A Textbook of Clinical Pharmacology and Therapeutics

• in hepatocellular failure to reduce formation and/or
  absorption of neurotoxins produced in the bowel;


• occasionally in drug-induced constipation.

BULK LAXATIVES

Plant fibre

Plant fibre is the portion of the walls of plant cells that resists
digestion in the intestine. The main effect of increasing the
amount of fibre in the diet is to increase the bulk of the stools
and decrease the bowel transit time; this is probably due to the
ability of fibre to take up water and swell. Fibre also binds
organic molecules, including bile salts. It does not increase the
effective caloric content of the diet, as it is not digested or
absorbed.
The main uses of plain fibre (e.g. bran) are as follows:

• in constipation, particularly if combined with a spastic colon.
  By increasing the bulk of the intestinal contents, fibre slowly
  distends the wall of the colon, and this causes an increase in
  useful propulsive contraction. The main result is a return of
  the large bowel function towards normal. Similar results are
  obtained in diverticular disease in which there is colon
  overactivity associated with a high intraluminal pressure.


• the proposed effects of fibre in preventing large-bowel
  carcinoma, piles, appendicitis, coronary artery disease and
  varicose veins are still speculative.
  The starting ‘dose’ of bran is a dessertspoonful daily and
  this can be increased at weekly intervals until a satisfactory
  result is obtained. It may be mixed with food, as it is difficult
  to swallow if taken ‘neat’.

Adverse effects and contraindications

Bran usually causes some flatulence which is dose related.
Phytates in bran could theoretically bind calcium and zinc
ions. Bran should be avoided in gluten enteropathy and is
contraindicated in bowel obstruction.

Other bulk laxatives

Methylcellulosetakes up water in the bowel and swells, thus
stimulating peristalsis. It is a reasonable substitute if bran is
not satisfactory.

OSMOTIC AGENTS

For many years, these have been thought to act by retaining
fluid in the bowel by virtue of the osmotic activity of their
unabsorbed ions. The increased bulk in the lumen would then
stimulate peristalsis. However, 5 g of magnesium sulphate
would be isotonic in only 130 mL and acts within one to two
hours, well before it could have reached the colon, so mech-
anisms other than osmotic effects must account for its laxative
properties. It has been postulated that, because magnesium
ions can also contract the gall-bladder, relax the sphincter of
Oddi and increase gastric, intestinal and pancreatic enzyme
secretion, they may act indirectly via cholecystokinin.

Magnesium ions themselves may also have direct pharmaco-

logical effects on intestinal function.

Magnesium sulphate(Epsom salts) and other magnesium

salts are useful where rapid bowel evacuation is required. It

should be remembered that a certain amount of magnesium

may be absorbed, and accumulation can occur in renal failure.

Macrogols are inert polymers of ethylene glycol which

sequester fluid in the bowel; giving fluid with macrogols may

reduce the dehydrating effect sometimes seen with osmotic

laxatives.

Phosphate enemas are useful in bowel clearance before

radiology, endoscopy and surgery.

Lactuloseis a disaccharide which passes through the small

intestine unchanged, but in the colon is broken down by

carbohydrate-fermenting bacteria to unabsorbed organic

anions (largely acetic and lactic acids) which retain fluid in the

gut lumen and also make the colonic contents more acid. This

produces a laxative effect after two to three days. It is effective

and well tolerated, but relatively expensive. It is of particular

value in the treatment of hepatic encephalopathy, as it dis-

courages the proliferation of ammonia-producing organisms

and the absorption of ammonia.

LUBRICANTS AND STOOL SOFTENERS

These agents were formerly believed to act by softening or

lubricating the faeces, but they act at least in part in a similar

manner to stimulant purgatives by inhibiting intestinal elec-

trolyte transport.

DIOCTYL SODIUM SULPHOSUCCINATE

Dioctyl sodium sulphosuccinateis a surface-active agent that

acts on hard faecal masses and allows more water to penetrate

the mass and thus soften it. Its use should be confined to

patients with faecal impaction, and it should not be given over

long periods.

ARACHIS OIL

Enemas containing arachis oillubricate and soften impacted

faeces and promote a bowel movement.

CHEMICAL STIMULANTS

Many of the agents in this class (e.g. castor oil,phenol-

phthalein) are now obsolete because of their toxicity, but senna,

co-danthramerandbisacodylare still useful if bulk laxatives

are ineffective. Glycerolsuppositories act as a rectal stimulant

due to the local irritant action of glyceroland are useful if a

rapid effect is required. Phosphate enemas are similarly useful.

LAXATIVE ABUSE

Persistent use of laxatives, particularly in increasing doses,

causes ill health.

CONSTIPATION 257