Pharmacokinetics morphine

Scott CS, Riggs KW, Ling EW, Fitzgerald CE, Hill ML, Grunau RV et al. Morphine pharmacokinetics and pain assessment in premature newborns. J Pediatr 1999 135(4) 423-9. 

Pannuti, F., et al. 1982. Control of chronic pain in very advanced cancer patients with morphine hydrochloride administered by oral, rectal and sublingual routes. Clinical report and preliminary results on the morphine pharmacokinetics. Pharmacol Res Commun 14 369. 

Davis, T., et al. 1993. Comparative morphine pharmacokinetics following sublingual, intramuscular and oral administration in patients with cancer. Hospice J 9 85. 

M. E. Ward, A. Woodhouse, L. E. Mather, S. J. Farr, J. K. Okikawa, P. Lloyd, J. A. Schuster, and R. M. Rubsamen, Morphine pharmacokinetics after pulmonary administration from a novel aerosol delivery system, Clin. Pharmacol Ther 62 596 (1997). 

Courteix, C., Bourget, P., Caussade, F., Bardin, M., Coudore, F., Fialip, J., and Eschalier, A. (1998). Is the reduced efficacy of morphine in diabetic rats caused by alterations of opiate receptors or of morphine pharmacokinetics . Pharmacol. Exp. Ther. 285, 63—70. 

Zelcer N, van de Wetering K, Hillebrand M, et al. Mice lacking multidrug resistance protein 3 show altered morphine pharmacokinetics and morphine-6-glucuronide antinociception. Proc Natl Acad Sci USA 2005 102 7274—7279. 

Dahlstrom B, Paalzow LK, Segre G, et al. 1978. Relation between morphine pharmacokinetics and analgesia . J. Pharmacokinet. Biopharm. 6 41. 

Cepeda MS, Farrar JT, Roa JH, et al. Ethnicity influences morphine pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther 2001 70(4) 351-61. 

B. E. Dahlstrom, L. K. Paalzow, G. Segre, and A. J. Agren, Relation between morphine pharmacokinetics and analgesia. J Pharmacokinet Biopharm 6 41-53 (1978). 

DR Stanski, L Paalzow, PO Edlund. Morphine pharmacokinetics GLC assay versus radioimmunoassay. J Pharm Sci 71 314, 1982. 

Ketoprofen reduced morphine-associated respiratory depression, and did not alter morphine pharmacokinetics. Similarly, diclofenac did not alter morphine pharmacokinetics in one study. Improved pain relief and reduced adverse effects have been found when morphine was given with lomoxicam, ketoprofen, or ketorolac. However, in another, diclofenac slightly increased respiratory depression despite reducing morphine use, possibly because of persistent levels of an active metabolite of morphine. Diclofenac did not affect the pharmacokinetics or analgesic effects of codeine in healthy subjects. Intramuscular diclofenac did not affect the pharmacokinetics of methadone solution in cancer patients. Ibuprofen did not appear to interact... 

Hydromorphone (I) and hydrocodone (II) belong to the morphine group of drugs and are used invariably in combination with other ingredients in a number of proprietory antitussive and analgesic antipyretic mixtures. However, interest in the pharmacokinetics of hydromorphone and hydrocodone in human subjects required an adequate assay for drug levels in plasma. 

Dershwitz M, Walsh JL, Morishige RJ, Connors PM, Rubsamen RM, Shafer SL, Rosow CE (2000) Pharmacokinetics and pharmacodynamics of inhaled versus intravenous morphine in healthy volunteers. Anesthesiology 93 619-628. 

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... 

Some, but not all of ibogaine s effects may involve pharmacokinetic actions. Although ibogaine does not alter brain morphine or alcohol levels, it does alter amphetamine levels, suggesting a possible hepatic interaction (Click et al. 1992a Rezvani et al. 1995). 

The use of prodrugs with higher lipophrlicity compared to the parent molecule is realized in the classical example of heroin and morphine. Heroin, the di-acetyl derivative of morphine, penetrates the BBB by one log order better than morphine and is cleaved by tissue esterases to release the active parent drug. As follows from fhe pharmacokinetic principles shown in Section 2.3.2.1 (Eq. 2.3), brain concentration is a function of bofh BBB permeability, reflected by and plasma area under the curve ... 

Pharmacokinetics Pharmacokinetic profiles are summarized in the table below using morphine as the standard. Data based on IM administration unless otherwise noted. ... 

Pharmacokinetics plays a very important role in the manner in which opioids are abused. Morphine and many of its derivatives are slowly and erratically absorbed after oral administration, which makes this route suitable for long-term management of pain but not for producing euphoria. In addition, opioids undergo considerable first-pass metabolism, which accounts for their low potency after oral administration. Heroin is more potent than morphine, although its effects arise primarily from metabolism to morphine. The potency difference is attributed to heroin s greater membrane permeability and resultant increased absorption into the brain. 

Zakowski M.I., S. Ramanathan, and H. Turndorf (1993). A 2-dose epidural morphine regimen in cesarean-section patients—pharmacokinetic profile. Acta Anaesthesiologica Scandinavica 37 584—589. 

Pharmacokinetics Variably absorbed from the GI tract. Protein binding low. Metabolized in liver. Primarily excreted in urine as morphineglucuronide con j ugates and unchanged drug—morphine, codeine, papaverine, etc. Unknown if removed by hemodialysis. Half-life 2-3 hr. 

Miotto K, McCann M, Basch J, Rawson R ling W (2002). Naltrexone and dysphoria fact or myth American Journal of Addictions, 11, 151-60 Mitchell TB, White JM, Somogyi AA Bodmer F (2003). Comparative pharmacodynamics and pharmacokinetics of methadone and slow-release oral morphine for maintenance treatment of opioid dependence. Drug and Alcohol Dependence, 11, 85-94 Mitchell TB, White JM, Somogyi AA Bochner F (2004). Slow-release oral morphine versus methadone a crossover comparison of patient outcomes and acceptability as maintenance pharmacotherapies for opioid dependence. Addiction, 99, 940-5 Mitka M (2003). Office-based primary care physicians called on to treat the new addict. Journal of the American Medical Association, 290, 735-6... 

Central nervous system depression is the usual effect of morphine, and sedation and drowsiness are frequently observed with therapeutic doses. When given in the absence of pain morphine may sometimes produce dysphora—an unpleasant sensation of fear and anxiety. The most important stimulatory effects of morphine in man are emesis and miosis. Miosis, due to stimulation of the Edinger-Westphal nucleus of the third nerve, occurs with all opioids. The combination of pinpoint pupils, coma, and respiratory depression are classical signs of morphine overdosage. Stimulation of the solitary nuclei may also be responsible for depression of the cough reflex (antitussive effect). Pharmacokinetics and metabolism... 

In neonates, and especially in premature infants, the mechanism for glucuronide conjugation is poorly developed. Renal function is also very inefficient. The pharmacokinetics of morphine in neonates is thus markedly different from that in older children and adults. This, together with age-related differences in the development of opioid receptors, may explain their increased sensitivity to morphine. 

---