Drug contraindicated in renal failure is
B i.e. Pethidine Meperidine (pethidine, demerol), a phenylpiperidine is metabolized chiefly in liver to nonmeperidine, which is eliminated by the kidney and liver. In patients or addicts who are tolerant to the depressant effects of meperidine, large doses repeated at sho interval may produce an excitatory syndrome including hallncination, tremors, muscle twitches, dilated pupils, hyperactive reflexes and convulsions. These excitatory symptoms are d/t accumulation of normeperidine, which has a half life of 15-20 hours, compared to 3 hours for meperidine. In patients with cirrhosis, the bioavailability of meperidine is --80% increased and t1/2 of both meperidine and normeperidine are prolonged. Since normeperidine is eleminated by kidney and liver, decreased renal or hepatic function predispose to neurotoxic effects of nor-meperidineQ. Meperidine is also not recommended for the treatment of chronic pain b/o concerns of metabolite toxicity. It should not be used for longer than 48 hours or in doses > 600 mg/day. Major pathway for morphine metabolism is conjugation with glucuronic acid forming morphine -6- glucuronide and morphine -3- glucuronide. Morphine-6-glucuronide is twice as potent as morphine with somewhat longer t1/2. (t1/2 of morphine is 2 hours) and pharmacological actions indistinguishable from those of morphine. With chronic morphine administration, the 6-glucuronide accounts for most of analgesia and its blood levels exceed those of morphine. Morphine-6-glucuronide is excreted by kidney, so its levels increase in renal failure, perhaps explaining morphine's potency and long action in compromised renal function. So in patients with renal failure decreased protein binding of morphine (resulting in higher plasma free drug level) and accumulation of morphine -6- glucuronide predispose them to respiratory depression. So morphine is given cautiously in low doses in renal failure. Respiratory depression is also repoed in patients with CRF receiving sufentanyl. Except for slightly decreased protein binding, the free drug volume of distribution and clearance of alfentanil appears to be unaffected by renal failure. Fentanyl, has sho half life and its metabolites are inactive. Therefore, it is a good choice in patients with renal diseaseQ. In renal disease (renal failure) remifentanil > fentanyl > alfentanil > sufentanil are safe. Whereas morphine (d/t morphine 6 glucoronide) 1/t respiratory depression is used very cautiously in low dose and meperidine (pethidine) is contraindicated d/t very long acting metabolite nor-meperidine causing neurotoxic excitatory syndrome.
Morphine
Pethidine
Fentanyl
Alfentanil