Diamorphine respiratory

One of the earliest attempts(68,69) at developing a nondependence-inducing morphine derivative resulted in the preparation of heroin (3,6-diacetylmor-phine or diamorphine) by acetylation of morphine. Reports of its reduced respiratory depression and dependence liability were soon shown to be mis-Ibunded, but its superior analgesic effects in animals and humans (twice morphine) are demonstrable. Pharmacological examination(70) of acyl derivatives of morphine showed that heroin and its higher and lower acyl homologs... 

The blood concentration of free morphine as a metabolite of diamorphine also correlates well with the survival time, at least over 24 hours. Average blood concentrations of morphine observed in cases where death has occurred from circulatory shock and respiratory arrest less than 3 hours after administration are 3 to 10 times greater than those seen after deaths following prolonged coma (3 to 24 hours). 

Opioid analgesics are used intrathecally and extradurally. They diffuse into the spinal cord and act on its opioid receptors (see p. 333) they are highly effective in skilled hands for postsurgical and intractable pain. Respiratory depression may occur. The effect begins in 20 min and lasts about 5 h. Diamorphine or other more lipid-soluble opioids, such as fentanyl, may be used. 

Transdermal fentanyl was the cause of an opioid overdose when a 77-year-old man with a history of severe arthritis developed respiratory failure after starting epidural diamorphine-bupivacaine mixture for postoperative pain (50). The fentanyl patch was removed, the epidural infusion was stopped, and naloxone was given to counteract the excessive opioid effects. 

Alsahaf MH, Stockwell M. Respiratory failure due to the combined effects of transdermal fentanyl and epidural bupi-vacaine/diamorphine following radical nephrectomy. J Pain Symptom Manage 2000 20(3) 210-13. 

A 14-year-old boy with staphylococcal pneumonia secondary to influenza developed adult respiratory distress syndrome. It was decided to suppress his voluntary breathing with opioids and use assisted ventilation and he was therefore given phenoperidine and diazepam for 11 days, and later diamorphine with lorazepam. Despite receiving diamorphine 19.2 mg in 24 hours his respiratory drive was not suppressed. On day 17, despite serum morphine and lorazepam levels of320 and 5.3 micrograms/mL, respectively, he remained conscious and his pupils were not constricted. Later animal studies confirmed that lorazepam opposed the respiratory depressant effects of morphine. ... 

Heroin (3,6-O-diacetylmorphine, diamorphine) was first synthesized from morphine by an English chemist, CR Wright, in 1874, and was introduced commercially as a morphine-like analgesic by the Bayer Company of Germany in 1898. Heroin was initially used as a morphine and codeine substitute for the treatment of tuberculosis and other respiratory illnesses. However, it quickly became apparent that this drug was more toxic than morphine and exhibited equivalent abuse liability and tolerance-... 

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