Blood morphine

A 43-year-old man was found dead in bed after injecting metamfetamine and morphine the night before. An autopsy showed mild edema of the brain and lungs, fatty liver, and active HCV hepatitis. The postmortem findings suggested hyperthermia. The blood metamfetamine concentration was 550 ng/ml, and the blood morphine concentration was 760 ng/ml. 

An unbound morphine blood concentration of 100 ngl ml or more is considered potentially fatal. However, fatal cases of heroin intoxication occur in patients with blood morphine concentrations below 100 ng/ml. In 62 cases of heroin intoxication, death was associated with unbound morphine heart blood concentrations below 100 ng/ml in 21 cases and 100 ng/ml or over in 41 cases (51). In the 21 with low concentrations, respiratory tract infections occurred more often, and plausible causes of death were identified in 19. 

Koch A, Reiter A, Meissner C, Oehmichen M. Ursache des Todes von Heroinkonsnmenten mit niedrigen Morphin-Konzentrationen im Bint. [Canse of death in heroin users with low blood morphine concentration.] Arch Kriminol 2002 209(3-4) 76-87. 

Death In a study of heroin related deaths over 9 years there was a significant reduction in blood morphine concentrations in deaths during 2001-2006 (mean 0.4mg/l) compared with concentrations during 1998-2000 (mean 0.5mg/l) [74"=]. These findings are consistent with the sustained reduction in the purity of street heroin. 

Darke S, Duflou J, Torok M. A reduction in blood morphine concentrations amongst heroin overdose fatalities associated with a sustained reduction in street heroin purity. Forensic Sci Int 2010 198 118-20. 

Use in hepatic or renal disease the elimination half-life of morphine may be prolonged in patients with reduced metabolic rates and with hepatic and/or renal dysfunction. Hence, care shoidd be exercised in administering preservative-free morphine epiduraUy to patients with these conditions, since high blood morphine levels, due to reduced clearance, may take several days to develop. 

For quantitative results consistency in units is advised and should not be given with more significant digits than the accuracy will allow. For example, there is no point in reporting a result for blood morphine as 0.162 mg/L when the accuracy and precision of the method is 20%. A result of 0.16 mg/L would suffice. 

Morphine. This alkaloid exerts both a depressing and a stimulating action on the central nervous system, the depression affecting the brain especially the sensation of pain and the respiration the cerebral motoi functions are less affected. The stimulant action in the cord is best seen in the cold-blooded animals, when it may develop into tonic convulsions. In higher animals, but rarely in man, there may be some indication of this stimulant action. In cats it may also involve the motor areas, and they... 

Thehaine stands at the other end of the series from morphine and is a convulsant poison rather than a narcotic (see table, p. 261). Hildebrandt states that it excites the reflexes of cold-blooded animals but in dogs it exerts a narcotic and anti-emetic effect resembling that of morphine rather than that of chloromorphide. The alkaloid is scarcely used in medicine as such, but is a primary material for the preparation of certain of the modern morphine derivatives, such as hydroxydihj dro-codeinone and methyldihydromorphinor.e. 

Opioids are easily absorbed subcutaneously and intramuscularly, as well as from the gastrointestinal tract, nasal mucosa (e.g., when heroin is used as snuff), and lung (e.g., when opium is smoked). About 90% of the excretion of morphine occurs during the first 24 hours, but traces are detectable in urine for more than 48 hours. Heroin (diacetyhnorphine) is hydrolyzed to monoacetylmorphine, which is then hydrolyzed to morphine. Morphine and monoacetylmorphine are responsible for the pharmacologic effects of heroin. Heroin produces effects more rapidly than morphine because it is more lipid soluble and therefore crosses the blood-brain barrier faster. In the urine, heroin is detected as free morphine and morphine glucuronide (Gutstein and Akil 2001 Jaffe et al. 2004). 

Although controversial, findings as to how chronically administered morphine modulates neutrophil chemotaxis and function, a growing consensus believes that morphine is suppressive in the recruitment and functional aspects of these cells during an innate immune response. When peripheral human blood neutrophils were pretreated with exogenous opioids, lL-8-induced chemotaxis was inhibited (Grimm et al. 1998). Conversely, Simpkins et al. reported an increase in neutrophil chemotaxis... 

Chao CC, Molitor TW, Close K, Hu S, Peterson PK (1993) Morphine inhibits the release of tumor necrosis factor in human peripheral blood mononuclear cell cultures. Int J Immunopharmacol 15 447 53... 

Peterson PK, Sharp BM, Gekker G, Jackson B, Balfour HH Jr (1991) Opiates, human peripheral blood mononuclear cells, and HIV. Adv Exp Med Biol 288 171-178 Peterson PK, Gekker G, Schut R, Hu S, Balfour HH Jr, Chao CC (1993) Enhancement of HlV-1 replication by opiates and cocaine the cytokine connection. Adv Exp Med Biol 335 181-188 Peterson PK, Gekker G, Hu S, Sheng WS, Molitor TW, Chao CC (1995) Morphine stimulates phagocytosis of Mycobacterium tuberculosis by human microglial cells involvement of a G protein-coupled opiate receptor. Adv Neuroimmunol 5 299-309 Peterson PK, Molitor TW, Chao CC (1998) The opioid-cytokine connection. J Neuroimmunol 83 63-69... 

The peptides will now be considered individually in some detail. It must be noted that the large molecular size of the peptides means that they are even less likely to cross the blood-brain barrier than classical transmitters and the instability of peptides means that full functional studies require non-peptide agonists and antagonists. Whereas nature has provided morphine and medicinal chemists have made naloxone, tools are lacking for many other peptides. 

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