Opioid tolerance addiction

Christie MJ (2008) Cellular neuroadaptations to chronic opioids tolerance, withdrawal and addiction. Br J Pharmacol 154 384-396... 

Use opioids with caution in patients with alcoholism or other drug dependencies because of the increased frequency of opioid tolerance, dependence, and the risk of addiction observed in these patient populations. Abuse of opioids in combination with other CNS depressants can result in serious risk to the patient. 

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. 

Opioids are addicting. Tolerance and dependence may occur with prolonged use of high doses. Instruct patient/family to use a pain scale and a pain diary if necessary. 

Opioids are addicting. Tolerance and dependence may occur with prolonged use of high doses. 

Herman, B.H., Vocci, F., Bridge, P., 1995. The effects of NMDA receptor antagonists and nitric oxide synthase inhibitors on opioid tolerance and withdrawal — medication development issues for opiate addiction. Neuropsychopharmacology 13, 269-293. 

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... 

Opioid analgesics are one of the few classes of medications available to treat severe levels of pain. Adding another drug to an opioid (compounding) may enhance analgesia, minimize adverse effects, reduce opioid tolerance and/or potentially deter overuse or abuse. Most astute chnicians recognize that concerns about abuse and addiction should not prevent the proper management of pain. In response. 

Major gastrointestinal effects include decreased gut motility and changes in secretion of gastric and intestinal fluids. Morphine and most p receptor agonists cause pupillary constriction. Some tolerance to this effect may develop, but addicts with high opioid levels will still have miosis. Respiratory depression is the usual cause of death from opioid overdose. 

Long -term sequelae of chronic pancreatitis include dietary malabsorption, impaired glucose tolerance, cholangitis, and potential addiction to opioid analgesics. 

Upregulation of the cyclic AMP pathway is one mechanism underlying opiate addiction. The mechanisms by which opiates induce tolerance, dependence and withdrawal in specific target neurons has been a major focus of research for many years. The inability to account for prominent aspects of opiate addiction solely on the basis of alterations in endogenous opioid peptides or in opiate receptors has shifted attention to postreceptor mechanisms [66]. 

A derivative of methadone, L-a-acetyl-methadol (LAAM) has been approved for the treatment of opioid addiction. In some addicts whose degree of tolerance is not known, the patient is first given methadone to stabilize the withdrawal signs and is then switched to LAAM. LAAM has an advantage over methadone in that it has a longer duration of action. Dosing is required only three times per week in most addicts to prevent withdrawal. 

The pupils become dilated and there are associated signs of hyperactivity of the sympathetic nervous system, such as hypertension and pilomotor stimulation. The mechanism(s) underlying tolerance and dependence are poorly understood. While acute activation of Gi/o-coupled receptors leads to inhibition of adenylyl cyclase, chronic activation of such receptors produces an increase in cAMP accumulation, particularly evident upon withdrawal of the inhibitory agonist. This phenomenon, referred to as adenylyl cyclase superactivation, is believed to play an important role in opioid addiction. 

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