Naloxone pharmacokinetics

Opioids also interact with excitatory amino acid neurotransmitters. At lower micromolar concentrations, p agonists (e.g., DAMGO) enhance NMDA activity in the nucleus accumbens, but inhibit non-NMDA activity (Martin et al. 1997). At higher concentrations (5 pM), NMDA currents are reduced. Conversely, central administration of glutamate can precipitate a withdrawal syndrome in morphine-dependent animals, similar to the opioid antagonist naloxone. NMDA mechanisms also appear to be involved in the development of morphine tolerance. Competitive and noncompetitive NMDA antagonists and inhibitors of nitric oxide synthase reduce or eliminate tolerance to morphine (Elliott et al. 1995 Bilsky et al. 1996). However, this does not occur for tolerance to k opioids. Pharmacokinetics... 

Pharmacokinetic properties Oral naloxone is extensively metabolized in the gut and liver, predominantly by glucuronidation of the phenol function (Berkowitz, 1976). 

Berkowitz, B.A. The relationship of pharmacokinetics to pharmacological activity morphine, methadone and naloxone, Clin. Pharmacokinet. 1976, 1, 219-230. 

Vollmer, K.O. [Pharmacokinetic aspects of the Valoron-N principle. Balanced pharmacokinetics of nortilidine and naloxone], Fortschr. Med. 1988, 106, 593-596. 

Even small doses of fentanyl can cause respiratory depression. Delayed respiratory depression can be a particular problem in the elderly, in whom the half-life is approximately three times longer than in younger patients (6). Respiratory depression has been reversed with nalbuphine doxapram could only antagonize this effect for 2-5 minutes (7). However, the need for prolonged treatment of respiratory depression with naloxone, because of pharmacokinetic variability and/or transdermal drug reservoir, has been emphasized by several authors (SEDA-16, 80) (SEDA-17, 80). 

Artru A A 1990 Hypocapnia and diazepam reverse and midazolam or fentanyl attenuates ketamine induced Increase of cerebral blood volume and/or cerebrospinal fluid pressure. In Domino E F (ed) Status of ketamine in anesthesiology. NPP Books, Ann Arbor, Ml, p. 119 Aurich C, Aurich J E, Klug E 1993 Naloxone affects gastrointestinal functions and behaviour in horses. Deutsche Tierarztiiche Wochenschrift 100 314-315 Ballard S, Shults T, Kownacki A A et al 1982 The pharmacokinetics, pharmacological responses and behavioral effects of acepromazine in the horse. 

Preliminaiy evidence suggests that buprenorphine does not affect the antiretrovirai efficacy or pharmacokinetics of delavirdine and efavirenz. Deiavirdine may increase buprenorphine plasma levels and efavirenz may decrease buprenorphine levels, but the clinical significance has not been fully investigated. Delavirdine given with buprenorphine/naloxone has been shown to slightly prolong the QT interval. 

Other studies include the pharmacokinetics of codeine and metabolic morphine derived from it, the inhibition of tolerance to morphine by naloxone, a review of the tolerance and dependence mechanism for morphine, studies of plasma ° and brain levels affected by the alkaloids, the teratogenic potency of codeine, and the metabolism of morphine. " Analytical methods for the determination of morphine and related compounds in body fluids, for improved recovery from biological tissues, and methods of radio-immunoassay have been described. 

Panchagnula R, Bokalial R, Shatma P, Khandavilli S (2005) Transdtumal delivery of naloxone skin permeation, pharmacokinetic, irritancy and stability studies. Int J Pharm 293 213-223... 

Douglas Bruce R, Moody DE, Chodkowski D, Andrews L, Fang WB, Morrison J, et al. Pharmacokinetic interactions between buprenor-phine/naloxone and raltegravir in subjects receiving chronic buprenorphine/naloxone treatment. Am J Drug Alcohol Abuse 2013 39(2) 80-5. 

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