Dr Theresa John Pharmacology Lecture Notes, B Nursing Science, LASUCOM February 2 2022.

Drugs Used in the treatment of Gastrointestinal Diseases

Objectives:

1) Be familiar with the mechanisms of action, clinical uses, examples, and special features of drugs of
the following groups:

 Emetics
 Antiemetics e.g. for chemotherapy-induced emesis
 Digestants, pancreatic supplements, appetite stimulants and carminatives (antiflatulence)
 Drugs for Acid Peptic Disorders: peptic ulcers, gastroesophageal reflux disease (GERD)
 Purgatives
 Antidiarrheals
 Drugs for Gall Stones
 Antiinflammatory Drugs

2) After study of this topic, you should be able to answer the revision questions at the end of these
notes

DRUGS ACTING ON EMESIS

INTRODUCTION

Nausea and vomiting are features of motion sickness, pregnancy, hepatitis, chemotherapy, and other
conditions. Vertigo (a sensation of whirling) and loss of balance (giddiness) may be caused by disease
affecting the inner ear or the vestibular nerve. The area postrema is a structure in the medulla
oblongata in the brainstem that controls the vomiting reflex pathway. The vomiting centre (VC) in the
area postrema initiates and controls the act of emesis, which involves contractions of the digestive tract.
The vomiting centre is mainly activated by (1) nervous impulses (Vagus) from the GIT (involving GIT 5HT3
receptors) and other parts of the body resulting in a reflexive activation; (2) by impulses from the higher
brain centres; and (3) by signals from the chemoreceptor trigger zone (CTZ). The CTZ contains receptors
for dopamine, serotonin, opioids, acetylcholine and substance P. Stimulation of these receptors give
rise to N&V through respective signal pathways. The neurotransmitter substance P (NK1) is found in
high concentrations in the VC and appears to be involved in the final common pathways that give rise to
vomiting. The chemoreceptor trigger zone, which lies outside of the blood-brain barrier, detects emetic
agents (chemicals and hormones) in the blood and communicates with the adjacent nucleus tractus
solitarii (NTS) of the VC. Emetic drugs directly activate the CTZ through dopamine D2 and 5HT3
receptors. Emetogenic chemotherapy releases substance P (NK1) which stimulates the CTZ and the
nucleus tractus solitarii (NTS). The vestibular system of the inner ear functions mainly in motion sickness.
Inputs travel via the eighth cranial nerve or the vestibulocochlear nerve and H1 receptors are abundant
in this system.
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Anti-emetics block the vomiting reflex or centers.

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 Dr Theresa John Pharmacology Lecture Notes, B Nursing Science, LASUCOM February 2 2022.

EMETICS
Emetic drugs are usually administered in emergency situations after ingestion of a toxin or poison. They
remove most of the stomach content. Drugs used act centrally to stimulate the vomiting center directly
or via the CTZ.
Activated charcoal is not an emetic but we mention it as the treatment of choice in acute oral overdose,
used to bind drugs and poisons, preventing their absorption. But it is not useful in all cases. It should
not be used for cyanide, lithium, alcohol, iron tablets or for strong acids or bases. These specific cases of
poisoning are treated with specific antidotes. Activated charcoal used for poisoning is produced as
powder to be mixed with water. Activated charcoal is also available in tablet or capsule forms for
alleviation of gas but this form is not used for poisoning.
Centrally acting drug apomorphine directly stimulates the chemoreceptor trigger zone and vomiting
center.
Reflexly acting ipecacuanha (which contains the alkaloid emetine) directly stimulates receptors in the
gastric and duodenal mucosa, activating the afferent fibres of the vagus nerve leading to the vomiting
center. About 15-30 ml ipecac syrup is given. It takes 15 minutes to produce vomiting.
Locally acting alum, ground mustard seed in water, or concentrated sodium chloride (common salt)
irritate the mucosa causing expulsion of gastric contents. Domestic emetics include strong coffee,
especially for narcotic poisoning.
Emetics are used in:
a. Acute cases of poisoning
b. Alcoholic intoxication
c. Removal of foreign bodies from the oesophagus
All emetics are contraindicated in:
a. Corrosive poisoning with strong acid or strong alkali
b. CNS stimulant drug poisoning
c. Morphine or phenothiazine poisoning
d. Kerosine or petroleum poisoning
e. Unconscious patient
Many drugs produce vomiting as an adverse effect. These include emetine (antiprotozoan),
Morphine (analgesic), apomorphine (dopaminergic agonist in CTZ, antiparkinsonian), aspirin (analgesic),
amiodarone (used in arrhymias), quinine (antimalarial), digitalis (used for CHF), chloroquine
(antimalarial), diltiazem (CCB), ergot derivatives (used against hemorrhage), erythromycin (antibiotic),
tetracyclines (antibiotics), fluroquinolones (antibacterial), metronidazole (semisynthetic antibiotic), and
anticancer drugs.
Anticancer drugs are particularly notorious for causing vomiting.
Highly emetogenic drugs include: cisplatin, nitrogen mustard, carmustine, streptozocin, dacarbazine,
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and dactinomycin.
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 Dr Theresa John Pharmacology Lecture Notes, B Nursing Science, LASUCOM February 2 2022.

Moderately emetogenic drugs include: cyclophosphamide, doxorubicin, carboplatin, mitomycin,

asparaginase, and azacitidine.
Mildly emetogenic drugs include: fluorouracil, methotrexate, etoposide, vincristine, and bleomycin

DRUGS USED AS ANTIEMETICS

Antiemetics may act on the VC or on the CTZ.

The 7 classes of drugs used as antiemetics are: serotonin (5HT ) receptor antagonists, dopamine
receptor antagonists, histamine receptor antogonists,
antimuscarinics, neurokinine 1 receptor antagonists,
cannabinoids, and corticosteroids.

Antiemetic actions on the VC are generally through

anticholinergic or antihistaminergic actions.

Antiemetic actions on the CTZ are generally through

antidopaminergic or 5HT3 antagonist action.

SEROTONIN RECEPTOR BLOCKERS:

The 5HT3 receptor antagonist ondansetron is used in treating

highly emetogenic chemotherapy . It is effective and long
acting. A single i.v or p.o. dose is given prior to chemotherapy.
Its side effects are headache and electrocardiographic changes.
Other serotonin antagonist antiemetics are granisetron,
tropisetron, palonosetron, and dolasetron.

PHENOTHIAZINES AND BUTYROPHENONES

Some antipsychotic drugs (neuroleptics) that block dopamine

receptors have antiemetic properties against moderately
emetogenic chemotherapy, post anesthetic N&V, disease *
induced vomiting (e.g. gastroenteritis, uraemia, liver disease)
and to a lesser extent in radiation sickness and morning sickness. An example is the phenothiazine
prochlorperazine (Compazine, Stemetil) which has D2 blocking properties and suppresses the labyrinth,
producing antivertigo and antiemetic actions. Chlorpromazine (Thorazine), thiethylperazine (Torecan),
perphenazine (Trilafon), and promethazine (Phenergan) are also used.

Other drugs are antipsychotic butyrophenones droperidol (Inapsine), and haloperidol (Haldol). They
may be used against cancer chemotherapy induced emesis but they have adverse extrapyramidal effects
and are sedative. In endoscopy, the sedative effect of droperidol is helpful when the drug is used in
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combination with painkiller opioids and relaxing benzodiazepines. Domperidone (Motilium) is another
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antiemetic butyrophenone.
 Dr Theresa John Pharmacology Lecture Notes, B Nursing Science, LASUCOM February 2 2022.

DOPAMINE D2 RECEPTOR BLOCKERS

Domperidone is also a peripheral D2 receptor antagonist and a motility stimulant. It is used as an

antiemetic, gastroprokinetic, and galactogogue. It is given orally or rectally.

SUBSTITUTED BENZAMIDES

Metoclopramide (Reglan) is a prokinetic that acts on the GIT, stimulating gastric peristalsis and gastric
emptying. Metoclopramide blocks dopamine D2 receptors both in the CTZ and peripherally. It is used to
treat and prevent nausea and vomiting, to promote emptying of the stomach in delayed gastric
emptying, and in gastroesophageal reflux disease. It acts through D2 and 5HT antagonism and has
limiting extrapyramidal CNS side effects. It causes sedation, diarrhea, and extrapyramidal symptoms
and releases prolactin. It crosses the placenta and is secreted in milk. Metoclopramide,
trimethobenzamide (Tigan), alizapride (Plitican), and cisapride (Propulsid) are various substituted
benzamides that are active in high doses against strongly emetogenic chemotherapy and other forms of
emesis but not in motion sickness.

ANTICHOLINERGICS AND H1- ANTIHISTAMINERGICS

Motion sickness responds to anticholinergics and H1antihistaminergics. Antidopaminergics do not work.

For morning sickness, drugs should be avoided and are a last
resort. Some muscarinic receptor antagonist such as
scopolamine (Transderm-Scop) and H1-receptor antagonists
such as diphenhydramine (Benadryl) are useful in motion
sickness but not useful against emetics that act directly on the
chemoreceptor trigger zone. Scopolamine (hyoscine) blocks the
cholinergic connection of the vestibular apparatus to the
vomiting centre. Amongst antihistamines (which may also have
anticholinergic, and antidopaminergic actions): cyclizine is used
for motion sickness, meclizine with long duration of action is
used for sea sickness, cinnarizine (which inhibits Ca influx in the
endolymph) is used for motion sickness and vestibular disorders
(antivertigo) , promethazine (Amovine) is used for severe
morning sickness of pregnancy when necessary, and
dicyclomine is used for prophylaxis of motion sickness and
morning sickness. They are generally not used in chemotherapy *
but promethazine or diphenhydramine are combined with metoclopramide for CINV for additive emetic
effect and to lower extrapyramidal effects of metoclopramide. Doxylamine is marketed combined with
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pyridoxine for morning sickness.

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 Dr Theresa John Pharmacology Lecture Notes, B Nursing Science, LASUCOM February 2 2022.

MARIJUANA

Cannabinoid receptors are found all over the body. Marijuana effects on the brain are complex and
include effects on the VC and appetite center. Specific cannabinoids are used as antiemetics.
Dronabinol (Marinol) is used to treat nausea and vomiting, including CINV when other treatments are
not effective. It is also used to treat loss of appetite. Chronic use causes withdrawal symptoms such as
irritability, insomnia, diarrhea, hot flashes. Nabilone (Cesamet) is another cannabinoid antiemetic.

BENZODIAZEPINES

Benzodiazepines inhibit CNS GABA receptors resulting in numerous effects (sedative, hypnotic,
anxiolytic, antiepileptic, and muscle relaxant properties).

The drugs lorazepam (Ativan) and alprazolam (Xanax) are weak

anti-emetics but their other beneficial effects such as sedative,
anxiolytic, and amnesic properties make them useful.
Lorazepam is used as prophylaxis before chemotherapy. It is
sometimes used in cases when other antiemetics have failed.

CORTICOSTEROIDS

Dexamethasone (Decadron) and methylprednisolone (Medrol)

effectively prevent CINV. The mechanism of action in this is
not clear.

NK1 (SUBSTANCE P) RECEPTOR ANTAGONIST

Aprepitant and other NK1 receptor antagonists block substance

P (neurokinin 1) that causes vomiting. These drugs block emesis
through the area postrema, nucleus tractus solitarius, and
visceral efferent nerves. They prevent both centrally and *
peripherally induced vomiting. They prevent delayed emesis
which can occur in some patients on cancer chemotherapy.
Such delayed emesis may not respond to the 5HT antagonists
which block only the acute emesis. Aprepitant which crosses the bbb is used with other antiemetic
medications as prophylaxis against CINV and to prevent N&V after surgery. Aprepitant is given orally or
IV. Rolapitant has a half-life of 180h and is used for CINV. Fosaprepitant is given by IV infusion and is
rapidly converted to aprepitant. Netupitant-palonosetron is an oral combination medication.

COMBINATION ANTIEMETIC THERAPY:

All the strong antiemetic drugs: serotonin antagonists, substituted benzamides, phenothiazines,
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butyrophenones, and corticosteroids are powerful antiemetics but have serious side effects. Anti-
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 Dr Theresa John Pharmacology Lecture Notes, B Nursing Science, LASUCOM February 2 2022.

emetic drug combinations with secondary drugs are necessary in order to decrease the toxicity of
primary drugs.

Examples of combinations are:

 dexamethasone and ondansetron

 dexamethasone, diphenhydramine, metoclopramide and droperidol.
 lorazepam, dexamethasone and metoclopramide
 diphenhydramine, dexamethasone and metoclopramide

DIGESTANTS AND PANCREATIC SUPPLEMENTS

A digestant is a substance, such as hydrochloric acid or a bile salt or enzyme, that promotes or aids
digestion. Examples are pancrelipase and lactase enzyme tablets. They are used in pancreatic
insufficiency. Pharmaceutical products may be a combination of various components which
synergistically aid digestion. For example: Zypan® is a combination of pancreatin, pepsin, and betaine
hydrochloride, and pH balance. The pancreatin is coated with stearic acid to protect it from stomach
acid and allow it reach the intestine. Another preparation, papaya, is from Carica papaya (paw paw).

Pancreatic supplements are used for digestive disorders based on pancreatic dysfunction or pancreatic
insufficiency, (but not recommended for cystic fibrosis and chronic pancreatis). Pancreatin is an extract
of pancreas containing protease, lipase, and amylase. H2 antagonist and PPIs given beforehand prevents
inactivation by gastric acid and pepsin. Enteric coated formulations deliver enzymes to the duodenum
safely and do not need acid inhibitors. Enzyme doses are individually regulated and depends on feeding,
e.g. for lipase, 50,000 -75,000 units with a meal and 25,000 units with a snack may be used. Pancreatic
enzyme preparations include Creon®, Nutrizym®, Pancrease® and Pancrex®.
Exocrine pancreatic insufficiency is often treated with addition of supplements of the fat-soluble
vitamins A, D, E, and K. Antioxidants such as vitamin C and selenium are used to help decrease
inflammation

APPETITE STIMULANTS

These include centrally acting adrenergic agents: benzphetamine, phentermine, diethylproprion,

mazidol, phendametrazine, phenylpropanolamine; serotonergic agents: dexfenfluramine,
fenfluramine, floxetine. Sibutramine works via adrenergic and serotonergic receptors.

CARMINATIVES

These drugs promote expulsion of gas (flatulence) from the GIT. They include sodium bicarbonate,
peppermint oil, cardamom tincture, oil of dill, and ginger tincture.
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 Dr Theresa John Pharmacology Lecture Notes, B Nursing Science, LASUCOM February 2 2022.

DRUGS FOR ACID PEPTIC DISORDERS

Acid-peptic disease includes peptic ulcers which may be gastric or duodenal, gastroesophageal reflux,
and pathologic hypersecretory states such as Zollinger-Ellison Syndrome.

Causative factors for acid peptic disorders include:

 Non-steroidal anti-inflammatory drug (NSAID) use

(aspirin, indomethacin, ibuprofen, etc.)
 infection with gram-negative Helicobacter pylori (95%
duodenal ulcers, 70% gastric ulcers)
 hypersecretion of gastric hydrochloric acid secretion and
pepsin
 inadequate mucosal defense against gastric acid

Treatments include:

1) Eradicating H. pylori infection with antimicrobial drugs.

H. pylori infection is diagnosed by endoscopic biopsy of the

gastric mucosa or noninvasively by serology and urea breath test.

Treatment of H. pylori infection is by two weeks treatment with:

triple therapy: a proton pump inhibitor (PPI) is used with either

metronidazole or amoxicillin plus clarithromycin

OR

quadruple therapy: bismuth subsalicylate, metronidazole,

tetracycline plus a PPI

2) Reducing gastric acid. Parietal cells of the gastric mucosa

secrete hydrochloric acid. Acetylcholine, histamine, and
gastrin all stimulate their own receptors which in turn activate
protein kinases that switch on the proton pump (H+/K adenosine
triphosphatase (ATPase). This pump exchanges ions: K+ for
hydrogen ions. The hydrogen ions are secreted into the lumen of
the stomach. *

On the other hand prostaglandin E2 via binding to its own

receptors diminishes gastric acid production.

 Decreasing secretion is achieved by using H2-receptor antagonists and PPIs

 Neutralizing acidity is achieved by using antacids
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 Dr Theresa John Pharmacology Lecture Notes, B Nursing Science, LASUCOM February 2 2022.

**

3) protecting the gastric mucosa with

 Increased bicarbonate mucus secretion – by using misoprostol a prostaglandin analogue

 Protective coating with sucralfate.

HISTAMINE H2-RECEPTOR ANTAGONISTS

The drugs cimetidine, ranitidine, famotidine, and nizatidine are histamine H2-receptor antagonists
which, given at bedtime, are effective against nocturnal acid secretion (which depends largely on
histamine). They competitively block the binding of histamine to H2 receptors and their actions are fully
reversible. Because they reduce acid secretion, they are used for acid-peptic disorders such as

 duodenal and gastric ulcers but recurrence is common if H. pylori is present and antimicrobials
are not given
 acute stress ulcers for which H2-receptor antagonists (except nizatidine) are given by
intravenous infusion, tolerance may occur
 gastroesophageal reflux disease or heartburn for which low doses of H2-receptor antagonists are
used. It may take about 1h for symptoms to be relieved.
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H2 blockers may be given orally or iv.

 Dr Theresa John Pharmacology Lecture Notes, B Nursing Science, LASUCOM February 2 2022.

Pharmacokinetics and side effects of H2-receptor antagonists

These drugs are given orally or iv.

Cimetidine is given by 800mg daily doses.

Cimetidine is notable because it inhibits cytochrome P450

isoenzymes. Thus the metabolism of another drug given
concomitantly can be slowed if the drug metabolism depends
on one of these enzymes. Toxic drug reactions are a potential
for warfarin, diazepam, phenytoin, quinidine, carbamazepine,
theophylline, and imipramine which are metabolized by these
enzymes.

Cimetidine also produces antiandrogenic (prolactin-

stimulating) effects. It can cause gynecomastia and
galactorrhea, Cimetidine is metabolized by the liver.

Ranitidine is longer acting and is 5-10 fold more potent than

cimetidine in reducing acid secretion. At the daily dose, 300mg,
ranitidine lacks the side effects of cimetidine. It is metabolized
by the liver.

Nizatidine is similar to ranitidine in action and potency.

Nizatidine is eliminated mainly by the kidney.

Famotidine is 20 -50 times more potent than cimetidine. It is

metabolized by the liver.

Side effects of H2-receptor antagonists include headache,

dizziness, diarrhea, and muscular pain, reversible
gynocomastia, elevated serum prolactin and galactorhea,
altered estrogen metabolism in men, inhibition of hepatic p450
enzymes. Hepatic metabolism of drugs such as warfarin, *
phenytoin, and theophylline may be inhibited. In the elderly or
in patients given the drugs intravenously other central nervous system effects that may occur are
confusion and hallucinations.

PROTON PUMP INHIBITORS

The drugs omeprazole, dexlansoprazole, lansoprazole, rabeprazole , pantoprazole, and esomeprazole

are inhibitors of the H+/K+-ATPase proton pump. They irreversibly block the proton pump suppressing
acid secretion until new H+/K+-ATPase is produced (this takes about 18 hrs).
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 Dr Theresa John Pharmacology Lecture Notes, B Nursing Science, LASUCOM February 2 2022.

They are weak bases and are therefore produced as pro-drugs. The pro-drugs have an acid-resistant
enteric coating which protects them from degradation by gastric acid. In the alkaline medium of the
duodenum, the coating is removed and the pro-drug, a weak base in alkaline medium, is absorbed into
the circulation and reaches the parietal cell where it is converted to the active form within the acid
medium of the parietal cell.

Proton pump inhibitors react with a cysteine residue of the H+/K+-ATPase to form a stable covalent
bond. This is why the acid inhibitory action is irreversible and acid secretion only begins again with
synthesis of new enzyme.

Onset of action is quick, under 1 h; except lansoprazole which takes 1-2 h.

Oral omeprazole combination product with sodium bicarbonate is produced for faster absorption.

They cause diminished acidity over a long period which allows peptic ulcers to heal. PPIs are used to heal
chronic peptic ulcer and acid peptic diseases. In addition:

1. PPIs reduce the risk of bleeding from ulcer caused by aspirin and other NSAIDs.
2. PPIs are used with antimicrobial regimens to eradicate H. pylori.
3. PPIs are used for stress ulcer treatment and prophylaxis.
4. PPIs are used to treatment gastro-esophageal reflux disorder (GERD), erosive esophagitis, and
active duodenal ulcer.
5. PPIs are used for Zollinger-Ellison syndrome (a pancreatic gastrin-producing tumor which causes
hypersecretion of HCl), sytemic mastocytosis and multiple endocrine neoplasia.

Pharmacokinetics and side effects of PPIs

PPIs are produced as delayed-release formulations, are given orally, and have a half-life of 1.5hrs. They
can inhibit 100% gastric acid secretion with a single daily dose.

For maximum effect, PPIs should be taken 30 minutes before breakfast or the largest meal of the day.
H2 antagonists reduce the activity of the proton pump and PPIs require active pumps to be effective. If
an H2-receptor antagonist is also needed, it should be taken well after the PPI for best effect. PPI
metabolites are excreted in urine and feaces.

Adverse side effects of PPIs include: nausea, diarrhea, headache, GI disturbance and bone fractures
(there is increased risk with long-term (1 year or greater) use and the hip, wrist, and spine may be
affected).

PROSTAGLANDINS

Prostaglandin E1 and E2 are naturally produced by the gastric mucosa. This is part of the stomach’s
homeopathic mechanisms. They stimulate secretion of mucus and bicarbonate and increase mucosal
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blood flow when needed. They are cytoprotective. PGE2 inhibits secretion of HCl.
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Pathogenesis of peptic ulcers involves deficiency in prostaglandin E2.

 Dr Theresa John Pharmacology Lecture Notes, B Nursing Science, LASUCOM February 2 2022.

Misoprostol is the synthetic prostaglandin used therapeutically. It is a stable analog of prostaglandin E1.

Misoprostol may be used prophylactically in patients who are taking noxious NSAIDs, such as elderly
patients and those with ulcer recrudescence.

Misoprostol produces uterine contractions and is contraindicated during pregnancy.

Dose-related diarrhea and nausea are the most common adverse effects.

ANTIMUSCARINIC AGENTS

Cholinergic muscarinic receptor stimulation increases gastrointestinal motility and secretory activity.
Not all antimuscarinics are useful in peptic ulcers; they have numerous effects.

Dicyclomine can be used as an adjunct in the management of peptic ulcer disease. Its side effects such
as cardiac arrhythmias, dry mouth, constipation, and urinary retention, limit its use.

ANTACIDS

Antacids are weak bases. They react with gastric acid to form a salt and water. This diminishes gastric
acidity (increase gastric pH). The digestive enzyme pepsin (a protease) is inactive at a pH greater than 4.
Antacids thus reduce peptic activity and pathologic auto-digestion associated with some ulcers.

Antacids immediately and efficiently neutralize stomach acid. However this action is temporary and
depends on amount of food in the stomach. Delayed gastric emptying because of presence of food
allows more time for the antacid to react.

Systemic antacids include: calcium, aluminum, or magnesium based antacids. Nonsystemic antacid is
sodium bicarbonate.

Calcium carbonate (CaCO3) reacts with HCl to form CO2 and CaCl2 and is commonly used. It causes acid
rebound more than NHCO3. Insoluble calcium carbonate and calcium stearate can cause nephrolithiasis
and fecal compaction. Repeated use can produce milk-alkali syndrome (excess calcium in the body).

Aluminum- and magnesium-containing antacids are used for symptomatic relief of peptic ulcer disease
and GERD. They may also promote healing of duodenal ulcers.

Aluminum hydroxide gel forms a protective layer that helps to protect ulcers. Aluminum ions inhibit
pepsin directly. This adds to the increased pH effect of aluminum hydroxide in decreasing peptic
activity. Aluminum hydroxide reacts with HCl to form insoluble aluminum chloride which causes
constipation.

Magnesium hydroxide (milk of magnesia) forms poorly absorbed magnesium salts and produces
diarrhea.
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Magnesium trisilicate is slow acting and with a more sustained effect than other antacids. It forms a
silicon dioxide gelatinous adsorbent mass which prolongs the antacid effect. The magnesium produces
diarrhea.

Preparations that combine both aluminum and magnesium are used in an effort to maintain normal
bowel function.

NaHCO3 is water soluble. It acts rapidly and has a transient action. Tends to cause rebound secretion of
gastric acid neutralizing its effect thus may need once an hour dosing to maintain its effect. It should
only be used for a short time because absorbed salt may cause systemic alkalosis and alkaline urine.

MUCOSAL PROTECTIVE AGENTS

Cytoprotective agents enhance mucosal protection mechanisms. They may prevent mucosal injury,
reduce mucosal inflammation, and promote mucosal healing.

Sucralfate

This is a complex of aluminum hydroxide and sulfated sucrose. It polymerizes at pH 4. It forms complex
gels with epithelial cells, selectively binding with necrotic ulcer tissue, thus creating a physical barrier
against back-diffusion of HCl, pepsin or bile. It prevents degradation of the mucosa by pepsin and acid.
It may also absorb bile salts and stimulate endogenous prostaglandins. Sucralfate prevents stress ulcers
and is also effective in the treatment of duodenal ulcers.

Sucralfate requires acid medium to act and should not be taken with H2 blockers or PPIs.

It requires multiple daily dosing and produces drug–drug interactions within the GI thus its therapeutic
usefulness is limited.

Bismuth subsalicylate

This cytoprotective preparation has multiple actions: antimicrobial against H. pylori and antipeptic
actions and increased mucus secretion, plus interaction with glycoproteins in necrotic mucosal tissue to
coat and protect the ulcer. Bismuth can be combined with antibiotics such as metronidazole and
tetracycline to obtain high healing rates of peptic ulcers. Bismuth blackens teeth and stool.

PROKINETICS

These drugs are used for gastroesophageal reflux and gastroparesis (delayed gastric emptying).
Cisapride and metoclopramide act on 5HT3 and dopamine D2 receptors in gastric smooth muscle and
accelerate gastric emptying. Cisapride stimulates the release of acetyl choline in the myenteric plexus
resulting in increased esophageal sphincter tone and decreased reflux.

Side effects of these drugs are diarrhea, drowsiness, extrapyramidal effects (parkinsonism and tardive
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dyskinesia).
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DRUGS USED AS ANTIDIARRHEALS

The major factors in diarrhea are increased motility of the gastrointestinal tract and decreased
absorption of fluid.

Antidiarrheal drugs include

1) antimotility agents
2) adsorbents,
3) fluid and electrolyte transport modifiers.

ANTIMOTILITY AGENTS

Drugs that activate presynaptic opioid receptors in the enteric nervous system inhibit acetylcholine
release and decrease peristalsis. Drugs with such action that are used as antimotility agents are
morphine-like agents: diphenoxylate and loperamide. Their side effects include drowsiness, abdominal
cramps, and dizziness. They should not be used in young children or in patients with severe colitis.
Diphenoxylate is also combined with anticholinergic atropine.

ADSORBENTS

Drugs used as absorbents:

 adsorb intestinal toxins or microorganisms and/or

 coat or protect the intestinal mucosa.

Examples are methylcellulose and aluminum hydroxide.

Kaolin and pectin increase viscosity of the gut contents and also adsorb bacteria and toxins.

Adsorbents are not as effective as antimotility agents and produce luminal drug-drug interactions.

FLUID AND ELECTROLYTE TRANSPORT MODIFIERS

Bismuth subsalicylate decreases fluid secretion in the gut. It is used for traveller’s diarrhea. It causes
black tongue and black stools.

DRUGS USED AS LAXATIVES

Laxatives accelerate movement of gut contents. They cause electrolyte imbalances when used
chronically. They may cause dependence. Chronic stimulation of the colon can lead to chronic colonic
distention and therefore perpetuation of the perceived need for laxatives.
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1) Stimulant laxatives
2) Bulk laxatives
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3) Saline and osmotic laxatives

 Dr Theresa John Pharmacology Lecture Notes, B Nursing Science, LASUCOM February 2 2022.

4) Stool softeners
5) Lubricant laxatives
6) Chloride channel activators

STIMULANTS LAXATIVES

Senna is a natural compound containing sennosides which are anthraquinone glycosides. It is a widely
used orally active drug. It clears the bowels within 8-10 hours. It also stimulates water and electrolyte
secretion into the bowel .

Bisacodyl is a potent stimulant of the colon acting directly on nerve fibers in the mucosa. It is available
as suppositories and enteric-coated tablets.

Castor oil is broken down in the gut to ricinoleic acid, a powerful irritant and stimulant of peristalsis. It
should be avoided in pregnant women because of potential for stimulating uterine muscles.

Phenolphthalein was included in many OTC laxatives for many decades but it is now known to cause
cancer.

BULK LAXATIVES

Bulk laxatives are indigestible polysacharrides such as cellulose (bran) derived from fruits and
vegetables, ispaghula, and agar. They include hydrophilic colloids that form gels in the large intestine,
cause water retention, increased bulk of stool, and intestinal distension, thereby inducing peristaltic
activity. Bran, methylcellulose, and psyllium seeds are used for chronic constipation.

SALINE AND OSMOTIC LAXATIVES

SALTS

Saline cathartics are non-absorbable salts (anions and cations) that hold water in the intestine by
osmosis. Commonly used preparations are magnesium citrate, sodium phosphate, and magnesium
hydroxide. Dietary fibres are also used.

Water distention of the bowel increases intestinal activity and produces defecation within a few hours.

OSMOTICS

Lactulose is a semisynthetic disaccharide sugar. Given orally, it takes 48 hours to act and must be given
regularly. It is not susceptible to intestinal enzymes but is degraded by colonic bacteria into lactic,
formic, and acetic acids creating osmotic pressure, causing fluid accumulation, colon distension, soft
stools, and defecation.

Lactulose is also used for the treatment of hepatic encephalopathy because it reduces ammonia levels.
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Sorbitol is non-absorbable and attracts water.

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 Dr Theresa John Pharmacology Lecture Notes, B Nursing Science, LASUCOM February 2 2022.

COLONIC LAVAGE SOLUTIONS

Electrolyte solutions containing polyethylene glycol (PEG) are used as colonic lavage solutions in
preparation for radiologic or endoscopic procedures.

STOOL SOFTENERS

These are emollient laxatives or surface-active agents (surfactants) that become emulsified with the
stool, softening it and easing passage. Detergents such as dioctyl sodium sulfosuccinate (docusate
sodium), docusate calcium, and docusate potassium may take days to act and are typically used for
prophylaxis rather than acute treatment. Ducosate is often used when it is necessary to avoid straining
to pass stool such as after a heart attack or after surgery.

LUBRICANT LAXATIVES

Mineral oil and glycerin suppositories facilitate the passage of hard stools. Arachis oil (groundnut oil,
pea nut oil) administered in enemas is used to soften stool and promote bowel movement. Some
people are allergic to groundnuts. Sodium sulphate enema is also used.

CHLORIDE CHANNEL ACTIVATORS

Lubiprostone activates chloride channels thereby increasing fluid secretion into the intestinal lumen
without change in electrolyte balance. The fluid facilitates the passage of luminal contents and eases
stooling. It is quickly metabolized in the stomach and jejunum. It can cause nausea. It is used for chronic
constipation because it is not associated with tolerance or dependence or luminal drug-drug
interactions (because of little time in the lumen) .

DRUGS USED TO DISSOLVE GALLSTONES

Small calcified bile stones may be dissolved with prolonged oral administration of the bile acid
ursodeoxycholic acid, an inhibitor of enzymatic production of cholesterol.

ANTIINFLAMMATORY DRUGS

These are used for Crohn’s disease which affects the entire gut or ulcerative colitis which affects

only the large bowel.

Local and systemic corticosteroids such as prednisolone are used for attacks but not for maintenance
because of their side effects. Oral budesonide is an exception because it is a slow release formulation
and does not suppress the adrenals.
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Amino salycilates are used for mild disease or for maintenance after glucocorticoids. Sulfasalazine
(combination of 5-aminosalicylic acid and the carrier sulphonamide sulphapyridine) is cleave by colonic
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 Dr Theresa John Pharmacology Lecture Notes, B Nursing Science, LASUCOM February 2 2022.

bacteria releasing active drug 5 aminosalicylic acid. The sulphonamide is absorbed and produces side
effects (nausea, rashes, blood disorders).

Mesalazine , olsalazine, are less toxic 5-aminosalicylate drugs (without sulphonamide).

Inflammatory bowel disease that does not respond to corticosteroids or salicylates may be treated with
immunosuppressant azathioprine, mercaptopurine, methotrexate, or the anti TNF-alpha antibody
infliximab.

REVISION QUESTIONS

 Discuss the use of drugs as emetics and anti-emetics

 Write an essay on H2-receptor antagonists.
 Discuss the use of proton pump inhibitors.
 Classify, giving examples, and explain the mechanisms of action of drugs used to treat
diarrhea.
 Discuss the properties of various drugs used as laxatives.
 Write an essay on the treatment of peptic ulcer.
 Write short notes on digestants, pancreatic supplements, appetite stimulants, and
carminatives.

REFERENCES

Illustrations marked * are taken from:

Lippincott Illustrated Reviews. Pharmacology. 6th Edition. Ed: Harvey R. A.

Illustrations marked** are taken from

Lippincott’s Illustrated Reviews. Pharmacology. 2nd Edition. Ed: Harvey R. A. and Champe P.C.

Other texts used are:

Basic and Clinical Pharmacology, Lange, 11th Edition,. Eds: Katzung B. G., Masters S. B., and Trevor A. J.

Godman and Gilman’s The Pharmacological Basis of Therapeutics. 13th Edition. Eds: Brunton L. L. , Hilal-
Dandan R. and Knollmann B. C.
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