(ĐTĐ) – Morphine (INN) (MS Contin, MSIR, Avinza, Kadian, Oramorph, Roxanol, Kapanol) is a potent opiate analgesic medication and is considered to be the prototypical opioid.
Morphine is the most abundant alkaloid found in opium, the dried sap (latex) derived from shallowly slicing the unripe seedpods of the opium, or common or edible, poppy, Papaver somniferum. Morphine was the first active principle purified from a plant source and is one of at least 50 alkaloids of several different types present in opium, Poppy Straw Concentrate, and other poppy derivatives. Morphine is generally 8 to 17 per cent of the dry weight of opium, although specially-designed cultivars reach 26 per cent or produce little morphine at all, under 1 per cent, perhaps down to 0.04 per cent. The latter varieties, including the Przemko and Norman strains of the opium poppy, are used to produce two other alkaloids, thebaine and oripavine, which are used in the manufacture of semi-synthetic and synthetic opioids like oxycodone and etorphine and some other types of drugs. Morphine can be found in industrially useful concentrations in some crops of the Iranian poppy (P. bracteatum), oriental poppy (P. orientale), and white poppy (P. album) while lower concentrations may be found in a handful of the other 200+ members of the poppy family—as well as in some species of hops and mulberry trees. Morphine is produced most predominantly early in the life cycle of the plant and past the optimum point for extraction, various processes in the plant produce codeine, thebaine, and in some cases low quantities of hydromorphone, dihydromorphine, dihydrocodeine, tetrahydrothebaine, and hydrocodone. The human body also produces small amounts of morphine and metabolises it into a number of other active opiates.
In clinical medicine, morphine is regarded as the gold standard, or benchmark, of analgesics used to relieve severe or agonizing pain and suffering. Like other opioids, e.g. oxycodone (OxyContin, Percocet, Percodan), hydromorphone (Dilaudid, Palladone), and diacetylmorphine (heroin), morphine acts directly on the central nervous system (CNS) to relieve pain. Morphine has a high potential for addiction; tolerance and psychological dependence develop rapidly, although physical addiction may take several months to develop.
Trade names
Morphine is marketed under many different brand names in various parts of the world:
| Morphine brand names |
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History
An opium-based elixir has been ascribed to alchemists of Byzantine times, but the specific formula was supposedly lost during the Ottoman conquest of Constantinople. Around 1522, Paracelsus made reference to an opium-based elixir which he called, laudanum from the Latin word laudare meaning “to praise.” He described it as a potent pain killer, but recommended that it be used sparingly. In the late eighteenth century, when the East India Company gained a direct interest in the opium trade through India, another opiate recipe called ‘laudanum’ became very popular among physicians and their patients.
Morphine was discovered as the first active alkaloid extracted from the opium poppy plant in December 1804 in Paderborn, Germany by Friedrich Sertürner. The drug was first marketed to the general public by Sertürner and Company in 1817 as an analgesic, and also as a treatment for opium and alcohol addiction. Later it was found that morphine was more addictive than either alcohol or opium, and its extensive use during the American Civil War allegedly resulted in over 400,000 sufferers from the “soldier’s disease” of morphine addiction. This idea has been a subject of controversy, as there have been suggestions that such a disease was in fact a fabrication; the first documented use of the phrase “soldier’s disease” was in 1915.Diacetylmorphine (better known as heroin) was synthesized from morphine in 1874 and brought to market by Bayer in 1898. Heroin is approximately 1.5–2 times more potent than morphine on a milligram-for-milligram basis. Using a variety of subjective and objective measures, one study estimated the relative potency of heroin to morphine administered intravenously to post-addicts to be 1.80–2.66 mg of morphine sulfate to 1 mg of diamorphine hydrochloride (heroin).Morphine became a controlled substance in the US under the Harrison Narcotics Tax Act of 1914, and possession without a prescription in the US is a criminal offense. Morphine was the most commonly abused narcotic analgesic in the world until heroin was synthesized and came into use. Until the synthesis of dihydromorphine (ca. 1900), the dihydromorphinone class of opioids (1920s), and oxycodone (1916) and similar drugs, there generally were no other drugs in the same efficacy range as opium, morphine, and heroin, with synthetics still several years away (pethidine was invented in Germany in 1937) and opioid agonists amongst the semi-synthetics were analogues and derivatives of codeine such as dihydrocodeine (Paracodin), ethylmorphine (Dionine), and benzylmorphine (Peronine). Even today, morphine is the most sought after prescription narcotic by heroin addicts when heroin is scarce, all other things being equal; local conditions and user preference may cause hydromorphone, oxymorphone, high-dose oxycodone, or methadone as well as dextromoramide in specific instances such as 1970s Australia, to top that particular list. The stop-gap drugs used by the largest absolute number of heroin addicts is probably codeine, with significant use also of dihydrocodeine, poppy straw derivatives like poppy pod and poppy seed tea, propoxyphene, and tramadol.
The structural formula of morphine was determined by 1925. At least three methods of total synthesis of morphine from starting materials such as coal tar and petroleum distillates have been patented, the first of which was announced in 1952, by Dr. Marshall D. Gates, Jr. at the University of Rochester. Still, the vast majority of morphine is derived from the opium poppy by either the traditional method of gathering latex from the scored, unripe pods of the poppy, or processes using poppy straw, the dried pods and stems of the plant, the most widespread of which was invented in Hungary in 1925 and announced in 1930 by the chemist János Kábay.In 2003, there was discovery of endogenous morphine occurring naturally in the human body. Thirty years of speculation were made on this subject because there was a receptor that apparently only reacted to morphine: the mu3 opiate receptor in human tissue. Human cells that form in reaction to cancerous neuroblastoma cells have been found to contain trace amounts of endogenous morphine.
Indications
Morphine can be used as an analgesic to relieve:
- pain in myocardial infarction
- pain in sickle cell crisis
- pain associated with surgical conditions, pre- and postoperatively
- pain associated with trauma
- severe chronic pain, e.g., cancer
- pain from kidney stones (renal colic, ureterolithiasis)
- severe back pain
Morphine can also be used:
- as an adjunct to general anesthesia
- in epidural anesthesia or intrathecal analgesia
- for palliative care (i.e., to alleviate pain without curing the underlying reason for it, usually because the latter is found impossible)
- as an antitussive for severe cough
- in nebulized form, for treatment of dyspnea, although the evidence for efficacy is slim. Evidence is better for other routes.
- as an antidiarrheal in chronic conditions (e.g., for diarrhea associated with AIDS, although loperamide (a non-absorbed opioid acting only on the gut) is the most commonly used opioid for diarrhea).
- for remarkable relief of acute pulmonary edema through an unknown mechanism
- To lower and stabilise blood glucose in diabetics and combat other diabetic effects including diabetic neuropathy — morphine and whole opium preparations were used for this purpose well into the 1960s in North America and Europe and in much curtailed fashion now and in other countries. Morphine will also impact hypertension, levels of lipids like cholesterol in blood, and improve laboratory indices in certain types of anaemia, although whole opium preparations are preferred for these purposes if allowed. Most often, chronic pain patients with one or more of the four above conditions are treated with morphine rather than synthetics like pethidine.
- Experimentally for refractory depression. Morphine, hydromorphone, opium products and the like were used on-label for depression from antiquity or prehistoric time up into the middle 1950s.
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