Drugs acting on GIT disorders

Drugs Acting on Gastro-instestinal
Disorders
Lecture by:
Mr. Mukul Tambe
PhD Scholar,
MIT WPU,
School of Pharmacy,
Pune.
Tuesday, 27 April 2021 1

DIGESTANTS,
CARMINATIVE,
APPETITE SUPPRESSANTS

APPETITE SUPPRESSANT
ANOREXIA
Energy intake > Energy expenditure
stored as adipose
Appetite
Satiety
Absorption
Metabolic rate
Thermogenesis
Physical action

Genetic Factors
Energy expenditure↓
Environmental
Factors
Energy intake ↑
Neuroendocrine
regulation
OBESITY
•Psychological aspect
•Cultural & Socioeconomic
aspects
•Hormones
• Neurotransmitter
• Enzymes
•Receptors
•Total caloric content
•Composition of the diet
•Resting metabolic rate
•Thermo genesis
•Physical activity

Classification Of Drugs
CENTRALLY ACTING ADRENERGIC AGENTS-
Benzphetamine,phentermine,diethylpropion,mazidol,phendimetrazine,pheny
lpropanolamine.
SEROTONERGIC AGENTS:
Dexfenfluramine, Fenfluramine, Floxetine
ADRENERGIC-SEROTONERGIC AGENTS:
Sibutramine

DIGESTANTS OR APPETITE
STIMULANTS
• These are substances intended to promote digestion of food.
• A number of proteolytic, amylolytic and lipolytic enzymes are marketed in combination formulations.
• Vigorously promoted for dyspeptic symptoms and as appetite stimulants or health tonics.
• They are occasionally beneficial, only when elaboration of enzymes in GIT is deficient.
• Their routine use in tonics and appetite improving mixtures is irrational.

1. Pepsin Maybe used along with HCl in gastric achylia.
2.Papain It is a proteolytic enzyme obtained fromraw papaya. Its
efficacy after oral ingestion is doubtful.
3.Pancreatin:
It is a mixture of pancreatic enzymes obtained from hog and pig
pancreas. It contains amylase, trypsin and lipase, and is indicated
in chronic pancreatitis or other exocrine pancreatic deficiency
states.

4. Diastase and Takadiastase These are amylolytic enzymes obtained
from the fungus Aspergillus oryzae. They have been used in pancreatic
insufficiency.
5. Methyl polysiloxane (Dimethyl polysiloxane, Simethicone,
Dimethicone)
It is a silicone polymer—reduces surface tension and collapses froth,
‘antifoaming agent’.
It is not absorbed from g.i.t. and is pharmacologically inert.
Added to antacid, digestant and antireflux preparations, it is briskly
promoted as a remedy for ‘gas’, a very common gastric complaint.
It is also claimed to coat and protect ulcer surface, to aid dispersion of
antacids in gastric contents, and to prevent gastroesophageal reflux.

CARMINATIVES
“Promotes expulsion of gases from the Gastro-intestinal tract and
give a feeling of warmth and comfort in the epigastrium”
Sodium bicarbonate 0.6-1.5g
Peppermint oil- 0.06-0.1 ml
Cardomom tincture – 1-2 ml
Oil of Dil- 0.06-0.2 ml
Ginger tincture -0.6-1.0 ml

Sodium bicarbonate reacts with acid and form Carbon dioxide which distends stomach relaxes LES
(lower esophageal sphincter) followed by eructation (reflex that expels gas noisily from the stomach
through the mouth).
Other contains volatile oils which give irritant action with motility and relaxation of lower
esophageal sphincter which ends with warmth feeling and comfort
USES:
Dyspepsia
Discomfort in the upper abdomen
Gas formation
Feeling of fullness
Burning sensation

BITTERS

PLANT BITTERS
• Bitters are the edible natural products mostly consumed
before any normal meals to stimulate as well as enhance the
appetite.
• Bitter glycoside: Digestive, Stomachic and Febrifuge.
• Class of alkaloids: Characteristic bitter taste.
• These are also used as anti-tumour and anti-malarial agents.

•Bitters increases the appetite and stimulates
digestion by acting on the mucous membranes of
the mouth.
•It also increases the flow of bile, stimulate repair
of gut wall lining and regulate the secretion of
insulin and glucagon.
•They reflectively induce stimulation on the
salivary gland and the secretion of gastric juice.

GENTIAN
•Synonyms:
Yellow Gentian, Gall weed, Bitter wart, Radix
Gentianae.
•Biological Source:
It consist of dried rhizome and roots of Gentiana
lutea Linn.
•Family :
Gentianaceae.

CHEMICAL CONSTITUENTS
• It consist of the bitter glycoside GENTIOPICRIN as active constituent.
• Other bitter compounds are Genticin, Amaropanin, Amarogentin &
Amaoswerin.
• It also contains Gentiin, Gentiamarin, Gentisic
acid, Tannins, Pectin and calcium oxalates.

USES
1. Potent stomachic and treats GI problems like
indigestion.
2. Emmenogoggue (enhance menstrual flow)
3. To treat arthritis, sore throat, Jaundice
4. Gentian extract are used in variety of foods
and cosmetics.

KALMEGH
• Synonyms: Andrographis Paniculata, Kalmegh
• Biological cource: The drug consist of dried or fresh leaves and aerial
portion of the plants Andrographis paniculata Nees.
• Family: Acanthaceae.

Chemical Constituents
•It contains a bitter compound andrographolide up to 1 %
•It is diterpene lactone.
•Some other compounds such as neoandrographolide,
andrographosterol, andrographiside, flavonoids,
phenolic compounds and some waxy material are
present.

Uses
1. It is used as bitter tonic and stomachic.
2. It is used in the treatment of torpid liver (impaired nerve
impulses) and jaundice.
3. The decoction of the plant is used as blood purifier.
4. The decoction of the leaves is given with spices such as
cardamom, clove or cinnamon for stomach ailment in
infants.
5. It produce enzyme induction.

CHIRATA
• Synonyms: Chiretta, Chirayta, Bitter stick
• Biological source: It consist of the dried entire herb of Swertia chirata
Hamilton.
• Family: Gentianaceae

Chemical Constituents
• It contains bitter glycosides amrogentin
amroswerin 0.03%.
0.04 % and
• The other two extremely bitter principles ie chiratin and
ophelic acid also present in crude drug.
• Other compound include chiratol, mangiferin, swertianin,
chiratanin, chiratenol.

Uses
2. It is also used as antimalarial in some part of
India.

PICRORHIZA
• Synonyms: Picrorhiza, Kutki
• Biological source: It consist of dried rhizomes and roots of Picrorhiza
kurroa Royle.
• Family: Scrophularelareaceae

Chemical constituents
•It contains cyclopentanopyran monoterpenoids, a class
of glycosides.
•It contains picroside I, Picroside II and kutkoside up to
3-4 %
•The drug also contains about 9 % cathartic acid.

Uses
2. It is also used as laxatives in small doses and
cathartic (produce psychological relief) in large
doses.
3. It is used as hepatoprotective in Jaundice.
4. It is also used as liver tonic.

Drugs for
Peptic Ulcer & GERD

Introduction
• Peptic ulcer- localized loss of gastric as well as duodenal
mucosa.
• Peptic ulcer- both gastric & duodenal ulcer.
• Imbalance primarily between Aggressive factors and Defensive
factors:
Aggressive
factors, e,g,
acid, pepsin,
NSAID, H.Pylori
etc
Defensive
factors-
mucus,
mucosal blood
flow, HCo3- &
PGE2

• Ulcers occur 5 times more common in duodenum.
• 95% occur in duodenal bulb or pylorus.
• Benign gastric ulcers- 60% in antrum.
• 25% at the junction of antrum & fundus of
lesser curvature.
• Presents as gnawing dull hunger like pain in
epigastric region.
• Barium meal X-ray- ulcer crater.

Drug treatment of peptic ulcer
Goals of antiulcer therapy:
• Relief from pain.
• Promotion of ulcer healing.
• Prevention of complications.
• Prevention of relapse.

Drugs which neutralize gastric acid
• Systemic antacids: Sodium bicarbonate
• Non systemic antacids:
1. Buffer type: Aluminium hydroxide,
Magnesium trisilicate, Magaldrate.
2. Non Buffer type: Magnesium hydroxide,
Calcium carbonate.
3. Miscellaneous: Alginates, Simethicone

Drugs which reduce Gastric acid secretion
• H2 receptor Antagonist
• Cimetidine
• Ranitidine
• Famotidine
• Nizatidine
• Roxatidine
• Loxatidine
• PG analogues
• Misoprostol
• Enprostil, Rioprostil
• Proton pump inhibitors
• Omeprazole
• Lansoprazole
• Pantoprazole
• Rabeprazole
• Esomeprazole
• Anticholinergics
• Propanthaline,
• Oxyphenonium,
• Pirenzipine, Telenzepine

Mucosal protective
drugs
• Sucralfate
• Colloidal
bismuth
subcitrate
• Ranitidine bismuth
citrate
Ulcer healing
drugs
• Carbenoxolone
Anti-Helicobacter pylori
drugs
• Amoxicillin
• Clarithromycin
• Tetracycline
• Metronidazole
• Ranitidine bismuth
citrate
• Bismuth subsalicylate
• Proton pump inhibitors

Antacids
• Antacids are weak bases that neutralize gastric HCl.
• Raises pH of the stomach and ↓ pepsin activity.
• Promotes mucosal defense by stimulation of PGs.
• Forms protective layer over gastric mucosa.
• Administered b/w meals & at bed time.
• Food prolongs neutralizing capacity.
• Potency expressed in terms of its acid neutralizing
capacity.

Systemic antacids
• Sodium bicarbonate- acts rapidly, has brief duration
of action, raises gastric pH to about 7.4.
• It has several demerits:
1. Absorbed systemically: large doses will induce
alkalosis
2. Produces CO2 in stomach→ distension, discomfort,
belching, risk of ulcer perforation.
3. Acid rebound occurs, but is usually short lasting.
4. Increases Na+ load: may worsen edema and CHF.

Uses:
• Restricted to casual treatment of heartburn provides
quick symptomatic relief
• Other uses are to alkalinize urine and to treat
acidosis.

Non systemic antacids
• Poorly absorbed from GI tract.
• Do not disturb systemic acid base balance.
• Do not elevate urinary pH.
Buffer type
• Aluminium hydroxide,
• Magnesium trisilicate,
• Magaldrate

Non Buffer type
Calcium carbonate
• Powerful antacids with fast action.
• Raises gastric pH above 7.
• Causes belching due to release of CO2.
• Excessive doses with milk causes hypercalcemia, renal
insufficiency & metabolic alkalosis called milk-alkali
syndrome.
• Acid rebound is marked as CaCl2 itself is gastrin
stimulant.
• Causes constipation due to Ca-stereate.

Drug interactions
• Al, Ca & Mg salts forms inert complexes and ↓absorption & BA
of
1. Tetracyclines
2. Fluroquinolones
3. Itraconazole
4. Digoxin
5. Iron salts & phosphates.
• ↓ absorption of acidic drugs like barbiturates, phenytoin &
NSAID’s

Miscellaneous adjuants to antacids
Simethicone (Dimethyl polysiloxane)
• Silicon polymer with water repellent properties.
• Acts as antifoaming agent & ↓ flatulence.
• Aids proper dispersion of antacid in gastric contents.
• Coats ulcer surface, prevents hiccups.
• Pharmacologically inert, not absorbed from GIT.
• Also used in topical skin preparations to prevent bed sores.

Sodium alginate
• Hydrophilic colloidal carbohydrate derivatives.
• Extracted from brown sea weeds.
• Used along with antacids/H2 blockers.
• Reacts with gastric acid to form a viscous gel (raft).
• Acts a mechanical barrier to ↓ heartburn & GERD.

H2- Receptor antagonists
Mechanism of action:
• Competitively inhibit H2 receptors on parietal cells.
• Suppresses basal & food induced acid secretion.
• Specific for H2, don’t inhibit H1 & H3 receptors.
• Blocks the action of histamine released from
ECL through gastric & vagal stimulation.
• Secretory responses to other stimuli (ACh, gastrin,
insulin, alcohol, food) are also attenuated.
• Markedly↓ gastric acid secretion for longer duration
& pepsin for shorter period.

• Blocks >90% of nocturnal acid & 60-70% of day time food
stimulated acid secretion.
• Therapeutic doses maintain 50% of inhibition for up to 10 hrs,
hence given twice daily.
• Cimetidine is a prototype drug others are-
• Ranitidine
• Famotidine
• Nizatidine
• Roxatidine
• Loxatidine

Clinical uses
• GERD (Gastro Esophageal Reflux Disease).
• Peptic ulcer (gastric & duodenal ulcer)disease.
• NSAID’S induced ulcer (PPI are preferred).
• Prevention of stress related gastric bleeding.
• Prevention of ulcer recurrence.
• Chronic urticaria as they ↑ efficacy of H1 blockers.

Proton pump inhibitors
• Most widely used drugs for peptic ulcer.
• Safe & efficacious.
• Omeprazole is the prototype.
• Esomeprazole
• Lansoprazole
• Pantoprazole
• Rabeprazole
• All are given orally, pantaprazole I.V
also.
• Available as enteric coated formulations.

Mechanism of action
• All PPIs are prodrugs. These are weak bases.
• Active entity is sulfenamide cation formed in parietal
cell.
• Enteric coating dissolves in alkaline intestinal lumen.
• Prodrug gets absorbed in the intestine.
• In parietal cell canaliculus they gets trapped due to
acidic pH.
• Undergoes molecular rearrangement to form
sulfenamide cation.

• Sulfenamide forms covalent disulfide bond with SH
group of proton pump.
• Should be taken in empty stomach, followed 1 hour
later by a meal
• Inactivates Proton pump irreversibly & shuts off acid
secretion.
• PPIs also inhibit gastric mucosal CA, ↓HCO3
-
• Tenatoprazole: longer half life than other PPIs.
• Inhibits nocturnal acid secretion effectively.
• Potassium competitive acid pump blockers.
• Newer class of drugs under development.

• Secretion resumes gradually over 3-5 days of
stopping the drug.
• PPI undergoes rapid first pass & metabolized by liver.
• Dose reduction needed only in severe liver
impairment.
• I.V pantaprazole should be given as 24 hrs continuous
infusion.
• Compensatory hypergastrinemia has been observed
on long term use.

Clinical uses
• PPIs inhibit fasting & food stimulated acid secretion.
• Duodenal & gastric ulcer disease.
• GERD.
• NSAIDs induced ulceration.
• Prevention of ulcer recurrence.
• H. pylori assosiated ulcers. 2 antibiotics+ PPI BD.
PPI continued OD for 4-6 weeks to promote ulcer
healing.
• Aspiration pneumonia.

Adverse effects
• These are minimal:
• Nausea, Loose stools, headache, abdominal pain,
muscle & joint pain, dizziness (3-5%).
• Rashes (1.5% incidence)
• Leucopenia and hepatic dysfunction are infrequent.
• On prolonged treatment atrophic gastritis has been
reported occasionally.

Anticholinergics
• Propantheline & Oxyphenonium are preferred as
they don’t cross BBB.
• Blocks basal secretions more effectively.
• ↑gastric emptying time and prolongs exposure of
ulcer bed to gastric acid. Relaxes LES.
• These disadvantages make them unsuitable for
peptic ulcer & GERD.
• Nonselective retains anticholinergic side effects.

Pirenzepine & Telenzepine
• Selective M1 receptor blockers used in Canada &
Europe for Rx of peptic ulcer.
• Effectively heal as well as prevent recurrence.
• At usual doses side effects are low.

PG analogues
Misoprostol (PGE1)
• Inhibit gastric acid secretion
• Enhance local production of mucus or bicarbonate
• Help to maintain mucosal blood
• Therapeutic use:
– Prevention of NSAID-induced mucosal
injury (rarely used because it needs frequent
administration – 4 times daily)

• Doses: 200 mcg 4 times a day
• ADRs:
– Diarrhoea and abdominal cramps
– Uterine bleeding
– Abortion
– Exacerbation of inflammatory bowel disease.
Contraindications:
1. Inflammatory bowel disease
2. Pregnancy (may cause abortion)

Sucralfate – ulcer protective
• Aluminium salt of sulfated sucrose .
• MOA:
– In acidic environment ( pH <4) it polymerises by
cross linking molecules to form sticky viscous gel
that adheres to ulcer crater- acts as acid resistant
physical barrier.
– Dietary proteins get deposited on this layer
forming another coat.
– May stimulate PGE2 synthesis & HCO3
- secretion.

• Bind epithelial & fibroblast growth factors which
promotes mucosal repair.
• SE: hypophosphataemia may occur.
• Concurrent antacids avoided.
• Uses:
– Prophylaxis of Stress ulcers
– Bile reflux gastritis
– Topically – burn, bedsore ulcers, excoriated skins
• Dose: 1 gm 1 Hr before 3 major meals and at bed
time for 4-8 weeks .

Colloidal Bismuth Subcitrate
(CBS)
• Mechanism of action
– CBS and mucous form glycoprotein complex
which coats ulcer crater
– ↑ secretion of mucous and bicarbonate, through
stimulation of mucosal PGE production
– Detaches H. pylori from surface of mucosa and
directly kills them

• Dose: 120 mg 4 times a day
• Adverse effects
– blackening of tongue, stools, dentures
– Prolonged use may cause osteodystrophy and
encephalopathy
– Diarrhoea, headache, dizziness

ANTI DIARRHOEALS

Introduction
Diarrheal diseases are major cause of morbidity and
mortality in developing countries.
Diarrhea is passage of too frequent, poorly formed
watery stools.
It could be due to various causes like infection,
toxins, anxiety and drugs.
Diarrhoea in india kills >5 million children/year.
Recurrent diarrhea is major cause of PEM in
children.

Maintainance of water and electrolyte balance in
GIT
Daily entry of fluid in to GI tract-
1.Ingestion of food and water - 2.5L
2.Metabolic processes in body endogenously - 7.5L.
Total -10L absorbed in epithelial cells as well as in colon.
Ultimate fluid content in faeces governed by-
1. Glucose linked sodium & water absorption due to osmotic
gradient.
2. Secretion of cl- ions into the gut-linked with secretion of
sodium and water.
3. Gut motility- Increased peristalisis in diarrhoea due to various
reasons.

TYPES OF DIARRHOEA
SECRETORY DIARRHOEA:
When intestinal wall looses its functional
integrity or gets damaged resulting in an
increased secretion of electrolytes into the
intestinal tract.
It could be due to bacterial infection (shigella,
salmonella),bacterial endotoxins (from E.coli,
vibrio cholerae), viral infections (rota virus), or
underlying pathology (inflammatory bowel
disease), due to side effects of drugs (antibiotics).

MOTILITY DISORDER DIARRHOEA:
Increased motility ↓es the contact period of the
faecal mass with the intestinal wall,so that lesser
amount of water is absorbed back from the faeces.
Eg: Irritable bowel syndrome

Principles in management of diarrhoeas
In diarroea there is increase in motility and
secretions in the gut with ↓ absorption of water
and electrolytes.
Approaches in treatment of diarrhoea:
1. Replacement of fluid and electrolytes.
2. Treatment of the cause.
3. Anti diarrhoeal agents.

Treatment of diarrhoea
Main stay of treatment is to correct the fluid and
electrolyte imbalance which is the cause of death.
Prompt administration of fluid and
electrolytes is life saving.
Non specific treatment:
a)Correction of fluid and electrolyte
imbalance: By ORS and IV fluids as per
severity of the dehydration.

b) Adequate nutrition: To prevent
malnutrition.
To maintain normal turnover of gastric
mucosal cells.
To maintain normal enzymatic
activity(Disaccharidase) to help in the
absorption of glucose, salt and water taken
orally.

ORAL REHYDRATION THERAPY
ORT restores and maintains hydration,
electrolyte and pH balance and is life saving in
most cases.
ORT -with NaCl, Glucose and water.
In the ileum, glucose enhances absorption of Na
and water follows.
Does not correct diarrhoea.
ORT- fluid loss of >5-10% BW.
I.V rehydration- fluid loss >10%BW or losing
>10 ml/kg/hr.

Rehydration with ORS (WHO)
NaCl
Kcl
2.6g
1.5g
Trisod citr 2.9g
Glucose 13.5g
Water 1L
Total osmolarity=245mOsm/L
Na+ : 75 mMol
20 mMol
65 mMol
10 mMol
K+ :
Cl- :
Citrate:
Glucose: 75 mMol
CONTENT
CONCENTRATION

Non-diarrhoeal uses of ORT
Post-surgical, post-burn, post-trauma
Rehydration and nutrition
Heat stroke
To change from parenteral to oral
route

Specific treatment
Classification of Antidiarrhoeals
Non antimicrobial anti diahrrhoeals
I. Antimotility agents:
diphenoxylate, loperamide, codeine.
II. Anticholinergic agents:
atropine, scopolamine
Specific anti infective agents
I. Antimicrobials:
co-trimaxozole, norfloxacin, doxycycline, erythromycin,
metronidazole
II. Antisecretary agents:
sulfasalazine, mesalazine

Anti-motility drugs
1. Diphenoxylate
2. Codeine
3. Loperamide

Common Properties
Opioid in nature.
Actions are mediated through kappa and Delta
opioid receptors present in enteric neuronals and
direct action on intestinal smooth muscle is seen.

Pharmacological Properties
Mu (μ) receptors
propulsive
movements,
absorption,
Increase small bowel
tone.
Diminish intestinal
secretions.
Delta receptors
promote absorption
and inhibit secretion.
Overall they increase the luminal transit
time

CODEINE
Opioid alkaloid, dose – 60 mg TDS
Peripheral action on intestine and colon
Constipation
No central action
Less dependence liablity
Side effects: nausea, vomiting, dizziness
Caution in children

Diphenoxylate
Synthetic opioid.
Action similar to codeine causing constipation.
Most marked antidiarrhoeal effect.
Crosses BBB = CNS effects.
Paralytic ileus, toxic megacolon in children.
It causes respiratory depression.
Contraindicated in children <6 yrs.

Loperamide
Opiate analogue.
Peripheral opioid with weak anticholinergic activity.
It inhibits secretion by directly interacting with calmodulin.
More potent than codeine in causing constipation.
CNS effects are rare.

Very little absorbed from intestine
No abuse liability
Longer duration (12hrs) than codeine and
diphenoxylate.
Most effective and best tolerated antimotility
drug.
Adverse effects:
Abdominal cramps, rashes, paralytic ileus,
toxic megacolon, abdominal distension.

Loperamide contd..
Contraindicated in children <4 yrs
Uses:
Antimotility drugs are used in-
Non infective diarrhea, traveller’s diarrheoa, idiopathic
diarrheoa in AIDS
C/I :In infective diarrhea,ulcerative colitis,irritable
bowel syndrome (as they  intraluminal pressure).

Anticholinergics:
Atropine decreases bowel motility and
secretion.
Poor efficacy in secretory diarrhea.
Use:
In nervous/drug induced (neostgmine).
In dysentry and diverticulitis.

Role of antimicrobials in diarrhoea
A. Regularly Useful In:
a) Cholera- Tetracycline/Co-trimoxazole, especially In Children.
b) Campylobacter Jejuni- Norfloxacin/Erythromicin.
c) Clostridium Difficile- Pseudomembranous Colitis- Metronidizole
d) Amoebiasis And Giardiasis- Metronidazole,
Diloxanide Furoate

B. Useful in severe states of:
a)Travellers Diarhoea Caused By E. Coli, Campylobacter-
Norflox/Co-trimaxozole/Doxycycline/Erythromycin.
b)Shigella Enteritis - Stools With Blood And Mucus-
Ciprofloxcin/Nalidixic Acid/Norfloxa.
c)Salmonella Enteritis- Fluroquinolones/Ampicillin.
D)enterocolitis- Y. Pestis- Co-trimoxazole/Ciprofloxcin.

Role of antimicrobials in diarrhoea
(cont….)
C. Never used in:
a) Irritable bowel syndrome.
b) coeliac disease
c) Tropical sprue
d) Diverticulitis,
e) Ulcerative colitis

NON SPECIFIC ANTIDIARRHOEALS
Antisecretory drugs:
Sulfasalazine, mesalazine, anticholinergics, opioids.
1.Sulfasalazine:it Is A Compound Of 5-amino
Salicylic Acid With Sulfapyridine Linked By Azo
Bond.
Azo Bond Is Split By Colonic Bacteria To Release 5-
asa And Sulfapyridine
5-ASA Has Local Anti-inflammatory Action

Mechanism of action of sulfasalazine
Poorly absorbed from intestine.
Azo bond is split by colonic bacteria to release 5-ASA and sulfapyridine.
Migration of inflammatory cells into bowel wall.
Exerts antiinflammatory and antisecretory effects.

Sulfasalazine contd…
USES – ulcerative colitis, crohn’s disease.
No antibacterial action is seen.
Adverse effects: absorbed sulfapyridine causes
rashes, fever, joint pain, heamolysis, blood
dyscriasis, headache, anaemia, folic acid deficiency.

Mesalazine
It is 5-ASA (active moiety).
It is formulated as delayed release preparation. It
delivers 5-ASA to distal small bowel and colon
Uses: In prevention of relapses in ulcerative
colitis.
Adverse effects: Nausea, diarrheoa, abdominal pain,
headache, rashes and hypersensitivity reactions,
Nephrotoxicity.
Contraindications:Renal and hepatic diseases.

Corticosteroids
Prednisolone 40 mg/day.
In inducing remission in ulcerative colitis,
crohn’s disease (drug of choice in
exacerabations).
Hydrocortisone enema in distal ulcerative
colitis, proctitis.

Laxatives &
Purgatives

Purgatives & laxatives are drugs that promote
evacuation of bowels, used in constipation and
dyschezia.
Constipation: Delayed passage of faeces through the
intestine.
Dyschezia: Derangement of defaecation process due
to
1. Pain arising from haemorrhoids or fissure
2. Presence of hard dehydrated faecal matter in the
rectum
2

Purgative: Stronger action resulting in more fluid evacuation
Laxative:Milder action, elimination of soft but formed
stools.
Aperients (to get rid off) < Laxatives (to loosen) <
Emolient (to smooth and soften) < Evacuant (to
empty) < Purgatives (to clean)< Cathartic (to utterly
clean)

9
1
Classification of Drugs
1. Bulk forming
Dietary fibre: Bran, Psyllium,
Ispaghula, Methylcellulose
2. Stool softener
Docusates (DOSS), Liquid paraffin
3. Stimulant purgatives
(a)Diphenylmethanes Phenolphthalein,
Bisacodyl, Sodium picosulfate

(b) Anthraquinones (Emodins)
Senna, Cascara sagrada
(c) 5-HT4 agonist: Prucalopride
(d) Fixed oil: Castor oil
4. Osmotic purgatives Magnesium salts:
sulphate, hydroxide, Sodium salts: sulfate,
phosphate Sod. pot. Tartrate, Lactulose

Laxatives are used
1.To treat constipation.
2. To avoid undue straining at defaecation in
cases having hernia, haemorrhoids or
cardiovascular disease.
3. Before or after surgery of any anorectal
disease.
4. In bedridden patients.
Laxatives

 Bulk-Forming Laxatives:
Wheat bran, Psyllium husk, Ispaghula,
Methyl cellulose.
 Osmotic Laxatives:
Lactulose, Glycerine suppositories
 Lubricant Laxatives :Liquid paraffin
 Surfactant Laxatives
Docusate (Dioctyl sodium sulfosuccinate)

 Bulk-Forming Laxatives:
Wheat bran consists of 40% dietary fibre
It absorbs water in the intestines, swells,
increases water content of faeces
Stimulate local peristalsis & defecation
reflexes by increasing faecal bulk
Dose : 20-40 g/ day, acts 1-3 days
S/E : Bloating
C/I : GIT ulcerations, adhesions, stenosis

 Osmotic Laxative:
Lactulose:
It is a semisynthetic disaccharide of fructose and
lactose.
neither digested, nor absorbed in the small intestine- retains
water.
Broken down by colonic bacteria- osmotically
active products.
Side effects: Flatulence, cramps

Dose of 10 g BD with plenty of water,
It produces soft formed stools in 1-3 days
Lactulose causes reduction of blood NH3
concentration by 25-50% in patients with
hepatic encephalopathy
Dose : 20 g TDS

Lubricant Laxatives
pharmacologically inert mineral, not
palative, but can be given in emulsified
form or with juices.
Liquid paraffin
Dose : 15-30 ml. Latency period: l-3 days
Side Effects :
 It is not palatable
Frequent use leads to the deficiency of fat
soluble vitamins
Leakage of oil past anal sphincter

Forcible
administration can
lead to aspiration
lipid pneumonia.
It also delays the
healing of enteric
fistula.
Foreign body
granulomas in the
intestine

Surfactant Laxatives: [STOOL SOFTENER]
Dioctyl sodium sulfosuccinate(Docusate)
It is an anionic detergent which softens the
stool by decreasing the surface tension of
fluids in the bowel.
It also acts as a wetting agent for the
bowel, because by emulsifying the colonic
contents it facilitates the penetration
of water into faeces 15

Dosage : 100-400 mg/day.
Indicated when straining at defaecation is
to be avoided
Side Effects:
Bitter in taste, Nausea, Cramps and
abdominal pain.
Prolonged use leads to Hepatotoxicity
16

18
Purgatives are used for complete colonic
cleansing
1. Prior to gastrointestinal endoscopic
procedure
2. To flush out worms after the use of an
anthelmintic drug
3. To prepare the bowel before surgery or
abdominal X-ray
4. Food/Drug poisoning
5. For post operative or post-Ml bedridden
patient

Osmotic Purgatives
Purgatives
lrritant Purgatives
I. Osmotic Purgatives:
a) Saline purgatives : Magnesium sulfate,
Magnesium hydroxide, sodium sulfate,
sod. phosphate, sod. pot. tartarate
b) Electrolyte osmotic purgative
Polyethylene glycol (PEG)-
19

a) Saline purgatives:
Mode ofAction:
 Increase the faecal bulk by retaining
water by osmotic effect, thus increasing
peristalsis indirectly.
 Doses : Mag. Sulfate : 5-15 g.
Mag. Hydroxide: 30 ml.
Sod. Sulfate : 10-15 g.
Sod. phosphate: 6-12 g.
Sod. pot. Tartrate : 8-15 g.
Dissolved in 200 ml of water & effects come
with in 2-3 hrs & Latency period is 1-3 hr20
s

Side Effects and Comments:
 Should be ingested with enough water
 Magnesium salts: Should not be used for
prolonged period in patients with renal
insufficiency due to the risk of
hypermagnesemia.
 Sodium salts should be avoided in
hypertensives & CHF

II. Irritant Purgatives:
(a) Anthraquinone group:
Senna, Cascara sagrada, andAloe.
(b)Organic irritants:
Phenolphthalein, Bisacodyl,
Sodium picosulfate.
(c) 5 HT4 Agonist: Prucalopride.
(d) Oils: Castor oil. 23

Senna, Cascara sagrada andAloe.
 Plant purgatives contain anthraquinone
glycosides [emodins]
 Active principle “anthrol” which acts
locally or is absorbed into circulation
 Acts on the myenteric plexus to increase
peristalsis and decrease segmentation
 Senna Dose: 12-25 mg hs, effects come
with in 6-8 hours, 24

Side Effects:
 Produce abdominal cramps & nausea
 Senna glycosides are secreted through milk.
 Chronic use leads to brown pigmentation of the colon known as
"melanosis coli".
25

Bisacodyl:
Activated in the intestine by deacetylation
 In the colon it irritate the mucosa,
produce mild inflammation and
secretion
Oral Dose : 5-10 mg hs.
The effect appears with in 8-10 hrs.
Suppositories act with in 20-40 min
Side Effects:
Abdominal cramps and skin rashes. Higher
doses can cause mucosal damage26

Choice of Drugs /Uses:
Functional Constipation
1. Spastic constipation
Dietary fibre
Bulk forming agents taken over weeks.
Stimulant purgatives are contraindicated.
2.Atonic constipation (sluggish bowel):
Due to old age, debility or laxative abuse
Bulk forming agent, Bisacodyl or senna
given once or twice a week 27

2. Bedridden patients
(MI, stroke, fractures, postoperative):
Prevent- Bulk forming, docusates, lactulose,
liquid paraffin.
3.To avoid straining at stools (hernia,
cardiovascular disease, eye
surgery) and in perianal afflictions (piles,
fissure, anal surgery)
Bulk forming agents, Docusates, lactulose
and liquid paraffin.

4.Preparation of bowel for surgery,
colonoscopy, abdominal X-ray
Saline purgative, bisacodyl or senna
5.After anthelmintics:
Saline purgative or senna
6.Food/ drug poisoning:
Saline purgatives

All laxatives are contraindicated in:
(i) Undiagnosed abdominal pain, colic or
vomiting.
(ii) Stricture or obstruction in bowel,
hypothyroidism, hypercalcaemia,
malignancies

Do you know which drugs can cause
constipation?
•Opioids
•Anticholinergics
•Antiparkinsonian,
•Antidepressants and Antihistaminics
•Almunium and Calcium groups of
Antacids
•Oral iron, clonidine, verapamil
Laxative abuse

Emetics
• Emesis =?
Drugs that produce/ induce vomiting is
called emetics

Mechanism of vomiting
• What is vomiting?
• It is the forceful expulsion of the contents of the
stomach via the mouth or sometimes through the
nose.
• The vomiting reflex is stimulated by two centers in
the medulla
1. Vomiting centre
2. Chemoreceptor trigger zone(CTZ)

How this CTZ is stimulated
• Tactile stimulation of the back of the throat, a
reflex to get rid of something that is too big or
too irritating to be swallowed
• Excessive stomach distention
• Increasing intracranial pressure by direct
stimulation
• Stimulation of the vestibular receptors in
the inner ear

• Intense pain fiber stimulation
• Direct stimulation by various chemicals,
including fumes, certain drugs, and debris
from cellular death
• CTZ is stimulated by several different
processes and initiates a complex series of
responses that first preparet he system for
vomiting and then cause a strong backward
peristalsis to rid the stomach of its contents.

Classification of Emetics
1.Stimulants of CTZ
a.Apomorphine
b.Morphine
2.Irritants of gastric mucosa
a.mustard
b.sodium chloride
3.Both CTZ stimulant and irritant effect
a.ipecacuanha
b.digitalis

Apomorphine
• It is obtained by treating morphine with
HCL
• MECHANISM?
• Produce vomiting in 5-10 minutes after
admn
• Dose- 2 to 4mg
• Route- subcutaneous/IM

MUSTARD
• It is a household remedy to induce
vomiting
• Dose- 1teaspoonful with water

Ipecacuanha
• It is obtained from the dried rhizomes and
roots of carapicheae ipecacuanha from
which it derives its name.
• Commonly available as syrup
• Dose- 15 to 20ml
• Induce vomiting witin
15 minutes

Antiemetics
• Drugs that prevent vomiting

CLASSIFICATION
1. Prokinetics
a.metochlorpramide
b.domperidone
2. Antimuscarinics
a.hyocine
b.meclozine
3.Antihistamines
a.cyclizine
b.promethazine(phenergan)
4. Neuroleptics
a.chlorpromazine
b.prochlorpromazine
5. 5-HT3 antagonists
a.ondancetron
b.granicetron

Prokinetics
• These drugs which promote gastrointestinal
motility and quicken gastric emptying
• Metoclorpramide(REGLAN)
It has both central and peripheral
effects
Central- blocks the dopeminergic
receptors
peripheral- increased gastric emptying
dose- 5- 10 mg

Metochlopramide (reglan)
• Dose- 5-10 mg
• Indications
post-operative vomiting, vomiting during
induction of anesthesia
•Side effects: restlessness,
drowsiness, dizziness,
and or dystonic reactions.

Domeperidone
• Action- Block the dopaminergic receptors in
the upper GIT
• Dose- 10mg,30mg tablets
1mg/ml syrup
Side effects: Headache, dizziness, dry mouth,
nervousness, flushing, or irritability

Antimuscarinics
• Action- Competitively inhibits action of
acetylcholine at muscarinic receptors
• Hyoscine –very effective in controlling
motion sickness
• Dose -0.4-0.6 mg p.o. 30 min before
journey
• It is a labrynthine sedative

Neuroleptics
• Action- they act by suppressing the CTZ so
they antagonize vomiting produced by drugs
which stiimulate CTZ
Eg; chlorpromazine
• dose; PO: 10-25 mg q4-6hr
IV/IM: 25-50 mg q4-6hr

5-HT3 Antagonists
• (5-HT3) receptor antagonists block the
vomiting reflex by inhibiting 5-HT3
receptors in the vomiting center , the
chemoreceptor trigger zone and in the
small intestine

Ondansetron (Emeset)
• Blocks 5HT3 receptors in git and CTZ
• Specially used In chemotherapy,post op
vomiting other drug induced vomiting
• Dose- 4mg in each ampule
• 4,8 mg tab

• Side effects:
Headache, constipation, and dizziness are the
most commonly reported side effects associated
with its use

Granisetron
• It is 10 to 15 times more potent than
ondansetron
• More effective in chemotherapy
• Dose – IV 1mg

Antihistamines
• They act by sedating the vomiting centre
• They are safer for long term use
• Effective in motion sickness and vomiting
due to labrynthine disoders
eg. Cyclizine
meclozine
dose- 50mg/ml inj
50mg tab

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