by increasing the amount of water retained in the lumen of the gut. Polyethylene glycol (PEG) (e.g. macrogol) and lactulose have therapeutic value in the treatment of constipation.47 Other osmotic laxatives include sorbitol, magnesium salts, and saline salts. PEG, lactulose, and sorbitol have the greatest safety margins. Use of saline or magnesium salts comes with a risk for significant electrolyte disturbance, especially in older people. Elders with normal renal function may become hypermagnesemic with chronic use, especially at higher doses.48 Magnesium salts should not be used in renal disease; and saline salts should be avoided in chronic renal failure, end‐stage liver disease, and heart failure. PEG appears to be the best tolerated overall in elders. Lactulose and sorbitol undergo bacterial metabolism in the gut, leading to increased symptoms of bloating, abdominal cramping, and flatulence in some patients and limiting their tolerability. A meta‐analysis of randomised controlled trials found osmotic laxatives to be superior to placebo in functional constipation.49 Compared with placebo, PEG improves stool consistency and stool frequency. In comparative trials, PEG was superior to lactulose, showing improved efficacy and fewer side effects.50 Trials also showed that PEG was non‐inferior to prucalopride (a prosecretory medication discussed below).51
Stimulant laxatives
Stimulant laxatives are widely used when osmotic laxatives have not had the desired effect. The adverse effects of stimulant laxatives in the treatment of constipation remain one of the most steadfast medical myths.8 Stimulant laxatives have been reported to damage the colon and cause laxative dependence. This perception may relate to the occurrence of melanosis coli, a dark‐brownish discoloration of the colon that occurs with long‐term use. The presence of melanosis coli has no functional significance. Prior studies reporting damage to the colonic enteric nerves and smooth muscle were anecdotal and uncontrolled. Many of these patients likely had pre‐existing abnormalities of the colon. When used at recommended doses, stimulant laxatives are unlikely to harm the colon.
Stimulant laxatives result in abdominal discomfort and electrolyte imbalance in some patients.52 The most commonly available stimulant laxatives include senna, bisacodyl, and sodium picosulfate. Compared with placebo, bisacodyl 10 mg daily for 3 days increased stool frequency, improved stool form, and reduced straining in adults with constipation.53 A comparison of bisacodyl with sodium picosulfate (uncontrolled) showed improvement with both in about three‐quarters of subjects.54
Secretagogues (prosecretory agents)
Prosecretory agents can be used as second‐line treatment after standard laxative therapy. Currently, they include linaclotide, plecanatide, and lubiprostone. Lubiprostone selectively activates chloride C‐2 channels to increase intestinal fluid secretion. Lubiprostone does not affect colonic motility or sensation in humans. Patients reported more spontaneous bowel movements with lubiprostone than placebo (six versus four per week, p = 0.001), with the majority of patients experiencing a bowel movement within the first 24 hours.55 The main side effect seen with lubiprostone was nausea. This effect is mitigated when the medication is taken with a meal and appears to be less problematic in elders.
Linaclotide and plecanatide increase cyclic guanosine monophosphate, stimulating chloride and bicarbonate secretion. This increases salt and water secretion into the intestinal lumen and attenuates visceral afferent pain signalling, leading to improved stool consistency and frequency. Linaclotide is available in many countries worldwide, but plecanatide is currently only available in the United States.56
Serotonin receptor agonists
Tegaserod is a selective partial serotonin (5‐HT4) receptor agonist that promotes gut motility and improves constipation symptoms but since 2007 is not recommended in the elderly due to an increase in cardiovascular ischaemic events.57 Prucalopride, a 5‐HT4 receptor antagonist, has been shown to treat chronic constipation by increasing colonic motility and transit. Trials have shown prucalopride can improve symptoms in severe chronic constipation over six months of symptoms despite treatment with at least two different classes of laxatives.57 Prucalopride was considered safe in the elderly with minimal cardiovascular‐related adverse events, but recent studies found it is associated with cardiac arrhythmias.
Opioid antagonists
Opiate pain medications are well known to cause constipation. Chronic opiate use results in constipation in up to 50% of individuals.58 Methadone and fentanyl may be less constipating than other morphine derivatives.59,60 Opiates potently slow gastrointestinal transit and allow enhanced intestinal absorption of fluid. A rational approach involves outlining a strategy to prevent constipation at the initiation of opiate use, although there have been no high‐quality studies to indicate the best strategy. Peripherally acting mu‐opioid receptor antagonists (PAMORAs) reverse opiate‐induced constipation without affecting the analgesic effects or causing withdrawal symptoms (e.g. nalexagol, naldemedine, and methylnaltrexone).61,62 A systematic review and network meta‐analysis of randomized controlled trials has shown PAMORAs to be superior to placebo in the treatment of opiate‐induced constipation.63 Methylnaltrexone improved stool frequency in opiate‐induced constipation. It is typically reserved for patients with more refractory symptoms as it is administered by injection every other day.64 PEG improved stool form in methadone‐induced constipation.65 Stimulant laxatives are also commonly used for opiate‐induced constipation.
Enemas
The use of enemas in the treatment of constipation is typically limited to the acute situation and institutionalized patients to help with rectal evacuation and prevent faecal impaction. There is no medical evidence to support the routine use of phosphate enemas in the treatment of constipation.66 The use of phosphate enemas is well described to cause serious hyperphosphatemia, especially in patients with renal insufficiency.67 Any enema must be used with caution owing to the risk of colonic perforation.68 Soap suds enemas should not be used. Small‐volume tap water enemas may be helpful in emptying the rectum. Larger‐volume tap water enemas may be used on occasion, but even these can result in hyponatraemia.69 Although generally considered beneficial, there is currently no trial evidence evaluating the use of arachis oil enemas. Retention enemas containing arachis oil both lubricate and soften impacted faeces and are routinely given at night. The patient’s allergy status must be checked as they contain nut oils.
Miscellaneous agents
Probiotics are widely available as a non‐pharmacological treatment option for constipation as components of bio yoghurts and dietary supplements. The faecal flora changes with increasing age, mostly by a fall in the numbers of bifidobacteria.70 It remains unclear if this is the cause or the effect of constipation. Large, randomized controlled trials have failed to show a significant benefit from treatment with probiotics.
Misoprostol, a prostaglandin agonist, stimulates intestinal secretion and intestinal transit. Its use is limited by the common occurrence of side effects, including abdominal pain and cramping.71 Its use is reserved for patients with refractory constipation.
Colchicine, well known for causing diarrhoea in the acute treatment of gout, may be used in patients refractory to other medications.72 Colchicine frequently causes increased symptoms of abdominal pain, limiting its use.
Glycerine suppositories have long been used as an over‐the‐counter agent for stimulating bowel movements. The medical literature is lacking in assessments of their effectiveness.
Neostigmine, an acetylcholinesterase inhibitor,
