In my work as an instructor/tutor for the USMLE Step 1, one of the most common requests is to discuss antiarrhythmics. By the end of this USMLE Step 1 lesson, you will be able to answer the following questions:
- What would be the effects of class I antiarrhythmics on cardiac depolarization? Why? Nodal, non-nodal, or both?
- What would be the effects of class III antiarrhythmics on ventricular myocyte action potential? Why?
- Class III antiarrhythmics – main effect on EKG intervals? Why? What does this increase the risk of?
- What would be the effects of class IA antiarrhythmics on cardiac depolarization? Why?
- What would be the effects of calcium channel blockers on heart rate? Why does this make sense?
- Calcium channel blockers would affect which EKG interval in particular? Why?
- What would be the overall effect of ACh on heart rate and conduction via the AV node? Why?
Note: this lesson builds on a previous lesson on ion channel physiology.
We will begin by considering ventricular myocyte action potentials, then move on to consider the special case of nodal tissue.
Ready for the recall-type USMLE Step 1 questions?
What effect would opening Na+ channels have on a cardiac cell’s membrane potential?
What effect would opening Ca++ channels have on a cardiac cell’s membrane potential?
What effect would opening K+ channels have on a cardiac cell’s membrane potential?
Ventricular myocyte action potential – how many phases are there? What are they?
On an EKG, the P-wave corresponds to what?
On an EKG, the QRS complex corresponds to what?
On an EKG, the T wave corresponds to what?
Phase 0 – Which ion channel(s) open/close? Effects on overall membrane potential?
Phase 1 - Which ion channel(s) open/close? Effects on overall membrane potential?
Phase 2 – Which ion channel(s) open/close? Effects on overall membrane potential?
Phase 2 – most closely corresponds to what on EKG? Why does this make sense?
The ST segment is typically flat, which would make sense, since during the plateau phase, there is minimal change in the net membrane potential
Phase 3 – Which ion channel(s) open/close? Effects on overall membrane potential?
Phase 3 – most closely corresponds to what on EKG?
NOTE: atrial repolarization also occurs, but is NOT typically seen on the EKG, as the atrium is much smaller, and the repolarization would be obscured by the presence of the large QRS
Phase 4 – Which ion channel(s) open/close? Effects on overall membrane potential?
Class I antiarrhythmics – affect what ion channel(s)/receptors?
IA, IB, or IC – which affects another ion channel? Which ion channel is this?
Wait!
I strongly recommend that you attempt to answer the final questions by yourself first, before looking at the answers. Remember, the USMLE Step 1 exam will test your ability to make connections on the spot. The more practice you have, the higher your score! Then, when you think you might know the answer (or are completely stumped), look at the answers below!
Ready for the recall-type USMLE Step 1 questions?
What would be the effects of class I antiarrhythmics on cardiac depolarization? Why? Nodal, non-nodal, or both?
Recall that nodal tissue does NOT use Na+ (only uses Ca++) in phase 0 depolarization
What would be the effects of class III antiarrhythmics on ventricular myocyte action potential? Why?
Class III antiarrhythmics – main effect on EKG intervals? Why? What does this increase the risk of?
Slows repolarization, so will prolong time between QRS complex (ventricular depolarization), and T wave (ventricular repolarization).
This will increase risk of TORSADES DE POINTES (you MUST know this for Step 1)
What would be the effects of class IA antiarrhythmics on cardiac depolarization? Why?
Prolong QT interval (also blocks K+ channels)
Next, we move on to discuss nodal tissue.
Ready for the recall-type USMLE Step 1 questions?
Nodal tissue action potential – how many phases are there? What are they?
Phase 0, 3, and Phase 4
Phase 0 – Which ion channel(s) open/close? Effects on overall membrane potential?
Phase 0 – why is the action potential determined by Ca++ channels, and not Na+ channels?
In order to activate Na+ channels generally in the heart, you must first REMOVE INACTIVATION from them (double-negative, I’m sorry). In order to remove inactivation, you must have a more negative membrane potential. This is ONLY possible in non-nodal tissue, because of the presence of the special K+ channel, called IK1.
In other words, nodal tissues HAS Na+ channels (oddly enough), but it does NOT use them, because the membrane potential does NOT become negative enough to remove inactivation of the Na+ channels.
Ca++ channels do not have this sort of regulation, and thus will be active in nodal tissue.
What is the next phase to occur following Phase 0?
Note there is NO phase 1 or 2 in nodal tissue
Phase 3 – Which ion channel(s) open/close? Effects on overall membrane potential?
Phase 4 – Which ion channel(s) open/close? Effects on overall membrane potential?
Phase 4 – what will happen eventually following slow depolarization? What Phase will this correspond to?
What special K+ channels are present in nodal tissue that are absent in ventricular tissue? What causes them to open, and what would be the effect?
What is the normal pathway of conduction through the heart, starting with the SA node?
When the conduction signal moves from SA node to atrium, what causes the atrial depolarization?
What structures allow for depolarization of the atrium in response to SA nodal depolarization? How?
Allows for direct connection of cytoplasm between adjacent cells. This allows for the direct transfer of ions (and thus the wave of depolarization) from one cell to the next.
What allows for depolarization of the AV node?
What does normal sinus rhythm mean?
What determines the heart rate assuming a normal sinus rhythm (i.e. the rhythm originates in the SA node)?
In other words, if the slope of the phase 4 depolarization is HIGHER → reach depolarization threshold FASTER → have MORE depolarizations in a given time period (i.e. heart rate ↑)
What determines the speed of conduction through the AV node?
Why does it make sense that it is phase 0 and NOT phase 4 depolarization that will determine this?
In the case of the SA node, phase 0 depolarization is reached because of SPONTANEOUS depolarization during phase 4. In other words, leaky Na+ and Ca++ channels → slow depolarization → reach depolarization threshold
In contrast, the AV node is depolarized directly following atrial depolarization. Note that this is NOT spontaneous, and is in fact triggered by the atrial depolarization itself.
Class II antiarrhythmics – affect what ion channel(s)/receptors?
Class IV antiarrhythmics – affect what ion channel(s)/receptors?
Wait!
I strongly recommend that you attempt to answer the final questions by yourself first, before looking at the answers. Remember, the USMLE Step 1 exam will test your ability to make connections on the spot. The more practice you have, the higher your score! Then, when you think you might know the answer (or are completely stumped), look at the answers below!
Almost there! Think about how nice it will be to finally understand the antiarrhythmics section in First Aid!!
What would be the effects of calcium channel blockers on heart rate? Why does this make sense?
Calcium channel blockers would affect which EKG interval in particular? Why?
Takes longer for signal to travel between atrium (P wave) to ventricle (QRS complex), because conduction through the AV node is slower → interval between P and QRS (PR interval) ↑
What would be the overall effect of ACh on heart rate and conduction via the AV node? Why?
What should you do next?
- Turn the narrative, “Pathogenesis to Presentation” questions into Anki cards by copy/pasting the question/answer into the “Front” and “Back” fields in Anki. Do the same for the fundamental facts that you were unfamiliar with, to maximize your chances of USMLE Step 1 success! Remember: the USMLE is a test of understanding, so the better you can understand these questions, the better your score!
- Add reverse cards when appropriate to your Anki cards
- Re-word the questions/explanations as desired, and BOLD the important text to make it easier to review in the future
- Learn something new? Something unclear? Comment below!
- If you liked this post, please consider sharing it on Facebook/Twitter! I judge the utility of these posts by the number of comments / shares they receive, so if you’d like more, or would like a particular topic addressed, please let us know!
Photos by: ZaaFari,Silvia3, and Kalumet.