Morphine
Morphine, formerly known as morphium, is an opiate found naturally in opium, a dark brown resin produced by drying the latex of opium poppies. It is mainly used as an analgesic. There are multiple 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; intravenously; or via rectal suppository. It acts directly on the central nervous system 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 sold under the brand names MS Contin and Kadian, among others. Generic long-acting formulations are also available.
Common side effects of morphine include drowsiness, euphoria, nausea, dizziness, sweating, and constipation. Potentially serious side effects of morphine include decreased respiratory effort, vomiting, and low blood pressure. Morphine is highly addictive and prone to abuse. If one's dose is reduced after long-term use, opioid withdrawal symptoms may occur. Caution is advised for the use of morphine during pregnancy or breastfeeding, as it may affect the health of the baby.
Morphine was first isolated in 1804 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 18531855. 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% 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. In 2023, it was the 156th most commonly prescribed medication in the United States, with more than 3million prescriptions. It is available as a generic medication.
Medical uses
Pain
Morphine is used primarily to treat both acute and chronic severe pain. Its duration of analgesia is about three to seven hours. Side effects of nausea and constipation are rarely severe enough to warrant stopping treatment.It is used for pain due to myocardial infarction and for labor pains. However, concerns exist that morphine may increase mortality in the event of non ST elevation myocardial infarction.
Morphine has also traditionally been used in the treatment of acute pulmonary edema. However, a 2006 review found little evidence to support this practice.
A 2016 Cochrane review concluded that morphine is effective in relieving cancer pain.
Shortness of breath
Morphine is beneficial in reducing the symptom of shortness of breath due to both cancer and non-cancer causes. In the setting of breathlessness at rest or on minimal exertion from conditions such as advanced cancer or end-stage cardiorespiratory diseases, regular, low-dose sustained-release morphine significantly reduces breathlessness safely, with its benefits maintained over time.Opioid use disorder
Morphine is used in a slow-release formulation for opiate substitution therapy in Austria, Germany, Bulgaria, Slovenia, and Canada for persons with opioid addiction who cannot tolerate either methadone or buprenorphine.Contraindications
Relative contraindications to morphine include:- respiratory depression when appropriate equipment is not available.
- Although it has previously been thought that morphine was contraindicated in acute pancreatitis, a review of the literature shows no evidence for this.
Adverse effects
Constipation
Like loperamide and other opioids, morphine acts on the myenteric plexus in the intestinal tract, reducing gut motility, and 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 increased 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, L-arginine, reversed morphine-induced changes in gut motility.Hormone imbalance
Clinical studies consistently conclude that morphine, like other opioids, often causes hypogonadism and hormone imbalances in chronic users of both sexes. This side effect is dose-dependent and occurs in both therapeutic and recreational users. Morphine can interfere with menstruation by suppressing levels of luteinizing hormone. Multiple studies suggest the majority of chronic opioid users have opioid-induced hypogonadism. This effect may cause the increased likelihood of osteoporosis and bone fracture observed in chronic morphine users. Studies suggest the effect is temporary., the effect of low-dose or acute use of morphine on the endocrine system is unclear.Effects on human performance
Most reviews conclude that opioids produce minimal impairment of human performance on tests of sensory, motor, or attentional abilities. However, recent studies have been able to show some impairments caused by morphine, which is not surprising, given that morphine is a central nervous system depressant. Morphine has resulted in impaired functioning on critical flicker frequency and impaired performance on the Maddox wing test. Few studies have investigated the effects of morphine on motor abilities; a high dose of morphine can impair finger tapping and the ability to maintain a low constant level of isometric force, though no studies have shown a correlation between morphine and gross motor abilities.In terms of cognitive abilities, one study has shown that morphine may negatively impact anterograde and retrograde memory, but these effects are minimal and transient. Overall, it seems that acute doses of opioids in non-tolerant subjects produce minor effects in some sensory and motor abilities, and perhaps also in attention and cognition. The effects of morphine will likely be more pronounced in opioid-naive subjects than in chronic opioid users.
In chronic opioid users, such as those on Chronic Opioid Analgesic Therapy for managing severe, chronic pain, behavioural testing has shown normal functioning on perception, cognition, coordination, and behaviour in most cases. One 2000 study analysed COAT patients to determine whether they were able to safely operate a motor vehicle. The findings from this study suggest that stable opioid use does not significantly impair abilities inherent in driving. COAT patients showed rapid completion of tasks that require the speed of responding for successful performance but made more errors than controls. COAT patients showed no deficits in visual-spatial perception and organization but did show impaired immediate and short-term visual memory. These patients showed no impairments in higher-order cognitive abilities. COAT patients appeared to have difficulty following instructions and showed a propensity toward impulsive behaviour, yet this did not reach statistical significance. It is important to note that this study reveals that COAT patients have no domain-specific deficits, which supports the notion that chronic opioid use has minor effects on psychomotor, cognitive, or neuropsychological functioning.