Laxatives

Laxatives

Laxatives promote and facilitate bowel
evacuation by acting locally to stimulate
intestinal peristalsis, to soften bowel
contents, or both.
1. Bulk laxatives. Distention of the
intestinal wall by bowel contents stimulates
propulsive movements of the gut
musculature (peristalsis). Activation of
intramural mechanoreceptors induces a
neurally mediated ascending reflex contraction
and descending relaxation
whereby the intraluminal
bolus is moved in the anal direction.
Hydrophilic colloids or bulk gels
comprise insoluble and nonabsorbable
carbohydrate substances that expand
on taking up water in the bowel.
Vegetable fibers in the diet act in this
manner. They consist of the indigestible
plant cell walls containing homoglycans
that are resistant to digestive enzymes,
e.g., cellulose.
Bran, a grain milling waste product,
and linseed (flaxseed) are both rich in
cellulose. Other hydrophilic colloids derive
from the seeds of Plantago species
or karaya gum. Ingestion of hydrophilic
gels for the prophylaxis of constipation
usually entails a low risk of side effects.
However, with low fluid intake in combination
with a pathological bowel
stenosis, mucilaginous viscous material
could cause bowel occlusion (ileus).
Osmotically active laxatives
are soluble but nonabsorbable particles
that retain water in the bowel by virtue
of their osmotic action. The osmotic
pressure (particle concentration) of
bowel contents always corresponds to
that of the extracellular space. The intestinal
mucosa is unable to maintain a
higher or lower osmotic pressure of the
luminal contents. Therefore, absorption
of molecules (e.g., glucose, NaCl) occurs
isoosmotically, i.e., solute molecules are
followed by a corresponding amount of
water. Conversely, water remains in the
bowel when molecules cannot be absorbed.
With Epsom and Glauber’s salts
(MgSO4 and Na2SO4, respectively), the
SO4
2– anion is nonabsorbable and retains
cations to maintain electroneutrality.
Mg2+ ions are also believed to
promote release from the duodenal mucosa
of cholecystokinin/pancreozymin,
a polypeptide that also stimulates peristalsis.
These so-called saline cathartics
elicit a watery bowel discharge 1–3 h after
administration (preferably in isotonic
solution). They are used to purge the
bowel (e.g., before bowel surgery) or to
hasten the elimination of ingested poisons.
Glauber’s salt (high Na+ content) is
contraindicated in hypertension, congestive
heart failure, and edema. Epsom
salt is contraindicated in renal failure
(risk of Mg2+ intoxication).
Osmotic laxative effects are also
produced by the polyhydric alcohols,
mannitol and sorbitol, which unlike glucose
cannot be transported through the
intestinal mucosa, as well as by the nonhydrolyzable
disaccharide, lactulose.
Fermentation of lactulose by colon bacteria
results in acidification of bowel
contents and microfloral damage. Lactulose
is used in hepatic failure in order
to prevent bacterial production of ammonia
and its subsequent absorption
(absorbable NH3 ! nonabsorbable
NH4
+), so as to forestall hepatic coma.
2. Irritant laxatives—purgatives
cathartics. Laxatives in this group exert
an irritant action on the enteric mucosa.
Consequently, less fluid is absorbed
than is secreted. The increased filling of
the bowel promotes peristalsis; excitation
of sensory nerve endings elicits enteral
hypermotility. According to the
site of irritation, one distinguishes the
small bowel irritant castor oil from the
large bowel irritants anthraquinone and
diphenolmethane derivatives.
Misuse of laxatives. It is a widely
held belief that at least one bowel
movement per day is essential for
health; yet three bowel evacuations per
week are quite normal. The desire for
frequent bowel emptying probably
stems from the time-honored, albeit


mistaken, notion that absorption of colon
contents is harmful. Thus, purging
has long been part of standard therapeutic
practice. Nowadays, it is known
that intoxication from intestinal substances
is impossible as long as the liver
functions normally. Nonetheless, purgatives
continue to be sold as remedies to
“cleanse the blood” or to rid the body of
“corrupt humors.”
There can be no objection to the ingestion
of bulk substances for the purpose
of supplementing low-residue
“modern diets.” However, use of irritant
purgatives or cathartics is not without
hazards. Specifically, there is a risk of
laxative dependence, i.e., the inability to
do without them. Chronic intake of irritant
purgatives disrupts the water and
electrolyte balance of the body and can
thus cause symptoms of illness (e.g.,
cardiac arrhythmias secondary to hypokalemia).
Causes of purgative dependence
(B). The defecation reflex is triggered
when the sigmoid colon and rectum are
filled. A natural defecation empties the
large bowel up to and including the descending
colon. The interval between
natural stool evacuations depends on
the speed with which these colon segments
are refilled. A large bowel irritant
purgative clears out the entire colon.
Accordingly, a longer period is needed
until the next natural defecation can occur.
Fearing constipation, the user becomes
impatient and again resorts to
the laxative, which then produces the
desired effect as a result of emptying
out the upper colonic segments. Therefore,
a “compensatory pause” following
cessation of laxative use must not give
cause for concern (1).
In the colon, semifluid material entering
from the small bowel is thickened
by absorption of water and salts
(from about 1000 to 150 mL/d). If, due
to the action of an irritant purgative, the
colon empties prematurely, an enteral
loss of NaCl, KCl and water will be incurred.
To forestall depletion of NaCl
and water, the body responds with an
increased release of aldosterone (p.
124), which stimulates their reabsorption
in the kidney. The action of aldosterone
is, however, associated with increased
renal excretion of KCl. The enteral
and renal K+ loss add up to a K+ depletion
of the body, evidenced by a fall
in serum K+ concentration (hypokalemia).
This condition is accompanied by
a reduction in intestinal peristalsis
(bowel atonia). The affected individual
infers “constipation,” again partakes of
the purgative, and the vicious circle is
closed (2).
Chologenic diarrhea results when
bile acids fail to be absorbed in the ileum
(e.g., after ileal resection) and enter
the colon, where they cause enhanced
secretion of electrolytes and water,
leading to the discharge of fluid stools.


2.a Small Bowel Irritant Purgative,
Ricinoleic Acid
Castor oil comes from Ricinus communis
(castor plants; Fig: sprig, panicle,
seed); it is obtained from the first coldpressing
of the seed (shown in natural
size). Oral administration of 10–30 mL
of castor oil is followed within 0.5 to 3 h
by discharge of a watery stool. Ricinoleic
acid, but not the oil itself, is active. It
arises as a result of the regular processes
involved in fat digestion: the duodenal
mucosa releases the enterohormone
cholecystokinin/pancreozymin into the
blood. The hormone elicits contraction
of the gallbladder and discharge of bile
acids via the bile duct, as well as release
of lipase from the pancreas (intestinal
peristalsis is also stimulated). Because
of its massive effect, castor oil is hardly
suitable for the treatment of ordinary
constipation. It can be employed after
oral ingestion of a toxin in order to hasten
elimination and to reduce absorption
of toxin from the gut. Castor oil is
not indicated after the ingestion of lipophilic
toxins likely to depend on bile acids
for their absorption.
2.b Large Bowel Irritant Purgatives
(p. 177 ff)
Anthraquinone derivatives (p. 176) are
of plant origin. They occur in the leaves
(folia sennae) or fruits (fructus sennae)
of the senna plant, the bark of Rhamnus
frangulae and Rh. purshiana, (cortex
frangulae, cascara sagrada), the roots of
rhubarb (rhizoma rhei), or the leaf extract
from Aloe species (p. 176). The
structural features of anthraquinone derivatives
are illustrated by the prototype
structure depicted on p. 177.
Among other substituents, the anthraquinone
nucleus contains hydroxyl
groups, one of which is bound to a sugar
(glucose, rhamnose). Following ingestion
of galenical preparations or of the
anthraquinone glycosides, discharge of
soft stool occurs after a latency of 6 to 8
h. The anthraquinone glycosides themselves
are inactive but are converted by
colon bacteria to the active free aglycones.
Diphenolmethane derivatives (p. 177)
were developed from phenolphthalein,
an accidentally discovered laxative, use
of which had been noted to result in
rare but severe allergic reactions. Bisacodyl
and sodium picosulfate are converted
by gut bacteria into the active colonirritant
principle. Given by the enteral
route, bisacodyl is subject to hydrolysis
of acetyl residues, absorption, conjugation
in liver to glucuronic acid (or also to
sulfate, p. 38), and biliary secretion into
the duodenum. Oral administration is
followed after approx. 6 to 8 h by discharge
of soft formed stool. When given
by suppository, bisacodyl produces its
effect within 1 h.
Indications for colon-irritant purgatives
are the prevention of straining at
stool following surgery, myocardial infarction,
or stroke; and provision of relief
in painful diseases of the anus, e.g.,
fissure, hemorrhoids.
Purgatives must not be given in abdominal
complaints of unclear origin.
3. Lubricant laxatives. Liquid paraffin
(paraffinum subliquidum) is almost nonabsorbable
and makes feces softer and
more easily passed. It interferes with
the absorption of fat-soluble vitamins
by trapping them. The few absorbed
paraffin particles may induce formation
of foreign-body granulomas in enteric
lymph nodes (paraffinomas). Aspiration
into the bronchial tract can result in lipoid
pneumonia. Because of these adverse
effects, its use is not advisable.