- Opioid therapy is essential for the proper management of patients with moderate to severe pain.
- Opioid-induced constipation (OIC) is a predictable event, affecting most patients on opioid therapy and related to the physiological presence of MOR receptors in the enteric nervous system.
- The severity of OIC and its impact on quality of life and adherence to treatment are high and well known in the literature.
- Prophylactic use of laxatives in patients on chronic opioid therapy should be the standard of care to reduce the intensity of this side effect.
- PAMORA are the rational choice in this condition when conventional laxative treatment does not improve patients’ symptoms.
- PAMORA is the only specific therapy based on the mechanism of action that causes OIC.
What we’re talking about
Patients requiring opioid therapy to control moderate-to-severe pain often also face opioid-induced constipation (OIC), a side effect that is likely to worsen quality of life as well as reduce efficacy and adherence to analgesic treatment.The prevalence of OIC ranges from 51% to 87% of cancer patients and from 41% to 57% of non-cancer patients and affects both strong and weak opioids.
In 30% of cases, the onset or worsening of constipation following the intake of an opioid leads the patient to reduce or independently interrupt the analgesic therapy in progress, with the risk of complications and recrudescence of pain. Unfortunately, in about 80% of cases the OIC does not improve with the intake of common laxatives and, due to this side effect, the phenomenon of tolerance does not arise.
Causes of opioid-induced constipation
OIC fits into a more complex picture defined as Opioid-Induced Bowel Dysfunction (OIBD) and is caused by the physiological activity of opioids on mu opioid receptors (MORs) constitutively present at the level of the myoenteric and submucosal nerve plexus of the gastrointestinal tract.
The binding of opioids with the receptors of the myoenteric plexus causes a reduction in intestinal propulsive activity and a basal increase in muscle tone, while at the level of the submucosal plexus there is a reduction in the secretion of chlorine-dependent water within the intestinal lumen with consequent dehydration of the contents and production of drier and harder stools.In most patients the result of these effects is the appearance or worsening of constipation that, if left untreated, is unlikely to improve with continued opioid intake.
Diagnosis
The ROMA-IV criteria define OIC as “worse or new constipation symptoms when initiating, modifying, or increasing opioid analgesic therapy.” Patients with OIC should have at least 2 of the following symptoms:
- less than 3 spontaneous evacuations per week;
- effort in at least a quarter of evacuations;
- loose or hard stools in at least a quarter of evacuations;
- feeling of incomplete evacuation and/or anorectal blockage in at least a quarter of evacuations;
- need for manual defecation in at least a quarter of evacuations.
Diagnosing OIC is particularly important because it is the only side effect of opioids that can be addressed with specific therapy based on the mechanism of action.
General considerations for the management of the OIC
It is important to warn all patients starting opioid therapy of the possibility of constipation and recommend some small attentions including the increase of dietary fiber, adequate hydration and physical activity within the limits imposed by the underlying pathology and analgesic control.It is also important to recommend continuous therapy with common laxatives for prophylaxis and treatment of OIC.
Specific treatment of OIC
A failure of laxative therapy a more targeted approach to the treatment of OIC involves the use of PAMORA, an acronym that stands for “Peripherally Acting MOR-Opioid Receptor Antagonists”.
PAMORA displaces the opioid from MOR receptors present in the gastrointestinal tract thereby helping to restore the physiological functioning of the enteric nervous system and intestinal transit. The molecules of this class of drugs contain voluminous lateral groups that hinder the passage of the blood-brain barrier and penetration into the central nervous system, thus not compromising the analgesic effects of opioids themselves. The PAMORA currently on the market in Italy are:
- methylnaltrexone, to be taken subcutaneously and administered at least 4 weekly doses, up to once a day;
- naloxegol, taken orally once daily on an empty stomach at least 30 minutes before or 2 hours after the first meal of the day;
- naldemedina, taken orally once a day with or without food, always at the same time.
Prescription of PAMORA
The prescription of PAMORA paid by the NHS, with note 90, is limited to subjects in chronic opioid therapy and diagnosis of opiate-induced constipation according to the criteria of ROMA-IV who simultaneously meet the following characteristics:
- chronic and continuous opioid therapy;
- resistance to treatment with at least two laxatives, one of which has an osmotic action (resistance is defined as non-response after 3 days).
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Source – https://www.univadis.it/viewarticle/sicp-stipsi-indotta-da-oppioidi-verso-una-terapia-mirata-2022a100296u