Meperidine metabolism

The answer is c. (Hardman, pp 543—544. Katzang, p 2533) Fentanyl is a chemical relative of meperidine that is nearly 100 times more potent than morphine. The duration of action, usually between 30 and 60 min after parenteral administration, is shorter than that of meperidine. Fentanyl citrate is only available for parenteral administration intramuscularly and intravenously. Tran sbuc cal ( lollipop ) and transdermal patches avoid first-pass metabolism of fentanyl. 

It is a cleavage of drug molecule by taking up a molecule of water. The most hydrolytic enzymes are found outside the endoplasmic reticulum, and in higher concentrations in liver, kidney and plasma. The metabolism of an ester by an enzyme esterase results in the formation of an acid and alcohol. The examples are meperidine, procaina-mide, pethidine and lidocaine etc. Meperidine is catalyzed by esterases to be changed into meperidinic acid and procainamide is catalyzed by amidases. 

Pethidine is metabolized chiefly in the liver, to mainly meperidinic acid and minor metabolite norpethidine, which are conju-... 

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Meperidine is in part demethylated in the body appearing as normeperidine in the urine. It is, however, for the most part hydrolyzed and excreted as free and conjugated meperidinic acid. The normeperidine is also partially hydrolyzed to normeperidinic acid, which is partly conjugated. Only a small part of the drug is excreted in an unchanged form. In humans, meperidine is metabolized at the rate of about 17% per hour, so that a single dose exerts its analgesic effect for 3 to 4 h. In the dog, on the other hand, its rapid metabolism (70 to 90% per hour) makes it difficult to induce tolerance or addiction. 

Postoperative shivering following mild hypothermia has been associated with increased myocardial oxygen demand, which may lead to myocardial ischemia (48). It can also cause increased intracranial pressure (49). In addition, shivering may result in metabolic acidosis secondary to increased carbon dioxide production. Shivering can be minimized by careful rewarming of the patient before extubation and by using low-dose meperidine or clonidine. 

Pond SM, Tong T, Benowitz NL, et al. (1981) Presystemic metabolism of meperidine to normeperidine in normal and cirrhotic subjects. Clin Pharmacol Ther 30 183-188. 

Pruritus is a frequent adverse effect after intrathecal administration, with an incidence of one-third with bupre-norphine (122) and diamorphine (123) and over 70% for both diamorphine and morphine (124,125). In one stndy the incidence of pruritns was higher with morphine than with methadone analgesia was also snperior (124). Pruritus has also been reported with intrathecal pethidine (meperidine). Treatment was not reported to be necessary. This effect is not reported to occnr after intrathecal beta-endorphin (126,127). The mechanism of prnritns is not well understood and has been attribnted to a distnr-bance of thiamine metabolism (128) and to a distnrbance of afferent inpnt at snpraspinal as well as at spinal receptor sites (129). 

Pethidine (meperidine) is about one-tenth as potent as morphine in terms of analgesia. It is metabolized in the liver by hydrolysis and conjugation, either directly or via N-demethylation to norpethidine. Norpethidine (norme-peridine) is significantly less analgesic, with a longer half-life (15-20 hours). 

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