Doctor of physiotherapy,pharmacology katzung Drugs used in GIT disorders

1. DRUGS USED IN
GASTROINTESTINAL
DISORDERS
PRESENTED BY :SIBGHA ABBAS

2. GASTROINTESTINAL TRACT
GIT serves many important functions:
Digestive
Excretory
Endocrine
Exocrine
And so on ………..

3. Flow chart

4. ACID-PEPTIC DISEASES
• Ulceration and erosion of lining of upper portion of GIT are common
problems that manifest as ;
• Gastroesophagal reflux disease (GERD)
• Gastric and duodenal peptic Ulcers
• Stress- related mucosal injury

5. DRUGS EFFECT
• Drugs used in acid-peptic diseases reduce intragastric acidity by
manipulating systems controlling acid secretion,promote moucsal
defenseor ,in the case of peptic ulcers,eradicate the bacterium
HELICOBACTER PYLORI,which is detectable in over 80% of
patients with duodenal ulcers.

6. Drugs used in acid-Peptic disesases
• Antacids
• H2-receptor anatagonists
• Proton pump inhibitors
• Sucralfate
• Misoprostol
• Colloidal Bismuth
• Antibiotics

7. ANTACIDS
❖Magnesium Hydroxide
❖Aluminium Hydroxide
❖Calcium Caebonate
❖Sodium Carbonate

8. ANTACIDS
MECHANISM OF ACTION
• Antacids are weak bases that;
• Neutralize stomach acid by reacting with protons in the lumen of gut
• Stimulate protective function of gastric mucosa
• Large doses need to raise pH
• Reduce the recurrence rate of peptic ulcers
• Magnesium hydroxide has a strong laxative effect
• Aluminum hydroxide has a constipating action

9. ❑ Pharmacokinetics:
Effective for few hours after administration.
❑ SIDE EFFECTS
AI & Mg are often combined because formulations containing AI alone cause constipation
and formulations containing Mg alone cause an osmotic diarrhea

10. H2- RECEPTOR ANTAGONISTS
• Cimetidine
• Ranitidine
• Famotidine
• Nizatidine

11. PHARMACOKINETICS
• Given orally ,distributed widely throughout the body
• Excreted mainly in urine
• Eliminated quite rapidly ,with a terminal half-life 1 to 3 hrs
• Approximately 30% of a dose is slowly inactivated by the liver’s
microsomal mixed-function oxygenase system
• Dosage must be decreased in hepatic and renal failure

12. MECHANISM OF ACTION
• Inhibit stomach acid production ,especially at night
• Decrease gastric acid secretion by reversibly binding to histamine H2
receptors located on gastric parietal cells, thereby inhibiting the
binding and activity of endogenous ligand histamine. H2 blockers
thus function as competitive antagoinist
• They are effective in the treatment of GERD,peptic ulcer,non- nuclear
dyspepsia and in the prevention of stress-related gastritis

13. ADVERSE EFFECTS
• Diarrhea
• Constipation
• Fatigue
• Drowsiness
• Headache
• Muscle aches
• H2blockers are metabolized in liver by cytochrome P450system

14. PROTON PUMP INHIBITORS
• Omeprazole
• Esomeprazole
• (dex)lansoprazole
• Pantoprazole
• Rabeprazole

15. PHARMACOKINETICS
• PPI is a pro drug which is activated by acid
• Activated PPI binds covalently to the gastric H+,K+-ATPase via
disulfide bond and inactivate parital cell H+,K+-ATPase
• They are lipophilic weak bases that diffuse into the parital cell
canaliculi,where they brcome protonated and concentrated more than
1000-fold

16. MECHANISM OF ACTION
• They block gastric H,K-ATPase, inhibiting gastric acid secretion.
• This effect enables healing of peptic ulcers,gastroesophagal reflux
disease,Barrett’s esophagus,and Zollinger-Ellison syndrome
• More effective than H2 antagonists for GERD and peptic ulcer
• Duration of action approximately 24 h,and they may require 3-4 d of
treatment to achieve their full effictivness
• They may decrease the oral bioavailability of vitamin B12 and certain drugs
that require acidity for their gastrointestinal
absorption(eg,digoxin,ketoconazole)

17. ADVERSE EFFECTS
• Diarrhea
• Abdominal pain
• Headache
• Chronic treatment with PPI may result in hypergastrinemia

18. SUCRALFATE
• Auminium sucrose sulfate,sucralfate is a small,poorly soluble ,molecule that
polymerize in the acid environment of stomach
• Polymer bind to injured tissue and forms a protecting coating over ulcer
beds
• Sucralfate accelerate healing of peptic ulcers and reduce reccurence rate
• Must be taken 4 times daily
• Sucralfate is too insoluble to have significant systemic effects when taken
orally
• Toxicity is very low

19. MISOPROSTOL
• Analog of PGE1, misoprostol increases mucosal protection and inhibit
acid secretion through direct stimulation of prostaglandinE1 receptors
on parietal cells in stomach
• Effective in reducing risk of ulcers in users of nonsteroidal anti-
inflammatory drugs (NSAIDs)
• TOXICITY:sedation,,abdominal pain ,dyspnea,fever, hypotension

20. COLLOIDAL BISMUTH
• ACTION:F.ormation of a protective coating on ulcerated
tissue,stimulation of mucosal protective mechanisms ,direct
anrtimicrobial effects and sequestration of enterotoxins
• Bismuth subsalicylate,a non-prescription formulation of bismuth and
salicylate,reduce stool frequency and liquidity in infection diarrhea
• Bismuth causes black stool

21. ANTIBIOTICS
• Chronic infection with H.pylori is treated with combination of antibiotics ,these amy
include;
• Amoxiciilin
• Clarithromycin
• Metronidazol
• Tinidazole
• Tetracyclin
• Levofloxacin
• Proton pump inhibitor drugs

22. DRUGS THAT PROMOTE UPPER
GASTROINTESTINAL MOTILITY
• Prokinetic agents such as;
• METOCLOPRAMIDE
• DOMPERIDONE
• ERYTHROMYCIN
• CHOLINOMIMETIC AGONISTS such as BETHANECHOL
• NEOSTIGMINE(ACETYLCHOLINESTRASE INHIBITORS)

23. MECHANISM OF ACTION
• Bethanechol:used for GERD and gastroparesis
• Neostigmine:treatment of hospitalized patients with acute bowl distention
• Erythromycin: promotes motility by stimulating motilin receptors,beneficial
for gastroparesis patients
• Metoclopramide and Domperidone:are D2 dopamine receptor antagonists
that promote gastrointestinal motility
• Metoclopramide when used chronically can cause symptoms of
parkinsonism,other extrapyramidal effects,and hyperprolactinemia
• Domperidone does not cross BBB so less likely to cause CNS toxicity

24. LAXATIVES
• They increase the probability of bowl movement by several
mechanisms:
• An irritant or stimulant action on bowl wall
• A bulk –forming action on the stool that evokes reflex contraction of
bowl
• A softening action on hard or impact stool
• Lubricating action that eases passage of stool through rectum

25. LAXATIVES

26. ANTIDIARRHEAL AGENTS
• Opoid
• Diphenoxylate(Formulated with antimuscarine alkaloids)
• Loperamide(formulated alone )
• Kaolin (hydrated magnesium aluminium silicate, combine with
pectin)
• Pectin (indigestible carbohydrate that absorbs bacterial toxins and
fluid ,resulting in decreasedstool liquidity)

27. DRUGS USED FOR IRRITABLE BOWL
SYNDROME
• Irritable bowl syndrome is associated with recurrent episodes of
abdominal discomfort plus diarrehea and constipation
• Discyclomine
• Hysocyamine
• Alosetron
• Lubiprostone
• Linaclotide

28. MECHANISM OF ACTION
• Dicyclomine and hyoscyamineare use as anti-spasmodics to relieve
abdominal pain
• Aosetron,a potent 5-HT3 antagonist,treatment of women with IBS with
diarrehea ,it can cause severe constipation and ischemic colitis that’s why it
is restricted
• Lubiprostone,laxative that activate type 2 chloride channel in small
intestine,treatment of IBS
• Linaclotide,binds and activate guanylyl cyclase-C on luminal intestinal
epithelial surface resulting increased cGMP lead to activation of type2
chloride channel.

29. DRUGS WITH ANTIMETIC ACTIONS
• METOCLOPRAMIDE
• Diphenhydramine
• Phenothiazines
• Scopolamine
• Dexamethasone
• Dronabinol
• Nabilone
• Ondansetron
• Granisetron
• Dolasetron
• Palonoestron
• Aprepitant(used in combination with other antimetic drugs)

30. DRUGS USED IN INFLAMMATORY
BOWL DISEASES
• Aminosalicylates: Drugs containing 5-aminosalicylic acid are ;
• Balsalazide,osalazine,sulfasalazine contain 5-ASA bound by
azo(N=N)bond to an inert compound ,another 5-ASA

31. MECHANISM OF ACTION
• 5-ASA involve inhibiting the synthesis of prostaglandins,inflammatory
leukotriens and cytokines
• 5-ASA generally known as mesalamine ,readily absorbed from small
intestine whereas absorption from colon is low

32. ADVERSE EFFECTS OF
SULFASALAZINE
• Nausea
• GIT upset
• Arthralgias
• Myalgias
• Bone marrow suppression
• Malaise

33. OTHER AGENTS
• Other drugs use in treatment of ulcerative colitis and crohn’s disease
include;
• Glucocorticoid(budesonide)
• Immunosuppresive antimetabolites(azathioprine,6-
mercaptopurine,methotrexate)
• Anti-tumor necrosis factor(TNF) drugs(infliximab,adalimumab,golimumab)
• Natalizumab(restricted in severe refractory Crohn’s disease)

34. PANCREATIC ENZYME
REPLACEMENTS
• Pancreatic lipase(pancrelipase)obtained from pigs
• Inactivated at pH lower than 4,should be taken as enertic –coated
capsulesunless pH is raised with antacids
• Used for STEATORRHEA,condition of decrease fat
absorption,increase fat excretion,due to inadequate secretion of
pancreatic lipase which is given orally

35. DRUGS THAT INHIBIT THE
FORMATION OF GALL STONES
• Ursodiol,used to inhibit the formation of cholesterol gallstones,dec.
the cholesterol content bof bile by dec. hepatic cholesterol secretion
and has other effects on hepatocyte canalicular membranes.