Meperidine addiction

Abstinence phenomena after withdrawal from meperidine hydrochloride are milder, come on more rapidly, and subside somewhat more quickly than the phenomena after withdrawal of morphine (50). Meperidine possesses addiction liability which is of a lower order than that of morphine. Yet 5 deaths occurred among the 32 cases of meperidine addiction which Polonio (6) summarized. Meperidine is dangerous when taken in amounts to satisfy dependence. Tremors, toxic psychoses, and convulsions were noted during experimental addiction to meperidine (6, 50). 

Addiction to meperidine is much more common than is addiction to codeine. Meperidine will produce physical dependence in individuals who have never been addicted to morphine, as well as in former morphine addicts. Although physical dependence is milder, the toxic effects of meperidine are so pronounced that meperidine addiction is even more undesirable than addiction to morphine (6, 50). 

The search for opioid analgesics which show reduced addiction liability ha.s centered largely on benzomorphan and morphinan derivatives. Some research has, however, been devoted to derivatives of the structurally simpler meperidine series. The preparation of one such compound, picenadol (59), starts with the reaction of N-methyl-4-piperidone with the lithium derivative from m-methoxybromobenzene. Dehydration of the first formed carbinol 51 gives the intermediate 52. Deprotonation by means of butyl lithium gives an anion which can be depicted in the ambident form 53. In the event, treatment of the anion with propyl bromide gives the product 54 from reaction of the benzylic anion. Treatment of that product, which now contains an eneamine function. 

The dangers of dependency and addiction clearly preclude the use of such compounds as morphine, meperidine, and methadone as treatment for diarrhea. Antidiarrheal specificity therefore is of paramount importance in choosing among the synthetic opioids and their analogues (e.g., diphenoxylate and loperamide). 

The time of onset, intensity, and duration of abstinence syndrome depend on the drug previously used and may be related to its biologic half-life. With morphine or heroin, withdrawal signs usually start within 6-10 hours after the last dose. Peak effects are seen at 36-48 hours, after which most of the signs and symptoms gradually subside. By 5 days, most of the effects have disappeared, but some may persist for months. In the case of meperidine, the withdrawal syndrome largely subsides within 24 hours, whereas with methadone several days are required to reach the peak of the abstinence syndrome, and it may last as long as 2 weeks. The slower subsidence of methadone effects is associated with a less intense immediate syndrome, and this is the basis for its use in the detoxification of heroin addicts. However, despite the... 

Meperidine (Schedule II) is a synthetic analgesic with opiate activity. It has 10-20% of the potency of morphine with all of the addictive side effects. It has a rapid onset of action and duration which makes its useful for relieving the pain associated with labor or as a preanesthetic before surgery. Its biotransformation produces normeperidine which has been associated with seizures. It was a botched clandestine attempt to synthesize a meperidine modification which produced the toxic drug that induced parkinson-type destruction of DA neurons in its users. 

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. 

Meperidine is available in the form of tablets (50 mg) for oral use or in solution (50 mg/ml) for intramuscular administration. It is administered in doses of 50 to 100 mg at 3- to 4-h intervals. Because of its antispasmodic effects, it is particularly useful in pain due to colic. It is also used prior to anesthesia, particularly cyclopropane. Meperidine is used in asthma, but its tendency to addiction limits its use in this condition to acute attacks. 

Meperidine has replaced morphine to a large extent in medical practice because of the physician s reluctance to use an opiate and the belief that meperidine manifests less undesirable side effects than does morphine. However, both of these assumptions are ill founded. Addiction to meperidine is much less amenable to treatment than is addiction to morphine. Meperidine, similar to morphine and codeine, causes spasm of the upper gastrointestinal tract and typical attacks of biliary colic in biliary tract disease. Meperidine, in doses giving an equal analgesic effect, induces as much respiratory depression as does morphine. Similar to morphine, it also crosses the placental barrier and must therefore be used cautiously in the latter stages of labor. 

Naloxone (Narcan) and naltrexone hydrochloride (Trexan) reverse the respiratory depressant action of narcotics related to morphine, meperidine, and methadone. They differ from other narcotic analgesics in several respects. Naloxone does not cause respiratory depression, pupillary constriction, sedation, or analgesia. However, it does antagonize the actions of pentazocine. Naloxone neither antagonizes the respiratory depressant effects of barbiturates and other hypnotics nor aggravates their depressant effects on respiration. Similar to nalorphine, naloxone precipitates an abstinence syndrome when administered to patients addicted to opiate-like drugs. 

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-... 

As a Schedule II opioid narcotic, meperidine is highly addictive. Treatment for opioid overdose usually involves administration of an opioid antagonist such as Narcan (naloxone), which reverses or blocks the effects of the drug. However, in some cases, those who overdose on meperidine do not respond well to opioid antagonists. 

Evidence indicates that proper meperidine prescription for legitimate medical concerns does not greatly increase the risk of addiction and abuse. Those in the medical community agree that more education is needed by both doctors and patients to help prevent the potential for abuse and addiction, so that patients truly in need are not denied access to meperidine based on misperceptions and fear. The benefits for individuals and society are great when pain is treated safely and effectively. 

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