Opiates administration routes

Opiates are widely used all over the world, but recently concerns about opiate use (and deaths from such use) have increased in Australia and the UK (45). The rate of opiate overdose deaths in these countries increased dramatically between 1985 and 1995. Throughout that period, it was four to ten times higher in Austraha than the UK, but the rate of increase may have been greater in the UK in the latter half of the period, since the difference in rate narrowed substantially during that time. Methadone maintenance treatment, estabhshed in Australia in 1969 and in the UK in 1970, has become the main treatment for opiate dependence in both countries. About half of the opiate deaths in the UK were attributed at least in part to methadone. By contrast, considerably fewer (18%) opiate overdose deaths in Austraha were attributed to methadone. The authors suggested that the discrepancy in the rates between the two countries could be artefacts of the differences in (a) the documentation of these deaths, (b) the rate of opiate dependence, (c) the route of opiate administration, (d) opiate purity, and, most importantly, (e) the method of delivery of methadone maintenance treatment. 

The identification of the morphine receptor spurred an effort in many laboratories to find an endogenous agonist for which that receptor was normally intended. Ultimately, a pair of pentapeptides that bound quite tightly to opiate receptors were isolated from mammalian brains. These peptides, called enkephalins (2, 3), show many of the activities of synthetic opiates in isolated organ systems. They do in fact show analgesic activity when injected directly into the brain. It is thought that lack of activity by other routes of administration is due to their rapid inactivation by peptide cleaving enzymes. 

In opiate abuse, smack ( junk, jazz, stuff, China white mostly heroin) is self administered by injection ( mainUning ) so as to avoid first-pass metabolism and to achieve a faster rise in brain concentration. Evidently, psychic effects ( kick, buzz, rush ) are especially intense with this route of administration. The user may also resort to other more unusual routes opium can be smoked, and heroin can be taken as snuff (B). 

Further pharmacological effects of deltorphins have been demonstrated under various experimental conditions. D-Ala-deltorphin improves memory consolidation in a passive avoidance apparatus in mice this effect is abolished by naltrindole [75]. D-Ala-deltorphin-II caused hypothermia in cold-adapted animals [76]. In contrast to mu opiate agonists, D-Ala-deltorphin-I, at low doses, stimulates respiratory activity in fetal lambs, and this effect is blocked by simultaneous administration of naltrindole [77], The peptide D-Ala-deltorphin-II inhibits diarrhea induced by castor oil and colonic bead expulsion, but it leaves the rate of transit through the small intestine unchanged [78,79]. By the SC route D-Ala-deltorphin-I inhibits acidified alcohol-induced gastric mucosal lesions [80], but by the ICV route, it fails to affect gastric secretion [81], The peptide is involved also in the control of ingestive behavior. It stimulates the intake of food [82] and of sucrose [83],... 

Smolka M, Schmidt LG. The influence of heroin dose and route of administration on the severity of the opiate withdrawal syndrome. Addiction 1999 94(8) 1191-8. 

Patients with cholestatic conditions such as gallstones, primary sclerosing cholangitis or Alagille s syndrome often suffer from pruritus that can be extremely debilitating. In such patients it would seem sensible to avoid medication that could exacerbate this symptom. Administration of opiates via the intrathecal and epidural routes lead to a high incidence of pruritus (up to 80% with epidural morphine) [2]. 

In common with other phenolic opiate analgesics, buprenorphine shows low peroral potency, suggesting a high first-pass metabolism effect indeed, work in rats has shown this to be the case. Intravenous studies have estimated that the extraction ratio of buprenorphine is 85% and that peroral systemic availability is consequently expected to be 15% or less. Although absorption from the mouth is slow and, therefore, not as useful as parenteral administration in the treatment of acute pain, it offers a major bioavailability advantage over the peroral route for this drug. If required, the patient can be given a parenteral dose of buprenorphine to achieve rapid pain relief and... 

Administration of opiates directly into the CNS (i.e., epidural and intrathecal/subarachnoid routes) has shown considerable promise in... 

Preservative-free morphine is contraindicated in those medical conditions which would preclude the administration of opioids by the intravenous route - allergy to morphine or other opiates, acute bronchial asthma, upper airway obstruction. 

Loimer N, Hofmann P, Chaudhry HR. Nasal administration of naloxone is as effective as the intravenous route in opiate addicts. Int J Addict April 1994 29(6) 819-27. 

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