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Old 04-08-2012
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Drug Phenytoin question from KLN

I’m having a hard time with understanding one of the review questions at the end of CNS Pharmacology section in KLN (question no. 6). I would appreciate your help


Which one of the following is characteristic of phenytoin?
A) Inhibition of hepatic cytochromes P450
B) First-order elimination at high therapeutic doses
C) Enhances the effects of estrogenic steroids
D) The drug is safe to use in pregnancy
E) Slows the rising phase of the action potential


I do understand why A-D aren’t the correct answers but I’m having difficulty with understanding why E is the correct one. Phenytoin is like Ib antiarrhytmic drugs, so it should decrease potential duration and tissue excitability. “Slowing the rising phase of the action potential” reminds me more of Ia drugs that block active Na channels. And phenytoin blocks inactivated Na channels.

Can anybody explain this please?
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Old 04-08-2012
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Default ALL class I

Well, all class I antiarrhythmics act on the rapid upstroke phase of the AP
(the voltage-gated Na channels) regardless of the state of activation.

They differ in their effect on the rapid depolarization (phase 3) of the AP.

Hope that helped
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Old 04-08-2012
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Default still confussed...

Thanks I'm still confussed though..

"Slows the rising phase of the action potential" - I understand it as prolonging 0 phase of action potential (the rising phase - just like quinidine does it)->prolonging action potential duration all together. Ib drugs don't prolong that phase, they decrease action potential duration instead! so that doesn't make any sense to me... any ideas?
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Old 04-08-2012
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Default Phrasing

Quote:
Originally Posted by Casandra View Post
Thanks I'm still confussed though..

"Slows the rising phase of the action potential" - I understand it as prolonging 0 phase of action potential (the rising phase - just like quinidine does it)->prolonging action potential duration all together. Ib drugs don't prolong that phase, they decrease action potential duration instead! so that doesn't make any sense to me... any ideas?
That's the way they manipulate the phrasing of the question for distraction

I think the wording "rising of the action potential" is for the gradient of the rise and not the duration of the rise (Phase 0) and all class I will do that by blocking the Na channels regardless of their selectivity for the state (activated/inactivated).

Their effect on the AP duration does not arrise from their activity on (phase 0) but rather on their activity on (phase 3). That's why class Ia prolong, and class Ib shorten the AP duration.
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Old 04-08-2012
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Default

Quote:
Originally Posted by Joe85 View Post
That's the way they manipulate the phrasing of the question for distraction
I guess I'm just starting to realize that

Quote:
I think the wording "rising of the action potential" is for the gradient of the rise and not the duration of the rise (Phase 0) and all class I will do that by blocking the Na channels regardless of their selectivity for the state (activated/inactivated).
Yeah.. that makes sense. Thank you Joe85 I also thought that by "slowing the rising phase" they mean delaying another potential firing up (meaning slowing the initiation of the next potential).

Quote:
Their effect on the AP duration does not arrise from their activity on (phase 0) but rather on their activity on (phase 3). That's why class Ia prolong, and class Ib shorten the AP duration.
hmm... I'm not sure if I got it right but are you saying that Ia drugs don't effect 0 phase? I kinda disagree with that. In Kaplan videos they specifically say that Ia drugs prolong 0 phase.
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Old 04-08-2012
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Default

blocks Na from getting in
less + charge getting in
hence, it takes longer for the potential to get to that positive level if needs
so it slows the rising phase of the action potential
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Old 04-08-2012
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Default :)

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Originally Posted by Dr.NickRiviera View Post
blocks Na from getting in
less + charge getting in
hence, it takes longer for the potential to get to that positive level if needs
so it slows the rising phase of the action potential
Thanks Dr.NickRiviera Yeah, I understand the general concept of mechanism of action The problem here for me was understanding what they mean by "the rising phase". At first I thought it was 0 phase and that's why the answer E didn't make any sense.
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