For cardio, let's go in the order of Kaplan, but refer to First Aid for what's most relevant.
ie) since Kaplan starts with Antiarrhythmic drugs, we'll start creating mnemonics for those even though these drugs are toward the end of First Aid.
Na Channel Blockers: Class 1A
Quinidine, Procainamide, disopyramide
- all increase action potential duration and effective refractory period
mn
- First Aid has a good one
- the Queen Proclaims Diso's pyramid
Toxicities
Quinidine
- M blocker and alpha blocking effects (as you can see, it's really important to have a solid foundation of basic pharm from earlier units!).
- Just think of a Queen dictator blocking any competition to the throne.
Procainamide
- Lupus- like syndrome
- I think of ProKane (the professional wrestler Kane). He wears a mask to cover the typical malar rash of the face and if you watch him move, he moves like he has arthritis and joint pain. Just google Kane and think of him (note: he's apparently become unmasked in recent years, but just ignore that...it was news to me!)
Thanks Sanjai for the great mneumonics. I'm little confused with the mechanism although this is quite basic stuffs.
ReplyDelete.
If you block [Na+] channel of the cardiac muscle, how would this increase the action potential duration? I mean, in order for depolarization to happen, you need to have [Na+] rushing into the cell. But if you block that channel, how would you even have depolorization? I don't think [Ca2+] would depolarize as [Ca2+] channel is a slow channel which would open during the plateau phase nor it is SA nodal activity (i think [Ca2+] causes depolarization in SA node while [Na+] causes depolarization in ventricular muscles).
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Any idea?
Hey Minsoo...sorry for the late response. I didn't realize you had commented until I opened the email. I thought it was a new post LOL!
ReplyDeleteI'm still at the start of the pharm, so my answer might not be deep as some others can give.
Basically, the Class 1A Na blockers are relevant for cardiac muscle. There's a certain concentration of drug you give which will block enough Na channels so that the Na influx is slowed down (not all Na channels are blocked; if all were blocked, you'd have sudden cardiac arrest). When you slow Na influx, you slow down the rate of depolarization (phase 0 in cardiac muscle)...the muscle cells are getting more +ve at a slower rate.
Whenever you slow down phase 0, you decrease the slope but everything else on the curve remains the same. So, if you draw the graph, you will see that the action potential duration has increased, thus there is more time before it can fire again (longer refractory period)
Class 1B and 1C are slightly different, binding to different states of the Na channel. I haven't covered it yet, so I'm not exactly sure of the consequences. I'm sure it will only mess with my current understanding and make things more confusing ... HAHAHA!!
Hi Minsoo:
ReplyDeleteHere is my understanding of this. The NA+ channel blockers work on specific channel conformation types rather than on the all the Na+ channels at once.
Class 1b works on refrac Na+ channels closed and keep them closed for longer...etc. You still get a depolarization, but just the refrac is longer, it takes longer to fire again. These are good drugs to counter current injury in an post-MI patient since they have ischemic tissues that have a lot Na+ in the cell. Because of this, the ischemic tissues have a slow conductance through them, this is the cause of most arrhythmia (difference in conduction causes irregular beating). The class 1b actually stops window current (which is Na+ leak in phase 1, 2, 3, slowing down conduction), keep the Na+ out, causing action potential to shorten, which speed up the conduction, decreasing arrhythmia.
The class 1a drugs bind to the open Na+ channel; hence, depolarization will take longer, action period will take longer, take more time to fire again.
The class 1C drugs stop all Na+ channels, which is a combination of class1a and 1b effect.
There is a nice graph on wikipedia, click on class I Na+ blocker, then you see the different mechanism.
http://en.wikipedia.org/wiki/Antiarrhythmic_agent#Class_I_agents
Basically, you were right, if you block Na+ channel, you would not have depolarization, but these drugs all work on different parts of the Na+ channel so nothing is all blocked all at once (even the class C's, i think)
Hope that helps,
D