digoxin toxicity

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digoxin toxicity

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baryar
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01/18/08 - 03:42 PM

lippincott says......

1=decreased SERUM LEVEL OF POTASSIUM is a major pre-disposing factor for digoxin toxicity

it also says

2=decreased INTRACELLULAR POTASSIUM is a major predisposing factor to digoxin toxicity

can anyone explain it please..........

are both of these statements true?..........or wat?

new_n_lost
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01/18/08 - 03:55 PM

Almost the same statements and both are true.

The Extracellular depletion (due to any cause) leads to a shift from intracellular compartment towards extracellular. Now the drug is essentially working on Na/K ATPase pump which functions by moving out the Na and moving in the K. Digioxin would itself induce a slight hyperkalemia. The most important point to be noted is that Digioxin DOESNT cause hypokalemia but rather Hypokalemia can potentiate the side effects in normal doses.
Thus any extracellular deficit seen in any ion will be replaced by first the intracellular shift and the later on deficiency will occur.

Edited by new_n_lost on 01/18/08 - 04:47 PM

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baryar
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01/18/08 - 04:07 PM

ATPase pumps Na out and K in...................digoxin blocks it..........how would decreased intracellular K predispose to digoxin toxicity

new_n_lost
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01/18/08 - 05:19 PM

baryar wrote:
ATPase pumps Na out and K in...................digoxin blocks it..........how would decreased intracellular K predispose to digoxin toxicity

The hypokalemia leads to decreased Resting membrane potential which leads to arrhythmia. http://cvphysiology.com/Arrhythmias/A007.htm << this might help you.

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Tiff
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01/18/08 - 05:41 PM

Once digoxin blocks the Na/K ATP pump, there leaves a certain amount of K inside the cell. The presence of this K controls the activity of digoxin. Here, K's purpose is to mediate the activity of digoxin. So if there's too much K inside the cell, then there is decreased digoxin activity. Alternatively, if there's no K inside the cell, digoxin doesn't have anything to counteract it and it's activity becomes uncontrolled...Hence digoxin toxicity. This is why patients on diuretics are more likely to become toxic.

Both statements are correct and for example would depict someone on diuretics (that are not potassium sparing of course) smiling face

baryar
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01/18/08 - 05:51 PM

baryar
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01/18/08 - 06:13 PM

new_n_lost wrote:
Almost the same statements and both are true.

The Extracellular depletion (due to any cause) leads to a shift from intracellular compartment towards extracellular. Now the drug is essentially working on Na/K ATPase pump which functions by moving out the Na and moving in the K. Digioxin would itself induce a slight hyperkalemia. The most important point to be noted is that Digioxin DOESNT cause hypokalemia but rather Hypokalemia can potentiate the side effects in normal doses.
Thus any extracellular deficit seen in any ion will be replaced by first the intracellular shift and the later on deficiency will occur.

1=decreased serum potassium

2=decreased intracellular potassium

both predispose to toxicity.............dont mistake it by thinking that both conditions do it when they co-exist............they do it separetly....... 1 can do it alone,2 can do it alone

but the issues is how???

Tiff
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01/18/08 - 08:06 PM

That's just what the mechanism is. Binding to Na/K ATPase is inhibited by each other.

When intracellular K is reduced digoxin is high. The resting membrane potential is reduced. (b/c of inhibited pump and decreased K in cell)

new_n_lost
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01/18/08 - 08:19 PM

Tiff wrote:
The presence of this K controls the activity of digoxin. Here, K's purpose is to mediate the activity of digoxin. So if there's too much K inside the cell, then there is decreased digoxin activity. Alternatively, if there's no K inside the cell, digoxin doesn't have anything to counteract it and it's activity becomes uncontrolled...Hence digoxin toxicity. This is why patients on diuretics are more likely to become toxic.

Hmm disagree on this its not the activity of K or K in any sense that controls the activity of Digioxin. Its the other way around.

The main purpose of Digioxin is the increase in magnitude of the action potential of the of the cardiac muscle fiber by increasing the intracellular concerntration of Na which then leads to the increased exchange of the sodium -calcium across the membrane. To remind myself this is how i have learnt the whole mechanism of Digoxin and its toxicity.

1. the main trigger for the AP in cardiac musle is influx of the Na through the fast channels which will not REOPEN until the cell has REPOLARISED. Thus avoiding tetnay or fasiculations.

2. Calcium channels or slow channels are now open calcium and sodium both enter thru these channels . This calcium also partakes in the contraction of the muscle. They maintain the plateau phase of the AP

3. The opening of the K channels brings the cell back to its original place and thus repolarisation begins. the K channels reset the ionic balance for another AP to occur by bringing back the cell to its resting state. (from Kaplan Physio pg 167-170 2004 ed)

Now for contraction in cardiac muscle to occur the sarcoplasmic reticulum has to release the calcium which is also helped by the presence of calcium in the cell due to the calcium channels. Digoxin uses the extra sodium thru the sodium -calcium exchange pump by keeping in the calcium so it can be used for the contraction.

The balance of the cell ionic concerntrations is also maintained by various ways but more importantly thru the ATPase pump which pumps Na out and K in using ATP.

The mechanism of Digoxin is to inhibit this pump which leads to increased intracellular Na conc. thus increasing the sodium-calcium exchange and more calcium is readily available inside the cell. Thus in essence Digoxin does the following.

1. Increase the refractory period by delaying the influx K ions back into the cell.
2. By prolonging the plateau phase i.e Ca channels it slows the conduction.
3. Increased Automaticity due to calcium overload.

Thus in a way Digoxin slows down the conduction velocity and increases the refractory period in cardiac muscle through both preventing the K flux into the muscle thereby increasing the refractory period and increasing the calcium content therefore a long plateau.

Now to the original question

In hypokalemia the original concerntration of K across the membrane get decreased thereby decreasing the Resting Membrane Potential which deteremines refractiveness of the cell and the cell itself becomes more responsive to slight ionic changes. Now add digoxin to the mix which delays the K influx in the cardiac muscle rendering it more excitable to AP thus causing extrasystoles or Premature beats which are due to enhanced presence of calcium inside the cells.

Key word i always remember is that Digoxin acts like a PANS drug. Soothes the heart and synchronizes it. It makes the Atria act faster all the while delayin the AV node thus making the ventricular contractions slower and synchronus. (Ref Katzung Board Review pg 115-118 7th Ed.)

Sorry for a very long post and i hope you do get my point and i seriously didnt end up confusing u. This is my understanding of the entire process.

Edited by new_n_lost on 01/18/08 - 08:31 PM

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Tiff
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01/18/08 - 08:40 PM

#10

Very well said. nod

new_n_lost
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01/19/08 - 06:59 AM

#11

well i hope the person who posted the initial query got the msg and didnt end up goin in circles.

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fluoxetin
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01/22/08 - 05:26 PM

#12

simply speaking, quoting Trevor,

digoxin and K+ compete with each other for the same binding site on Na/K ATP pump. A decrease in K+ concentration -> augments the effects of digoxin -> toxicity

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