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The UK remains addicted to opioid painkillers, despite the well-publicised US opioid crisis, public and professional education, and recent declines in prescriptions. Indeed, in 2019 the UK had the highest per capita consumption of prescription opioid analgesics out of 76 countries, including the USA, according to a study in eClinicalMedicine.
Opioids such as morphine, codeine and tramadol are invaluable for severe acute and cancer-related pain, including during palliative care. Opioids are also, however, the archetypal drug of addiction. According to Government statistics, half (48 per cent) of the 290,635 adults treated by drug and alcohol services in England between April 2022 and March 2023 abused opioids.
However, the focus on misuse and addiction overshadows opioid’s other serious risks, including constipation that can require surgery, reduced libido and sexual function, and impaired cognition, e.g. memory re-call, reasoning and solving problems. We asked leading expert Emma Davies, PhD, principal pharmacist: pain, analgesic stewardship and harm reduction, Cwm Taf Local Health Board, Wales, what pharmacy teams should look for and how they can help. “As opioids are so commonly prescribed, pharmacy teams should be familiar with their many potential adverse effects,” she says.
Gastrointestinal side effects
In the 19th century, some doctors treated cholera with opium, which counters diarrhoea by causing constipation. You can still buy over-the-counter (OTC) kaolin and morphine for diarrhoea. So, perhaps not surprisingly, up to 80 per cent of users experience opioid-induced constipation (OIC), according to the 2024 ‘Safe Management of Adverse Effects Associated with Prescription Opioids in the Palliative Care Population: A Narrative Review’ published in the Journal of Clinical Medicine. “It’s likely that many people don’t report gastrointestinal changes – possibly due to embarrassment. No one loves talking about their bowel habits,” Emma says.
Pharmacy teams should ask opioid users whether their bowel habits have changed, as OIC can end in a hospital admission. “A lived-experience trainer that I work with had regular admissions for opioid-induced faecal compaction, which eventually led to surgery. It was a turning point and led them to reducing and stopping their opioids after many years of use,” Emma recounts.
In some cases, increasing fluid intake and a healthy diet may alleviate OIC. “It is important to understand the person’s experience. A change in bowel habit may not be a problem if the person does not feel constipated or they are opening their bowels less often than usual,” Emma adds. “However, for other people, OIC can be really unpleasant, especially if they have an increase in pain because of constipation and cannot clear their bowels.”
Opioid users with OIC may need a combination of laxatives. Emma explains that opioids slow peristalsis: the wave-like movement of gastrointestinal muscles that propel the contents along the gut. Opioids also lead to water moving out of the bowel. So, faeces are ‘drier’ and harder to move. “An osmotic laxative, like lactulose, draws water back into the bowel and softens stools. Stimulant laxatives, such as senna and bisacodyl, promote peristalsis,” she says.
Opioid users who drink plenty of fluids (the NHS recommends six to eight cups or glasses of water, lower-fat milk and sugar-free drinks, including tea and coffee, a day) may be able to start with a stimulant laxative, which can take several hours to work, so Emma suggests patients take these before bed. “Adding an osmotic laxative is sensible if someone is struggling to pass a motion or the faeces are hard or dry,” she says. “It is really important to remind people taking osmotic laxatives to maintain a good fluid intake. Most of us do not drink sufficient fluids.”
“Fewer than one in 10 people with chronic pain benefit from opioids”
Bulk-forming laxatives may, however, exacerbate OIC. “If someone is constipated or is prone to constipation, then increasing fibre, such as Fybogel [ispaghula husk] alone, may make matters worse. People should see their GP if they continue to have difficulty opening their bowels after regular laxatives,” Emma says. “People are not always keen to take laxatives. But pharmacy teams should explain that they need daily laxatives to prevent OIC. Nevertheless, the best way to reduce OIC is to gradually stop opioids.”
OIC isn’t opioids’ only gastrointestinal adverse effect. For instance, between 25-30 per cent of opioid users experience nausea and vomiting, according to the ‘Safe Management of Adverse Effects Associated with Prescription Opioids in the Palliative Care Population’ review. Emma suggests advising patients that nausea is common after starting or increasing the dose of opioids. “Usually, nausea settles after a few days to a couple of weeks. Patients should see their GP if opioids cause vomiting or nausea that doesn’t settle with anti-emetics,” she adds. “Buccastem M [prochlorperazine] is a good OTC anti-emetic for a patient who feels really sick or has vomited. Buccastem M is placed under the tongue and does not need to be swallowed. As long as their mouth is moist, patients will be able to use Buccastem M to settle symptoms.”
Scratching an itch
The German Nobel Prize winner Paul Ehrlich discovered mast cells in 1879. Ehrlich noted that mast cells are full of granules, which we now know contain a cocktail of chemicals, including histamine. So, he called them mastzellen: well-fed cells. Up to one in 10 opioid users experience pruritus, partly because opioids seem to trigger histamine release from mast cells.
Pollen and other immune triggers can, however, cause mast cells to release histamine, which is why itch is a core symptom of rhinitis and eczema. “The timing of the onset of pruritus relative to starting or increasing the dose of the opioid is probably the biggest clue as to whether the itch is opioid-related or arises from other causes,” Emma says. “It’s worth asking if the person experienced itch with other opioids. However, opioids differ in their propensity to cause pruritus. Morphine and codeine seem to have higher rates of pruritus, probably because they cause more histamine release, than oxycodone and fentanyl. So, people who did not itch with one opioid may experience pruritus with a different drug.”
Emma suggests speaking to the pharmacist or referring to the GP if an opioid user develops pruritus. “A sedating anti-histamine like chlorphenamine is commonly suggested for opioid-induced pruritus, although non-sedating anti-histamines [e.g. cetirizine, loratadine and fexofenadine] are often preferable unless sleep is proving elusive,” she says.
Opioids, kidney function and age
“Nearly all opioids are excreted by the kidneys. So, when the kidneys don’t work efficiently, the opioid could accumulate. This makes the person more susceptible to overdose, toxicity and even death, especially if combined with other medicines like gabapentinoids and benzodiazepines. Remember that if someone is unwell, they might develop acute kidney impairment, which can rapidly increase the risk of opioid overdose and toxicity,” says principal pharmacist Emma Davies.
“As people age, the blood brain barrier becomes more permeable, increasing opioids’ effects on the brain, and it is reasonable to assume renal [kidney] and hepatic [liver] function will decline, even if patients don’t have ‘failure’ per se,” Emma adds. “Consequently, doses of opioids should reduce with ageing. The starting dose of opioids should also be lower in older people. For example, in chronic non-cancer pain in a 40-year-old, a reasonable starting dose of immediate release morphine would be 10mg but in someone age over 80 years, it would be 1mg.”
Cognitive effects
Opioid’s cognitive effects include difficulties with memory, thinking clearly and making decisions. Sedation and somnolence (drowsiness) can affect driving and a person’s ability to safely operate heavy machinery. “People may experience sedation and somnolence when they start taking opioids. Opioids can also worsen symptoms in people with other reasons for cognitive impairment, such as dementia, and can cause what appears to be progression of the underlying condition,” Emma says.
Several other drugs can impair cognition, including gabapentinoid analgesics (gabapentin and pregabalin), which are often combined with opioids. “Asking about symptom onset relative to starting either medicine may help work out which one is most responsible. Reducing one or other may noticeably improve cognitive symptoms. But if one or both medicines are causing more problems than benefits, the best longer-term option is to refer the patient to the GP to carefully reduce and stop one at a time,” Emma comments.
Hormonal effects
According to the 2024 statement from the Endocrine Society published in Endocrine Reviews, interest in the clinical changes caused by opioids’ hormonal effects “has intensified over recent years”. For example, opioid-induced deficiencies in gonadal (sex) hormones can cause erectile dysfunction, reduced muscle mass in men, menstrual changes, decreased libido, bone loss, depression and infertility, including possibly poor-quality semen.
Emma notes, however, that people with chronic pain may develop similar symptoms from different causes, including spinal injury and the menopause. “If someone reports or expresses concern about these sorts of symptoms, check how long they’ve been taking opioids. If it is more than a couple of months, the patient should be assessed by a GP who can discuss their options,” she suggests.
Opioid-related hormonal adverse events are probably underdiagnosed, particularly in men, because patients do not report the symptoms and, the Endocrine Society says, because healthcare professionals underappreciate these side-effects. “Too often, however, we assume that if adverse effects are going to occur, they will happen early in treatment. But opioids’ endocrine effects can ‘creep’ on over time rather than starting overnight. This means they may be missed or the association with the opioid is not picked up,” Emma adds.
Itch is a common side effect of opioid use, as opioids activate mast cells in the skin and release histamine.
Watch for chronic use
Fewer than one in 10 people with chronic pain are estimated to benefit from opioids – and our ailments, bodily functions (see boxout) and treatments change. So, pharmacy teams should watch for people who have been on opioids for several months or years.
“While opioids may have been a reasonable drug at a reasonable dose when first prescribed, the person may change. So, be aware of new conditions, new medicines that may alter how well someone can handle opioids or which may have similar adverse effects,” Emma suggests. “Regularly check in with people who use opioids or ask to purchase them OTC. If you notice that prescribed doses or purchases are increasing, find out why. If opioids or other analgesics are not reducing pain adequately and allowing the person to function normally, then they should seek advice on other ways of managing the pain.” Pharmacy teams can signpost people to the organisations in resources below.
Despite all the publicity, patients and professionals often underappreciate the range and severity of opioids’ side-effects. “People too often assume that analgesics, opioids especially, will work for everyone and if they still have pain after taking them, they just need more. In fact, if someone does not think opioids work for them, then they probably do not,” says Emma. “The best evidence for long-term pain management is often non-pharmacological, non-healthcare led, focussing and supporting individuals to regain confidence and function.”
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