Gastrointestinal Drugs

1-Drugs Used in Constipation and Diarrhea

DRUGS USED IN CONSTIPATION

A-Mild and Strong Purgatives
Constipation is a condition in which the bowel is evacuated at a longer interval or with difficulty. Causes
of constipation are: (1) Change of environment,
(2) Emotional tension,
(3) Disregard of the call to pass motion,
(4) Disease or abnormality of gastrointestinal tract,
(5) Adverse effects of drugs,
(6) Drying of stools (faecal impaction),
(7) Obstruction of intestine, and
(8) Severe illness with too small food intake.

Classification
Mild Purgatives
1-Bulk producing drugs
i. Isapgol: 4 to 5 gm once or twice a day.
ii. Agar-agar. 1 to 6 gm in divided doses.
iii. Bran: 12-24 gm daily in divided doses
iv. Methyl cellulose; 1 gm, 1-4 times daily
v. Sodium carboxy methyl cellulose: 1.5 gm, 1- 4 times daily .

2-Stool softeners
i. Dioctyl sodium sulfosuccinate; 50-500 mg daily
ii. Liquid paraffin: 15 ml per day

3-Mild saline purgatives:

i. Magnesium hydroxide:10 gm daily
ii. Sodium potassium tartrate:

Strong Purgatives
1-Osmotic Purgatives .
i. Magnesium sulfate (Magsufl)- 5-15 gm daily
ii. Lactulose. 30-50 ml (3.5 gm per 5 ml. 3 times a day)
iii. Glycerine. (a) As rectal suppositories: 3 gm.
(b) As glycerine-edible oil enema: 30-50 ml of each
iv. Polyethylene glycol: 250 ml every 15-20 minutes up to 4 litres over a period of 4 hours.
2-Irritant Purgatives .
i. Phenolphthalein: 60-120 mg daily
ii. Senna glycosides: 0.6 gm (1-2 tab daily)
iii. Bisacodyl:5-15 mg daily
iv. Cascara sagarada: 1-2 tab at bedtime
v. Castor oil: 15-25 ml daily

1
 MILD PURGATIVES
(Laxatives)

1-Bulk Producing Drugs .

These drugs absorb water and increase bulk in the intestine. So they make the stool soft and help in
the evacuation. The onset of their action is slow, about 12-24 hours. They are the safest purgatives.
Adverse effects are rare. Occasionally, flatulence may occur; this can be relieved by increasing the fluid
intake.
On chronic use, isapgol decreases plasma cholesterol by interfering with the absorption of bile acids.
So to obtain maximum benefit and to avoid the possibility of intestinal obstruction (rarely reported),
plenty of fluids should be taken along with these drugs
.
2-Stool Softeners
i. Dioctyl sodium sulfosuccinate: It is an effective stool softener. It is a detergent. It absorbs water by
reducing the surface tension of fluids in the stool. It increases the absorption of mineral oils, so it should
not be taken simultaneously with mineral oils.
ii. Liquid paraffin: It is an inert mineral oil. It lubricates the intestines. It makes the passage of stools
smooth and comfortable by forming a film or coating around the stools. It softens the stool by preventing
the absorption of water into the intestines. It is often recommended in cases in which straining to evacuate
may be harmful, e.g. piles(hemorrhoid), heart attack, pregnant women, after surgery on the rectum or
abdomen.
Indiscriminate and prolonged use of liquid paraffin is not desirable because it dissolves the fat-soluble
vitamins, e.g. A, D and K and impairs their absorption. So it may cause deficiency of fat soluble vitamins.
It prevents complete evacuation of bowels because its presence in rectum inhibits the stimulatory reflexes
to the intestine. It should not be taken along with dioctyl sodium sulfosuccinate as the latter promotes its
absorption from the intestine.

3-Mild Saline Purgatives .

i. Magnesium hydroxide: It is a mild laxative so it can be used even by pregnant women and children.
On oral ingestion, it builds up an osmotic pressure in the intestinal lumen and draws water into it from the
mucosal blood vessels to form the bulk. Thus, it makes the stools soft and stimulates peristalsis. Besides
purgative action, it counteracts acidity in the stomach. Its action starts after 2 to 6 hours. It may produce
flatulence in some people.
Plenty of fluid must be taken along with this purgative. Milk of Magnesia should be avoided in patients
with chronic kidney disease because of difficulty of its excretion.
ii. Sodium potassium tartrate: It is the basic ingredient of commonly used ENO's fruit salt and Seidlitz
powder. The latter consists of two packets; the blue packet contains 2.5 gm of sodium bicarbonate and 7.5
gm of sodium potassium tartrate, the white packet contains 2.2 gm of tartaric acid. The contents of white
packet are dissolved in a glass of water and then the contents of blue packet are added to the solution. The
interaction between sodium bicarbonate and tartaric acid yields carbon dioxide and so the drink
effervesces. It is pleasant to take and is drunk while it is effervescing. The gas present in the solution
distends the stomach and reflexly stimulates movements of the intestines. It also absorbs water from the
intestines which assists in forming the bulk and softening of the stools. Its action star after3-6 hours. It
should not be taken by who are on a sodium restricted diet, e.g. patients of heart failure, hypertension, etc.
STRONG PURGATIVES (Cathartics)
Strong purgatives are used for causing complete evacuation of the bowel. They should only used under
medical supervision. These purgatives should not be used for treatment of constipation because fully
evacuated bowels become inactive (atonic) and constipation usually follows for which a milder purgative
is again needed.
Their indications are:
►n cases of worm infestation along with drugs for killing the worms.
►To induce labor if the delivery does not occur at the expected time.

2
There are two types of strong purgatives:
1-Osmotic purgative: On oral administration certain salts are not much absorbed from gastrointestinal
tract. They are retained there and exert an osmotic effect. So they hold considerable amounts of water and
increase the intestinal bulk. In turn, they cause increase in the intestinal motor activity and evacuation by
mechanical stimulus.

i. Magnesium sulfate (Magsulf): It causes total evacuation of bowel in 1 to 3 hours. So it is usually

taken in the morning. It may cause dehydration because of excessive loss of fluids. It may cause serious
depression of central nervous system, even if a minute amount of magnesium is absorbed into the
bloodstream from the intestines.

ii. Lactulose: This is a synthetic non-absorbable disaccharide. It is metabolized into lactic acid and other
organic acids by bacteria in the distal ileum and colon. So lactulose and its metabolites produce
evacuation of the bowel by osmotic effect. Further, lactic acid can bind ammonia. Due to this, it is used in
the treatment of hepatic coma to produce 2-3 soft stools per day.

iii. Lactilol: It is a synthetic disaccharide. It is more palatable than lactulose and has similar actions.

iv. Glycerine: It softens and lubricates the dried up faeces by its osmotic action. It also stimulates rectal
contractions. It is employed in the form of suppositories as well as a glycerine-edible oil enema.
v. Polyethylene glycol: It is available as a powder or as a ready-to-use solution. It is isotonic solution. So
it doesn't cause dehydration. It is used:
a. To clean the bowel before surgery, colonoscopy and radiological procedures.
b. In acute poisoning

2. Irritant purgatives: Senna glycosides, bisacodyl, cascara sagrada and castor oil are irritant purgatives.
They act by causing irritation of the intestines. They usually produce purgation in 3 to 6 hours.
Phenolphthalein has a long duration of action as it is absorbed and re-excreted in the intestines (effective
for 2 to 3 days).
They may cause gripping or cramping pains in the abdomen. Sometimes there may be erosion of inflamed
mucosa leading to passage of mucous in stools. They may cause excessive loss of fluids and electrolytes.
Phenolphthalein may induce allergic reactions in 0.01% cases in the form of rashes and pigmentation of
the skin.
Important precautions in the use of irritant purgatives are:
(a) Should not be used for treatment of chronic constipation, pregnant women and in cases with previous
history of abdominal pain.
(b) Since these are secreted in the milk they should not be taken by feeding mothers.
(c) Avoid phenolphthalein if allergic reactions occur.
Important features of osmotic purgatives
• Act in the small and large intestines.
• Produce watery evacuation within 3-6 hours.
• Given early in the morning before breakfast
• Do not cause irritation
Therapeutic uses of purgatives
• In constipation due to diminished intestinal tone
• In drug induced constipation
• In food or drug poisoning
• In patients with severe neuromuscular disease
• In patients with hepatic encephalopathy
• To reduce the absorption of ammonia and toxins from colon.
• In patients with painful anal conditions (fissure, thrombosed piles) and in cardiac disease (acute
myocardial infarction), in order to avoid straining during defaecation.
• In patients with an ileostomy or colostomy to modify the effluent

3
• In children with encopresis and congenital /acquired mega colon.
• To eliminate the parasites following anthelmintic therapy.
• To clean the bowel before surgery, colonoscopy and radiological procedures.

DRUGS USED IN DIARRHEA

(Non-specific Anti-diarrheal Agents)
Frequent passage of liquid or semisolid stools is called diarrhea. It may be accompanied by abdominal
pain. It can be caused by enteric infection, food toxins, malnutrition, inflammation and drugs like
reserpine, synthetic prostaglandins, metoclopramide, domperidon, cholinergic drugs, quinidine and
purgatives. Dysentery is characterized by abdominal pain and passage of blood and mucous due to
infection or inflammation. For infective diarrheas specific chemotherapy is required.
Diarrhea may be non-specific. It may be caused by fear, anxiety or apprehension, indigestion and in
people on the move. This type of diarrhea can be treated by non-specific measures. These measures
provide symptomatic relief and do not treat the underlying cause. They reduce the frequency of stools and
change the consistency from liquid to semisolid.

1. Oral rehydration therapy: This therapy is effective in majority of patients with watery diarrhea which
lead to symptoms due to loss of fluid and electrolytes. As per WHO/ UNICEF recommendations this
therapy consists of:
Rx
Sodium chloride 3.5 gm
Potassium chloride 1.5 gm
Sodium citrate 2.9 gm
Glucose 20 gm
Water ad 1 Ltr.
If oral rehydration therapy is not adequate or the patient is severely dehydrated, administer
intravenous fluid and electrolytes.
2. Anti-motility agents: These drugs reduce peristalsis. So they help reabsorption of water by delaying
intestinal transit time. They also increase tone of the rectal sphincter. Tincture of opium and codeine were
used earlier but their use has been discontinued because of tolerance and chances of physical dependence.

Diphenoxylate
Is a congener of pethidine. It acts on opioid mu receptors. It is combined with atropine
(diphenoxylate 1 mg + atropine 0.025 mg). This combination (lomotil) is given in doses of 1 tablet every
3-4 hours. It may cause nausea, vomiting, abdominal discomfort, dryness of mouth and drowsiness. Since
these symptoms appear in children even at near therapeutic doses, its use has been banned in children
below the age of six years. Diphenoxin is an active metabolite of diphenoxylate and is available for
treatment of diarrhea.

Loperamide
Is also pethidine congener. It is sparingly absorbed. It also acts through stimulation of mu receptors.
It does not cause physical dependence and respiratory depression in therapeutic doses. However, it may
cause nausea, vomiting and abdominal discomfort. Recommended dose is 4-8 mg per day. Anti-motility
agents are contraindicated in infants and children because of danger of induction of paralytic
ileus(Obstruction of the intestine due to paralysis of the intestinal muscles).

3. Adsorbents:
Kaolin, pectin and chalk adsorbents. They absorb toxins. They have marginal anti-diarrhoeal effect.
Hence nowadays they are rarely used.
Bismuthsubsalicylate is an adsorbent as well as exerts local anti-inflammatory effect due to salicylate. It
is recommended for traveler's diarrhea in doses of 520 mg four times a day.

4
4. Antispasmodic drugs:
Atropine and oxyphenonium (antrenyl): These drug decrease cramps, abdominal pain and diarrhoea
associated with spasms of the intestines. They may be used alone or in combination with other anti-
diarrheal and anti-dysentery drugs. Atropine is used doses of 0.125 and 0.5 mg twice a day while
oxyphenonium in doses of 5 mg twice a day.
2-Drugs Used in Peptic Ulcer
Peptic ulcer is a major health problem. It is a wound inside the stomach or duodenum. It occurs due to
localized destruction of the inner wall (mucosa) of the stomach (gastric ulcer) or the upper part of the
small intestine (duodenal ulcer). It is usually associated with the hyperacidity. The causes of peptic ulcer
are complex. Two major factors in the genesis of peptic ulcer are:

(a) acid and pepsin secretion and

(b) gastroduodenal epithelial and mucosal resistance.
Excessive smoking and excessive use of alcohol, tea, coffee and certain drugs like corticosteroids,
phenylbutazone, indomethacin, reserpine, etc. may also be responsible for peptic ulcer. Important
symptom is sharp, penetrating and burning type of pain in the upper part of the abdomen which may be
aggravated by food.

ANTI-PEPTIC ULCER DRUGS

Antacids
1-Non-absorbable antacids:
a. Aluminium salts such as aluminium hydroxide, aluminium phosphate, dihydroxy aluminium
aminoacetate and aluminium carbonate (Dose: 200-600 mg every hour during acute attacks).
b. Magnesium salts such as magnesium trisilicate, magnesium hydroxide (Milk of magnesia), magnesium
oxide and magnesium carbonate (Dose: 250-500 mg every hour during the acute attacks).
c. Calcium carbonate.
2- Absorbable antacid such as sodium bicarbonate.
Mode of action: They neutralize gastric hydrochloric acid and prevent activation of pepsin. Aluminium
also binds pepsin. The trisilicate salt of magnesium and aluminium forms protective coating over ulcer
surface by forming hydrated silicon gel.
Use: Antacids mainly provide symptomatic, relief by reducing acid irritation of ulcers and to lesser extent
promote healing.
Adverse reactions: Although sodium bicarbonate causes rapid relief from pain, it is not used clinically
because it causes systemic alkalosis gastric distension, rebound acidity and milk alkali syndrome.
Aluminium salts induce constipation phosphate depletion on prolonged use and aluminium
encephalopathy on prolonged use in presence of renal failure. Magnesium salts product diarrhoea and
hypermagnesaemia in the presence of renal failure. Calcium salts cause constipation milk alkali
syndrome, rebound acidity and perforation of ulcer due to production of carbon dioxide. Clinically,
aluminium and magnesium salts are used in combination to counteract the side effects of each other.
Drug interactions:
a. Sodium containing antacid reduces antihypertensive effect of drugs.
b. Aluminium decreases the absorption of digoxin, tetracycline, isoniazid, iron salts and prednisolone.
c. Magnesium retards the absorption of tetracycline, digoxin and dicoumarol.
Anticholinergic Agents
1-MI and M2 receptor blockers like probanthine, oxyphenonium and dicyclomine.
2- Selective M1, receptor blockers like pirenzepine and telenzepine. They have minimum effect on heart,
intestine, and urinary bladder. So the adverse effects such as dryness of mouth, blurred vision and
headache are less common.
Mode of action: They act by reducing gastric acid secretion. They also inhibit gastric motility which may
be helpful in ulcer healing.

5
Use: Since they have weak antisecretory effect, they are used only as adjuvant to other anti-ulcer drugs.
Commonly used drug is pirenzepine. It is given in doses of 50 mg orally twice or thrice daily for 4-6
weeks.
Drug interactions: Non-selective anticholinergic drugs increase the absorption of digoxin, prednisolone,
and phenytoin by delaying intestinal transit time.
Histamine H2 Antagonists
These drugs, comprising cimetidine, ranitidine, famotidine, nizatidine and roxatidine, block histamine
H2 receptors. They block histamine-mediated acid secretion from gastric parietal cells and also reduce
gastrin and cholinergic acid secretion. They reduce both quantity and concentration of acid but have no
effect on mucous secretion and gastric motility.
Uses:
• Used in gastric and duodenal ulcers. They help in ulcer healing and prevent recurrence of ulcers.
• Gastric erosions with or without bleeding.
• Reflux oesophagitis.
• Stress ulcers (burns).
• Zollinger-Ellison syndrome.
• Chronic gastritis.
Dosage:
Ranitidine: 150 mg twice daily or 300 mg at bed-time for 4-6 weeks.
Famotidine: 20 mg twice daily or 40 mg at bedtime for 4-6 weeks.
Roxatidine: 75 mg twice daily or 150 mg at bedtime.
Nizatidine: 150 mg twice daily or 300 mg at bed-time for 4-6 weeks.
Loxatidine: Recently developed powerful noncompetitive H2 antagonist
Cimetidine is no more used.
Side effects: Gynecomastia and impotence are produced in males by cimetidine because of its weak
antiandrogenic activity. Cimetidine may produce mental confusion, hallucinations, drowsiness and
convulsions because it crosses blood-brain barrier.
Newer H2 blockers do not have anti-androgenic activity and have minimal access across the blood
brain barrier. They occasionally induce diarrhoea, headache, and vertigo, mild disorientation and skin
rashes.
Drug interactions:
1. Cimetidine potentiates the toxicity of propranolol, diazepam, theophylline, imipramine, lignocaine,
phenytoin, warfarin and phenobarbitone by inhibiting hepatic microsomal oxidase enzyme. However, in
therapeutic doses newer H2 antagonists have minimal hepatic enzyme inhibiting activity.
2. They retard absorption of ketoconazole due to reduction in gastric acidity.
Proton Pump Inhibitors
Omeprazole inhibits the so called proton pump by inhibiting the enzyme HK+-ATPase of the gastric
parietal cells. Omeprazole is a prodrug which is absorbed from small intestine. Its hepatic metabolite is
responsible for acid reduction.
Uses:
• It is used to treat gastric and duodenal ulcers, not responding to H2 antagonists because its long-term
use is likely to be hazardous.
• It is drug of choice for Zollinger-Ellison syndrome.
• Reflux oesophagitis
• NSAID induced ulcerations and bleeding.
Dose: 20 mg once daily for 4-6 weeks. However, for the treatment of Zollinger-Ellison syndrome higher
doses (up to 80 mg) may be required to be given for longer period.
Side effects: During short-term therapy, it causes nausea, diarrhoea, pain in abdomen, dizziness, and
headache. They are generally mild and do not require reduction in doses.
During long term therapy there occurs: gastrin-stimulated hyperplasia of gastric epithelium and bacterial
overgrowth due to sustained decrease in gastric acidity which converts ingested nitrates into carcinogenic
nitrosamines.

6
Drugs Providing Protection to Mucosa
1- Sucralfate: It is an aluminium containing salt of sucrose octasulfate.
Mode of action:
Sucralfate is a locally acting substance that in an acidic environment (pH < 4) reacts with hydrochloric
acid in the stomach to form a cross-linking, viscous, paste-like material capable of acting as an acid buffer
for as long as 6 to 8 hours after a single dose. It also attaches to proteins on the surface of ulcers, such as
albumin and fibrinogen, to form stable insoluble complexes. These complexes serve as protective barriers
at the ulcer surface, preventing further damage from acid, pepsin, and bile. In addition, it prevents back
diffusion of hydrogen ions, and adsorbs both pepsin and bile acids. Recently, it has been indicated that
sucralfate also stimulates the increase of prostaglandin E2, epidermal growth factors (EGF), and gastric
mucus.
Uses:
• Chronic gastric and duodenal ulcer
• Chronic gastritis.
Since sucralfate is effective only in acid medium, it should not be given along with antacids,
omeprazole or H2 antagonists. It effectively prevents ulcer recurrence.
Dose: 1 gm 6 hourly or 2 gm 12 hourly.
Side effects: It may cause constipation, nausea, dyspepsia, headache, itching and swelling of skin due to
allergy. Rarely aluminium toxicity may occur in renal failure.
2- Carbenoxalone: It is extracted from roots of the plant liquorice. It increases mucus and promotes
healing by increasing endogenous prostaglandin levels. However, this drug has little or no place in the
treatment of peptic ulcer because it retains water and salt causing high blood pressure.
3- Prostaglandins: Prostaglandins (PGE2 and PGI2) maintain gastroduodenal mucosal integrity. Hence,
their reduction (endogenous PG levels) leads to mucosal damage and ulceration. Natural PGs have
transient effects. Hence, synthetic analogues are used. They are:
• Misoprostol (methyl ester of 15 methyl PGE1),
• Enprostil (dehydro PGE2, derivative),
• Rioprostil (methyl PGE1, derivative),
• Arboprostil (15- methyl PGE2), and
• Trimoprostil (trimethyl-11 deoxy derivative of PGE2)
Out of these, misoprostal is available for clinical use. It is given in doses of 200 micrograms four times a
day.

Mode of action:
• They strengthen the so-called mucus bicarbonate barrier by increasing secretion of mucus and
bicarbonate.
• They prevent acid assault on mucosa by increasing phospholipid content of surface epithelium.
• They accelerate ulcer healing by increasing mucosal repair and restitution.
• They have protective effect on parietal cells of the stomach by increasing mucosal blood flow.
Uses:
• Chronic gastritis
• Duodenal ulcer
• NSAID induced ulceration and bleeding
Side effects: Diarrhoea, abdominal pain, nausea, dysmenorrhoea are fairly common. PGs are
contraindicated in pregnancy because they stimulate uterine muscles and can cause abortion or premature
labour.
Anti-Helicobacter Pylori Drugs
Helicobacter pylori or H pylori is a gram-negative bacillus. It has uniquely adopted to survival in the
hostile environment of stomach. It attaches to the surface epithelium beneath the mucus. It has high
urease activity. So it produces ammonia which maintains a neutral microenvironment around the bacteria
and promotes back diffusion of H+ ions.
It is now well know that H. pylori infection is one of the most important aetiological factors for peptic
ulcer. So it is appropriate to treat H. pylori in patients with peptic ulcer. Single drug regimens are not

7
advocated due to the potential for the development of antibiotic resistance. This is particularly true to
macrolides and nitroimidazoles, which are the key antimicrobials in the multi-drug regimens for H.
pylori. At present dual treatment combining a proton pump inhibitor (PPI) with either clarithromycin or
amoxicillin are also not used because of unacceptable low eradication rates.
Possible regimens for H. pylori infection are given in Table 7.1. Table 7.1: Regimen for eradication
of H. pylori.

Table 1
Regimens Dosage Duration H. pylori eradication
(in weeks) (in %)
Omeprazole 20 mg b.i.d. 2 60-80
Clarithromycin 500 mg b.i.d.
Colloidal bismuth subcitrate 120 mg q.i.d. 2 30-95
Tetracycline 500 mg q.i.d.
Metronidazole 400 mg q.i.d.
Omeprazole 40 mg o.d. 1-2 75-90
Amoxicillin 500 mg t.i.d.
Metronidazole 400 mg t.i.d.
Omeprazole 40 mg o.d. or 20 mg b.i.d. 1-2 85-95
Clarithromycin 250 mg b.i.d.
Metronidazole 400 mg b.i.d/t.i.d.
Omeprazole 40 mg o.d. or 20 mg b.i.d. 1-2 85-95
Amoxicillin 1 gm b.i.d.
Clarithromycin 250-500 mg b.i.d.
Omeprazole 20 mg o.d or b.i.d. 1 86-98
Colloidal bismuth subcitrate 120 mg q.i.d.
Tetracycline 500 mg q.i.d.
Metronidazole 400-500 mg q.i.d. or t.i.d.
Ranitidine bismuth citrate 400 mg b.i.d. 1-2 > 90
Clarithromycin 500 mg b.i.d
Metronidazole 500 mg b.i.d /t.i.d.
Comments
Although bismuth based triple therapy consisting of colloidal bismuth subcitrate, tetracycline and
metronidazole for two weeks is cheap, well investigated having high cure rate, it is not used in developing
countries because 80-90% of H. pylori strains are resistant to metronidazole.
So triple therapies with a combination of a proton pump inhibitor and two antibiotics have largely
replaced the use of the classical bismuth based triple therapy in almost all countries.
A new group of triple regimen has been developed which replaces proton pump inhibitor with
Ranitidine bismuth citrate. This regimen causes less acid suppression and also provides additional
antimicrobial action of bismuth. In an attempt to achieve 100 % eradication of H. pylori, a quadruple
therapy combination has been developed.
The major advantages of this regimen over the classical triple therapy are:
a. High and consistent eradication rate
b. A one-week treatment offering a cure rate similar to the classical triple therapy.
c. A significant reduction in complication seen with the two weeks of bismuth based triple therapy.
d. This regimen is also recommended as the rescue line therapy when the first line therapy fails.
3-Emetics, Anti-emetics
Nausea is a desire to vomit. It may or may not culminate in vomiting. Emesis or vomiting is a protective
mechanism. It serves to eliminate harmful substances from the stomach and duodenum. Emesis is a
coordinated act of medullary vomiting center(MVC) and the chemoreceptor trigger zone (CTZ), situated
in the area postrema in the floor of the fourth ventricle. The MVC contains mainly muscarinic cholinergic

8
receptors. CTZ has dopaminergic, histaminergic, muscarinic and serotonergic (5HT3) receptors while the
stomach is rich in dopamine (DA) receptors.
Nausea and vomiting may occur even to a healthy person due to indigestion, unpleasant smell,
unpalatable food, drugs and chemicals, motion sickness and pregnancy. Various diseases such as food
poisoning, acute abdominal emergencies (appendicitis, obstruction of intestines), diseases of the
gallbladder, liver, peritoneum, acute infective illnesses (hepatitis, cholera), meningitis, malaria), heart
diseases (myocardial infarction), etc. may cause nausea and vomiting.
EMETICS
These are the drugs which cause vomiting. Nowadays, they are not indicated in the treatment of
poisoning. Apomorphine is a DA receptor agonist. It stimulates CTZ and is used as an experimental
emetic agent. A large number of drugs (morphine, cytotoxic agents, digitalis glycosides, bromocriptine,
NSAIDs, theophylline etc.) are known to stimulate CTZ and induce nausea and vomiting as side effects.
ANTIEMETICS
They are employed for symptomatic relief of nausea and vomiting. The important anti-emetics are:
1. Phenothiazines (Prochlorperazine, triflupromazine, promethazine, chlorpromazine): These drugs act
by blocking D, receptors in CTZ. These agents are very effective in preventing vomiting due to almost
any cause including radiotherapy and cytotoxic agents. They produce extra-pyramidal symptoms,
drowsiness, hepatotoxicity as adverse effects.
2. Metoclopramide and domperidone: These drugs block D2 receptors in CTZ. They also act
peripherally (prokinetic action) by raising the tone of cardiac sphincter, relaxing pyloric sphincter and
increasing peristalsis of proximal ileum. They are useful to treat vomiting due to wide range of causes.
They are specific benefit in vomiting during anaesthesia and after surgery. Metoclopramide induces
extrapyramidal symptoms on prolonged use, drowsiness, infantile convulsion in large- doses and
hyperprolactinaemia, while Domperidone has lesser extrapyramidal side effects and hyperprolactinaemia.
Prokinetics are a class of drugs used on the digestive system. It includes all drugs whose primary effect is
to augment the speed of intestinal transit, by increasing the frequency of contractions in the small
intestine or making them stronger, but without disrupting their rhythm.
3. Cisapride: Although it is stretcturally related to metoclopramide it is devoid of DA receptor blocking
action. It increases gastrointestinal cholinergic activity and may produce abdominal cramps and
diarrhoea. It has prokinetic effect like domperidone.
4. Antihistaminics: Dimenhydrinate, promethazine, cyclizine, meclizine, cinnarizine are Hl receptor
antagonists. They may act as anti-emetic agents by virtue of significant anticholinergic activity. They are
used in motion sickness and labyrinthine disorders. Drowsiness, dry mouth, blurred vision may occur as
side effects.
5. 5HT3 receptor antagonists (Ondansetron, granisetron, zacopride): They act by blocking the 5-HT
heteroreceptor modulating DA synthesis and release. They are used to control emesis due to radiotherapy
and cytotoxic agents. They also have anti-anxiety effect. Flushing, headache, and constipation may occur
as side effects.
6. Other drugs: Glucocorticoids and nabilone (synthetic cannabinoid) are used with lorazepam and
ondensetron to treat re-fractory emesis due to cytotoxic agents.
Treatment of vomiting associated with pregnancy: Usually, no therapy is required during morning
sickness. However, in severe cases promethazine is used. In hyperemesis gravidarum(excessive vomiting
of pregnant women), pyridoxine supplement along with phenothiazines may be required.