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Retired NBME 22 Answers

nbme22/Block 3/Question#18 (reveal difficulty score)
An 85-year-old woman is diagnosed with a ...
Morphine is metabolized to active metabolites that accumulate ๐Ÿ” / ๐Ÿ“บ / ๐ŸŒณ / ๐Ÿ“–
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submitted by โˆ—moloko270(77)
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Morphine is metabolized in the liver to morphine-6-glucuronide and morphine-3-glucuronide, both of which are excreted by the kidneys. In the setting of renal failure, these metabolites can accumulate, resulting in a lowering of the seizure threshold. Morphine should therefore be used with caution with mild renal impairment and be avoided in the setting of renal failure.

source: https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/morphine-6-glucuronide

they gave a hint of increased creatinine level, plus older age can give a slowed down metabolism and CNS symptoms

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submitted by medstudied(0)
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can someone explain how morphine is degraded into active metabolites that accumulate? I couldn't find any sources that state this fact. Isn't it metabolized through the P450 system and excreted in urine?

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staygoodpupper  Morphine mostly undergoes phase II metabolism and is then excreted renally. Some of the metabolites are metabolically active, and her creatinine was a little elevated, so renal clearance could have been impaired. +11
celedkin  http://www.labpedia.net/test/177 the diagram in this article is useful to follow the metabolism of morphine +1



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submitted by โˆ—drzed(332)
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Unfortunately, I chose (C) thinking that the down-regulation of receptors would lead to needing higher doses for efficacy (patient is using a patient controlled pump), however tolerance to miosis does not develop, and thus eventually this side effect would occur.

Could anyone point out where my train of thought is incorrect? I suspect that my assumption of the patient increasing their dose is not warranted?

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aag  I also chose this, @drzed but looking back, if there was down-regulation of the receptors then she wouldnt have enough receptors to cause altered mental status and respiratory depression, side effects that you do develop tolerance to. How I would have remembered that morphine is metabolized to other active metabolites is beyond me. Happy studying hope this helps. +1
waterloo  He's also on a controlled analgesic pump. I've been on one before, and basically you can't keep pumping yourself constantly with it. You can hit the button, get a small dose, and then have to wait a bit of time to hit it again. The next time you hit the effect (at least for me) was always the same meaning I wasn't becoming tolerant to it (I was on one for a week). This controlled pump phrase has come up in another exam, which makes me think when they say that they want you to think this isn't someone who's taking alot of meds all the time. I also like aag thought process. +
l0ud_minority  time given was 3 days later. I think it would take longer than that for there to be downregulation of receptors. +



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