? How can you see the difference between partial and complete blocks?
If there’s a blockage in the AV node for example…
The SA will trigger a P wave, but then you don’t get the associated QRST…just more P waves. IF the AV node is working otherwise fine, the AV node will fire it’s own ventricular contractions, so you may get QRST still, just not associated with a P wave - they’re independent.
Complete = none of the QRST will be associated with a P wave Partial = some of the QRST will be associated with a P wave
