1. Opioids and the gut Job bag number: NP-EU-NAL-0059
Date of preparation: September 2017
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2. Opioids are an essential treatment for the management of chronic pain, as recognised by global guidelines1–5
“Opioids are highly effective and safe analgesics and their appropriate use by competent clinicians is a crucial element
in modern pain management.”
“If pain occurs, there should be prompt oral administration of drugs in the following order: nonopioids; then, as necessary, mild opioids; then strong opioids, until the patient is free of pain.”
“Analgesic treatment should start with drugs indicated by
the WHO analgesic ladder. Strong opioids are the mainstay of analgesic therapy in treating moderate–severe cancer-related pain.”
“Chronic opioid therapy can be an effective
therapy for carefully selected and monitored patients with chronic non-cancer pain.”
EFIC, European pain federation; ESMO, European Society for Medical Oncology; WHO, World Health Organization.
1. O'Brien T, et al. Eur J Pain 2017;21:3–19; 2. World Health Organization. WHO's cancer pain ladder for adults. Available at: Accessed: June 2017
3. Ripamonti CI, et al. Ann Oncol 2012;23 Suppl 7:vii139–54
4. Paice JA, et al. J Clin Oncol 2016;34:3325–45
5. Chou R, et al. J Pain 2009;10:113–30;
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3. Opioids bind to opioid receptors causing a reduction in neuronal excitability and inhibition of neurotransmitter release1–3
Opioid receptors are present on the cell surface of neurons involved in pain transmission/control3
Opioids exert their analgesic effect through binding and activating opioid receptors in the central and peripheral nervous system3
Once bound to the opioid receptors, opioids block the release of pain neurotransmitters resulting in the desired analgesic effect3
AC, adenylyl cyclase; ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate; Ca, calcium; G, g-protein coupled receptor; K, potassium.
1. Chahl LA. Aust Prescr 1996;19:63–5
2. Bell TJ, et al. Pain Med 2009;10:35–42
3. Trescot AM, et al. Pain Phys 2008;11:S133–53
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4. Opioid receptors are predominantly located in the central nervous system but are also present in peripheral tissues1
Opioids exert their effect via three main types of opioid receptors which are found throughout the body:1
mu (µ), kappa (κ) and delta (δ)
The most commonly used opioids for pain management act on the μ opioid receptor1
There is a high density of µ-receptors within the central nervous system responsible for analgesia1,2
µ-receptors are also widely distributed throughout the peripheral nervous system, including the gastrointestinal system3,4
1. Trescot AM, et al. Pain Phys 2008;11:S133–53
2. Chahl LA. Aust Prescr 1996;19:63–5
3. Bell TJ, et al. Pain Med 2009;10:35–42
4. Benyamin R, et al. Pain Physician 2008;11:S105–20.
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5. Opioid receptors are predominantly located in the central nervous system but are also present in peripheral tissues1
Decreased intestinal mucosal secretion
Increased fluid reabsorption, resulting in dry, hard, difficult-to- pass stools
Disordered ileocecal and anal sphincter function
Activation of the µ-receptors enteric system leads to a changes in the gastrointestinal tract:1,2
A reduction in longitudinal gut muscle contractions and stronger contractions of the circular muscle
The suppression of generating a peristaltic wave to propel digested food through the gut
Reduced bowel tone and contractility
1. Panchal SJ, et al. Int J Clin Pract 2007;61:1181–7
2. Holzer P. Neurosci Lett 2004;361:192–5.
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6. Opioid receptors are predominantly located in the central nervous system but are also present in peripheral tissues1
Flatulence
Hard, lumpy and dry stools
Straining
Bloating
Abdominal cramping/spasms
Sensation of incomplete evacuation or anorectal blockage
In the latest Rome IV criteria, OIC is defined as: “New or worsening symptoms of constipation when initiating, changing or increasing opioid therapy, that must include two or more of the symptoms defining functional constipation”1
Reflux/heartburn
Nausea/vomiting
Infrequent bowel movements
Pain when going to the toilet
Feeling full or heavy
Constipation
OIC, opioid-induced constipation.
1. Simren M, et al. Curr Gastroenterol Rep 2017;19:15
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7. Laxatives provide no or partial relief for patients with chronic OIC, as they don’t target the underlying pathophysiology1–3
The ultimate goal of OIC treatment is to alleviate constipation while maintaining analgesia1
Targeted therapies which specifically act on the pathophysiology, rather than the symptoms, may help offer patients greater relief from OIC2,4
Treatment pathway for OIC5
OIC, opioid-induced constipation; PAMORAs, peripherally acting μ- opioid receptor antagonists.
1. Bell TJ, et al. Pain Med 2009;10:35–42
2. Rumman A, et al. Exp Rev Quality Life Cancer Care 2016;1:25–35
3. Coyne KS, et al. Clinicoecon Outcomes Res 2014;6:269–81
4. Simren M, et al. Curr Gastroenterol Rep 2017;19:15
5. Kumar L, et al. Gastroenterol Res Pract 2014; doi: /2014/
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