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Morphine

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**Medical Uses**:
Morphine is used for treating acute and chronic severe pain.
– Effective for pain related to myocardial infarction, labor, and cancer pain.
– Traditionally used in acute pulmonary edema treatment.
– Beneficial in reducing shortness of breath from cancer and noncancer causes.
– Used in opioid substitution therapy for individuals intolerant to methadone or buprenorphine.

**Adverse Effects and Contraindications**:
– Relative contraindications include respiratory depression.
Morphine causes constipation by reducing gut motility.
– Hormone imbalances and hypogonadism common in chronic users.
– Concerns about increased mortality with non-ST elevation myocardial infarction.
– No evidence supports contraindication in acute pancreatitis.

**Addiction and Tolerance**:
Morphine is highly addictive and ranked as the most addictive substance.
– Tolerance develops through receptor phosphorylation and down-regulation.
– Former addicts prefer heroin and morphine over other opioids.
– Equipotent doses of heroin and morphine have similar effects.
– Tolerance occurs through multiple physiological processes.

**Pharmacology and Pharmacokinetics**:
Morphine primarily binds to the μ-opioid receptor in the CNS.
– Interacts with μ–δ-opioid receptor heteromer and κ-opioid receptor.
– Metabolized mainly in the liver, excreted in urine.
– Available in various formulations for different routes of administration.
– Extended-release formulations provide longer-lasting effects.

**Gene Expression and Immune System Effects**:
Morphine alters gene expression related to mitochondrial respiration and cytoskeleton proteins.
– Impacts immune system by acting on opiate receptors on immune cells.
– Chronic use can lead to alterations in cytokine production.
– Understanding gene expression changes is crucial for evaluating effects.
– Regulation of cytokines by morphine occurs through specific pathways.

Morphine (Wikipedia)

Morphine, formerly also called morphia, is a strong opiate that is found naturally in opium, a dark brown resin produced by drying the latex of opium poppies (Papaver somniferum). It is mainly used as an analgesic (pain medication). There are numerous methods used to administer morphine: oral; sublingual; via inhalation; injection into a muscle, injection under the skin, or injection into the spinal cord area; transdermal; or via rectal suppository. It acts directly on the central nervous system (CNS) to induce analgesia and alter perception and emotional response to pain. Physical and psychological dependence and tolerance may develop with repeated administration. It can be taken for both acute pain and chronic pain and is frequently used for pain from myocardial infarction, kidney stones, and during labor. Its maximum effect is reached after about 20 minutes when administered intravenously and 60 minutes when administered by mouth, while the duration of its effect is 3–7 hours. Long-acting formulations of morphine are available as MS-Contin, Kadian, and other brand names as well as generically.

Morphine
Clinical data
Pronunciation/ˈmɔːrfn/
Trade namesStatex, MS Contin, Oramorph, others
AHFS/Drugs.comMonograph
MedlinePlusa682133
License data
Pregnancy
category
  • AU: C
Dependence
liability
High
Addiction
liability
High
Routes of
administration
Inhalation (smoking), insufflation (snorting), by mouth, rectal, subcutaneous, intramuscular, intravenous, epidural, intrathecal
Drug classOpioid
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability20–40% (by mouth), 36–71% (rectally), 100% (IV/IM)
Protein binding30–40%
MetabolismLiver: UGT2B7
MetabolitesMorphine-3-glucuronide (90%)
Morphine-6-glucuronide (10%)
Onset of action5 minutes (IV), 15 minutes (IM), 20 minutes (PO)
Elimination half-life2–3 hours
Duration of action3–7 hours
ExcretionKidney 90%, bile duct 10%
Identifiers
  • (4R,4aR,7S,7aR,12bS)-3-Methyl-2,3,4,4a,7,7a-hexahydro-1H-4,12-methano[1]benzofuro[3,2-e]isoquinoline-7,9-diol
CAS Number
  • 57-27-2 checkY
    64-31-3 (neutral sulfate),
    52-26-6 (hydrochloride)
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.000.291 Edit this at Wikidata
Chemical and physical data
FormulaC17H19NO3
Molar mass285.343 g·mol−1
3D model (JSmol)
Solubility in waterHCl & sulf.: 60
  • CN1CC[C@]23C4=C5C=CC(O)=C4O[C@H]2[C@@H](O)C=C[C@H]3[C@H]1C5
  • InChI=1S/C17H19NO3/c1-18-7-6-17-10-3-5-13(20)16(17)21-15-12(19)4-2-9(14(15)17)8-11(10)18/h2-5,10-11,13,16,19-20H,6-8H2,1H3/t10-,11+,13-,16-,17-/m0/s1 checkY
  • Key:BQJCRHHNABKAKU-KBQPJGBKSA-N checkY
  (verify)

Potentially serious side effects of morphine include decreased respiratory effort, vomiting, nausea, and low blood pressure. Morphine is addictive and prone to abuse. If one's dose is reduced after long-term use, opioid withdrawal symptoms may occur. Common side effects of morphine include drowsiness, vomiting, and constipation. Caution is advised for use of morphine during pregnancy or breast feeding, as it may affect the health of the baby.

Morphine was first isolated between 1803 and 1805 by German pharmacist Friedrich Sertürner. This is believed to be the first isolation of a medicinal alkaloid from a plant. Merck began marketing it commercially in 1827. Morphine was more widely used after the invention of the hypodermic syringe in 1853–1855. Sertürner originally named the substance morphium, after the Greek god of dreams, Morpheus, as it has a tendency to cause sleep.

The primary source of morphine is isolation from poppy straw of the opium poppy. In 2013, approximately 523 tons of morphine were produced. Approximately 45 tons were used directly for pain, an increase of 400% over the last twenty years. Most use for this purpose was in the developed world. About 70 percent of morphine is used to make other opioids such as hydromorphone, oxymorphone, and heroin. It is a Schedule II drug in the United States, Class A in the United Kingdom, and Schedule I in Canada. It is on the World Health Organization's List of Essential Medicines. Morphine is sold under many brand names. In 2021, it was the 156th most commonly prescribed medication in the United States, with more than 3 million prescriptions. It is available as a generic medication.

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