Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2020 Publisher: Napp Pharmaceuticals Limited, Cambridge Science Park, Milton Road, Cambridge, CB4 0GW
Pharmacotherapeutic group: Natural opium alkaloid
ATC Code: N02A01
Morphine acts as an agonist at opiate receptors in the CNS particularly mu and to a lesser extent kappa receptors. Mu receptors are thought to mediate supraspinal analgesia, respiratory depression, and euphoria, and kappa receptors, spinal analgesia, miosis and sedation.
The principal actions of therapeutic value of morphine are analgesia and sedation (i.e., sleepiness and anxiolysis). Morphine produces respiratory depression by direct action on brain stem respiratory centres.
Morphine depresses the cough reflex by direct effect on the cough centre in the medulla. Antitussive effects may occur with doses lower than those usually required for analgesia.
Morphine causes miosis, even in total darkness. Pinpoint pupils are a sign of narcotic overdose but are not pathognomonic (e.g., pontine lesions of haemorrhagic or ischaemic origin may produce similar findings). Marked mydriasis rather than miosis may be seen with hypoxia in the setting of morphine overdose.
Morphine causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone is increased to the point of spasm resulting in constipation.
Morphine generally increases smooth muscle tone, especially the sphincters of the gastrointestinal and biliary tracts. Morphine may produce spasm of the sphincter of Oddi, thus raising intrabiliary pressure.
Morphine may produce release of histamine with or without associated peripheral vasodilation. Manifestations of histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes, sweating, and/or orthostatic hypotension.
Opioids may affect the hypothalamic pituitary adrenal and hypothalamic pituitary gonadal system resulting in adrenal insufficiency or hypogonadism respectively (see section 4.4).
In vitro and animal studies indicate various effects of natural opioids, such as morphine, on components of the immune system; the clinical significance of these findings is unknown.
Morphine is well absorbed from Sevredol tablets, however first pass metabolism does occur. Apart from the liver, metabolism also occurs in the kidney and intestinal mucosa. The major urinary metabolite is morphine 3-glucuronide but morphine 6-glucuronide is also formed. The half-life for morphine in the plasma is approximately 2.5-3.0 hours.
In male rats, reduced fertility and chromosomal damage in gametes have been reported. There are no other pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
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