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General questions 5-6: Digoxin and Normeperidine

General questions 5-6: Digoxin and Normeperidine
10.8
Question number five Mr. Smith is experiencing a steady decline in renal function and it needs to be placed on the digoxin for his cardiovascular condition which is true about the patient’s volume distribution for the digoxin(Vd)? Here again, we can sort of apply the method of elimination Choice A volume distribution increases due to decreased plasma protein binding . B volume distribution increases due to decreased tissue binding of the drug C volume distribution decreases due to decreased plasma protein binding of the drug and the D volume distribution decreases due to decreased tissue pointing of the drug.
69.6
D is the case because in renal failure the tissue uptake of the digoxin by the cardiac muscle is reduced and that result in the decrease of the volume of distribution So D is the correct answer. Corresponding to general question number five Some information or pharmacokinetic information on a specific club is always helpful So let’s review some PK information on digoxin. The digoxin has a half-life of about forty hours the bioavailability is 70% and a fraction of the drug excreted unchanged is 60% However the protein binding is 25% So it’s not extensively bound to plasma protein and that’s why tissue binding is more important for digoxin than plasma protein binding And there are two formulas for based on the population-based information.
151.7
So clearance is equal to creatinine clearance plus 0.33 and the volume distribution can be estimated based on that formula. So moving on to general question number six Here we have Normeperidine, an active metabolite of meperidine which is non-analgesic but is a CNS excitatory agent that causes seizures. Normeperidine is excreted by the kidneys without further biotransformation So if a patient received meperidine and develops severe renal failure which chemical moiety or which chemical moieties are likely to accumulate to toxic levels in the blood? Here we should recognize that normeperidine is an active metabolite and therefore meperidine is actually a poor drug so in renal failure, normeperidine is the moiety to accumulate.
230.4
Again some pharmacokinetic information will be helpful in making the right choice. Meperidine has a half-life of three hours. It is short because it is quickly turning into active metabolite. it is 95% metabolized and the bioavailability is 50% protein binding is moderate about 60% and that we also have the clearance and the volume of distribution
In this step, Prof. Lee discusses two general questions.
The fifth one is about the volume of distribution of digoxin. In renal failure, the tissue uptake of the digoxin by the cardiac muscle is reduced, resulting in the decrease of the volume of distribution.
Therefore, D is the correct answer.
Besides, the sixth one is about the metabolite of meperidine. However, it is obvious that normeperidine is an active metabolite; therefore, meperidine is actually a poor drug. Consequently, normeperidine is the moiety to accumulate.
Also, he provides some pharmacokinetics information on digoxin and meperidine, which is helpful for us to solve the questions.
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Pharmacokinetics: Drug Dosing in Renal Disease

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