Morphine
From Wikipedia, the free encyclopedia
- This article is about the opiate. See Morphine (band) for information about the alternative rock group.
 |
|
 |
|
|
Morphine
|
|
| Systematic (IUPAC) name | |
| 7,8-didehydro- 4,5-epoxy-17-methylmorphinan-3,6-diol |
|
| Identifiers | |
| CAS number | |
| ATC code | N02 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C17H19NO3 |
| Mol. mass | 285.4 |
| Pharmacokinetic data | |
| Bioavailability | ~30% |
| Protein binding | 30–40% |
| Metabolism | Hepatic 90% |
| Half life | 2–3 hours |
| Excretion | Renal 90%, biliary 10% |
| Therapeutic considerations | |
| Pregnancy cat. | |
| Legal status |
Controlled (S8)(AU) Schedule I(CA) Class A(UK) Schedule II(US) |
| Dependence Liability | Extremely High |
| Routes | smoked/inhaled, insufflated, Oral, SC, IM, IV |
Indicated for:
Recreational uses: Other uses: |
Contraindications:
|
| Side effects:
Atypical sensations:
Eye:
Skin:
|
Morphine (INN) (IPA: [ˈmɔ(ɹ)fin]) is a highly potent opiate analgesic drug and is the principal active agent in opium and the prototypical opiate. Like other opioids, e.g. Diamorphine (heroin), morphine acts directly on the central nervous system (CNS) to relieve pain, and at synapses of the nucleus accumbens in particular. Morphine is highly addictive when compared to other substances, and tolerance and physical and psychological dependences develop very rapidly.
Patients on morphine often report insomnia, visual hallucinations and nightmares.[citation needed]
The word "morphine" is derived from Morpheus, the god of dreams in Greek mythology. He is the son of Hypnos, god of sleep.
Contents |
[edit] Medical Uses
Morphine is used legally:
- As an analgesic in hospital settings for
- Pain after surgery
- Pain associated with trauma
- In the relief of severe chronic pain, e.g.
- Cancer pain
- Pain from kidney stones
- Back pain
- 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
- 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.
[edit] Contraindications
- acute respiratory depression
- acute pancreatitis (this may be a result of morphine use as well)
- renal failure (due to accumulation of the metabolite morphine-6-glucuronide)
- chemical toxicity (potentially lethal in low tolerance subjects)
- raised intracranial pressure, including head injury (exacerbation due pCO2 increases from respiratory depression)
[edit] Pharmacology
Morphine is a phenanthrene opioid receptor agonist – its main effect is binding to and activating the µ-opioid receptors in the central nervous system. Activation of these receptors is associated with analgesia, sedation, euphoria, physical dependence and respiratory depression. Morphine is known to bind very strongly to the µ-opioid receptors, hence its higher incidence of euphoria and dependence liability as compared to most other opioids. Morphine is also a κ-opioid and δ-opioid receptor agonist, κ-opioid's action is associated with spinal analgesia and miosis. δ-opioid is thought to play a role in analgesia.
The effects of morphine can be countered with opioid antagonists such as naloxone, naltrexone and NMDA antagonists such as ketamine or dextromethorphan.
Morphine is primarily metabolized into morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) via glucuronidation by phase II metabolism enzyme [UDP-glucuronosyl transferase-2B7] (UGT2B7). The phase I metabolism cytochrome P450 (CYP) family of enzymes has a role in the metabolism to a lesser extent. The metabolism occurs not only in the liver, but may also take place in the brain and the kidneys. M6G has been found to be a far more potent analgesic than morphine when dosed to rodents but crosses the blood-brain barrier with difficulty. M6G has been shown to be relatively more selective for mu-receptors than for delta- and kappa-receptors while M3G does not appear to compete for opioid receptor binding. The significance of M6G formation on the observed effect of a dose of morphine is the subject of extensive debate among pharmacologists.
[edit] Constipation
Like loperamide and other opioids, morphine acts on the myenteric plexus in the intestinal tract reducing gut motility, causing constipation. The gastrointestinal effects of morphine are mediated primarily by µ-opioid receptors in the bowel. By inhibiting gastric emptying and reducing propulsive peristalsis of the intestine, morphine decreases the rate of intestinal transit. Reduction in gut secretion and increases in intestinal fluid absorption also contribute to the constipating effect. Opioids also may act on the gut indirectly through tonic gut spasms after inhibition of nitric oxide generation. This effect was shown in animals when a nitric oxide precursor reversed morphine-induced changes in gut motility.
[edit] Gene Expression
Studies have shown that morphine can alter the expression of certain genes in human DNA. A single injection of morphine has been shown to alter the expression of two major groups of genes, for proteins involved in mitochondrial respiration and for cytoskeleton-related proteins.[1]
[edit] Chemistry
Most of the licit morphine produced is used to make codeine. It is also a precursor for both diamorphine and hydromorphone. Replacement of the N-methyl group of morphine with an N-phenylethyl group results in a product that is 18x morphine in its opiate agonist potency. Combining this modification with the replacement of the 6 hydroxyl with a 6 methylene produces a compound some 1440x morphine in potency, stronger than the Bentley compounds such as etorphine. If this compound was cut into regular heroin it is most unlikely that it would show up on any tests.
Interestingly, morphine has recently been found to be endogenously produced by humans, made by cells in the heart, pancreas and brain.[2] It has also been isolated from a range of other mammals, as well as toads and some invertebrates. What the normal endogenous role of morphine might be is unclear.
[edit] Legal classification
- In the United Kingdom, morphine is listed as a Class A drug under the Misuse of Drugs Act 1971.
- In the United States, morphine is classified as a Schedule II drug under the Controlled Substances Act.
- In Canada, morphine is classified as a Schedule I drug under the Controlled Drugs and Substances Act.
- In Australia, morphine is classified as a Schedule 8 drug under the Therapeutic Goods Act 1989 (2003).[3]
- Internationally, morphine is a Schedule I drug under the Single Convention on Narcotic Drugs.[4]
[edit] History and abuse
Morphine was first isolated in 1804 by the German pharmacist Friedrich Wilhelm Adam Sertürner (or Barnard Courtois), who named it "morphium" after Morpheus, the Greek god of dreams. But it was not until the development of the hypodermic needle (1853) that its use spread. It was used for pain relief, and as a "cure" for opium and alcohol addiction. Its extensive use during the American Civil War allegedly resulted in over 400,000 sufferers from the "soldier's disease" of morphine addiction.
Diamorphine (Heroin) was derived from morphine in 1874. As with other drugs, its possession without a prescription was criminalized in the U.S. by the Harrison Narcotics Tax Act of 1914.
Morphine is routinely carried by soldiers on operations in an autoinjector.
Morphine was the most commonly abused narcotic analgesic in the world up until heroin was synthesized and came into use. Even today, morphine is the most sought after prescription narcotic by heroin addicts when heroin is scarce.
In a randomised double-blind study with crossover at an outpatient clinic in Bern, Switzerland, morphine was proven to have stronger side-effects than heroin at equianalgesic doses. Respiratory depression, miosis, sedation, itchiness, and euphoria were more pronounced with morphine.[5]
[edit] See also
- Opioids
- Heroin
- Drug addiction
- Opium
- Psychoactive drug
- Recreational drug use
- Drugs and prostitution
- Poppy
- Illegal drug trade
[edit] References
- ^ Loguinov A, Anderson L, Crosby G, Yukhananov R (2001). "Gene expression following acute morphine administration". Physiol Genomics 6 (3): 169-81. PMID 11526201.
- ^ Chotima Boettcher, Monika Fellermeier, Christian Boettcher, Birgit Drager, and Meinhart H. Zenk. How human neuroblastoma cells make morphine. Proceedings of the National Academy of Sciences. June 14, 2005. 102(24): 8495–8500
- ^ http://www.tga.gov.au/index.htm
- ^ http://www.incb.org/pdf/e/list/yellow.pdf
- ^ http://opioids.com/heroin/versusmorphine.html
[edit] External links
- * Palliativedrugs.com Online palliative care formulary and bulletin board with over 22,000 registered. Free access after registration.
| Analgesics (N02A, N02B) | |
|---|---|
| Opioids | Bezitramide, Buprenorphine, Butorphanol, Dextromoramide, Dextropropoxyphene, Diamorphine, Dihydrocodeine, Fentanyl, Hydromorphone, Ketobemidone, Methadone, Morphine, Nalbufine, Nicomorphine, Opium, Oxycodone, Papaveretum, Pethidine, Piritramide, Tramadol (see also longer list) |
| Salicylic acid and derivatives | Aspirin (Acetylsalicylic Acid), Diflunisal, Ethenzamide -- See also: NSAIDs |
| Pyrazolones | Aminophenazone, Metamizole, Phenazone |
| Anilides | Paracetamol (acetaminophen), Phenacetin |
| Others | Ziconotide, Tetrahydrocannabinol, Ibuprofen, Ketoprofen, Mefenamic Acid, Naproxen, Diclofenac, Flurbiprofen, Diflunisal, Fenoprofen, Indomethacin, Ketorolac, Meclofenamate, Meloxicam, Piroxicam, Tolmetin |
