Other Narcotic Analgesics

Analgesia means lack of pain, and analgesics are substances that obtund the perception of pain without causing loss of consciousness. However, analgesics should not be given until the cause of pain has been determined. If a proper diagnosis is made, the use of an analgesic may not be 

Although analgesics may ameliorate the pain in all these conditions, their use should not be implemented until the pathology has been discerned and appropriate rehabilitative measures instituted. 

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A not uncommon side effect observed with morphine and some of the other narcotic analgesics is constipation due to decreased motility of the gastrointestinal tract. It proved possible to so modify pethidine as to retain the side effect at the expense of analgesic activity. Relief of diarrhea, it will be realized, is a far from trivial indication. Alkylation of the anion from diphenylacetonitrile (95) with ethylene dibromide gives the intermediate, 96. Alkylation of normeperidine (81) with that halide... 

Fentanyl transdermal is a transdermal system that is effective in the management of the severe pain associated with cancer. The transdermal system allows for a timed-release patch containing the drug fentanyl to be activated over a 72-hour period. A small number of patients may require systems applied every 48 hours. The nurse monitors for adverse effects in the same manner as for other narcotic analgesics (eg, the nurse notifies the primary health care provider if the respiratory rate is 10/min or less). 

Few studies have explored the efficacy of opioids specifically for OA. The APS recommends against the use of codeine and propoxyphene for OA because of the high incidence of adverse effects and limited analgesic effectiveness. Oxycodone is the most extensively studied of the agents recommended for OA. However, other narcotic analgesics such as morphine, hydromorphone, methadone, and transdermal fentanyl are also effective. 

Methadone (Dolophine). For over 30 years, methadone has been the mainstay of treatment for opiate dependence. A replacement therapy, methadone has been used both for detoxification and for long-term maintenance. It has a slower onset of action and is longer acting than other narcotic analgesics. It causes little of the euphoria produced by drugs such as heroin. 

Morphine depresses all phases of respiration (respiratory rate, tidal volume, and minute volume) when given in subhypnotic and subanalgesic doses (Figure 47.6). In humans, a morphine overdose causes respiratory arrest and death. Therefore, morphine and other narcotic analgesics should be used with extreme caution in patients with asthma, emphysema, and cor pulmonale, and in disorders that may involve hypoxia, such as chest wound, pneumothorax, or bulbar poliomyelitis. 

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. 

Chronic pain, especially back pain, is one of the most common maladies treated with hydromorphone and other narcotic analgesics. This type of pain can often be alleviated to the point where the person can function to some degree. Hydromorphone is also effectively used to treat cancer pain. Much of the pain associated with cancer involves what is called neuropathic pain. This is pain caused by interference or disruption of nerve cells and nerve transmission in the body. 

Hydromorphone, as with other narcotic analgesics, should be used with great caution when performing acts that require alertness, such as driving or operating heavy machinery. The most common side effects on the brain from taking hydromorphone are sedation and drowsiness. Dizziness and agitation also are known to occur... 

Hydromorphone is highly addictive. Its use needs to be carefully monitored by the treating physician. Longterm use of the drug can lead to physical and psychological dependency. Mood can also be affected by hydromorphone and other narcotic analgesics. Infrequently, hallucinations and disorientation can develop. Insomnia develops in a minority of cases. 

Hydromorphone affects the respiratory center in the brain, and this is why it suppresses the cough reflex. Hydromorphone is partially broken down, or metabolized, by the liver and is absorbed by a variety of tissues and organs, including the gastrointestinal tract, smooth muscle, skeletal muscle, pancreas, lungs, cardiovascular system, and central nervous system. Once metabolized by the liver, hydromorphone moves out of the body by way of the kidneys and into the urine. The precise mechanisms by which hydromorphone and the other narcotic analgesics work are not entirely known. 

The primary long-term concern of those who use hydromorphone is the risk of addiction. The National Institute on Drug Abuse has determined that persons who become addicted to hydromorphone and other narcotic analgesics are at increased risk of convulsion, overdose, and death. 

This situation became particularly acute with respect to the development of illicit analogs of fentanyl to derive heroin substitutes. Fentanyl is a synthetic opioid, a p-receptor agonist, and is about 100-200 times more potent than morphine as an analgesic. As with other narcotic analgesics, respiratory depression is the most significant acute toxic effect of the fentanyl derivatives. Fentanyl analogs can be 80-1000... 

Absolute contraindication to meperidine and relative contraindication to other narcotic analgesics because of high incidence of hyperpyrexic coma... 

Opioid receptor affinity labels have been reported for other narcotic analgesics, for example, piperidines, 293 294 benzomorphans, 295 296 and mor-phinans, 297,298 and the topic is further discussed in Chapter 13 (p. 445). Not only is the oxo-function in the 4,5-epoxymorphinan C-ring available for ready elaboration, but C-6 substituents, although they affect agonist potency, do not impair unduly receptor affinity. 299 301 ... 

Morphine is the standard opioid against which other narcotic analgesics are compared. Its potential side effects, however, along with potential for abuse and addiction, usually make it unsuitable for use in outpatients. Other opioids are preferred for the treatment of moderate to severe pain in most patients. Pharmacologic properties of the commonly used opioids are summarized in Table 7-6. 

Davis WM, Hatoum NS. Lethal synergism between morphine or other narcotic analgesics and propranolol. Toxicology 1979 14(2) 141-51. 

OTHER NARCOTIC ANALGESICS OF THE OPIUM AND SYNTHETIC GROUP... 

Morphine should be administered cautiously and in reduced dosages when other CNS depressants are used, including other narcotic analgesics, barbiturates. 

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