Opioid tolerance development

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... 

Osteoporotic vertebral compression fracture with excruciating pain and/or adverse elfects to opioid treatment or opioid tolerance developed in patients with formerly controlled pain. Failure of medical therapy is defined as minimal or no pain relief with the administration of analgesics for 3-4 weeks or achievement of adequate pain relief with only narcotic dosages that induce excessive intolerable adverse effects (constipation, urinary retention, and/ or confusion). 

Dumas, E. O., and G. M. Pollack. 2008. Opioid tolerance development a pharmacoki-netic/pharmacodynamic perspective. J. 10 537-551. 

Elliott K, Kest B, Man A, Kao B, Inturrisi CE. (1995). N-methyl-D-aspartate (NMDA) receptors, mu and kappa opioid tolerance, and perspectives on new analgesic drug development. Neuropsychopharmacology. 13(4) 347-56. 

Some patients undergoing long-term opioid treatment develop a tolerance with loss of analgesic efficacy. The mechanisms behind this effect are likely to be multi-faceted and partly determined by individual factors. There is widespread and documented experience that the tolerance developed in a particular individual is not developed in parallel for different opioids. Different sources therefore recommend... 

Tolerance to many of the effects of the depressants develops. Unlike opioids, barbiturate and benzodiazepine tolerance develops slowly. Also, tolerance is incomplete in some instances or does not influence some pharmacological effects. One such exception is the lack of tolerance to barbiturate lethality. The lethal dose in a tolerant individual is not much different from that of the general population. Cross-tolerance develops to some degree between the depressant classes of drugs. 

Constriction of the pupils is seen with virtually all opioid agonists. Miosis is a pharmacologic action to which little or no tolerance develops (Table 31-3) thus, it is valuable in the diagnosis of opioid overdose. Even in highly tolerant addicts, miosis is seen. This action, which can be blocked by opioid antagonists, is mediated by parasympathetic pathways, which, in turn, can be blocked by atropine. 

Evidence suggesting a fundamental role for VDCCs in the development of opioid tolerance and dependence... 

The development of acute tolerance and dependence evoked in mice by morphine can be suppressed by pretreatment with NTI. Multiple administration of either NTI or 5 NTII before and during chronic implantation with morphine pellets also substantially inhibits the development of morphine tolerance and dependence. These results suggest the use of 8 antagonists to be useful for the prevention of opioid tolerance and physical dependence without compromising the antinociceptive potency of p opioid receptor agonists (Abdelhamid et al., 1991). 

Drug dependence and self- or cross-tolerance develop with the use of opioid analgesics. Abrupt termination of therapy leads to severe withdrawal symptoms... 

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