The antitussive effects of opiate agonists are mediated through direct action on receptors in the cough center of the medulla. Cough suppression with meperidine occurs at doses necessary for analgesia. Intravenous meperidine results in more histamine release than equipotent doses of morphine, fentanyl or sufentanil. When administered orally, it undergoes extensive first-pass metabolism. Meperidine is less than one-half as effective when given orally as opposed to parenterally and it is recommended not to give meperidine via this route.
Meperidine is distributed widely, and it crosses the placenta and distributes into breast milk.
Meperidine is metabolized in the liver by hydrolysis to meperidinic acid followed by partial conjugation with glucuronic acid. Meperidine also undergoes N-demethylation to normeperidine, which then undergoes hydrolysis and partial conjugation. Normeperidine, an active metabolite of meperidine, is about half as potent as meperidine, but it has twice the CNS stimulation effects. Accumulation of this metabolite after repeated or high doses in patients with hepatic or renal impairment will occur. Acidification of the urine greatly enhances excretion of both meperidine and normeperidine.