This document summarizes drugs that affect the gastrointestinal tract. It discusses diseases of the GI tract and how drugs are organized based on the part of the tract they target. Key drug classes covered include H2 blockers, proton pump inhibitors, antacids, antiemetics, antibiotics, and more. The mechanisms and uses of these various drug classes are outlined in detail.

1. PHARMACOLOGY OF GIT
BS-HONOUR
MLT
CMLT NIH
MUHAMAD RIAZ
STUDENT OF PhD PHARMACOLOGY
QUAID –E- AZAM UNIVERSITY
ISLAMABAD.
CHAPTER 1

2. Diseases of GI Tract
• The gastrointestinal system is host to an extremely wide range of
diseases and disorders, that include
• Digestive disorders
• GI tract motility issues
• Cancers of GI tract tissues
• Gastroenteritis
• Dyspepsia
• Gastro-esophageal reflux disease (GERD)
• Peptic ulcers
• Infections ( H-Pylori )
• Constipation and
• Inflammatory Bowel Diseases and many others.

3. Drugs That Affect the GI Tract
ORGANIZATION OF CLASS
• The organization of these drugs is based on the
organization of the GI tract. There are drugs that
are used in treating ulcers in the stomach and
duodenum. There are also drugs that affect
motility in the upper GI tract. Then, moving down
to the large intestine, we can divide the agents into
those that enhance motility and those that reduce
motility. Finally, there are agents that specifically
target diseases of the lower GI tract.

4. Drugs That Affect the GI Tract
• H2 Blockers
• PPIs
• Antacids
• Promotility Agents (Metoclopramide)
• Anti emetics Drugs
• Emetics Drugs
• Anti diarrheal Drugs
• Laxatives Drugs
• Probiotics
• Antibiotics (to eradicate H-Pylori infection).

5. Histamine H2 receptor antagonists
• H2 receptor antagonists prevent histamine-induced acid
release. It binds reversibly with H2 receptor and inhibit
acid secretion, it includes:
• Cimetidine
• Ranitidine
• Famotidine
• Nizatidine
• These drugs are easily recognizable by the “-tidine”
ending.
• These drugs are used for the short-term treatment of
gastro esophageal reflux and peptic ulcer disease.

6. Proton Pump Inhibitors
(PPIs)
• Proton pump inhibitors (PPIs) are used to treat
• Gastric and Duodenal ulcers,
• Dyspepsia,
• Gastro-esophageal reflux disease (GERD) and
• NSAID-associated ulcers.
• Combined with anti bacterial, PPIs are used to
eradicate Helicobacter pylori infection.
• Can also be used to reduce the degradation of pancreatic
enzyme supplements in cystic fibrosis patients, and to
control excessive gastric acid production in Zollinger–
Ellison syndrome.

7. Proton Pump Inhibitors
• The “proton pump inhibitors” (the “..prazoles”) inhibit
the irreversibly Hydrogen- potassium adenosine-tri
phosphatase enzyme of the parietal cell of stomach. This
reduces acid secretion.
• Omeprazole
• Esomeprazole
• Dexlansoprazole
• Lansoprazole
• Pantoprazole
• Rabeprazole
• These drugs are superior to H2 antagonists in the
suppression of acid and in the healing of peptic ulcers

8. Prostaglandin Analogue
• The Prostaglandin analogue misoprostol is a synthetic
and approved for the treatment of gastric and duodenal
ulceration and NSAID-associated ulceration and
prophylaxis of NSAID-induced gastric and duodenal
ulcers.
• Misoprostol also induces labor, cause an abortion, and
also to treat postpartum bleeding due to poor
contraction of the uterus.
• It is taken by mouth when used to prevent gastric ulcers
in people taking non steroidal anti-inflammatory drugs
(NSAID). For abortions it is used by itself or in
conjunction with mifepristone or methotrexate.

9. Anti muscarinic drugs & Mucosal
protectants
• Anti muscarinic drugs such as the muscarinic
M1 receptor antagonist pirenzepine were used to
treat peptic ulcer, but are no longer widely used.

10. Antacids
• Antacids are weak bases that react with gastric acid to
form water and a salt to diminish gastric acidity.
• Antacids are used to relieve symptoms in dyspepsia and
in gastro-esophageal reflux disease and usually contain
aluminum or magnesium compounds.
• They should be given when symptoms occur or are
expected, usually between meals and at bedtime. They
may have to be given several times each day.
• Although they may help with ulcer-healing, their impact
is much less than for anti secretory drugs. Liquid
preparations are usually more effective than tablet
preparations.

11. Antacids
• e.g. aluminum hydroxide ( AlOH2), and magnesium
hydroxide Mg(OH)2, calcium carbonate (CaCO3 ) and
trisilicate Sodium bicarbonate, Simeticone and alginates.
• Alginates, added as protectants, may be useful in gastro-
esophageal reflux disease.
• 1. CaCO3 +HCL
• 2. AlOH2 + HCL
• 3. NaOH2 + HCL
• Note : Antacids are taken after meals for maximum
effectiveness.
CO2 + CaCl2
CO2 + AlOH2
NaCL + H2O

12. Mucosal Protective agents
• These are also known as cytoprotective compounds.
They work by a. preventing mucosal injury b. reducing
inflammation c. healing existing ulcers.
• 1.Sucralfate forms a protective coating on the mucosa,
particularly ulcerated areas.
• Constipation is the main side effect of Sucralfate.
• Note : Sucralfate requires acidic PH for activation, it
should not be administered with PPIs, H2 blockers or
antacids.
• 2.Bismuth subsalicylate it inhibits the activity of pepsin,
increases secretion of mucus, and it protects the ulcer
tissues. This agent is used as a component of Quadruple
therapy to heal H-pylori related peptic ulcers.

13. Mucosal protectants
• Mucosal protectants such as sucralfate may be
used to manage benign gastric and duodenal
ulceration and chronic gastritis, and as a
prophylactic for stress-induced ulcers.
• Sucralfate aids healing by forming a viscous,
protective layer on the ulcer's surface, but does
not prevent new ulcer formation.

14. Probiotics
• Probiotics are defined by the World Health
Organization as living microorganisms that have
health benefits when ingested in adequate
amounts.
• The most widely studied probiotics for
gastrointestinal conditions are from
the Lactobacillus and Bifido bacterium genus.
• E.g Enterogermina ampules

15. Antibiotics
• Amoxicillin
• Bismuth compounds
• Clarithromycin
• Metronidazole
• Tetracycline
• Ciprofloxacin

16. Anti Emetic Drugs
• Causes Of nausea & Vomiting :
• Motion sickness
• Pregnancy
• GI illness
• Gastritis
• Chemotherapeutic agents
• Severe pain of the body organs

17. Mechanisms that trigger vomiting
• Two brain stem sites have a key role in the vomiting reflex
pathway.
• 1. chemoreceptor trigger zone (CTZ)
( end of the fourth ventricle )
• 2. Vomiting center
• chemoreceptor trigger zone is located in the area postrema. It is
outside of the blood brain barrier. It can respond directly to
chemical stimuli in the blood or CSF.
• The vomiting center is located in the lateral reticular formation of
the medulla, coordinates the motor mechanisms of vomiting.
• The vestibular system functions mainly in the motion sickness.
• Dopamine receptor type 2 & Serotonin type 3 (5-HT3)

18. Antiemetic Drugs
1. Phenothiazine
2. 5-HT3 Serotonin receptor antagonists
3. substituted Benz amides
4. Butyrophenones
5. Benzodiazepines
6. Corticosteroids
7. Substance P receptor antagonist

19. 1. Phenothiazine
• Drug name : Prochlorperazine
• It acts by blocking the dopamine receptor in the
CTZ.
• It is affective against low or moderately emeto
genic causing agents, although increasing the dose
improves antiemetic activity & adverse affects are
dose limiting.

20. 2. 5-HT3 receptor blocker
• Dolasetron
• Ondasetron ( ONSET )
• Granisetron
• Palonosetron
• These agents selectively block 5HT3 receptors
in the periphery & in the CTZ.
This class of agents is important in treating
CINV ( chemotherapy induced nausea &
vomiting), because of their superior efficacy &
longer duration of action.

21. 2. 5-HT3 receptor blocker uses
• Prior to Chemotherapy
• All grades of emetogenic therapies
• Management of post operative nausea and
vomiting.
• These are extensively Metabolized in liver,
however ondasetron require dose adjustments in
patients with hepatic insufficiency.
• Excretion via kidney in urine.
• Side effect : QT prolongation

22. 3. Substituted Benz amides
• Drug name : Metoclopramide
• It causes inhibition of dopamine in the CTZ.
• It enhances GI motility and is useful for patient with gastropresis.
Metoclopramide has both peripheral and central effects.
Centrally, it is a dopamine antagonist and has produced
extrapyramidal side effects. Peripherally, it stimulates release of
acetylcholine
• 4. Butyrophenones
• Droperidol & haloperidol both act by blocking dopamine
receptors. These are moderately effective antiemetic drugs.
• Side effect : QT prolongation

23. 5.Benzodiazipines
• Lorazepam & alprazolam
• Low antiemetic effect
• Sedative, anxiolytics & amnestic properties.
• 6. Corticosteroids
• Dexamethasone & methyl prednisolone
• Used alone are effective against mild to moderate
vomiting.
• Commonly used in combinations with other agents
, antiemetic mechanism is unknown but it may
cause blockade of prostaglandins.

24. 7. Substance P/ Neurokinin-1
receptor blocker
• Apripetant
• Netupitant
• Rolapitant
• These drugs targets the neurokinin receptor in the
vomiting center and blocks the action of substance
P.
Usually used in combinations with other antiemetic
drugs.

25. 8. Combination regimens
• Antiemetic drugs often used in combinations to increase
efficacy or to decrease toxicity.
For examples
• Dexamethasone & ondasetron
• Dexamethasone, diphenhydramine, droperidol &
metoclopramide.
• Dexamethasone, diphenhydramine & metoclopramide.
• Dexamethasone, Lorazepam & metoclopramide

26. Anti obesity agents
• Orlistat is a lipase inhibitor being used to treat
obesity.
• Orlistat binds to pancreatic and gastric lipase and
inactivates the enzyme.
• This reduces the absorption of dietary fat by about
30%.
• Adverse effects include flatulence, oily spotting,
and fecal urgency.