Continuing Education Activity

FDA-approved usage of morphine sulfate includes moderate to severe pain that may be acute or chronic. Most commonly used in pain management, morphine provides major relief to patients afflicted with pain. Clinical situations that benefit greatly by medicating with morphine include management of palliative/end-of-life care, active cancer treatment, and vaso-occlusive pain during sickle cell crisis. Morphine also has off-label uses for painful conditions. This activity outlines the indications, mechanism of action, methods of administration, important adverse effects, contraindications, monitoring, and toxicity of morphine, so providers can direct patient therapy to optimal outcomes when pain relief is needed.

Objectives:

• Review the mechanism of action of morphine.
• Identify the approved and off-label indications for using morphine.
• Explain the contraindications and adverse events associated with morphine.
• Describe interprofessional team strategies for improving care coordination and communication to properly use morphine to improve patient outcomes in the varied scenarios where it can be effective.

Indications

FDA-approved usage of morphine sulfate includes moderate to severe pain that may be acute or chronic. Most commonly used in pain management, morphine provides significant relief to patients afflicted with pain.[1] Clinical situations that benefit significantly by medicating with morphine include management of palliative/end-of-life care, active cancer treatment, and vaso-occlusive pain during sickle cell crisis. Morphine is widely used off-label for almost any condition that causes pain. In the emergency department, morphine is given for musculoskeletal pain, abdominal pain, chest pain, arthritis, and even headaches when patients fail to respond to first and second-line agents.[2] Morphine is rarely used for procedural sedation. However, for small procedures, physicians will sometimes combine a low dose of morphine with a low dose of benzodiazepine-like lorazepam.

Patients that are actively having acute coronary syndrome are often given morphine in the emergency setting before going to the cath lab. Morphine to relieve pain during a myocardial infarction (MI) has been in use since the early 1900s. In 2005, an observational study raised some concerns, but there are very few effective alternatives. Morphine is a potent opioid; it decreases pain, which in turn leads to a decrease in the activation of the autonomic nervous system. These are desirable effects when a patient is having an MI. Additionally, morphine has hemodynamic side effects that can be beneficial during an MI.[3] 

Morphine can decrease heart rate, blood pressure, and venous return. Morphine can also stimulate local histamine-mediated processes.[4] In theory, the combination of these can reduce myocardial oxygen demand.

Mechanism of Action

Morphine is considered the classic opioid analgesic with which other painkillers are compared. Like other medications in this class, morphine has an affinity for delta, kappa, and mu-opioid receptors.[5] This drug produces most of its analgesic effects by binding to the mu-opioid receptor within the central nervous system (CNS) and the peripheral nervous system (PNS).[6] The net effect of morphine is the activation of descending inhibitory pathways of the CNS as well as inhibition of the nociceptive afferent neurons of the PNS, which leads to an overall reduction of the nociceptive transmission.

Administration

Morphine administration can occur through various vehicles. Its administration is most often via the following routes: orally (PO), intravenously (IV), epidural, and intrathecal. Oral formulations are available in both immediate and extended-release for the treatment of acute and chronic pain. Pain that is more severe and not well controlled may be manageable with single or continuous doses of IV, epidural, and intrathecal formulations.[2] Infusion dosing can vary significantly between patients and largely depends on how naive or tolerant they are to opiates. It is interesting to point out that IV morphine formulation is also commonly given intramuscularly (IM). Morphine is also available as a suppository.[7] Morphine is widely used and abused. As a result of this, people have found ways to insufflate (snort) the medication.[8] Morphine is also available as an oral solution and can be administered sublingually. Sublingual morphine is very popular in palliative care.

Adverse Effects

Among the more common unwanted effects of morphine use is constipation. This effect occurs via stimulation of mu-opioid receptors on the myenteric plexus, which in turn inhibits gastric emptying and reduces peristalsis. Other common side effects include central nervous system depression, nausea, vomiting, and urinary retention. Respiratory depression is among the more serious adverse reactions with opiate use that is especially important to monitor in the postoperative patient population.[9] Other reported side effects include lightheadedness, sedation, and dizziness. Patients often report nausea and vomiting, which is why in many emergency departments, morphine administration is with an antiemetic such as ondansetron.[10] Other effects include euphoria, dysphoria, agitation, dry mouth, anorexia, and biliary tract spasm, which is why some physicians will avoid morphine when patients present with right upper quadrant pain and they suspect possible biliary tract pathology. Morphine can also affect the cardiovascular system and reportedly can cause flushing, bradycardia, hypotension, and syncope. It is also important to note that patients can experience pruritis, urticaria, edema, and other skin rashes.

Contraindications

Morphine is an extremely beneficial medication when used appropriately. However, in certain situations, this medication may be strongly contraindicated. Extreme caution is necessary with severe respiratory depression and asthma exacerbation cases since morphine can further decrease the respiratory drive. Additionally, morphine should be avoided in cases of previous hypersensitivity reaction and immediately discontinued in the presence of an active reaction.[11] Caution is also necessary with the concurrent use of monoamine oxidase inhibitors (MAOIs) as these medications have an additive effect with morphine. This combination can then trigger severe hypotension, serotonin syndrome, or increase respiratory depression in patients. GI obstruction is another important contraindication.[1] It is also considered by many as a contraindication to provide opioids to individuals that have a history of substance misuse, especially if a patient has had a history of abusing opioids. Although this is a very controversial topic, most clinicians would agree that pain requires management.[12] However, most will agree and acknowledge that there are alternatives to opioid analgesics.

Monitoring

The efficacy and therapeutic index of morphine are assessable with a combination of subjective and objective findings. Controlling pain, which is usually the first symptom evaluated in patients, is the ultimate goal of morphine use. Other essential parameters requiring monitoring include mental status, blood pressure, respiratory drive, and misuse/overuse.[2] Although it may seem intuitive, it is also important to monitor what other medications a patient is taking. This list includes but is not limited to prescription medications. All patients taking morphine should understand the need to avoid any other substances that could lead to respiratory depression.[13] These medications include but are not limited to alcohol, additional opioids, benzodiazepines, and barbiturates. Patients can become apneic at lower doses if combining morphine with any of these substances.

Toxicity

Morphine can potentially be a lethal medication when not used properly.[14] It causes a host of symptoms related to depression of the CNS. Severe respiratory depression is the most feared complication of morphine in cases of overdose. Immediate injection of naloxone is required to reverse the effects of morphine.

Enhancing Healthcare Team Outcomes

Ordering and administering morphine requires an interprofessional team of healthcare professionals, including clinicians, mid-level practitioners, nurses, and pharmacists.[15] However, patients may be transferred throughout the hospital while under the effects of these medications. Morphine use, monitoring, and administration can utilize many resources, including laboratory technologists, pharmacists, and nurses/nursing assistants. Without proper training and careful monitoring, often starting in the emergency department, patients can develop serious side effects and have adverse reactions to morphine. The clinician is responsible for coordinating the care, which includes the following:

• Ordering the drug
• Monitoring the patient for signs and symptoms of respiratory depression[16]
• Administering the drug
• Consulting with the pharmacist about the use of morphine with other medications that can cause respiratory depression.
• Consulting with a specialist if an overdose or allergic reaction occurs.
• Consulting with the radiology if a patient has received morphine prior to imaging
• Consulting with the cardiologist if using morphine in a STEMI[17]

Review Questions

• Access free multiple choice questions on this topic.
• Comment on this article.

References

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11.

Kim M, Custodio RJ, Botanas CJ, de la Peña JB, Sayson LV, Abiero A, Ryoo ZY, Cheong JH, Kim HJ. The circadian gene, Per2, influences methamphetamine sensitization and reward through the dopaminergic system in the striatum of mice. Addict Biol. 2019 Sep;24(5):946-957. [PubMed: 30091820]

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13.

Briggs SB, Hafenbreidel M, Young EJ, Rumbaugh G, Miller CA. The role of nonmuscle myosin II in polydrug memories and memory reconsolidation. Learn Mem. 2018 Sep;25(9):391-398. [PMC free article: PMC6097765] [PubMed: 30115760]

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Kim K, Zheng F, Zhan CG. Oligomerization and Catalytic Parameters of Human UDP-Glucuronosyltransferase 1A10: Expression and Characterization of the Recombinant Protein. Drug Metab Dispos. 2018 Oct;46(10):1446-1452. [PMC free article: PMC6130470] [PubMed: 30111624]

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Disclosure: Patrick Murphy declares no relevant financial relationships with ineligible companies.

Disclosure: Samuel Bechmann declares no relevant financial relationships with ineligible companies.

Disclosure: Michael Barrett declares no relevant financial relationships with ineligible companies.