monam84
Forum Senior
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Can someone please explain the following to me: How does digoxin prolong the PR interval? And how does hypokalemia cause digoxin toxicity? I know this is high yield, but for some reason I just cant comprehend it. Thanks.
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| new_n_lost
Politically InCorrect
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MOA of Digioxin
Digitalis glycosides bind specifically to Na+/K+-ATPase, inhibit its enzymatic activity, and impair active transport of extruding sodium and transport of potassium into the fibers (3:2 ratio). As a result, intracellular sodium ([Na+]i) gradually increases, and a gradual, small decrease in intracellular potassium ([K+]i) occurs. Cardiac fiber [Ca2+ ]i is exchanged for extracellular sodium (3:1 ratio) by a transport system that is driven by the concentration gradient for these ions and the transmembrane potential; increase in [Na+]i is related crucially to the positive inotropic effect of digitalis.
The positive inotropic effect of digitalis has 2 components. - Direct inhibition of membrane-bound sodium- and potassium-activated adenosine triphosphatase (Na+/K+-ATPase), which leads to an increase in the intracellular concentration of calcium ([Ca2+]i)
- Associated increase in a slow inward calcium current (iCa) during the action potential (AP) (This current is the result of movement of calcium into the cell, and it contributes to the plateau of the AP.)
The electrophysiological effects of cardiac glycosides include
(1) decreased resting potential (RP) or maximal diastolic potential (MDP), which slows the rate of phase-0 depolarization and conduction velocity,
(2) decrease in action potential duration (APD), which results in increased responsiveness of fibers to electrical stimuli,
(3) enhancement of automaticity, which results from an increase in the rate of phase-4 depolarization and from delayed after-depolarization.
In general, cardiac glycosides slow conduction and increase the refractory period in specialized cardiac conducting tissue by stimulating vagal tone. Digitalis has parasympathetic properties, which include hypersensitization of carotid sinus baroreceptors and stimulation of central vagal nuclei.
The atria and ventricles exhibit increased automaticity and excitability, resulting in extrasystoles and tachydysrhythmias. Conduction velocity is reduced in both myocardial and nodal tissue, resulting in increased PR interval and atrioventricular (AV) block accompanied by decrease in QT interval.
Hypocalcemia doesnt effect Digioxin but Hypercalcemia does effect it.
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| new_n_lost
Politically InCorrect
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The most common precipitating cause of digitalis intoxication is depletion of potassium stores, which occurs often in patients with heart failure as a result of diuretic therapy and secondary hyperaldosteronism. - Other causes include the following:
- Myocardial infarction or ischemia
- Hypercalcemia
- Renal insufficiency
- Also consider drug interactions. Drugs that have been reported to potentiate digoxin toxicity include the following:
- Verapamil, diltiazem, nifedipine
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FORUM RULES-- Those who believe in telekinesis, raise my hand. I get enough exercise just by pushing my luck --P4U World.." The pure and simple truth is rarely pure and never simple."
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| monam84
Forum Senior
Topics: 35
Posts: 135
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I understand the ionotropic effects its the electro phy i need sum understanding of:
"The electrophysiological effects of cardiac glycosides include
(1) decreased resting potential (RP) or maximal diastolic potential (MDP), which slows the rate of phase-0 depolarization and conduction velocity,
(2) decrease in action potential duration (APD), which results in increased responsiveness of fibers to electrical stimuli,
(3) enhancement of automaticity, which results from an increase in the rate of phase-4 depolarization and from delayed after-depolarization. "
#1 Wouldnt the resting membrane be more positive because of the increased Na and Ca (just to clarify, are we talking about phase 0 in nodal cells?)
#2 How does the APD decrease? (is it because of the increased efflux of K)
If I could understand this my goal for the day would be done. 
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| virgola82
Forum Guru
Topics: 85
Posts: 348
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I HATE DIGOXIN!! Everytime time I study it I unserstant it in a different way.... I decided it's easier to memorize these electric effects; I mean I've searched for the same explanations you were looking for a lot of time on Goodman&Gillman, Katzung, Hurst etc and never found a decent explanation, so...
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| edie
I can, and I will.
Topics: 26
Posts: 1,235
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Simple explan of mechanical effect:
1. Know that it stops Na+/K+ ATPase. IC sodium increases somewhat.
2. This little bit of Na+ affects the Na+/Ca2+ exchanger; less Ca2+ removed from cell.
3. Add this bit of calcium to what gets put out by SR = increased contractile force.
4. Autonomic outflow also affected, which deals with the electrical function. I can't comment on this part, still working through it
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| drduck
Forum Guru
Topics: 82
Posts: 529
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i is better not to go in details of such deals.......
but drugs like digoxin. warfarin, aspirin, lithium........all too important...........cant run from that....
better thing is to do more questions........
u will easily know what to read what to leave..
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| po
Forum Elite
Topics: 39
Posts: 356
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 nnl,edie.
and about increasing vagal outflow,as nnl said;'Digitalis has parasympathetic properties, which include hypersensitization of carotid sinus baroreceptors and stimulation of central vagal nuclei.'
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| ahmed-tarik
Forum Newbie
Topics: 0
Posts: 1
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K binds to the same site as Digoxin, so hypokalaemia enhances toxicity.
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