Drugs Affecting

GI Functions
 I. Treatment of Peptic Ulcer
Acid-peptic diseases include hyperacidity, GERD
(gastro-esophageal reflux disease), stress induced
mucosal erosions and peptic ulcers (gastric or
duodenal). A localized loss of gastric or duodenal
mucosa leads to the formation of peptic ulcer. Peptic
ulcer arises when the mucosal protective factors are
impaired and aggressive factors dominate. Ulcers
occur five times more in the duodenum
(predominantly in the duodenal bulb and pyloric
channel). Benign gastric ulcers are located mainly in
the antrum.
The Nobel Prize in Physiology or Medicine (2005) was awarded jointly
to Barry J. Marshall and J. Robin Warren "for their discovery of the
bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease"
J. Robin Warren (2005) Barry J. Marshall (2005)
A. Antacids (Drugs Neutralizing Gastric Acid)

Antacids are weak bases that neutralize gastric hydro-

chloric acid. They raise the pH of the stomach contents,
decrease the acid load delivered to the duodenum and
reduce the activity of pepsin. Antacids are given between
meal and at bed time when symptoms of hyperacidity
usually occur; the presence of food in the stomach can
prolong their neutralizing capacity.

1.Systemic Antacids: Sodium bicarbonate acts rapidly,

has a brief effect and raises the pH of gastric secretion to
7.4. On neutralizing gastric asid (HCl), it forms carbon
dioxide (CO2) and sodium chloride (NaCl).
Formation of CO2 results in gastric distention and belchi
that can be dangerous if ulcer is near perforation. Unrea
alkali is absorbed and can raise the pH of blood (system
alkalosis) and the urine. Absorption of NaCl may increas
sodium load and this may exacerbate fluid retention in
patients with hypertension and CHF. The sudden releas
of CO2 can cause “rebound acidity”.

2. Non-systemic Antacids are poorly absorb

a) Buffer Type Non-systemic Antacids
•Aluminium hydroxide
•Magnesium trisilicate
•Magaldrate
These drugs have slow onset but longer effect and raise
the gastric pH to 3.5–4. The pepsin activity is inhibite
around pH 4. “Rebound acidity” is not a problem.
Aluminium hydroxide and Magnesium trisilicate neu
ralize gastric hydrochloric acid to form aluminium chlorid
and magnesium chloride which further react with intest
bicarbonates to form aluminium carbonate and magnes
carbonate. Sodium chloride formed in these reactions g
reabsorbed to compensate the loss of chlorides during
gastric acid neutralization. Buffer type non-systemic
antacids do not disturb the acid-based balance of the b
Aluminium hydroxide can cause constipation and
Magnesium trisilicate – diarrhoea, as a side effect.
Magaldrate is a hydrated complex of Aluminium and
Magnesium hydroxide sulfate.

b) Non-Buffer Type Antacids (Calcium carbonate

and
Magnesium hydroxide) are powerful drugs with fast
onset
of action, and raise gastric pH > 7.
Like Sodium bicarbonate Calcium carbonate may
cause
belching due to liberation of carbon dioxide. It can
cause
constipation too, due to formation of calcium stearate.
Magnesium hydroxide does not liberate carbon
and therefore has water-repellent properties. It acts as
an antifoaming agents and reduces gastric flatulence. It
not absorbed from GIT.

B. Drugs, Reducing Gastric Acid Se

1. Proton Pump Inhibitors (PPIs)

•Esomeprazole
•Lansoprazole
•Omeprazole
•Pantoprazole
•Rabeprazole
PPIs are the most widely used drugs for peptic ulcer
PPIs are prodrugs. In the parietal cells they undergo
molecular rearrangement to sulfenamide cation
(active metabolite). This cation makes a covalent
disulfide bond with –SH group of gastric proton pump
H+/K+-ATPase. Thereby PPIs inactivate the proton pum
irreversibly and shut off the acid secretion.
PPIs also inhibit gastric mucosal carbonic anhydrase
and reduce bicarbonate secretion to mucus.

ADRs: diarrhoea, headacke, inhibition of vitamin B12,

hypochlorhydria and risk of enteric infections.
2. Antagonist of H2-receptors (H2-blockers)
 – for treatment of peptic ulcer:
•Cimetidine (? …)
•Famotidine
•Nizatidine
•Ranitidine
•Roxatidine

3. Prostaglandin analogues

•Misoprostol (PGE1) and Enprostil (PGE2)
4. Anticholinergics (M1-blockers)
•Pirenzepine and Telenzepine
C. Mucosal Protective Drugs
•Sucralfate (aluminium salt of sulfated sucrose) in acidic
environment (pH < 4) polymerizes and forms a gel over
ulcer crater which acts as acid resistant physical barrier
also stimulates mucosal synthesis of PGE2 and secretio
of bicarbonates. Sucralfate is administered orally. It is n
effective in preventing or healing NSAIDs induced ulcer
•Colloidal Bismuth Subcitrate in gastric acidic media
converts into bismuth oxychloride and bismuth citrate w
chelate glucoproteins and amino acids at ulcer base to
an acid resistant coating. It stimulates PGE, mucus and
D. Anti-Helicobacter Pylori Drugs

Peptic ulcer, although a multifactorial disease, al

due to colonisation of mucosa by H. pylori: in 90%
with duodenal ulcers, 60 to 70% – with gastric ulce
50% in patients with non-ulcer dyspepsia. H. pylor
accepted as a cause of chronic atrophic gastritis to
risk factor for gastric adenocarcinoma and to some
extent for non-Hodgkin’s lymphoma affecting stom
H. pylori produces urease which hydrolyses urea in
H. pylori infection can be detected by a “urea breath te
but the test is not used after the treatment with PPIs.
Since H. pylori becomes less virulent in absence of acid
a combination of an antibiotic with PPIs (or H2-blockers
more efficacious in eradicating this Gram (–) bacterium.

Preferred anti-Helicobacter pylori Comb

•Dual therapy (7–10 days).
 Omeprazole (40 mg OD) + Amoxicillin (1000 mg BD)

•Triple therapy (14 days)

 Omeparzole (or lanzoprazole), plus Clarithromycin,
 plus Amoxicilin (resp. Metronidazole, or Tetracycline)
Treatment of
Peptic Ulcer
Action of Anti-Ulcer drug groups
 Antacids

 Weak bases that neutralise acid

 Also inhibit formation of pepsin
(As pepsinogen converted to pepsin at acidic pH)
 Present day antacids :
Aluminium Hydroxide
Magnesium Hydroxide
 Not part of Physician prescribed regimen
 OTC drug for symptomatic relief of dyspepsia
 Antacids – cont…

Duration of action :
 30 min when taken in empty stomach
 2 hrs when taken after a meal
Side effects :
 Al3+ antacids – constipation (As they relax gastric
smooth muscle & delay gastric emptying)
 Mg2+ antacids – Osmotic diarrhoea .
 In renal failure Al3+ antacid – Aluminium toxicity
&
Encephalopathy
 Antacids – Common additives

 Simethicone – Decrease surface tension ,thereby

reduce bubble formation
Added to prevent reflux .
 Alginates - Form a layer of foam on top of
gastric contents & reduce reflux
 Oxethazaine – Surface anaesthetic
 Antacid - Interactions

 Adsorb drugs and form insoluble complexes

that are not absorbed .

Clinical importance :
Interactions can be avoided by taking
antacids 2 hrs before or after ingestion of other
drugs .
 Now answer this question

 Is it rational to combine aluminium hydroxide

and magnesium hydroxide in antacid
preparations ?
 Answer

 Combination provides a relatively fast and

sustained neutralising capacity .
(Magnesium Hydroxide – Rapidly acting
Aluminium Hydroxide - Slowly acting )

 Combination preserves normal bowel function.

(Aluminium Hydroxide – constipation
Magnesium hydroxide – diarrhoea )
 Histamine H2 Receptor Antagonist
 Reversible competitive inhibitors of H2 receptor

 Highly selective, No action on H1 or H3

receptors
 Very effective in inhibiting nocturnal acid
secretion ( as it depends largely on Histamine )
 Modest impact on meal stimulated acid
secretion (As it depends on gastrin, acetyl
choline and histamine)
 Cimetidine Ranitidine Famotidine Nizatidine

Bioavailability 80 50 40 >90
Relative Potency 1 5 -10 32 5 -10
Half life (hrs) 1.5 - 2.3 1.6 - 2.4 2.5 - 4 1.1 -1.6
Duration of 6 8 12 8
action (hrs)
Inhibition of 1 0.1 0 0
CYP 450
Dose mg(bd) 400 150 20 150
H2 Blockers–Side effects & Interactions

 Extremely safe drugs

 Cimetidine causes gynecomastia, galactorrhea
(as it is antiandrogenic & increases orolactin level)
 Cimetidine inhibits CYP450 & increases conc.
of Warfarin, Theophylline, Phenytoin, Ethanol.
 Now answer this question

 Your friend wants to take a H2 antagonist before

he takes alcohol to avoid gastric irritation .He
consults you .Which H2 antagonist will you ask
him to take ?
 Answer :

Famotidine

Explanation :
All H2 antagonist except famotidine inhibit
gastric first pass metabolism of ethanol and
increase its bioavailability .
 Proton Pump Inhibitors

 Most effective drugs in antiulcer therapy

 Irreversible inhibitor of H+ K+ ATPase

 Prodrugs requiring activation in acid environment

 Weakly basic drugs & so accumulate in canaliculi

of parietal cell
 Activated in canaliculi & binds covalently to
extracellular domain of H+ K+ ATPase
 Acid secretion resumes only after synthesis of
new molecules
 Proton Pump Inhibitors

Omeprazole 20 mg o.d.
Esomeprazole 20 - 40 mg o.d.
Lansoprazole 30 mg o.d.
Pantoprazole 40 mg o.d.
Rabeprazole 20 mg o.d.
 Poton Pump Inhibitors – Kinetics
 Given as enteric coated granules in capsule or
enteric coated tablets
 Pantoprazole also given intravenously

 Half life – 1.5 hrs

 Since it requires acid for activation - given 1 hr
before meals
Other acid suppressing agents not coadministered
 Now answer this question
 It is given in the previous slides that the half life of
proton pump inhibitors is 1.5 hours only and
these drugs are generally given once daily. How
this can be justified ?

 Answer :
P.P.I - Irreversible inhibitors of H+K+ATPase
(Hit and run drugs)
 P.P.I. – Side effects & Interactions

 Extremely safe drugs

 Causes hypergastrinemia which leads to

carcinod tumor in rats
 But no evidence of such tumors in man
 Inhibit CYP 450 & hence metabolsim of
warfarin, phenytoin, etc
 Pantoprazole & Rabeprazole have no significant
interactions
 Now Answer this Question

A patient comes to your clinic at midnight

complaining of heart burn. You want to relieve his
pain immediately. What drug will you choose?
 Answer :
Antacids

Explanation :
Antacids neutralise the already secreted
acid in the stomach. All other drugs act by
stopping acid secretion and so may not relieve
symptoms atleast for 45 min.
 Mucosal Protective Agents

 Sucralfate

 Misoprostol
 Colloidal Bismuth compounds
 Sucralfate

 Salt of sucrose complexed to sulfated aluminium

hydroxide
 In acidic pH polymerises to viscous gel that
adheres to ulcer crater
 Taken on empty stomach 1 hr. before meals

 Concurrent antacids, H2 antagonist avoided

( as it needs acid for activation )
 Misoprostol

 PGE1 analogue

 Modest acid inhibition

 Stimulate mucus & bicarbonate secretion

 Enhance mucusal blood flow

 Approved for prevention of NSAID induced ulcer
 Diarrhoea & cramping abd. pain – 20 %
 Not so popular as P.P.I are more effective & better
tolerated
 Colloidal Bismuth Compounds

 Coats ulcer, stimulates mucus & bicarbonate

secretion
 Direct antimicrobial activity against H.pylori

 May cause blackening of stools & tongue

 Not used for long periods – bismuth toxicity

Available compounds :
 Bismuth subsalicylate – in USA
 Bismuth sobcitrate – in Europe
 Bismuth dinitrate
 Now answer this question

 A pregnant lady (first trimester) comes to you

with peptic ulcer disease. Which drug will you
prescribe for her ?
 Answer :

Antacids or Sucralfate

 Explanation ;
H2 antagonists cross placenta and are also
secreted in breast milk. Safety of Proton pump
inhibitors not established in pregnancy.
Misoprostol causes abortion .
 Can you identify these people ?

Nobel prize
Medicine –
2005

Discovery
of H.pylori &
its role in
ulcer

Barry J Marshall J. Robin Warren

Eradication of H.pylori
 Triple Therapy

 The BEST among all the Triple therapy regimen is

Omeprazole / Lansoprazole - 20 / 30 mg bd
Clarithromycin - 500 mg bd
Amoxycillin / Metronidazole - 1gm / 500 mg bd

 Given for 14 days followed by P.P.I for 4 – 6 weeks

 Short regimens for 7 – 10 days not very effective
 Triple Therapy – cont …
Some other Triple Therapy Regimens are

 Bismuth subsalicylate – 2 tab qid

Metronidazole - 250 mg qid
Tetracycline - 500 mg qid

 Ranitidine Bismuth citrate - 400 mg bd

Tetracycline - 500 mg bd
Clarithromycin / Metronidazole - 500 mg bd
 Quadruple Therapy

 Given when Triple Therapy fails

 Omeprazole / Lansoprazole - 20 / 30 mg bd
Bismuth subsalycilate - 2 tabs qid
Metronidazole - 250 mg qid
Tetracycline - 500 mg qid
Now you have learnt about drugs used for treating
peptic ulcer ? Are there any drugs that can cause peptic
ulcer ?

Drugs causing peptic ulcer

 Non Steroidal Anti Inflammatory Drugs
(NSAIDs)
 Glucocorticoids

 Cytotoxic agents
 Stress induced ulceration after head trauma

Cushing’s ulcer
 Stress induced ulceration after severe burns

Curling’s ulcer
 II. Antiemetic Drugs
Vomiting means expulsion of gastric contents through
mouth due to mass antiperistalsis. It is often preceded
by nausea. Vomiting can be life saving, physiological
response to the ingested toxic substances. It also can
be an adverse reaction of radiation and antineoplastic
agents. Vomiting also occurs in early pregnancy, during
migraine attack, in motion sickness, etc.
The CTZ at the base of the 4th ventricle has numerous
receptors: D2-, 5-HT3-, M-, H1-, for SP etc. Stimulation of
different receptors are involved in different pathways
leading to emesis.
Main Antiemetic Drugs
(1) 5-HT3-receptor antagonists (setrons)
Dolasetron, Granisetron, Ondansetron
(Zofran – tab. 8 mg), Tropisetron
(2) Neurokinine-1 (NK1-, SP1-) receptor
antagonists: Aprepitant, Fosaprepitant (prodrug)
(3) D2-receptor antagonists
Neuroleptics: Chlorpromazine, Prochlorperzine, Haloperidol
Prokinetics: Domperidone, Metoclopramide
(4) H1-blockers: Diphenhydramine, Doxylamine,
Promethazine
(5) M-cholinolytics: Scopolamine (Scopoderm TTS)
(6) Miscellaneous Antiemetic Agents
5-HT3-receptor antagonists
block 5-HT3-receptors bothperipherally (on vagal nerve
terminals) and centrally (CTZ). Granisetron is the most
potent antiemetic compared to ondansetron and dolasetron.
These drugs are most effective when given i.v. 30 min prior
to anticancer chemotherapy (granisetron – 10 mcg/kg).
These doses may be repeated every 24 h.

Neurokinine-1 (NK1-, SP1-) receptor antagonists

(Aprepitant etc.) have the similar indications.

D2-receptor antagonists
Phenothiazines (prochlorperazine, thiethylperazine) and
butyrophenone group of antipsychotics (droperidol) can be
used to treat postoperative nausea and vomiting.
 Emetogenic activity
Cisplatin
Carmustine

Cyclophosphamide
Mitomycin C
L-Asparginase
Antiemetic activity
Fluorouracil 5-HT3-blockers
Methotrexate D2-blockers

Etoposide Glucocorticoids
H1-blockers
Vincristine
Prokinetic antemetic
Metoclopramide is D2-receptor antagonists but in high doses
it also blocks 5-HT3-receptors. It crosses BBB. Its prokinetic
action (stimulation of GI motility) is connected with stimulation
of 5-HT4-receptors, present on excitatory interneurons, which
enhances ACh release from primary cholinergic neurons in
myenteric plexus. Metoclopramide is used as antiemetic and
as gastrokinetic agent to accelerate gastric empting prior to
giving emergency general anaesthesia in case the patient
has taken food less than 4 h before. This drug may also be
successful in stopping persistent hiccups. Being a central and
peripheral D2-blocker it produces sedation, muscle dystonia,
in high doses – extrapyramidal effects, galactorrhoea in
females and gynecomastia in males.
• Domperidone has a similar mechanism of action as metoclopramide,
but it is a peripheral D2-blocker. Its antiemetic efficacy is lower than
metoclopramide. It is also used to prevent the emetic side effect of
levodopa or bromocriptine without affecting their antiparkinsonian
effect.

• H1-blockers with anticholinergic properties (Cyclizine,

• Diphenhydramine) are useful for prevention or treatment of motion
sickness and vertigo due to labirinth dysfunction.
• Doxylamine can be used in morning sickness (vomiting during the
first trimester of pregnancy, due to the effect of increased oestrogen
level on CTZ.
• Pyridoxine serves as a cofactor for the glutamate decarbo- xylase
and thus increases the synthesis of GABA which acts as inhibitory
neurotransmitter at CTZ.
• Anticholinergic drugs: Hyoscine (Scopolamine)
• is used in motion sickness as TTS.
• Miscellaneous Antiemetic Agents
• GCS: Dexamethasone, Methylprednisolone
• Canabinoides: Nabilone and Dronabinol stimulate CB1-
• receptors present on neurons around the vomiting center and are
used in oncology. Their hallucinogenic activity is weak.
• Anxiolytics: Aprazolam, Diazepam, Lorazepam
• Others: Benzocaine, Sodium citrate, T-ra Menthae
 Anti emetics

Dr. Muhammad Owais Ismail

Director, PG Program (BHS) and
Associate Professor,
ZMC, Ziauddin University, Karachi
VOMITING is a highly integrated
and complex upper GIT reflex involving both somatic / neural pathways.

• A Reflex loss of upper GIT contents

through mouth

Manikandan 61
 CAUSES
INFECTIONS GASTRODUDL ACUTE
DISEASES ABDOMINAL
DISORDER
•Gastroenterits PEPTICULCER
•UTI •GASTRIC ULCER
•Appendicitis
•Hepatitis •Gastroparesis
•Cholecystitis
DM,Scleroderma,
•Pancreatitis
Drugs.
•Intestinal
Obstruction

Manikandan 62
 causes
CNS DISORDER METABOLIC OTHERS

•vestibular neuritis •Diabetic • Pain MI

•Migraine Ketoacidosis •Alcholism
•Meningitis •Uraemia •Psychogenic
•rasied intracranial •Addisons disease
Pressure

Manikandan 63
 Emetogenic Potential of Antineoplastic agents

Navari RM. Pathogenesis-based treatment of chemotherapy – induced nausea and vomiting – Two
new agents. J Support Oncol 2003;1:89-103
 DRUGS
CENTRAL PERIPHRAL

•APOMORPHINE •Rapidly Acting

OTHERS Salts of CSO4 ,ZnSO4
•NSAID Hypertonic salt sol
•Antibiotics Mustard in warm water
•Digoxin •Slowly Acting
•Cytotoxic drugs Vegetable irratant
NHCO3

Manikandan 65
Manikandan 66
 Pathophysiology of Emesis

Cancer chemotherapy
Cerebral cortex
Opioids Smell
Sight Anticipatory emesis
Thought
Chemoreceptor Vestibular
Vomiting Centre
Trigger Zone Motion nuclei
(medulla) sickness
(CTZ) Muscarinic, 5 HT3 & Muscarinic
(Outside BBB) Histaminic H1 Histaminic H1
Dopamine D2
5 HT3,,Opioid Chemo & radio therapy
Receptors
Gastroenteritis

Pharynx & GIT

5 HT3 receptors
Manikandan 67
 Approaches in the management of CINV

Serotonin Dopamine

Substance P Emetic center Acetylcholine

Endorphins Histamine
 Now answer this question

Which group of drugs can be used as antiemetics ?

 Serotonin 5 HT3 Antagonists

 Dopamine D2 Antagonist

 Anticholinergics
 H1 Antihistaminics
 Cannabinoids

Manikandan 69
 Serotonin 5 HT3 Antagonist

 Potent antiemetics

 Even though 5 HT3 receptors are present in

vomiting centre & CTZ, the antiemetic action is
restricted to emesis caused by vagal stimulation.
 High first pass metabolism
 Excreted by liver & kidney

 No dose reduction in renal insufficiency but needed

in hepatic insufficiency
 Given once or twice daily – orally or intravenously.

Manikandan 70
Drugs Available

 Ondansetron 32 mg / day
 Granisetron 10 mg / kg / day
 Dolasetron 1.8 mg / kg / day
Indications

 Chemotherapy induced nausea & vomiting – given

30 min. before chemotherapy.
 Postoperative & postradiation nausea & vomiting

Manikandan 71
Adverse Effects
 Excellent safety profile

 Headache & constipation

 All three drugs cause prolongation of QT interval,
but more pronounced with dolasetron.

Manikandan 72
 Dopamine D2 Antagonist

 Antagonise D2 receptors in CTZ.

 Drugs available
Metoclopramide 2.5 mg b.d
Domperidone 10 mg b.d
 Both drugs are also prokinetic agents due to their 5
HT4 agonist activity.
 Domperidone – oral ; Metoclopramide – oral & i.v

 Metoclopramide crosses BBB but domperidone

cannot.
Manikandan 73
 Now answer this question

Which is a better antiemetic – Metoclopramide or

Domperidone ?

 As CTZ is outside BBB both have antiemetic

effects.
 But as metoclopramide crosses BBB it has
adverse effects like extrapyramidal side effects..
 Domperidone is well tolerated.

Manikandan 74
 Phenothiazines & Butyrophenones

 Phenothiazines

Prochlorperazine
Promethazine
 Phenothiazines are antipsychotics with potent
antiemetic property due to D2 antagonism.
 Butyrophenone
Droperidol
 Droperidol used for postop. nausea & vomiting,
but cause QT prolongation.
Manikandan 75
 H1 Antihistaminics

 Most effective drugs for motion sickness

 Drugs available
Meclizine
Cyclizine
Dimenhydrinate
Diphenydramine
Promethazine – Used in pregnancy, used by
NASA for space motion sickness
Manikandan 76
 Anticholinergics

 Scopolamine (hyoscine) – used as transdermal

patch for motion sickness

Cannabinoids

 Dronabinol – used as adjuvant in chemotherapy

induced vomiting.It is a psychoactive substance
 Nabilone

Manikandan 77
 Now answer this question

 A physician prescribed Tab.Ondansetron for

prophylaxis of motion sickness. Even though
ondansetron is a potent antiemetic it didn’t
produce any effect in this patient. Can you
explain why ?
 Explanation :

Vestibular nuclei has only muscarinic and H1

histaminic receptors.

Manikandan 78
 III. Laxative and Purgative
Drugs
• Laxatives provide elimination of soft semisolid stool
• Purgatives provide more watery evacuation.
• Laxatives are used: to treat constipation; to avoid undue
straining at defecation in cases of hernia, haemorrhoids
or CVD; before or after surgery of any anorectal disease;
in bedridden patients. Lactulose is an osmotic laxative
drug. It is nonabsorble- indigestible disaccharide (sugar),
which increases fecal bulk by hydrophilic and osmotic
action. It is given in dose of 10 g orally. Latency period is
1 to 3 days. Lactulose is also used for treatment of
hepatic encephalopathy.
• Liquid paraffin is an inert mineral oil.
• Liquid pararaffin is a fecal lubricant and stool softner as it retards water
absorption from the stool. It is given 15 to 30 ml per day at bed time. Latency
period is 1 to 3 days.
• Purgatives are used for complete colonic cleansing prior to GI endoscopic
procedures or before intestinal operation. Purgatives may also be needed to
flush out warms after the use of anthelmintic drugs. In low doses purgatives
can be used as laxatives too.
• Osmotic Purgatives include: Saline purgatives (Magnesium Sulfate) and
Electrolyte purgatives (PEG – PolyEthylene Glycol, which is a
nonabsorbable sugar). They act on small and on large intestine. Saline
purgatives are soluble inorganic salts which increase the fecal bulk by
retaining water by osmotic effect, thus increasing peristalsis. These agents
also release CCK which further helps in increasing intestinal secretion and
peristalsis. Saline purgatives should be ingested with enough water to
protect vomiting. These drugs can cause electrolyte disturbances and must
be avoided in patients with CVD as well as during pregnancy.
• Irritant purgatives
• Antraquinone group: Senna, Cascara and
Aloë
• Organic agents: Bisacodyl, Sodium
picosulfate
• Oils: Castor oils

Aloë vera
• All irritant purgatives stimulate peristalsis by irritant action of
intestinal mucosa. They also stimulate colonic electrolyte and
fluid secretion by altering the absorptive and secretory activity
of the mucosal cells.
• Senna, Cascara and Aloë occur naturally in plants. Senna is
more commonly used. These plant agents contain
anthraquinone glycosides with purgative action. The organic
irritants are prodrugs. The primary site of action of their active
metabolites is in the colon. Bisacodyl is activated in the
intestine by deacetylation. In the colon Sodium picosulfate is
converted to the active metabolite.

• Castor oil is hydrolyzed in the intestine by pancreatic lipase to

ricinolic acid which increases the intestinal motility.
 IV. Antidiarrhoeal Agents
• Diarrhoea is an abnormal increase in the frequency and the liquidity
of stool. Increased motility of GIT and the decreased ability of
intestine to absorb water from the stool are the major factors,
causing diarrhoea.

• Osmotic diarrhoea may cause by ingestion of some type of meal, use

of some osmotic substances, lactulose or magnesium containing
antacids, lactase enzyme deficiency.

• Secretory diarrhoea occurs when the intestinal wall loses its

functional integrity or gets damaged resulting in an increased
secretion of electrolyte in the intestinal tract. This may be due to
some bacterial infection (Schigella, Salmonella), bacterial endotoxins
(from E. coli, V. cholerae, S. aureus), viral infections (rotavirus etc.),
protozoal infections (Lamblia intestinalis, E. histolytica), underlying
pathology (inflam-matory bowel disease) or due to side effects of
drugs (anti- biotics, anticancer agents, colchicine, prostaglandins,
orlistat, acarbose). Excess of bile also causes diarrhoea.
• Motility disorder diarrhoea. Increased
motility reduces then contact time of the
stool with the intestinal wall, so that lesser
amount of water is absorbed back from the
faces.Motility disorders include IBS,
scleroderma, diabetic neuro-pathy,
vagotomy etc. Some drugs can increase
intestinal motility: prokinetic antiemetics,
bethanechol, digitalis, quinidine, ampicillin
(causes disbiosis); neurosis, etc.
Treatment of infective diarrhoeas needs proper diagnosi and
suitable antibiotic and/or antiprotozoal drug. For symptomatic
relief of non-specific diarrhoes are used:

 (1) Antimotility and Antisecretory Agents

a) Opioid agonists which does not cross BBB
• Loperamide (Imodium®) and Racecadotril (Hidrasec®)
These drugs stimulate mu- and delta-receptors, present
in the small and large intestines. Activation of mu-receptors
decreases peristaltic movements. Activation of delta-
receptors contributes to their antisecretory effects.
Although all opioids such as morphine and codeine have
antidiarrhoeal effects, their CNS effects and dependence
liability limit their usefulness. Loperamide directly stimulates
mu- and delta-receptors. Racecadotril blocks enzyme
encephalinase and increases local concentration of
enkephalins in intestinal mucosa which then stimulate
mu- and delta-receptors. This drug can be used orally from
children under 5 years old (including babies), but
Loperamide is contraindicated in children < 5 years old.

b) Miscellaneous Agents

•Carbo activatus (absorbent drug)
•Bismuth subsalicylate reduces stool frequency and
liquidity in acute diarrhoea due to inhibition of
PG synthesis. Bismuth has some antimicrobial and
mucosal protective effect too.
(2) Fluid and Electrolyte Replacement

During diarrhoea, a glucose-coupled transport continues

in the intestines which causes water and electrolyte losses
through the stools.
 V. Treatment of Inflammatory
Bowel Disease

• Ulcerative colitis and Crohn’s disease are two

important inflammatory bowel diseases. The
pathogenesis of these diseases involves
autoimmune mechanism and imbalance
between proinflammatory and anti-inflammatory
cytokines. The main drugs, used in the treatment
of these diseases are aminosalicylates, GCS
and some immunosuppressants.
Antidiarrhoeal agents must be avoided in active and
severe ulcerative colitis as they can lead to dilatation of
the colon and its perforation.

Aminosalicylates (sulfasalazine, olsalazine) con

5-aminosalicylic acid (5-ASA) moiety bound by an azo
(N=N) bond to an inert moiety or by another 5-ASA
molecule. 5-ASA inhibits the synthesis of PGs by inhibit
COX, like salicylates, as well as inhibiting the productio
cytokines. 5-ASA also inhibits the activity of nuclear
factor-kB, which is an important transcription factor for
pro-inflammatory cytokines. It suppresses the generatio
of superoxide free radicals. Aminosalicylates induce and
GCS (Prednisone, Prednisolone) have been the main
of the treatment for acute/severe exacerbations of irritab
bowel disease. Moderately severe attacks of ulcerative
colitis should be treated orally with systemic GCS.

Immunosuppressive Agents
•Cyclosporine may induce remissions in case of severe
 ulcerative colitis unresponsive to GCS.
•Azathioprine, mercaptopurine
•Methotrexate is useful in controlling relapse of Crohn’s
 diseases unresponsive to GCS or azathioprine
•Infliximab is a chimeric (25% mouse and 75% human)
and macrophage functions. Consequently, the release o
other proinflammatory cytokines (IL-1, 2, 8; collagen
and metaloproteinases) is prevented. It is administere
by i.v. infusion. A single dose of infliximab (5 to 10 mg/k
induces remission in approximately 40% of patients with
Crohn’s disease. An additional dose after 8 weeks
produces long-lasting remission.
•Adalimumab is a recombinant human anti-TNF-alpha-
monoclonal antibody. It is given s.c. and has a longer
plasma half life. It has lesser side effects
compared to infliximab.
 VI. Drugs used in Pancreatic
Insufficiency
• Pancreatic enzyme agents contain a mixture of amylase, lipase and
proteases. They are the mainstay of the treatment of the pancreatic enzyme
insufficiency which is most commonly caused by cystic fibrosis, chronic
pancreatitis or pancreatic resection. Exocrine pancreatic enzyme
insufficiency leads to fat and protein indigestion which in turn causes
steatorrhoea, azotorrhoea, vitamin deficiency and weight loss.
– Festal, Kreon,
– Mezym forte, Panzytrat
 VII. Hepatoprotectors

Drugs which stimulate regenerative processes

•Acidum oroticum, Essentiale, Silymarin
Drugs which stimulate fat infiltration
•Thioctic acid (Acidum aphfa-lipoicum)
Derivatives of Methionine: Ademethionine
Interferons (in viral hepatitis)
•Interferon alfa-2a
•Peginterferon alfa-2a
•Interferon alfa-2b
Antiviral vaccines: Hepatitis A and B vaccine,
•Hepatitis A vaccine, Hepatitis B vaccine
 IX. Probiotics – regulators
VIII. Drugs Acting on of intestinal or other
Biliary tract bacterial flora

• Choleretic Drugs: • BioGaia, Linex,

Cholagol, Cholamin, Lactoflor, Lactagyn®
Febichol (vaginal flora),
• Cholekinetic Drugs: • Normoflor, Probien®
Oleum olivarum,
Rowachol
• Drugs which improve the
solubility of cholesterol
gallstones:
Ursodeoxycholic acid