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Decreased first pass metabolism
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Decreased phase 1 metabolism
Increased first pass metabolism
Increased phase 1 metabolism
Increased phase 2 metabolism
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Administering a medication per rectum rather than orally allows for a partial bypass of first-pass metabolism by the liver because some of the medication is absorbed directly through the mucosal membrane into the systemic circulation. First-pass metabolism describes the phenomenon by which the systemic concentration of drugs can be dramatically decreased from the concentration first absorbed by the gastrointestinal tract. First-pass metabolism can occur at the level of gastrointestinal enterocytes but more commonly is the result of hepatic metabolism of drugs. This first-pass phenomenon is important because it can dramatically decrease the bioavailability of a drug compared to when the drug is administered in an intravenous manner. Also, medical conditions such as cirrhosis that impact liver metabolism as well as drugs that affect the cytochrome P450 system can result in accidental overdosing or underdosing of medications that are subject to significant levels of first-pass metabolism. This is because the P450 complex is a major pathway for liver metabolism of pharmaceuticals. Lee et al. studied whether the effects of first-pass metabolism could be recapitulated in an organoid model. They found that the effects of docetaxel were neutralized by a model organoid. They recommended studying the metabolism of drugs during development in order to ensure that they can withstand first-pass metabolism. Incorrect Answers: Answers 2 and 4: Phase 1 metabolism describes the oxidation, reduction, and hydrolysis of drugs through the cytochrome P450 and related systems. Decreased phase 1 metabolism would occur in elderly patients but is not affected by the method of drug delivery. Increased phase 1 metabolism is seen in younger patients but is not affected by the method of drug delivery. Answer 3: Increased first-pass metabolism would not occur because some of the medication bypasses the liver when absorbed through the rectal mucosa. In contrast, all of a medication taken orally must pass through the liver prior to entering the systemic circulation. Answer 5: Phase 2 metabolism describes glucuronidation, acetylation, and sulfation reactions that result in the renal excretion of drugs. Increased phase 2 metabolism would be seen in patients who are fast acetylators but would not be affected by the method of drug delivery. Bullet Summary: Medications undergo less first-pass metabolism when administered per rectum rather than orally because some absorption through the rectal mucosa bypasses the liver.
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