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 the 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.

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 the majority 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.

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.

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.

Morphine is an incredibly useful medication when used appropriately. However, in certain situations, this medication may be strongly contraindicated. Extreme caution must be used with severe cases of respiratory depression and asthma exacerbation 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.