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Opioids have emerged as an important therapeutic solution for severe, chronic, and resistant pain. Estimates suggest that approximately 20% of the patients presenting to doctors with pain-related diagnoses receive an opioid. Among the different types of opioids, morphine and oxycodone are widely used as strong painkillers to manage pains of extremely high intensities. However, debate exists about their relative potency, side effects, tolerability, and side effects.

Is morphine or oxycodone stronger? What are the differences between them? Is morphine an opioid drug? This article aims to shed light on morphine and oxycodone as two different types of opioids and compare them in terms of results, side effects, and abuse liability.

Opioids refer to a class of drugs derived from the opium poppy plant. These medications are widely implied in the treatment of pain secondary to various pathologies. Opioids work by attaching themselves to certain receptors in the brain in order to interrupt pain transmission. Despite sharing a herbal origin, opioids carry a serious risk of addiction, overdose, and abuse. Hence, their use is highly-regulated and limited to cases where the pain is unresponsive to other medications of lower strengths.

Both morphine and oxycodone are narcotic painkillers and belong to the opioid category. Hence, they share the same mechanism of action in order to manage pain.

The human brain comprises three different types of proteins called opioid receptors; namely μ, δ, and κ receptors.  Both morphine and oxycodone directly target these receptors (particularly μ and κ receptors) and bind to them. This interrupts the transmission of pain signals between the body and the brain, thereby reducing the pain sensation.

Common Indications

Morphine and oxycodone are commonly prescribed to relieve the pain of moderate to severe intensity. Because of their high strength, they are often prescribed when the pain fails to respond to other analgesic medication of lower potency. Common indications of use for morphine and oxycodone include:

  • Musculoskeletal pain
  • Abdominal pain
  • Cancer pain
  • Chest pain
  • Pain-related to arthritis
  • Severe forms of headache

Recent guidelines suggest oxycodone and morphine both as the first-line opioid analgesics to manage moderate to severe pain, such as cancer pain. Several trials have been conducted to compare their painkiller efficacy as well as monitor their adverse effects. Despite the limitations and differences in study designs, most of these research trials have demonstrated no significant difference, particularly as the first-line agent for cancer pain. Therefore, Oxycodone is often regarded as a “morphine equivalent” analgesic.

However, a number of studies comparing various opioid painkillers have found differences in terms of potency. While both are able to effectively alleviate muscle pain, the overall analgesic effect of oxycodone has repeatedly been found to be higher than morphine. Moreover, evidence also suggests a faster pain relief with oxycodone as compared to morphine.

The discrepancies in the potency of morphine and oxycodone can be due to the passage of these opioids through the blood-brain barrier. While both drugs are equally hydrophilic with a similar tendency to reach the brain, oxycodone particles seem to cross the blood-brain barrier more actively than morphine through a transporter that is yet to be identified. Due to this higher rate of transportation, the concentration of oxycodone is much higher in the brain as compared to plasma. The reverse is true for morphine which is more abundant in the plasma as compared to in the brain. The difference in concentration is highly appreciable as the number of unbound oxycodone levels in the brain has been revealed to be six times more than those of morphine. These significant differences could be one possible explanation for why oxycodone is more efficacious in certain groups of people than morphine even at similar plasma levels.

The mixed results warrant further research and analysis and suggest a person-tailored approach in terms of establishing efficacy for pain management.

The side effects related to morphine and oxycodone resemble closely due to their common drug class. While most of them are avoidable by closely following the recommended guidelines and avoiding an overdose, some adverse effects still affect users.

The following side effects are attributed to the use of morphine:

  • Drowsiness
  • Headache
  • Mood changes
  • Nervousness
  • Stomach cramps
  • Dry mouth
  • Difficult/painful urination
  • Pinpoint pupils/ small pupils

On the other hand, the use of oxycodone can lead to one or more of the following adverse effects:

  • Nausea
  • Vomiting
  • Lightheadedness
  • Dizziness
  • Constipation
  • Drowsiness

Most of the side effects are manageable with simple modifications. For example, exercising, increasing fiber intake in the diet, and using a laxative after consulting with a doctor can manage constipation. Similarly, lightheadedness and dizziness can be avoided by keeping it slow whenever you rise from a lying or sitting position.

Opioids such as morphine and oxycodone are widely discussed in terms of abuse and addiction liability. They essentially trigger the following two types of effects in the users:

  • Positive effects such as feeling euphoric, dreamy, carefree, high, stimulated, social, and mellow with pleasant bodily sensations.
  • Negative effects such as dysphoria, dislike, irritability, dizziness, difficulty in concentration, dry mouth, headache, sluggish feelings, and unpleasant thoughts

Oxycodone has been found to exert fewer negative effects as compared to morphine and other opioids. As a result, it has demonstrated significantly higher “take again” ratings as compared to morphine. Moreover, oxycodone has also been found to have high likability scores, making it a favorable opioid in patients with pain.

In simpler words, due to a low risk of negative symptoms, people prefer taking oxycodone to morphine. Hence, the abuse liability and addiction potential can be assumed to be much higher for the former than for the latter.

Morphine is available in multiple forms, including solution, extended-release tablet, and extended-release capsule. The oral solution is commonly prescribed every four hours or as needed whereas the tablets and capsules are given every 8 or 12 hours depending on the intensity of pain. It is recommended to follow the directions on the prescription label and ask the doctor if something is not clear as overdose can lead to potentially life-threatening side effects.

Oxycodone comes as a solution, concentrated solution, tablet, capsule, and their extended-release variants. All variants are usually prescribed every 4 to 6 hours or as needed, depending on the patient’s needs. They can be taken with or without food; however, it is suggested to follow one method of consumption for every dose. Presoaking, chewing, or crushing the tablets is not recommended.

Both morphine and oxycodone have been widely used to alleviate neuropathic pain in humans. While the latter has been described as more potent, the former is related to a lesser risk of abuse and addiction. Whether one is better than the other, in individual patients or in general, is a highly controversial topic, and warrants head-to-head comparisons in clinical settings.



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