Tolerance opioids

Stafford K, Gomes AB, Shen J, et al p-Opioid receptor downregularion contributes to opioid tolerance in vivo. Pharmacol Biochem Behav 69 233—237, 2001... 

Kraus J, Bomer C, Giannini E, HoUt V (2003) The role of nuclear factor kappaB in tumor necrosis factor-regulated transcription of the human mu-opioid receptor gene. Mol Pharmacol 64 876-884 Law PY, Loh HH, Wei LN (2004) Insights into the receptor transcription and signaling implications in opioid tolerance and dependence. [Review] [123 refs]. Neuropharmacology 47(Suppl 1) 300-311... 

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

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. 

Fentanyl transdermal system should only be used in patients who are already receiving opioid therapy, who have demonstrated opioid tolerance, and who require a total daily dose at least equivalent to fentanyl transdermal system 25 mcg/h. 

Patients who are considered opioid-tolerant are those who have been taking, for a week or longer, morphine 60 mg/day or more, or oral oxycodone 30 mg/day or more, or oral hydromorphone 8 mg/day or more, or an equianalgesic dose of another opioid. 

Do not administer fentanyl transdermal system to children younger than 2 years of age. Administer to children only if they are opioid tolerant and 2 years of age or older. 

High potency (HP) injection - HP injection is a highly concentrated solution of hydromorphone intended for use in opioid-tolerant patients. Do not confuse HP injection with standard parenteral formulations of injection or other opioids. Overdose and death could result. 

Oxycodone CR tablets are not intended for use as an as-needed analgesic. Oxycodone 80 and 160 mg CR tablets are for use in opioid-tolerant patients only. These tablet strengths may cause fatal respiratory depression when administered to patients not previously exposed to opioids. 

The most important factor to be considered in determining the appropriate dose is the extent of pre-existing opioid tolerance. Reduce initial doses in elderly or debilitated patients. 

Use has not been established with opioid-tolerant children younger than 16 years of age. Keep out of the reach of children. 

Dose selection - Maintain each patient at the lowest dose providing acceptable pain control. Unless the patient has pre-existing opioid tolerance, use the lowest dose, 25 mcg/h, as the initial dose. 

Pediatric patients initiating therapy on a fentanyl transdermal system 25 mcg/h should be opioid-tolerant and receiving oral morphine equivalents 60 mg/day or more. 

Levo-Dromoran If necessary, increase the dose to up to 3 mg every 6 to 8 hours, after adequate evaluation of the patient s response. Higher doses may be appropriate in opioid-tolerant patients. Adjust dosage according to the severity of the pain the patient s age, weight, physical status, and underlying diseases use of concomitant medications and other factors. 

Levorphanol Tartrate The effective daily dosage range, depending on the severity of the pain, is 8 to 16 mg in 24 hours in the nontolerant patient. Total oral daily doses of more than 16 mg in 24 hours are generally not recommended as starting doses in non-opioid-tolerant patients. 

The MS Contin 200 mg tablet is for use only in opioid-tolerant patients requiring daily morphine-equivalent dosages of 400 mg or more. Reserve this strength for patients who have already been titrated to a stable analgesic regimen using lower... 

Infumorph The recommended initial epidural dose in patients who are not tolerant to opioids range from 3.5 to 7.5 mg/day. The usual starting dose for continuous epidural infusion, based upon limited data in patients who have some degree of opioid tolerance, is 4.5 to 10 mg/day. The dose requirements may increase significantly during treatment, frequently to 20 to 30 mg/day. 

Take care to use low initial doses of CR tablets in patients who are not already opioid tolerant, especially those who are receiving concurrent treatment with muscle relaxants, sedatives, or other CNS-active medications. 

Special instructions for 80 and 160 mg CR tablets For use in opioid-tolerant patients only. 

CR tablets, 80 and 160 mg, are for use only in opioid-tolerant patients requiring daily oxycodone equivalent dosages of at least 160 mg for the 80 mg tablet and at least 320 mg for the 160 mg tablet. Take care in the prescribing of these tablet strengths. Instruct patients against use by individuals other than the patient for whom it was prescribed, as such inappropriate use may have severe medical consequences, including death. 

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. 

One should be cautious in the choice of dosage if opioid tolerance has occurred and a switch is planned. If there is pronounced tolerance the new opioid should normally be initiated at the recom-... 

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

Diaz, A., Ruiz, F., Florez, J., Pazos, A., Hurle, M.A. Regulation of dihydropyridine-sensitive Ca++ channels during opioid tolerance and supersensitivity in rats, J. Pharmacol. Exper. Ther. 1995, 274, 1538-1544. 

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