does digitoxin blow anyone else away?

[Ramoray]

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Well first off i want to say arythmias and digitoxin is ****ing confusing and i have wasted a day on antiarythmiacs and digitoxin and all that kinda **** and i still dont get most of it. Anyway what i just thought of all day is doesnt it seem shocking that somethign like digitoxin that blocks the NA/K pump doesnt compeltely dismantle our body. I mean that pump is in every single tissue everywhere. It just seems odd that a drug like that doesn immediatly kill someone. I dont know i just thought it was wierd. By the way does anyone have a grasp on digitoxin and can explain to me all about its electrical effects. I dont need to know what they are as i know that but why they occur and the basis of the electrical currents woudl be nice. If not i understand as its kinda lengthy. thanks

 

[Idiopathic]

There are toxic effects, and the dose that is typically used to treat CHF is slightly less than the dose that would cripple one.

The things to know about dig:

1) Indications: heart failure, INCREASES mortality in women (probably not testable)

2) Action: indirectly increases cytosolic calicium stores, by altering the Na/Ca exchanger effect, and keeping the cell from getting rid of calcium. This 'extra' Ca just sitting in the cell causes stronger contraction during excitation.

3) INTERACTIONS: digitalis is notorious for its drug interaction possibilities, and I would know the interaction profile of dig as well as that of warfarin.


When all was said and done, in-depth questions about dig and anti-arrythmics comprised maybe 2 questions on my exam. Make of it what you will.

 

[idq1i]

doesnt it seem shocking that somethign like digitoxin that blocks the NA/K pump doesnt compeltely dismantle our body. I mean that pump is in every single tissue everywhere. It just seems odd that a drug like that doesn immediatly kill someone.

Well, if you take enough of it, it will kill you. Therapeutic dig concentrations are in the ng.

Couple more facts:
Dig cancels out some sympathetic stimulation by increasing baroreceptor sensitivity.

Dig causes partial depolarization of cells -> decreases excitability

 

[Pox in a box]

Well, if you take enough of it, it will kill you. Therapeutic dig concentrations are in the ng.

Couple more facts:
Dig cancels out some sympathetic stimulation by increasing baroreceptor sensitivity.

Dig causes partial depolarization of cells -> decreases excitability

Dosis sola facit venenum

("All things are toxic; only the dose determines the poison")

Theophrastus Bombastus von Hohenheim, called Paracelsus, ca 1500 A.D.

 

[Idiopathic]

Well, if you take enough of it, it will kill you. Therapeutic dig concentrations are in the ng.

Couple more facts:
Dig cancels out some sympathetic stimulation by increasing baroreceptor sensitivity.

Dig causes partial depolarization of cells -> decreases excitability

Huh, wouldnt that increase excitability? It seems like it would decrease the threshold.

And this is too involved for step 1.

 

[idq1i]

Huh, wouldnt that increase excitability? It seems like it would decrease the threshold.

And this is too involved for step 1.

the way it was explained to us:

Dig causes baroreceptors to become more sensitive to high blood pressure maintained by high sympathetic tone. Increased discharge of receptors leads to some withdrawal of sympathetic tone, resulting in relative vasodilation.

Disclaimer 1: This works only in the max NE release state
Disclaimer 2: I agree. It probably is beyond the scope of Step 1.

 

[Idiopathic]

I was referring to the partial depolarization, which should increase cell excitability (also would increase fatigue, etc.)

 

[idq1i]

I was referring to the partial depolarization, which should increase cell excitability

Partial depolarization -> less of a gradient for sodium to come in -> less excitability, smaller refractory period.

That's how I look at it

 

[Ramoray]

see what i mean this **** is confusing. I think it depends on how depolarized you are. Like in the vent if you are at like -50 you are depoliarzed but i think almost all the NA channels are deactivated or alot of them at this point so even though you are closure to threshold, you have no Na channels to depolarize when threshhold hits so all in all you would be less exciatable.

 

[Ramoray]

Partial depolarization -> less of a gradient for sodium to come in -> less excitability, smaller refractory period.

That's how I look at it

gradients have nothing to do with excitability, rather only the magnitude of phase 0. your answer wouldnt explain a decrease in excit

 

[idq1i]

gradients have nothing to do with excitability, rather only the magnitude of phase 0. your answer wouldnt explain a decrease in excit

If you want to be a physio purist, maybe

If a cell is partially depolarized, it has less excitability. The Na+ gates open less promptly and less completely. Phase 0 (aka excitability) attains a lesser slope.

BTW, we are arguing an academic that will never see the light of day on Step 1

 

[Ramoray]

its not an academic its simple cell membrane physio which i think is good to understand or atleast it helps put a understanding behind memorizing all those antiarythmics and stuff. Plus it helps understand the cardiac cycle. I never said it was showing up on step 1 i was just trying to get a better understanding because i think the stuff is confusing

 

[Idiopathic]

If you want to be a physio purist, maybe

If a cell is partially depolarized, it has less excitability. The Na+ gates open less promptly and less completely. Phase 0 (aka excitability) attains a lesser slope.

BTW, we are arguing an academic that will never see the light of day on Step 1

I am going to respectfully disagree with you. The closer a cell is to threshold, the more likely it is to depolarize. Now, after that, many factors come into play, but as far as the excitability of the cell (as a single event), it would be hard to convince me that it is less excitable.

Now, the result of the excitation can be debated, but the actual excitation cannot, I believe. I know this is pure semantics, and I am sorry for that.

 

[idq1i]

its not an academic its simple cell membrane physio which i think is good to understand or atleast it helps put a understanding behind memorizing all those antiarythmics and stuff. Plus it helps understand the cardiac cycle. I never said it was showing up on step 1 i was just trying to get a better understanding because i think the stuff is confusing

There is a smaller membrane potential (Vm) when you have more Na inside. Therefore, your upstroke (phase 0) will lean to the right. This is what I meant by "gradient" and excitability.

There is also automaticity, which increases with dig. This happens because the cell is closer to the threshold, where it is more likely to fire, but fire "slower". This is what Idiopathic was talking about.

Perhaps our schools used different definitions when talking about the same thing

 

[idq1i]

I am going to respectfully disagree with you. The closer a cell is to threshold, the more likely it is to depolarize. Now, after that, many factors come into play, but as far as the excitability of the cell (as a single event), it would be hard to convince me that it is less excitable.

Now, the result of the excitation can be debated, but the actual excitation cannot, I believe. I know this is pure semantics, and I am sorry for that.

See my last response. A smaller Vm driving the Na in will give a phase 0 of a smaller slope. I suppose I'm using (as I have been taught in the context of my pharm course) "excitable" to describe what I see, rather than reserving the term for a technical book example.

Edit: that barely makes sense to me . Need sleep...will fix tomorrow

 

[bonovox]

I am going to respectfully disagree with you. The closer a cell is to threshold, the more likely it is to depolarize. Now, after that, many factors come into play, but as far as the excitability of the cell (as a single event), it would be hard to convince me that it is less excitable.

Now, the result of the excitation can be debated, but the actual excitation cannot, I believe. I know this is pure semantics, and I am sorry for that.

Excitability of a membrane depends on the ion channels involved, because through ion channels is how the cell responds to a stimuli. To use an extreme example, if all of your fast sodium channels are inactivatd, your membrane will be refractory and unexcitable. Remember, past the threshold, an action potential ensues because of a self-sustaining opening sodium channels and influx of sodium ions. Automaticity and excitability are NOT the same thing.

That said, digoxin does HAVE A DIRECT ELECTRICAL EFFECT OF increasing excitability by shortening action potential duration (this effect, at high doses, predominates over the increased refractoriness through vagal tone stimulation seen at therapeutic doses). The reason action potential duration is shortened doesn't have to do with it being closer to threshold, but rather, increased K efflux (shortening the time required for repolarization, Ca dependent K+ channels) and incactivation of Ca++ channels (decreasing the depolarizing Ca current, inactivated by elevated intracellular Ca) which both result as a consequence of ELEVATED INTRACELLULAR Ca++!!

 

[Ramoray]

wasnt my initial question for someone to CLARIFY this! jk jk this stuff is hard to visualize and grasp. electricity in the hearts is a close 2nd to the 400 heart sounds and their characteristics in the heart. not long ago i thought cardiology would be cool but this year i realized its my least fav subject sometimes

 

[HiddenTruth]

wasnt my initial question for someone to CLARIFY this! jk jk this stuff is hard to visualize and grasp. electricity in the hearts is a close 2nd to the 400 heart sounds and their characteristics in the heart. not long ago i thought cardiology would be cool but this year i realized its my least fav subject sometimes

Ever thought about letting the Harrisons collect some dust 'till after step 1? Maybe you won't be so confused then. 😉

 

[Ramoray]

Ever thought about letting the Harrisons collect some dust 'till after step 1? Maybe you won't be so confused then. 😉

ya buddy well see who drops a better score. why dont you go read FA another 100 times and then well compare scores.. ok later

 

[Pox in a box]

Ever thought about letting the Harrisons collect some dust 'till after step 1? Maybe you won't be so confused then. 😉

I'd rather read Harrison's 1/2 times through than read First Aid twice through any day.

 

[HiddenTruth]

I'd rather read Harrison's 1/2 times through than read First Aid twice through any day.

Well, props to you, if u can read it half time through in one day and fully understand, and retain it. I think I wiould do that too then.

 

[HiddenTruth]

ya buddy well see who drops a better score. why dont you go read FA another 100 times and then well compare scores.. ok later

Can I call you, "p53"? 🙄 Relax! It was a joke!
Oh, and I have no doubt that you will outscore me.

 

[idq1i]

ya buddy well see who drops a better score. why dont you go read FA another 100 times and then well compare scores.. ok later

Lol! Don't steal my strategy!

(although I am using Cecil and Emedicine)

I gave up on FA. The lack of depth was frustrating me. (I guess it explains the 99th percentile on path shelf 😎 )

 

[Pox in a box]

Well, props to you, if u can read it half time through in one day and fully understand, and retain it. I think I wiould do that too then.

I didn't say I've done it or would...that would take me over a year.

I'm just saying someone who reads Harrison's is going to drop a pimpslap on Step 1 compared to the same person just reading First Aid over and over.