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Old 05-05-2011
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Drug Why Digoxin decreases the heart rate?

If digitalis increases contractility why does the heart rate decrease? this is from Katzung review page 123.

Thank you for your help
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By "increasing contractility", I believe it means that digitalis increases the power of contractions, rather than the number of contractions.

Digitalis inhibits the Na+/K+ ATPase pumps of the cardiac myocytes. This increases intracellular sodium concentration. Now remember that cardiac myocytes also have Na+ - Ca++ exchanger. Intracellular accumulation of Na+ leads to intracellular accumulation of Ca++. These Ca++ ions lengthen the cardiac action potential, especially Phase 0 the depolarization phase. Thus the myocytes stay depolarized longer than normal.

That's why the heart rate is decreased despite the stronger contractions.

Hope that helps
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vrnda
Digitalis (digoxin) has a direct action by blocking NA/K ATPase in the heart,which lead to the inactivation of the NA/CA exchanger. OK...

but digoxin has an indirect action too by inhibiting the NA/K ATPase in the brain,so this result in increase vagal or parasympathetic activity which in turn facilitates decrease heart rate,improve filling and by gigiving more time,increase cardiac output.
it also stimulate the sympathetic,but any organ with dual innervation,you know that the parasympathetic will always predominate.

kaplan pharm,page 100.
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Old 05-05-2011
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Default cvs question from fa

thank you.
can you also tell me what phosphorylation has to do with L type calcium channel and phospholamban- this is from firstaid2010 page 279
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Quote:
Originally Posted by qentank View Post
By "increasing contractility", I believe it means that digitalis increases the power of contractions, rather than the number of contractions.

Digitalis inhibits the Na+/K+ ATPase pumps of the cardiac myocytes. This increases intracellular sodium concentration. Now remember that cardiac myocytes also have Na+ - Ca++ exchanger. Intracellular accumulation of Na+ leads to intracellular accumulation of Ca++. These Ca++ ions lengthen the cardiac action potential, especially Phase 0 the depolarization phase. Thus the myocytes stay depolarized longer than normal.

That's why the heart rate is decreased despite the stronger contractions.

Hope that helps
Hmm, I thought it was Phase 2 because it will allow more Ca2+ to enter the cell which will also prolong the time in between depolarization and repolarization aswell as increasing the force of contraction.
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vrnda
phospholamban regulates Ca pump in cardiac muscle and skeletal muscle.

But, the important thing is that phospholamban only inhibit the cardiac sarcoplasmic reticulum to release calcium when it is in the unphosphorilated state. when the phospholamban get phosphorilated by the protein kinase A, its ability to block the Ca release from the sarcoplasmic reticulum is lost.


phospholamban unphosphorilated = active = inhibit calcium release.
phospholamban phosphorilated = inactive = release of calcium

Thank you for the question b/c i always concentrate in the Na/K ATPase and N/Ca pump.
hope you understand it.
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about the L-type calcium channel,
you know,there is 2 important types of calcium channels:the L type and the T-type.
the L-type act more in the heart and skeletal muscle.
whereas the T-type act more in the brain and this is the T type that we block in the treatement of seizures with drugs like valproic acid and ethosuximide.
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Old 05-06-2011
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thank you for your help

another q i have is if the attending comes to the rounds and hands you some basic lab values(hb, hematocrit, plt, etc) and asks you to calculate blood volume of the patient. how do you do this?
from what i learned you have to use formula Plasmavolume/1-hematocrit.
so, if hematocrit was 40% and we take plasma volume to be 3L the blood volume comes out to be 5 L.

What happens if there is a patient who was infused w/ fluids or had lost blood thru bleed? do we simply just use the formula without altering the plasma volume
to get the total blood volume? or do we make some adjustments in the plasma volume level?

Thank you
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Old 05-06-2011
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Quote:
Originally Posted by patelMD View Post
Hmm, I thought it was Phase 2 because it will allow more Ca2+ to enter the cell which will also prolong the time in between depolarization and repolarization aswell as increasing the force of contraction.
The ca going in during phase 2 is referring to the ventricular action potential.
the ca going in during phase 0 is referring to the Pacemaker actionpotential

page 256-257 Fa 2010
pls correct me if i'm wrong
thank you
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