Induced Tolerance

Tolerance develops to the narcotic and analgesic actions of morphine, so that increasingly larger doses are needed to render patients pain free. Tolerance develops to many effects of morphine such as analgesia, euphoria, narcosis, respiratory depression, hypotension, and antidiuresis. Morphine-induced bradycardia may be experienced. However, no tolerance develops to morphine-induced miosis or constipation. If the administration of morphine is discontinued, the tolerance is lost and the preaddiction analgesic doses of morphine become effective once more. 

---

In rare cases, initiation of specific immunotherapy with insect venom leads to recurrent anaphylaxis, even with antihistamine premedication. In those cases, comedication with omalizumab (anti-IgE) has been reported to induce tolerance. In a case of recurrent anaphylaxis to induction of specific immunotherapy, the injection of 300 mg of omalizumab between 4 days and 1 h reportedly led to tolerance [42]. This approach also appears worthy of consideration in patients with both idiopathic recurrent anaphylaxis and mastocytosis who do not respond to standard antimediator therapy, as has been described in 2 atopic patients with ISM [43]. Most patients with mastocytosis and idiopathic anaphylaxis, however, are sufficiently controlled by standard antimediator therapy with antihistamines with or without low-dose corticosteroids. 

Frank, L., Iqbal, J., Hass, M and Massaro, D. (1989). New rest period protocol for inducing tolerance to high ox) n exposure in adult rats. Am. J. Physiol. 257, L226-L231. 

Cote IL, Bowers A, Jaeger RJ. 1983. Induced tolerance to acrylonitrile toxicity by prior acrylonitrile exposure. Res Commun Chem Pathol Pharmacol 42 169-172. 

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]. 

It is ironic that possibly the first animal model of relevance to immunotoxicology was reported by Portier and Richet in 1902 [45] in an attempt to induce tolerance to a sea anemone toxin, they accidentally produced a shock reaction in dogs. Since this was not the protective effect they had hoped to produce (phylaxis for protection in Greek), they named the reaction anaphylaxis [46], The irony, of course, is that this serious reaction, mediated by IgE in humans, has proven to be notoriously difficult to predict based on animal studies. This is no trivial issue, since anaphylaxis is a serious, life-threatening reaction associated with exposure to drugs, foods, cosmetic ingredients, and other exogenous substances [47],... 

Hammerberg, C., Duraiswamy, N., and Cooper, K. D., Temporal correlation between UV radiation locally-inducible tolerance and the sequential appearance of dermal, then epidermal, class II MHC+ CDllb+ monocytic/macrophagic cells, J. Invest. Dermatol. 107, 755-763, 1996. 

Schwarz, A. et al., Interleukin-12 prevents ultraviolet B-induced local immunosuppression and overcomes UVB-induced tolerance, J. Invest. Dermatol. 106, 1187-1191, 1996. 

Aragane, Y. et al., Involvement of dectin-2 in ultraviolet radiation-induced tolerance, J. Immunol. 171, 3801-3807, 2003. 

If only a low level of receptor activation is required in order to obtain a full response, one would predict that receptor desensitization would be a smaller problem with THIP, muscimol, and other GABAa agonists used as hypnotics. In an animal study, Lancel and Langebartels showed that 5-d treatment with THIP produced sustained effects on sleep parameters, whereas a benzodiazepine in a similar paradigm induced tolerance-like effects after only 5 d of treatment (52). Accepting that only... 

Primary hepatocyte cultures have been used as a tool to predict the hepatotoxicity of many compounds such as nonsteroidal anti-inflammatory drugs (Castell et ah, 1988), psychotropic drugs (Boelsterli et ah, 1987), immunosuppressant drugs (Boelsterli et ah, 1988), and salicylates (Tolman et ah, 1978). Rat primary hepatocyte cultures have also been shown to be a good model for examining the mechanisms of metallothionein-induced tolerance to cadmium toxicity (Liu et ah,... 

Liu, J., Kershaw, W.C. and Klaasen, C.D. (1990). Rat primary hepatocyte cultures are a good model for examining metallothionein-induced tolerance to cadmium toxicity. In Vitro Cell. Dev. Biol. 26 75-79. 

Haefely, W., Biological basis of drug-induced tolerance, rebound, and dependence. Contribution of recent research on benzodiazepines, Pharmacopsychiatry, 19, 353-361,1986. 

Welburn PJ, Starmer GA, Chesher GB, Jackson DM. (1976). Effect of cannabinoids on the abdominal constriction response in mice within cannabinoid interactions. Psychopharmacoiogia. 46(1) 83-85. Welch SP. (1997). Characterization of anandamide-induced tolerance comparison to delta 9-THC-induced interactions with dynorphinergic systems. Drug Aicohoi Depend. 45(1-2) 39-45. 

Welch SP. (1997). Characterization of anandamide-induced tolerance comparison to delta 9-THC-induced interactions with dynorphinergic systems. Drug Alcohol Dependence. 45(1-2) 39-45. 

Schwarz A. Beissert S. Grosse-Heitmeyer K. Gunzer M. Bluestone JA. Grabbe S. Schwarz T Evidence for functional relevance of CTLA-4 in ultraviolet-radiation-induced tolerance. J Immunol 2000 165 1824-1831. 

McCue D, Ryan K, Wraith DC, Anderton SM Activation thresholds determine susceptibility to peptide-induced tolerance in a heterogeneous myelin-reactive T cells repertoire. J Neuroimmunol 2004 156 96-106. 

---