1. How it works

• Morphine is an analgesic (pain-reliever) that may be used to treat moderate-to-severe pain that is unresponsive to other, less potent, pain-relieving medicines.
• Morphine works by binding mainly to mu-opioid (MOP) receptors in the brain and the periphery, including the stomach. Activation of MOP receptors in the midbrain is thought to be a major mechanism of opioid-induced analgesia. When morphine binds to MOP receptors it indirectly stimulates descending inhibitory pathways and 5-hydroxytryptamine and enkephalin-containing neurons that ultimately result in a reduction in nerve transmission from the periphery to the brain. Morphine has very strong pain-relieving effects.
• Morphine belongs to the group of medicines known as narcotic analgesics. It may also be called an opiate agonist, an opioid analgesic, or an opioid.

2. Upsides

• May be used to treat severe acute pain. Considered the analgesic of choice for ST-segment-elevation MI (STEMI).
• Can be given for moderate-to-severe chronic pain in certain populations, such as the terminally ill.
• May be given by injection for pain that occurs during labor.
• Consider for acute pulmonary edema (not caused by a chemical irritant) for its cardiovascular effects and to allay anxiety.
• Has been used to manage symptoms of neonatal opiate withdrawal in neonates exposed to opiates while in the uterus.
• Usually reserved for pain that is not controlled by other pain-relieving medicines.
• Can be given epidurally or intrathecally for severe pain. Using these routes provides pain relief for prolonged periods without loss of motor, sensory, or sympathetic function.
• Available as immediate-release tablets, extended-release tablets and capsules, rectal preparations, solutions, and injections.
• The oral solution is available in 3 different strengths: 10 mg/5mL, 20 mg/5mL, and 100 mg/5mL. The 100 mg/5mL preparation should only be used in opioid-tolerant people.
• Has strong pain-relieving effects.
• Generic morphine is available.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Nausea, vomiting, dizziness, blurred vision, rashes, and sweating. Constipation caused by morphine may be severe and laxatives are typically required.
• Drowsiness may affect a person's ability to drive or operate machinery.
• Avoid alcohol at all times (alcohol can increase blood levels of morphine leading to a fatal overdose).
• Rarely, serious, life-threatening, breathing problems may occur. The risk is greater with slow-release forms, in people with pre-existing respiratory disease, in seniors or the frail, or in those taking other medications that cause respiratory depression (such as benzodiazepines).
• Consider prescribing naloxone at the same time for patients who are at increased risk of opiate overdosage, or who have household members, such as children, who are at risk for accidental ingestion or overdosage.
• There is a large variability in the way different people respond to morphine.
• Extended-release preparations, such as Avinza, Kadian, MS Contin, or Oramorph SR, should only be used for moderate-to-severe pain that requires around-the-clock opiate therapy for an extended period.
• IM administration is preferable to subcutaneous injection if repeated parenteral doses are needed because repeated subcutaneous injections may cause local tissue irritation, pain, and induration. Morphine sulfate injections pose a substantial risk of overdosage if used inappropriately.
• Known to cause addiction and dependence; the risk is higher in people with disturbances in their mental health. May be misused and legitimate supplies of products containing morphine may be sought out by drug seekers. Restrict quantities and only prescribe at the lowest dose for the shortest time.
• There have been several dosing errors associated with morphine, commonly associated with confusion between different concentrations and between mg and mL. These errors may cause inadvertent overdosage and death. When morphine is prescribed ensure the dosage is clear and not easily confused.
• Abrupt discontinuation of any morphine-containing medication in a person who has become physically dependent on it may lead to a withdrawal syndrome and symptoms such as restlessness, pupil dilation, watery eyes and a runny nose, sweating, muscle aches, insomnia, irritability, and gastrointestinal complaints. Babies born to mothers who are physically dependent on morphine will also be physically dependent.
• Interaction or overdosage may also cause serotonin syndrome. Symptoms include mental status changes such as agitation, hallucinations, coma, or delirium; a fast heart rate; dizziness; flushing; muscle tremor or rigidity; and stomach symptoms (including nausea, vomiting, and diarrhea).
• May not be suitable for people with pre-existing respiratory depression or respiratory disease, thyroid problems, seizure disorders, or a head injury, people with gastrointestinal obstruction, or who have recently taken monoamine oxidase inhibitors.
• Morphine is a Schedule II controlled substance which means it has a high potential for abuse which may lead to severe psychological or physical dependence.
• There is a Risk Evaluation Mitigation Strategy (REMS) medication guide associated with one or more preparations of morphine to ensure the benefits outweigh the risks.
• Should not be used during pregnancy or breastfeeding unless specifically recommended and monitored by a doctor. Can cause life-threatening withdrawal symptoms in a newborn.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

Morphine is a very effective pain reliever but commonly causes constipation and carries a high risk of addiction and dependence. It interacts with several other medications, which can increase the risk of severe side effects, and alcohol should be avoided.

5. Tips

• Take morphine exactly as directed by your doctor. Never increase or decrease the dosage without talking to your doctor first.
• Check your morphine prescription is what you were expecting. There have been several dosing errors associated with morphine and if something looks different on your prescription, talk to your doctor or pharmacist about it.
• Report any breathing difficulties to your doctor immediately.
• Do not drive or operate machinery or perform hazardous tasks if morphine makes you drowsy.
• Do not drink alcohol (may contribute to sedative and other adverse effects).
• Laxatives may be needed to treat constipation and antiemetics may be used to relieve nausea.
• Swallow slow-release or extended-release forms whole; do not crush, chew, or attempt to dissolve. Slow-release forms should only be given to people requiring round-the-clock pain relief who have been trialed previously on immediate-release morphine. The capsules of some preparations may be opened, such as Avinza or Kadian, and the contents sprinkled on applesauce. Do not use extended-release preparations, such as Kadian on an as-needed (PRN) basis.
• Keep well out of reach of children; even one accidental dose can be fatal.
• Be careful when measuring morphine solution to ensure the correct dosage is given.
• Taper off dosage under medical supervision after extended administration as withdrawal symptoms may result.
• Withdrawal symptoms (symptoms may include muscle and bone pain, diarrhea, insomnia, or vomiting) may occur if long-term morphine is stopped abruptly; discontinue slowly on a doctor's advice.
• Avoid alcohol while taking this medicine.
• May lower blood pressure on standing; take your time when going from a lying down to a standing up position.
• Some morphine preparations have a REMS medication guide to inform you of the benefits and risks of morphine.
• The need for continued treatment with morphine should be assessed at regular intervals.
• Do not take other medications with your morphine without asking your doctor or pharmacist if they are suitable. Morphine interacts with several other medications and it may be dangerous for you to take them together.

6. Response and effectiveness

• The pain-relieving effects of morphine are usually seen within 60 minutes and may last up to 15 hours. The onset of effect and the duration of action depend on the formulation of morphine used.

7. Interactions

Medicines that interact with morphine may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with morphine. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with morphine include:

• 5-HT₁ receptor agonists, such as almotriptan, rizatriptan, or sumatriptan
• anesthetics (epidural)
• anticoagulants, such as warfarin (may enhance the effect)
• antidepressants, such as tricyclic antidepressants (eg, amitriptyline), monoamine oxidase inhibitors (eg, isocarboxazid, phenelzine, and tranylcypromine), or SSRIs (eg, fluoxetine, sertraline)
• anticonvulsants, such as carbamazepine, phenytoin, phenobarbital, or primidone
• amphetamines, such as dextroamphetamine
• antipsychotics (such as butyrophenones, phenothiazines, or thioxanthenes) and atypical antipsychotics (eg, olanzapine, quetiapine, ziprasidone)
• antiemetics, such as ondansetron
• any medication that may cause drowsiness, such as amphetamines, benzodiazepines (eg, diazepam, lorazepam), first-generation antihistamines (such as doxylamine or promethazine), metoclopramide, or opioids (such as codeine or oxycodone)
• buprenorphine
• buspirone
• cimetidine
• dextromethorphan
• diuretics, such as furosemide
• ipratropium or other anticholinergics
• isocarboxazid
• lithium
• muscle relaxants, such as baclofen, carisoprodol, or cyclobenzaprine
• neuromuscular blocking agents, such as rocuronium or vecuronium
• opiate partial agonists, such as butorphanol, nalbuphine, or pentazocine
• pentazocine
• sedative/hypnotics, such as butabarbital, eszopiclone, or zolpidem
• St. John's wort
• Tryptophan.

Avoid drinking alcohol or taking illegal or recreational drugs while taking morphine.

Benzodiazepines and other CNS depressants may cause profound sedation, respiratory depression, coma, and death when taken with morphine.

Note that this list is not all-inclusive and includes only common medications that may interact with morphine. You should refer to the prescribing information for morphine for a complete list of interactions.