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Old 10-16-2011
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Question Volume of distribution & metablosim

Hello everybody

1) What are the factors that increase or decrease volume of distribution ?
2) Does increasing the Vd of a drug increase or decrease its metabolism and thus half-life ?
3) Does Vd increase or decrease in pregnancy ? and thus drugs half life ?


Many thanks in advance !
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Old 10-17-2011
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1) What are the factors that increase or decrease volume of distribution ?
Answer: VD is increased in liver and kidney failure as they cause edema (fluid retention). VD is decreased in dehydration, septic shock.

2) Does increasing the Vd of a drug increase or decrease its metabolism and thus half-life ?
Answer: Half-life is determined by (a) drug clearance rate (CL) either by kidly or liver and (b) volume of distribution (VD) and the relationship is:
t1/2 = Ln2*VD/CL. Therefore, you see increased VD will give you higher half time. That is why drugs lingering around much longer in kidney/liver failure px since they have much higher volume distribution (this larger amount of volume will take much longer to be excreted).


3) Does Vd increase or decrease in pregnancy ?
Answer: Remember most pregnant women gain > 11 kg during pregancy??? Therefore, total body weight (including body fluid) and body fat increase throughout pregnancy. This means larger volume of distribution. The half life will be increased. Also they gain a lot of fat during pregnancy, you might want to watch out for fat-soluble drugs !!!!
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Must Know Pharmacodynamics:

Vd=Drug administered IV/ [drug] concentration in plasma

Cl=0.7 x Vd / t1/2

LD=Css x Vd

MD=Css x CL
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