Opiates drug interactions

The following drug classes may have a potential drug interaction with nevirapine Antiarrhythmics, anticonvulsants, antifungals, calcium channel blockers, cancer chemotherapy (cyclophosphamide), ergot alkaloids, immunosuppressants, motility agents, opiate agonists. 

There are some clinically important pharmacodynamic drug-drug interactions to be mentioned. Antipsychotics will potentiate the central depressant effects of sedatives and of alcohol. They will also increase the risk of respiratory-depressant effects of opiates. Inducers of drug metabolic enzymes like for example rifampicin and several antiepileptics, may increase the elimination rate of antipsychotic agents and thus decrease their efficacy. 

Spectroscopic techniques for the study of drug interactions with biological systems, 5, 55 The Stereoelectronic effects at opiate receptor their influence on affinity and intrinsic activity,... 

Lehmann, K.A., Kriegel, R., Ueki, M. Clinical relevance of drug interactions between opiates and calcium channel blockers, Anaesthesist 1989, 38, 110-115. 

Whereas these and other beneficial drug interactions are well known and often used in clinical practice, some interactions that are currently considered to be adverse also may be applied therapeutically. For example, the analgesic effects of meperidine and the opiates are augmented by the concurrent administration of MAO inhibitors. This interaction can be used to increase the desirable effects of the analgesics without having to increase the dose. The regimen may have a place in the relief of severe chronic pain in patients with terminal malignant disease. 

Telepchak, Thomas F. August, and Glynn Chaney, 2004 Handbook of Drug Interactions A Clinical and Forensic Guide, edited by Ashraf Mozayani and Lionel P. Raymon, 2004 Dietary Supplements Toxicology and Clinical Pharmacology, edited by Melanie Johns Cupp and Timothy S. Tracy, 2003 Buprenophine Therapy of Opiate Addiction, edited by Pascal Kintz and Pierre Marquet, 2002... 

In vitro inhibition of CYP2D6 activity by methadone (K = 3 M) predicted drug interactions in vivo. This finding was confirmed in 42 abusers of oral opiates undergoing treatment with methadone (Wu et al. 1993a). 

The cited literature indicates that there is much evidence in favor of the suggestion that opiate drug effects involve Ca + disposition in some way. However, the multiple, and mutually interdependent actions of Ca + in neuronal function make it difficult to establish at which sub-cellular site or sites significant opiate-Ca + interactions are occurring. 

This is especially true since a number of Ca2+-dependent effects are known to be susceptible to opiate action. The picture is further complicated by the possibility that in some cases opiate effects may not involve Ca +, while in the instances where opiate-Ca + interactions can be demonstrated, the effects on Ca + may be either directly related to drug action or may be the indirect consequence of other opiate actions such as effects on body temperature, pH or oxygen tension. 

The efflux transporter P-gp is a major determinant of the pharmacokinetics and pharmacodynamics of loperamide, a potent opiate. The main reason that loperamide does not produce opioid CNS effects at usual doses in patients is a combination of slow dissolution, first-pass metabolism, and P-gp-mediated efflux, which prevents brain absorption, perhaps contributing to its low addiction potential. Loperamide produced no respiratory depression when administered alone, but when administered with a P-gp inhibitor, respiratory depression occurred, which could not be explained by increased plasma loperamide concentrations. This effect demonstrates the potential for important drug interactions by inhibition of P-gp efflux transporter. The lack of respiratory depression produced by loperamide, which allows it to be safely used therapeutically, can be reversed by a drug causing P-gp inhibition, resulting in serious toxic and abuse potential. 

The demonstration of the covalent attachment of the label to the receptor requires the use of in vitro opiate assay systems since persistent changes in in vivo opiate sensitivity that might be induced by potential affinity labels cannot be interpreted unambiguously. Two in vitro systems have been used to study opiate drug-receptor interactions in some detail. 

Drug-drug interactions Eighteen patients who were given telaprevir and methadone showed no decrease in methadone concentration or any signs of opiate withdraw [55 ]. A meffl-analysis of FAERS from 1997 to 2011 showed increased risk of cardiac arrhythmias in patients on antiretroviral drugs and methadone [43 ]. 

Drug-drug interactions Treatment of pain with opiates can be complicated by respiratory depression and lethargy from overmedication. Buprenorphine is hepatically metabolised by the CYP3A4. Coadministration with a CYP3A4 inhibitor, ketoconazole had no effect on the metabolism of buprenorphine from a transdermal patch delivering drug at 10 Tg/h [91 -]. 

The balance between hydrophobicity and hydrophilicity also determines the clinical characteristics of opioid analgesics, compounds that reduce pain without reducing consciousness (much). Dozens of opioids are in routine clinical use, and one reason so many are available is that they have different onset times and durations of action. This allows clinicians to choose the right one for a given circumstance. Most opioid drugs interact with a single type of receptor, the p-opiate receptor, which, like most cellular components, is lipophilic. Consequently, the primary determinant of onset time is lipophilicity, just as it is for local anesthetics and nonsteroidal anti-inflammatory drugs. 

O DONAHUE has isolated a naturally occurring peptide from brain that can produce responses similar to PCP when administered to animals. The results are reminiscent of the early studies of the opiopeptides that interact with opiate receptors and produce effects like narcotic drugs when administered to animals. 

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