Opioid acute actions

The opioid antagonists naloxone and naltrexone bind to aU three opioid receptors, p, K, and 8. These compounds are antagonists due to their inability to elicit downstream effects of these receptors once bound (Sarton et al. 2008 Yaksh and Rudy 1977). Interestingly, both antagonists have a high binding affinity for MORs. Naloxone is used to reverse the effects of an acute opioid overdose because of its rapid onset of action. Naltrexone elicits similar actions, but has a longer onset and duration of action and hence, is used for the maintenance of treatment for opioid addicts. 

The intoxicating effects of opioids appear to be due to their action as agonists on mu (p) receptors of the opioid neurotransmitter system. Competitive p opioid antagonists such as naloxone and naltrexone acutely reverse many of the adverse effects of opioids. To date we do not have specific antagonists for most other abused substances, so rapid pharmacologic reversal of intoxication is usually not possible. 

Drug dependence Administer cautiously to people who are known or suspected to be physically dependent on opioids, including newborns of mothers with narcotic dependence. Reversal of narcotic effect will precipitate acute abstinence syndrome. Repeat administration The patient who has satisfactorily responded should be kept under continued surveillance. Administer repeated doses as necessary, because the duration of action of some narcotics may exceed that of the narcotic antagonist. Respiratory depression Not effective against respiratory depression due to nonopioid drugs. 

Tramadol is a central-acting analgesic, effective for mild to moderate acute and chronic pain. It impairs nociception by a unique mechanism that is not completely understood. In animal models, it binds to the /u. opioid receptor and is a weak inhibitor of serotonin and norepinephrine reuptake, actions similar to those ascribed to the SSRIs and TCAs. Seizures have been reported in patients taking tramadol. Abuse potential is low, but does exist. 

Direct toxic effects of the opioid analgesics that are extensions of their acute pharmacologic actions include respiratory depression, nausea, vomiting, and constipation (Table 31-4). In addition, tolerance and dependence, diagnosis and treatment of overdosage, and contraindications must be considered. 

The major application of naloxone is in the treatment of acute opioid overdose (see also Chapter 58). It is very important that the relatively short duration of action of naloxone be borne in mind, because a severely depressed patient may recover after a single dose of naloxone and appear normal, only to relapse into coma after 1-2 hours. 

In addition to the strong p-opioid action, calcium and calmodulin antagonism are involved in the anti-diarrheal activity. The compound is used for the treatment of acute and chronic diarrhea and for the management of colostomies and ileostomies (Heel et al., 1978b, Wheeler 2000). 

The opioids may modulate the actions of the immune system by effects on lymphocyte proliferation, antibody production, and chemotaxis. Natural killer cell cytolytic activity and lymphocyte proliferative responses to mitogens are usually inhibited by opioids. Although the mechanisms involved are complex, activation of central opioid receptors could mediate a significant component of the changes observed in peripheral immune function. In general, these effects are mediated by the sympathetic nervous system in the case of acute administration and by the hypothalamic-pituitary-adrenal system in the case of prolonged administration of opioids. 

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