This document summarizes drugs used to treat gastrointestinal disorders. It discusses drugs for peptic ulcers and GERD, including H2 blockers like ranitidine, proton pump inhibitors like omeprazole, and anti-H. pylori regimens. It also covers antacids, antiemetics, prokinetic drugs, and 5-HT3 antagonists used to treat nausea and vomiting. The mechanisms of action, uses, and side effects of these various drug classes are presented.

1. GASTROINTESTINAL DRUGS
Dr. Banhisikha Adhikari
MD Pharmacology
I.P.G.M.E&R

2. • Drugs for Peptic Ulcer and GERD
• Antiemetic, Prokinetic and Digestant Drugs
• Drugs for Constipation and Diarrhoea
Pathophysioloy
Class of drugs
Mechanism of action
Pharmaocokinetic features
Uses
Adverse effects

3. PEPTIC ULCER
• occurs in gastrointestinal tract exposed to gastric acid and pepsin -
stomach and duodenum
• Etiology is not clearly known
• A variety of psychosomatic, humoral and vascular derangements
• Helicobacter pylori - contributor to ulcer formation and recurrence
Defensive factors
gastric mucus and
bicarbonate secretion,
prostaglandins, nitric oxide,
high mucosal blood flow,
innate resistance of the
mucosal cells
Aggressive factors
acid, pepsin, bile and
H. pylori
IImbalance

4. Regulation of gastric acid secretion

5. Goals of therapy
• Peptic ulcer is a chronic remitting and
relapsing disease lasting several years.
The goals of antiulcer therapy are:
• Relief of pain
• Ulcer healing
• Prevention of complications (bleeding,
perforation)
• Prevention of relapse.

6. Approaches for the treatment of
peptic ulcer
1. Reduction of gastric acid secretion
(a) H2 antihistamines: Cimetidine,Ranitidine,
Famotidine, Roxatidine
(b) Proton pump inhibitors: Omeprazole,
Esomeprazole, Lansoprazole, Pantoprazole,
Rabeprazole,
(c) Anticholinergic drugs:
Pirenzepine,Propantheline, Oxyphenonium
(d) Prostaglandin analogue: Misoprostol

7. 2. Neutralization of gastric acid (Antacids)
(a) Systemic: Sodium bicarbonate,Sod. citrate
(b) Nonsystemic: Magnesium hydroxide, Mag.
trisilicate, Aluminium hydroxide gel, Magaldrate,
Calcium carbonate
3. Ulcer protectives: Sucralfate, Colloidal
bismuth subcitrate (CBS)
4. Anti-H. pylori drugs: Amoxicillin, Clarithromycin,
Metronidazole, Tinidazole,Tetracycline

8. H2 ANTAGONISTS
• Marked inhibition of gastric secretion (all phases) due to
competitive H2 blockade
• Four H2 antagonists cimetidine, ranitidine, famotidine and
roxatidine are available in India
CIMETIDINE - first H2 blocker to be introduced.
Well absorbed orally .
Well tolerated .
Common side effects headache, diarrhoea/constipation,
dizziness
Inhibitor of several Cytochrome P-450
Use has declined due to incidence of male sexual dysfunction
and several drug interactions

9. • Ranitidine- 5 times more potent than cimetidine
Longer duration of action with greater 24 hr acid
suppression
No antiandrogenic action
Overall incidence of side effects is lower
• Famotidine- binds tightly to H2 receptors and
exhibits longer duration of action despite an
elimination t½ of 2.5–3.5 hr
5–8 times more potent than ranitidine
• Roxatidine- pharmacodynamic, pharmacokinetic
and side effect profile is similar to ranitidine, but
twice as potent and longer acting

10. PROTON PUMP INHIBITORS (PPIs)
• Omeprazole, Esomeprazole, Lansoprazole, Pantoprazole,
Rabeprazole
• have overtaken H2 blockers for acid-peptic disorders
• Most powerful inhibitor of gastric acid secretion.
• Inhibit resting as well as that stimulated by food or any of the
secretagogues
• react covalently with H+K+ATPase enzyme
• inactivate it irreversibly
• have high degree of selectivity of action
• Minimal adverse effects. Nausea, loose stools, headache,
abdominal pain, muscle and joint pain
• All PPIs are administered orally in enteric coated form

11. • Omeprazole: It is the prototype member
dose dependent suppression of gastric acid secretion;
without anticholinergic or H2 blocking action
bioavailability is reduced by food should be taken in empty
stomach 1 hr before meal
Esomeprazole : It is the S-enantiomer of omeprazole; have
higher oral bioavailability
• Pantoprazole: It is similar in potency and clinical efficacy to
omeprazole, but is more acid stable and has higher oral
bioavailability
• Rabeprazole : cause fastest acid suppression

12. USES
• Peptic ulcer: Gastric and duodenal-
prophylaxis, treatment, relapse
• Bleeding peptic ulcer
• Stress ulcers
• Gastroesophageal reflux disease (GERD)
• Zollinger-Ellison syndrome
• Aspiration pneumonia

13. PROSTAGLANDIN ANALOGUE
• PGE2 and PGI2 serve cytoprotective role
• inhibit acid secretion
• promote mucus and HCO3¯ secretion
• Misoprostol (methyl-PGE1 ester) is a longer acting
synthetic PGE1 derivative
• inhibits acid output dose dependently.
• side effects and multiple daily dosing - Patient
acceptability is poor
• primary indication - prevention and treatment of
NSAID associated gastrointestinal injury and blood
loss

14. ANTACIDS
• basic substances
• Neutralize gastric acid and raise pH of gastric contents
• Peptic activity is indirectly reduced
• potency of is expressed in terms of acid neutralizing
capacity (ANC): defined as number of mEq of 1N HCl that are
brought to pH 3.5 in 15 min by a unit dose of the antacid
preparation
• Systemic antacids: potent, rapidly acting but
infrequently used due to systemic side effects
• Nonsystemic antacids : salts of magnesium and
aluminium used in combination for better tolerabilty
and reduced side effects.

15. ULCER PROTECTIVES
• Sucralfate: basic aluminium salt of sulfated sucrose
• polymerizes at pH < 4 by cross linking of molecules, assuming
a sticky gel-like consistency.
• strongly adheres to ulcer base
• acts as a physical barrier preventing acid, pepsin and bile from
coming in contact with the ulcer base
• Colloidal bismuth subcitrate: a colloidal bismuth
compound; water soluble but precipitates at pH < 5
• mechanism of action is not clear: probably increase gastric
mucosal PGE2, mucus and HCO3¯ production. detach and
inhibit H.pylori directly

16. ANTI-HELICOBACTER PYLORI DRUGS
• is a gram negative bacillus
• attaches to surface epithelium beneath the mucus
• maintains a neutral microenvironment around the
bacteria
• promotes back diffusion of H+ ions
• causation of
chronic gastritis,
dyspepsia,
peptic ulcer,
gastric lymphoma and
gastric carcinoma

17. • Antimicrobials against H. pylori are:
amoxicillin,
clarithromycin,
tetracycline and
metronidazole/tinidazole
• Eradication of H. pylori concurrently with PPI
therapy of peptic ulcer: faster ulcer healing,
prevents ulcer relapse

18. • US-FDA approved regimen is: Lansoprazole 30 mg + Amoxicillin
1000 mg+ clarithromycin 500 mg, all given twice daily for 2 weeks.
• National Formulary of India (NFI, 2010): 1 week consisting of:
Omeprazole 40 mg OD + Metronidazole 400 mg TDS + Amoxicillin
500 mg TDS.
• Quadruple therapy: CBS 120 mg QID +tetracycline 500 mg QID +
metronidazole 400mg TDS + omeprazole 20 mg BD for failure cases.

19. GERD
• Reflux of acid gastric contents into lower 1/3rd of esophagus
• Functional disorder: relaxation of lower esophageal sphincter
(LES) in the absence of swallowing
• causes esophagitis, erosions, ulcers, pain on swallowing,
dysphagia, strictures, and increases the risk of esophageal
carcinoma.
• Treatment: Proton pump inhibitors (PPIs)
H2 blockers
Antacids
Sodium alginate
Prokinetic drugs: Metoclopramide,
cisapride

20. Antiemetic Drugs

21. Physiology of Emesis
• stimulation of the emetic centre situated in the
medulla oblongata- Vomiting
• Multiple pathways are involved
• chemoreceptor trigger zone (CTZ) and nucleus
tractus solitarius (NTS) - relay areas for afferent
impulses arising in the g.i.t, throat and other viscera
• CTZ is also accessible to
blood borne drugs,
mediators,
hormones,
toxins

22. • Emetics like Apomorphine, Ipecacuanha are
used when a poison has been ingested
• CTZ and NTS express a variety of receptors:
histamine H1,
dopamine D2,
serotonin 5-HT3,
cholinergic M,
neurokinin NK1 ,
cannabinoid CB1 and
opioid μ receptors
• through which the emetic signals are relayed
and are targets of antiemetic drug action.

24. CLASSIFICATION
1. Anticholinergics : Hyoscine, Dicyclomine
2. H1 antihistaminics: Promethazine, Diphenhydramine,
Dimenhydrinate, Cinnarizine.
3. Neuroleptics: Chlorpromazine(D2 blockers), Triflupromazine
4.Prokinetic drugs: Metoclopramide, Domperidone, Cisapride,
Mosapride, Itopride
5. 5-HT3 antagonists: Ondansetron, Granisetron, Palonosetron,
Ramosetron
6. NK1 receptor antagonists : Aprepitant, Fosaprepitant
7. Adjuvant antiemetics: Dexamethasone, Benzodiazepines,
Dronabinol

25. • ANTICHOLINERGICS:
Hyoscine - most effective drug for motion sickness.
by blocking conduction of nerve impulses across a cholinergic
link in the pathway leading from the vestibular apparatus to
the vomiting centre
• H1 ANTIHISTAMINICS:
useful mainly in motion sickness and to a lesser extent in
morning sickness, postoperative and some other forms of
vomiting
• NEUROLEPTICS:
act by blocking D2 receptors in the CTZ
useful in drug induced and postoperative nausea and vomiting
(PONV). Disease induced vomiting: gastroenteritis, uraemia,
liver disease, migraine

26. PROKINETIC DRUGS
• promote gastrointestinal transit and speed gastric emptying
by enhancing coordinated propulsive motility
• Metoclopramide
Introduced as a ‘gastric hurrying’ agent, a commonly used
antiemetic
MOA involves- a) D2 antagonism
b) 5-HT4 agonism
c) 5-HT3 antagonism
generally well tolerated but Long-term use can cause
parkinsonism, galactorrhoea and gynaecomastia
• Effective and popular drug for many types of vomiting—
postoperative, drug induced, disease associated (especially
migraine)
• Also used as a gastrokinetic, in Dyspepsia and other functional
g.i. disorders, GERD

27. • Domperidone: D2 receptor antagonist
antiemetic and prokinetic actions have a lower ceiling
extrapyramidal side effects are rare
Side effects Are much less than metoclopramide
• Cisapride: prokinetic with little antiemetic property
restores and facilitates motility throughout the g.i.t.,
including colon
however predisposes to torsades de pointes/ventricular
fibrillation. Subsequently withdrawn from the market

28. 5-HT3 ANTAGONISTS
• Ondansetron, Granisetron, Palonosetron, Ramosetron
• Distinct class - developed to control cancer chemotherapy
/radiotherapy induced vomiting
• effective in PONV and disease/drug associated vomiting
• Blocks 5-HT3 receptors on vagal afferents in the g.i.t. as well as
in NTS and CTZ
• generally well tolerated except headache and dizziness
• superiority in terms of efficacy as well as lack of side effects
and drug interactions has been demonstrated over
metoclopramide and phenothiazines

29. NK1 RECEPTOR ANTAGONISTS
• Aprepitant, Fosaprepitant
• high affinity NK1 receptor antagonist blocks the emetic action
of substance P at CTZ
• Oral aprepitant combined with standard i.v. ondansetron+
dexamethasone regimen significantly enhanced the
antiemetic efficacy against high emetogenic cisplatin based
chemotherapy
• Effective against acute as well as delayed phase of vomiting
• Particularly useful in patients undergoing multiple cycles of
chemotherapy

30. Important topics
• Regulation of gastric acid secretion
• Anti ulcer drug classification
• H2 blockers
• Proton pump inhibitors
• Anti H pylori regimens
• Rationale behind antacid combination
• Antiemetic classification
• Prokinetic agents
• 5HT3 antagonists