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Old 08-25-2015
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Default Q. maintenance & loading dose

Q. I didn't understand why in renal or liver disease, dosage of the same drug when given as maintenance dose is decreased and when it is given as loading dose is usually unchanged. Is it because maintenance dose passes through liver/kidney but loading dose bypasses liver/kidneys? I know, We can find the difference in their formula but still I couldn't understand it conceptually . In the formula of maintenance dose, there is clearence and in the formula of loading dose there is no clearence.Does this mean, when the drug is given as maintenace dose, there is hepatic/renal clearence and since liver/kidney is damaged, we should decrease the dose to avoid toxicity; AND, when the same drug is given as loading dose, there is no hepatic/renal clearence (or no metablism) and thus doesn't require to decrease dose (dose is unchanged) even when there is renal/liver disease? .But, it is really weird to imagine this way. Can anybody pls cast light on this.Thanks. (From-FA, pharmacokinetics)
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Old 08-25-2015
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Quote:
Originally Posted by Aumsai View Post
Q. I didn't understand why in renal or liver disease, dosage of the same drug when given as maintenance dose is decreased and when it is given as loading dose is usually unchanged. Is it because maintenance dose passes through liver/kidney but loading dose bypasses liver/kidneys? I know, We can find the difference in their formula but still I couldn't understand it conceptually . In the formula of maintenance dose, there is clearence and in the formula of loading dose there is no clearence.Does this mean, when the drug is given as maintenace dose, there is hepatic/renal clearence and since liver/kidney is damaged, we should decrease the dose to avoid toxicity; AND, when the same drug is given as loading dose, there is no hepatic/renal clearence (or no metablism) and thus doesn't require to decrease dose (dose is unchanged) even when there is renal/liver disease? .But, it is really weird to imagine this way. Can anybody pls cast light on this.Thanks. (From-FA, pharmacokinetics)

First of all you are right about the difference in formulas. However you are forgetting what exactly is loading dose? Its formula: Css x vd means that you wanna attain a steady state quickly before starting the patient on maintenance dose. We wanna do that because if the level of the drug is not on steady state / desired state you wont have any effect of the drug because its below the concentration. So you give loading dose to quickly reach that state and it depends on Volume of distribution (vd). when u give the drug IV you wanna know how well or how it will distribute into different compartments, cuz in the end you just want the drug to stay enough in blood so it can perform its effect. You dont care about elimination cuz that happens after some time. Then when you give maintenance dose say 5 mg/hr or whatever you have to worry about clearance because some of the drug will leave the body so u wanna give enough that it stays above its Median effective concentration. Think of it as short term and quick enough to have effect (loading) and long term mainentance (mainentance)
Going to maintenance level Css takes time thats why u give loading dose to it quickly reaches that leveland does it job after that u give maintenance dose slowly looking at clearance.
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Thanks mk09 for the explanation.But, my specific question is- why in renal or liver disease, dosage of the same drug when given as maintenance dose is decreased and when it is given as loading dose is usually unchanged?

Here is my assumption. Pls verify and correct me as required.

May be because, we give loading dose especially in severe infections and life-threatening conditions and in such a case, we are not worried even if the loading dose might cause some adverse effect on kidney/liver becoz in such a critical condition , we want to achieve the steady state ASAP and benefits of giving loading dose outweigh the risk it causes to liver/kidney.Thus, we don't decrease loading dose of the drug even in liver/kidney disease. But, maintenance dose is decreased because we are still worried about the diseased liver/kidney as they can't metabolize normally and if we don't decrease the dose, there might be problem due to drug's toxicity.

Guys! do u agree with me? Do u have any other explanations for the above mentioned question???
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it has nothing to do with kidney/damage.

you give loading dose once instantly to increase blood concentration of the drug --> later on -> it gets distributed in the body depending on VD and then left over goes out in the kidney.

..whereas maintenance dose has already distributed whereever it had to go and the remainder is being eliminated .. you are giving maintence in the contant fashion to maintain blood level
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Thanks mk09.I got the concept u explained.

But, U said it has nothing to do with liver/kidney disease, then, why in FA> pharmacokinetic >dosage calculation, it's mentioned as follows:

"In renal and liver disease, maintenance dose is decreased and loading dose is usually unchanged"

This extract clearly tells that maintenance & loading dose can vary if the patient has kidney & liver disease. Pls think over it.Thanks again.
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Old 08-26-2015
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Quote:
Originally Posted by Aumsai View Post
Thanks mk09.I got the concept u explained.

But, U said it has nothing to do with liver/kidney disease, then, why in FA> pharmacokinetic >dosage calculation, it's mentioned as follows:

"In renal and liver disease, maintenance dose is decreased and loading dose is usually unchanged"

This extract clearly tells that maintenance & loading dose can vary if the patient has kidney & liver disease. Pls think over it.Thanks again.
Well ofcourse the maintenance dose would vary. The kidney and liver excrete/detoxify drugs they get rid of it. . So if they arent working the drug wil remain in body and increase bioavailability.

When i said it has nothing to do with renal damage it was for your piint about "the drugg causing damage to the kidney " which isnt prt of the discussion.

Its only about clearance by the kidney and liver; they "clear" the drug from the body.
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Yes, now it's more clear.Thanks mk09.
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Quote:
Originally Posted by Aumsai View Post
Yes, now it's more clear.Thanks mk09.
No problm
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