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Application in drug adjustment : Examples

Application in drug adjustment : Examples
Applications in drug overdose of hemodialysis. So based on the above table that we just look at, which drugs are dialyzable? We know that there are phenobarbital and the salicylic acid. But does that means only phenobarbital and salicyclic acid a good candidate for drug detoxification by hemodialysis? The answers is not necessarily. Because hemodialysis maybe carry out for a longer time in an overdose situation. Where hemodialysis is typically lasts for two to four hours. Also the toxic blood level may be critical in the early hours of drug overdose. And if we can reduce that high toxic blood level at the early stage of overdose. Then we can overcome the life threatening period and then followed by conventional life support.
So here we are going to look at several examples for adjustment and dialysis if necessary. Here we look at carbamazepine. Carbamazepine is 1% excreted unchanged since it’s 99% metabolized. Therefore, there’s no change in dosage in renal failure if necessary. And also there’s no adjustment in hemodialysis. The other example is azithromycin. The fraction excreted unchanged is 12% so the drug is primarily metabolized, so there’s no need for change in dosage in renal failure either. And their is no needs for adjustment in hemodialysis . So this two examples are no adjustment in dialysis due to metabolism. Also no adjustment in dialysis due to non-dialyzability. The fact that the drug is simply non-dialyzable. For example cetirizine.
The fraction of the drug excreted unchanged is 71 percent. However, the protein binding is 98%. Because of the high protein binding, the drug is not dialyzable. However, because the fraction excreted by the kidney is high. Therefore, when the GFR is less than 10 milliliters per minute, then the dose is typically reduced to 50 percent. And therefore non-dialysis got same dose came to be administered to the patient. Let’s look at another example. Allopurinol. Allopurinol is 12% excreted unchanged. However, it is metabolized to an active metabolite, which is oxypurinol. Now, since the metabolite is active and it is excreted by the kidneys.
Therefore when the GFR is less than 10 milliliters per minute, then the dose need to be reduced to one half or even one third. And the hemodialysis, on the day of hemodialysis, then we would give the dose a hundred milligrams after the hemodialysis session. Cefaclor is another example. Fraction excreted unchanged is 77 percent, protein binding is 25 percent. Because the high fraction of drug excreted by the kidneys, when the GFR is less than 10, then the dose is typically reduced to 50%. And this 50% dose is also given to dialysis patient. However it’s given at the end of dialysis.

In this video, Prof. Lee explains the application in drug overdose first.

Following that, he shows how to change dosing in renal failure and gives plenty of examples.

Due to non-dialyzability, there is no need to adjust the dose for Cetirizine in the case.

On the contrary, for Allopurinol and Cefaclor in the cases, we should dose 100mg q24h and 250 mg respectively after dialysis on dialysis days.

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Pharmacokinetics: Drug Dosing in Renal Disease

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