Meperidine tolerance

Nalbuphine is less likely to depress respiratory function than meperidine Tolerance to ocular and gastrointestinal effects develops rapidly during chronic use Mental retardation, microcephaly, and underdevelopment of the mid face region in an infant is associated with chronic maternal abuse of (A) Amphetamine Cocaine Ethanol Mescaline Phencyclidine... 

Seizures Seizures may be aggravated or may occur in individuals with or without a history of convulsive disorders if dosage is substantially increased above recommended levels because of tolerance. Observe patients with known seizure disorders closely for hydromorphone-, meperidine-, morphine-, or tramadol-induced seizure activity. 

The patient who uses meperidine repeatedly may develop a tolerance to the drug s analgesic effect and physical dependence. 

The answers are 264-c, 263-c. (Katzung, pp 519, 535-537.) Heroin and other opioids (such as morphine and meperidine) exhibit a high degree of tolerance and physical dependence. The tolerance rate magnitudes to all of the effects of opioids are not necessarily the same. The physical dependence is quite clear from the character and severity of withdrawal symptoms, which include vomiting spasms, abdominal cramps, diarrhea, and acid-base imbalances among others. 

Opiate preparations, usually given as paregoric, are effective and fast acting antidiarrheal agents. These agents are also useful postoperatively to produce solid stool following an ileostomy or colostomy. A meperidine derivative, diphenoxylate, is usually dispensed with atropine and sold as Lomotil. The atropine is added to discourage the abuse of diphenoxylate by narcotic addicts who are tolerant to massive doses of narcotic but not to the CNS stimulant effects of atropine. 

Meperidine shows certain relationships to both morphine and atropine in its action. Similar to morphine, it exerts a generalized depression of the CNS but, in ordinary doses, does not affect the cough reflex. Similar to morphine, it induces euphoria, and its continued use leads to tolerance and addiction. However, its euphoric and sedative effects are less than that of morphine addiction due to meperidine is more serious than that due to morphine. Meperidine is an effective analgesic,... 

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. 

People that use meperidine for acute pain, such as after an injury, typically do not have long enough exposure to develop tolerance and addiction. People with chronic pain, however, may develop some tolerance and physical addiction in the sense that, if they stop the drug, their pain returns. Only rarely, though, do people using opioids long-term for legitimate medical reasons devel-... 

Adverse effects Large doses of meperidine cause tremors, muscle twitches, and rarely, convulsions. The drug differs from opioids in that in large doses it dilates the pupil and causes hyperactive reflexes. Severe hypotension can occur when the drug is administered postoperatively. When used with major neuroleptics, depression is greatly enhanced. Administration to patients taking monoamine oxidase inhibitors (see p. 123) can provoke severe reactions such as convulsions and hyperthermia. Meperidine can cause dependence, and can substitute for morphine or heroin in use by addicts. Cross-tolerance with the other opioids occurs. 

Diphenoxylate is an opiate (schedule V) with antidiarrheal properties. It is usually dispensed with atropine and sold as Lomotil. The atropine is added to discourage the abuse of diphenoxylate by narcotic addicts who are tolerant to massive doses of narcotic but not to the CNS stimulant effects of atropine. Diphenoxylate shonld be used cautiously in patients with obstructive jaundice because of its potential for hepatic coma, and in patients with diarrhea cansed by pseudomembranous colitis because of its potential for toxic megacolon. In addition, it should be used cautiously in the treatment of diarrhea caused by poisoning or by infection by Shigella, Salmonella, and some strains of E. coli because expulsion of intestinal contents may be a protective mechanism. Diphenoxylate should be used with extreme caution in patients with impaired hepatic function, cirrhosis, advanced hepatorenal disease, or abnormal liver function test results, because the drug may precipitate hepatic coma. Because diphenoxylate is structurally related to meperidine, it may cause hypertension when combined with monoamine oxidase inhibitors. As a narcotic, it will augment the CNS depressant effects of alcohol, hypnotic-sedatives, and numerous other drugs, such as neuroleptics or antidepressants that cause sedation. 

The pattern and overall incidence of untoward effects that follow the use of meperidine are similar to those observed after equianalgesic doses of morphine, except that constipation and urinary retention may be less common. Patients who experience nausea and vomiting with morphine may not do so with meperidine the converse also may be true. As with other opioids, tolerance develops to some of these effects. The contraindications generally are the same as for other opioids. In patients or addicts who are tolerant to the depressant effects of meperidine, large doses repeated at short intervals may produce an excitatory syndrome including hallucinations, tremors, muscle twitches, dilated pupils, hyperactive reflexes, and convulsions. These excitatory symptoms are due to the accumulation of normeperidine, which has a half-life of 15 to 20 hours compared with 3 hours for meperidine. Opioid antagonists... 

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