drugs used in GIT diseases

1. Drugs acting on
gastrointestinal tract
Dr abdifatah mahdi
Pharmacology lecture
Qalinsame college

2. Drugs acting on gastrointestinal
tract
1- Drugs used for peptic ulcer disease
2- Drugs used for to control chemotherapy
induced emesis
3- Antidiarrheals
4- Laxatives
5- Drugs acting on inflammatory bowel
diseases.

3. Drugs used to treat peptic ulcer disease

4. Acid production
watch this video
https://www.youtube.com/watch?v=6Nzr89rxaNo
Iam gonna explain but you have to watch this
video again and again to understand how does
these drugs work.

5. How it works

6. Peptic ulcer
Psychosomatic disorder in about 10% of
adults, due to imbalance between
gastric acid secretion and mucosal
resistance (production of mucus and
bicarbonate).

9. Pud causes and sypmtoms

10. The major causative factors for peptic ulcer
1- Non-steroidal anti-inflammatory drugs
(NSAIDs)
2- Infection with gram negative Helicobacter
pylori (H. Pylori ): in 70% of G.U and
90% of D.U
3- Increased hydrochloric acid secretion
4- Inadequate mucosal defense against gastric
acid and pepsin

12. Treatment approaches include
1- Antimicrobial therapy : Eradication the H.
pylori infection.
2- Drugs that decrease gastric acid secretion:
use of H2 antagonists and /or proton pump
inhibitors.
3- Drugs that neutralize gastric acid: Use of non
absorbable antacids.
4- Drugs that enhance mucosal defense:
Providing agents that protect the gastric mucosa
from damage, such as misoprstol and sucralfate.
5- Stop smoking

14. 1- Antimicrobial agents
To document infection with H. pylori,
endoscopic biopsy of the gastric mucosa or
various noninvasive methods are utilized
including serologic tests and urea breath
tests.
Eradication of H. pylori is closely associated
with the gastric ulcers and low recurrence
rates

15. 1- Antimicrobial agents
Currently, either Triple therapy consisting of a PPI
with either metronidazole or amoxicillin plus
clarithromycin, or Quadruple therapy of bismuth
subsalicylate and metronidazole plus tetracycline
plus a PPI.
Course: administered for a 2-week course.
This usually results in a 90 percent or greater
eradication rate.
Note:
 Single antimicrobial drug is less effective
 Switching of antibiotics is also not recommended (do
not substitutes one antibiotic with other)

16. 2-Drugs that decrease gastric acid
secretion:
A- H2 -receptor antagonist
B- Inhibition of the H/K- ATPase proton
pump
C- Prostaglandins
D- Antimuscarinic agents (anticholinergic
agents)

18. 2- Regulation of gastric acid secretion
A- H2 -receptor antagonist
By blocking the binding of histamine to H2
receptor, these agents reduce the intracellular
concentrations of cyclic AMP and thereby
secretion of gastric acid. They inhibit basal,
food stimulated and nocturnal secretion of
gastric acid after a single dose.
 Cimetidine (prototype, its utility is limited
because of adverse effects and drug interaction).
 Ranitidine
 Famotidine
 Niatidine

19. H2-receptor Blockers
Daily
dosage
Relative
potency
Trade
name
Scientific
name
800 mg H.S
or 400 mg
Bid
1x
Tagamet
Cimetidine
300 mg H.S or
150 mg Bid
4-10x
Zantac
Ranitidine
40 mg H.S or
20 mg Bid
20-50x
Pepcid
Famotidine
300 mg H.S or
150 mg Bid
4-10x
Axid
Nizatidine

20. A- H2 -receptor antagonist
Therapeutic uses
1- Peptic ulcer ( G. U, D.U)
2- Gastrophageal reflux disease (GERD)
3- Hhypersecretory conditions :
A. Zollinger – ellison syndrome ( gastrin secreting tumor)
B. Systemic mastocytosis
C. Multiple endocrine neoplasia ( MEN ) .
4- pre-anesthesia: (emergency and labour) to decrease
incidence of mendelson's syndrome (aspirating
gastric acid causing aspirating pneumonitis).
5- Controlling symptoms of gastric carcinoma.
6- Hiatus hernia (H.H).
7- Acute stress ulcer
8-Iatrogenic ulcer.

21. Side effects
Headache, diarrhea, dizziness, and muscle
pain
For cimetidine can also have antiandrogen
effects gynecomasa and galactorrhea.
Cemitidine also inhibit liver metabolism
cause many drug interactions

22. 2- Regulation of gastric acid secretion
B- Inhibitors of the H⁺/K⁻-ATPase proton
pump
Omeprazole- the prototype
Lansoprazole
Pantoprazole
Rabeprazole
Esomeprazole

23. Uses
1- Erosive esophagitis and active duodenal
ulcer
2- Long-term treatment of pathologic
hypersecretory condition conditions
(Zollinger-Ellison syndrome in which gastrin
is increased)
3- In the treatment of GERD
4- Reduce risk of bleeding from an ulcer by
NSAIDs

24. Adverse effects
1- Generally well tolerated, but concerns
about long term safety have been raised
due to increased secretion of gastrin (in
animal studies with increase in gastric
carcinoid tumors)
2- Drug interaction in the oxidation of many
drugs such as warfarin.

25. 2- Regulation of gastric acid secretion
C- Prostaglandins –
Misoprostol –prostaglandin analogue of E1
Synthetic analog of PGE1, it prevents G.U in
patients taking NSAIDs, chronic D.U and
G.U.
Side Effects: Dysmenorhea and rash
Contraindications: Pregnancy

26. 2- Regulation of gastric acid secretion
D- Antimuscarinic agents
Dicycamine, a cholinergic antagonist, can
be used as an adjunct in the management
of peptic ulcer and zollinger-Ellison
syndrome.
Side effects:
1- cardiac arrhythmias
2- urinary retention limit its use.

27. 3- Neutralization of gastric acid:
Antacid
They are weak bases that react with gastric
acid to form water and salt.
Pepsin is inactive at a pH greater than 4.
Antacid reduces H. pylori and stimulate
prostaglandin synthesis.

28. Therapeutic uses
 Combination of aluminum and magnesium
can be used for duodenal ulcer.
 Aluminum hydroxide- causes constipation
 Magnesium trisilicate- causes diarrhea
 Calcium carbonate is used as calcium
supplement for the treatment of osteoporosis
 Antacid containing sodium such as sodium
bicarbonate should be considered in patients
with hypertension or congestive heart failure
and pregnant mother.

29. - Enhancement of mucosal resistance:
Mucosal protective agents
Sucralfate
This complex of aluminum hydroxide and
sulfated sucrose binds to positively charged
groups in proteins of both normal and
necrotic mucosa. By forming complex gels
with epithelial cells. Sucralfate creates a
physical barrier that impairs that diffusion of
HCl and prevents degradation of mucus by
pepsin and acid.
It also stimulates prostaglandin release as
well as mucus and bicarbonate output.

30. Colloidal bismuth
In addition to their antimicrobial actions,
they inhibit the activity of pepsin, increase
secretion of mucus, and interact with
glycoprotein in necrotic mucosal tissue to
coat and protect the ulcer crater.
Bismuth chelate:

31. 3- Drugs used to control vomiting
 Vomiting : is a protective mechanism to remove harmful or irritant
substances from upper GIT , controlled by vomiting center in medulla.
 EMETICS:- are those drugs who cause vomiting.
 Vomiting needs to be induced only when an undesirable substance
(poison) has been ingested.
 Those drugs are :-
Apomorphine:- It is a semisynthetic derivative of morphine; acts as a
dopaminergic agonist on the CTZ. Injected i.m./s.c. in a dose of 6 mg, it promptly
(within 5 min) induces vomiting
Ipecacuanha

32. All emetics are contraindicated in
CNS stimulant drug poisoning
o
Unconscious patient: may aspirate the
vomitus, because laryngeal reflex is
likely
to be impaired

33. How vomiting occur?

Emesis Vomiting occurs due to stimulation of the emetic (vomiting) centre
situated in the medulla oblongata. Multiple pathways can elicit vomiting .

The chemoreceptor trigger zone (CTZ) located in the area postrema and the
nucleus tractus solitarius (NTS) are the most important relay areas for
afferent impulses arising in the G,I,T throat and other viscera. The CTZ is
also accessible to bloodborne drugs, mediators, hormones, toxins, etc.
because it is unprotected by the blood-brain barrier. Cytotoxic drugs,
radiation and other g.i. irritants release 5-HT from enterochromaffin cells
→ acts on 5-HT3 receptors present in CTZ and CTZ cells produce ACH
then ACH attach to the vomiting centers Muscuranic receprtor and here
vomiting arise immediately.

34. Mechanism of vomiting

35. 2- Drugs used to control vomiting

36. 2- Drugs used to control vomiting
1-Anticholinergic : Hyosine or Scopolamine
(Atropine)
2-H1-blockers: Cyclizine , Meclizine ,
Diphenhydramine, dimenhydrinate ,
promethazine
3-Dopamine ( D2) antagonists:
-Metoclopramide ( plasil) , Domperidone
(CRTZ , gut).
-Haloperidol (CRTZ).
-Chlorpromazine(largactil), Promazine ,
prochlorperazine (Stemetil) (CRTZ,vomiting
center)

37. 2- Drugs used to control vomiting
4- 5-HT3-Blockers : Ondansetron,
Tropisetron & granisetron.
5-Others : Dexamethasone ,
methylprednisolone , Diazepam &
lorazepam.

38. 3- Drugs used to control chemotherapy
induced emesis
Mechanism of action-
They reduce the attachment of receptors to
their legand.

39. Drugs used to control vomiting
Phenothiazines
Prochlorperazine acts by blocking
dopamine receptors. Although increasing
the dose improves antiemetic activity, side
effects including:
 Hypotension and restlessness are dose
limiting.
 Extrapyramidal symptoms and sedation.

40. 5-HT3 serotonin-receptor blockers
Ondansetron, granisetron are selectively
block 5-HT3 receptor in the periphery
(visceral vagal afferent fibers) and in the
brain. (chemoreceptor trigger zone).
Headache is the common side effect. These
drugs are costy.

41. Substituted benzamides
Metoclpramide is highly effective at high doses against
the highly emetogenic cisplatin( is a chemotherapy
medication used to treat a number of cancers.
These include testicular cancer, ovarian cancer,
cervical cancer, breast cancer)
Antidopaminergic side effects, including sedation, diarrhea
and extrapyramidal symptoms.
The adverse reaction are most common in younger patients

42. 1-Metoclopramide (plasil):
Prokinetics(drugs promoting GIT motility )
Antiemetic , prokinetic , blocks dopamine
receptors in CRTZ , enhances actions of
Ach on M-receptors in GIT, elevates the
tone of lower esophageal sphincter,
increasing peristalsis & emptying upper
GIT , it also stimulates prolactin
secretion leading to galactorrhea .

43. Indications:
Nausea , vomiting , pre-anesthesia ,
GERD , radiotherapy , endoscopy &
migraine .
Side effects :
-extrapyramidal dystonia , torticollis ,
Parkinsonism , gynaecomastia &
lactation .