Constipation is the infrequent or diffi cult evacuation of faeces. There is no exact defi nition, but it is a reduction in normal stool frequency accompanied by hardening of stools. Constipation that is not secondary to underlying disease or caused by factors such as side-effects of drugs or laxative abuse is known as simple or functional constipation and may be self-treated with advice from a pharmacist.
Causes
Constipation can be broadly divided into two types:
1. Simple (functional): constipation with no underlying pathology. There are various causes but it is often due to insuffi cient fl uid or fi bre in the diet, or reduced mobility. It can usually be corrected with dietary or lifestyle measures or short-term use of laxatives. Several drugs also cause constipation as a side-effect.
2. Secondary: constipation with an underlying pathological cause. It requires referral for medical investigation.
Epidemiology
Constipation is common; it is thought to affect a quarter of the population at some time.
Women are three times more likely to suffer than men.
The condition is especially prevalent in the elderly, with up to 40% of people over 65 suffering.
Signs and symptoms
Bowel frequency reduced below normal for the individual (‘normal’ can be from twice or three times daily to once or twice weekly).
Straining in attempt to defecate, with possible abdominal pain and a feeling of incomplete emptying of the bowel.
Stools are harder than normal.
There may be abdominal bloating and discomfort.
Stools may be specked with bright blood, due to bleeding from haemorrhoids caused by straining.
Children with constipation may be irritable and lose their appetite.
Differential diagnosis
Causes of secondary constipation include:
bowel obstruction
carcinoma
faecal impaction
irritable-bowel syndrome
hypothyroidism
drug side-effects.
(See Symptoms and circumstances for referral below for further details of signs and symptoms of these conditions.)
Symptoms and circumstances for referral
constipation for more than 7 days with no identifi able cause
recurrent constipation
colicky pain, nausea and vomiting, and abdominal distension (may indicate bowel obstruction)
constipation accompanied by weight and appetite loss (may indicate carcinoma)
blood in stools, which appear tarry and red or black (may indicate carcinoma)
bright blood on stools or in lavatory pan. This usually indicates haemorrhoids, which is often not serious but should be diagnosed by a doctor
alternating constipation and diarrhoea in elderly patients, which may indicate faecal impaction and overfl ow. In younger patients, alternating constipation and diarrhoea may indicate irritable-bowel syndrome
constipation with associated weight gain, lethargy, coarse hair or dry skin (may indicate hypothyroidism)
suspected adverse drug reaction. Constipation is a common side-effect of drugs with antimuscarinic actions, including:
– older antidepressant drugs, such as amitriptyline and imipramine
– antiparkinsonian drugs, such as orphenadrine, procyclidine and trihexphenidyl (benzhexol)
– antipsychotics, such as chlorpromazine and other phenothiazines.
Other drugs that can cause constipation include:
opioid analgesics (morphine, codeine, dihydrocodeine)
aluminium-containing antacids
antihypertensives (such as verapamil)
iron.
Treatment
Laxatives can be broadly classified into five groups depending on their mode of action:
1. bulk-forming
2. stimulant
3. osmotic
4. faecal softeners
5. faecal lubricants.
Bulk-forming laxatives
Bulk-forming laxatives contain ispaghula husk (the seed coats of a species of plantain), sterculia (a gum from a tropical shrub) or methylcellulose (a semisynthetic hydrophilic colloid).
These contain polysaccharides or cellulose derivatives that pass through the gastrointestinal tract undigested. They increase faecal volume through three mechanisms:
1. adding directly to the volume of the intestinal contents
2. softening the faeces
3. adding to faecal mass by acting as substrates for the growth of colonic bacteria.
They provide the closest approximation to the natural process of increasing faecal volume and are normally the first-line recommendation for functional constipation.
They usually act within 24 hours, but 2–3 days of medication may be required for a full effect.
They are not absorbed so have no systemic effects. They do not interact with other medicines and do not appear to interfere significantly with drug absorption.
Adverse effects and disadvantages are relatively minor. They include:
– risk of oesophageal and intestinal obstruction if preparations are not taken with suffi cient water
– abdominal distension and flatulence
– some bulk laxatives contain glucose, which needs considering in diabetes
– they may not be suitable for patients who must restrict their fluid intake severely.
Stimulant laxatives
Stimulant laxatives are thought to act mainly by stimulating the intestinal mucosa to secrete water and electrolytes, through one or both of two mechanisms:
1. inhibition of the sodium pump (the enzyme sodium/potassium adenosine triphosphatase), preventing sodium transport across the intestinal wall, leading to the accumulation of water and electrolytes in the gut lumen
2. increased production of fluid in the intestine through action on cyclic adenosine monophosphate and prostaglandins, which promote active secretory processes in the intestinal mucosa.
Stimulant laxatives may also cause direct damage to mucosal cells, thereby increasing their permeability and allowing fluid to leak out, increasing fl uid volume in the intestine.
The length of time for individual stimulant laxatives to take effect following oral administration varies according to their site of action, which may be in the small intestine, the large intestine, or both, but they normally work within
4–12 hours of administration. Doses are usually taken at bedtime to produce an effect the next morning. Suppositories produce much faster results, usually within an hour.
The main adverse effects of stimulant laxatives are:
– griping and intestinal cramps
– following prolonged use, fluid and electrolyte imbalance and loss of colonic smooth-muscle tone resulting in a vicious circle in which larger and larger doses are needed to produce evacuation, until eventually the bowel ceases to respond at all and constipation becomes permanent. Stimulant laxatives should therefore be used for only short periods of a few days at most, to re-establish bowel habit.
Stimulant laxatives are not contraindicated in pregnancy, but should be avoided in the first trimester. They are generally not recommended, and most are not licensed, for use in children under 5.
Stimulant laxatives fall into two main groups: diphenylmethane derivatives and anthraquinones.
Diphenylmethane derivatives
Compounds available are bisacodyl and sodium picosulfate.
Bisacodyl
Bisacodyl acts mainly via stimulation of the mucosal nerve plexus of the large intestine, so takes longer to act (6–10 hours after oral administration) than laxatives acting in the small intestine. It is minimally absorbed and appears to exert no systemic effects. It causes gastric irritation; there are therefore no oral liquid presentations and tablets are enteric-coated.
Sodium picosulfate
Sodium picosulfate becomes active following metabolism by colonic bacteria so it has a relatively slow onset of action, usually within 10–14 hours. It can be used in young children.
Anthraquinones
Anthraquinones are naturally occurring glycosides used in the form of standardised plant extracts. They are thought to act through a combination of direct stimulation of the intramural nerve plexus and interference with absorption of water across the intestinal wall.
Dantron and senna are the only anthraquinone laxatives in current use.
Based on studies in rodents, dantron is believed to be potentially carcinogenic. It is a prescription-only medicine (POM) and is indicated for use only in terminally ill patients. It is available in combination with poloxamer ‘188’ (an organic osmotic laxative) as co-danthramer, and with docusate (see below) in co-danthrusate.
Senna is widely used.
Senna is secreted in breast milk and large doses may cause increased gastric motility and diarrhoea in infants, so it should therefore be avoided by nursing mothers.
Senna is excreted via the kidney and may colour the urine a yellowish-brown to red colour depending on its pH.
Osmotic laxatives
Osmotic laxatives are either inorganic salts or organic compounds which are poorly absorbed and create a hypertonic state in the intestine. To equalise osmotic pressure, water is drawn from the intestinal wall into the lumen, raising the intraluminal pressure by increasing the volume of the contents, thus stimulating peristalsis and promoting evacuation.
Inorganic salts
Inorganic salts used as osmotic laxatives are:
– magnesium sulphate
– magnesium hydroxide
– sodium sulphate.
The effects of the inorganic salts are rapid: large doses produce a semifluid or watery evacuation within 3 hours and smaller doses act in 6–8 hours.
Magnesium salts are also believed to act by stimulating the secretion of the hormone cholecystokinin, which promotes fluid secretion and motility in the intestine.
Some absorption of inorganic laxative salt ions occurs but in normal, healthy individuals the amounts are too small to be toxic and the ions are rapidly excreted via the kidney.
Accumulation of magnesium ions can occur in the presence of renal impairment, causing toxic effects in the central nervous system and altered neuromuscular function through hypermagnesaemia. As renal function tends to decline with age, elderly patients should be advised against regular use of
magnesium-containing laxatives.
Absorption of sodium salts can result in water retention and a rise in blood pressure, and chronic use should be avoided in patients with renal insufficiency, oedema, high blood pressure or congestive heart failure.
The main side-effects of inorganic osmotic laxatives are nausea and vomiting.
Large doses of inorganic laxatives can produce dehydration, so enough water should always accompany a dose to avoid a net loss of body water.
Organic osmotic laxatives
Lactulose
Lactulose is a synthetic disaccharide.
It is broken down by colonic bacteria, mainly to lactic acid, to produce a local osmotic effect and therefore takes much longer to act than inorganic osmotic laxatives.
72 hours of regular dosing may be required to produce an effect, which may be seen as a disadvantage by patients seeking rapid results.
Lactulose has a sweet taste, which makes it more palatable for children, to whom it can be safely given, but many adults find the large dose volumes required (up to 30 ml) sickly and a deterrent to compliance.
Serious adverse effects with lactulose are rare. Relatively minor side-effects, although they may be sufficient to discourage compliance, occur in about 20% of patients taking full doses and include flatulence, cramp and abdominal discomfort, particularly at the start of treatment.
Lactulose is a disaccharide of galactose and fructose and includes some lactose, so cannot be used by patients with galactose or lactose intolerance and must be used with caution in diabetes.
Macrogols
Macrogols (polyethylene glycols, PEGs), are condensation polymers of ethylene oxide and water.
They are presented as powders that are dissolved in water and taken as a single daily dose.
They appear to act more effectively and rapidly than lactulose, and have been suggested as the laxative of fi rst choice for children.
Glycerol
Glycerol is a highly hygroscopic trihydric alcohol that appears to attract water of hydration into the intestine. It is also believed to have a direct mild irritant effect and may have some lubricating and softening actions.
It is inactive by mouth as it is readily absorbed and extensively metabolised in the liver.
Glycerol is administered in the form of suppositories, which usually act within 15–30 minutes.
It is a useful laxative for babies and young children.
Faecal softener
Docusate sodium
Docusate sodium is an anionic surfactant that lowers the surface tension of the intestinal contents, allowing fluid and fat to penetrate, emulsify and soften faecal material for easier elimination. Evacuation is achieved without straining. It is also thought to be a stimulant similar to the anthraquinones. A laxative effect usually occurs within 1–3 days.
Used alone docusate is a weak laxative, but it is considered useful for patients who must avoid straining, for example, following an operation or myocardial infarction.
Docusate is non-absorbable and non-toxic but it is believed to facilitate the transport of other drugs across the intestine, and could thereby increase their
action and adverse effects.
Faecal lubricant Liquid paraffi n
Liquid paraffi n is a purifi ed mixture of liquid hydrocarbons obtained from petroleum.
It is indigestible and absorbed only to a small extent. It penetrates and softens faeces, coating the surface with an oily film that facilitates its passage through the intestine.
It has limited usefulness as an occasional laxative where straining must be avoided.
It has several drawbacks that make it unsuitable for regular use:
– It can seep from the anus and cause irritation.
– It may interfere with the absorption of fat-soluble vitamins.
– It is slightly absorbed into the intestinal wall where it may set up foreign-body granulomatous reactions.
– It may enter the lung through aspiration and cause lipoid pneumonia.
It should not be used in the presence of abdominal pain, nausea or vomiting and should never be used for children.
Additional advice
To help prevent constipation:
– Eat a diet high in fi bre, including wholegrains, fruits and vegetables.
– Cut down on food low in fi bre, such as white bread, cakes and sugar.
– Drink plenty of fl uids, the equivalent of at least 8–10 glasses of water a day. Hot drinks may stimulate bowel movements.
– Take regular exercise to improve digestion and bowel function and reduce stress, which can cause constipation.
– Establish a regular bowel habit. The best time to try for a bowel motion is usually the fi rst hour after breakfast, when the gastrocolic refl ex is activated. Be patient and sit for at least 10 minutes if necessary, regardless of whether you manage to pass a stool. Don't strain.
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