Esomeprazole

Esomeprazole works by binding irreversibly to the H+/K+ ATPase in the proton pump.

Inhibition dramatically decrease the secretion of hydrochloric acid into the stomach

1. Esomeprazole
Madhuka Perrera

2. Gastrointestinal Tract
(Alimentary Canal)

3. Organs of the digestive system
1.Gastrointestinal tract
Mouth
Pharynx
Esophagus
Small intestine
Large intestine
Anus
2.Accessory digestive organs
 Salivary glands
 Pancreas
 Liver
 Gallbladder
 Teeth
Gastrointestinal Tract
(Alimentary Canal)

4. Accessory Digestive Organs
Pancreas
Glandorganin thedigestiveandendocrine system
It secretes pancreatic fluid that contains digestive enzymes
that pass to the small intestine. These enzymes help to further
break down the carbohydrates, proteins, & lipids in the chyme
As anendocrine glandproducing several importanthormones,
includinginsulin,glucagon

5. Accessory Digestive Organs
Salivary glands
Parotid glands
Submandibular glands
Sublingual gland

6. Liver
Largest gland in the body
Connected to the gall bladder
Produce bile
Gall bladder
Stored bile form liver
Bile introduced into the duodenum in the
presence of fatty food
Accessory Digestive Organs

7. Accessory Digestive Organs
Teeth
Role is to masticate food
Classification of Teeth
Incisors
Canines
Premolars
Molars

8. Mouth (Oral Cavity)
Processes of the mouth
Mastication (chewing ) of food
Mixing masticated food with saliva
Initiation of swallowing by the tongue
Allowing for the sense of taste
Mouth can absorb Simple carbohydrate , glucose

9. Small intestine
Small intestineis the part of theGI tractfollowing
thestomachand followed by thelarge intestine
The primary function is absorption of nutrients from
food.
Subdivisionsof the small intestine
Duodenum
Jejunum
Ileum

10. Large Intestine
Locations of Colon
Ascending colon
Transverse colon
Descending colon
Sigmoid colon

11. Large Intestine
Functions
Absorptions of Water
Eliminate indigestible food from the body as feces
Does not participate in digestions of food
Structures of the Large Intestine
Cecum : First part of the large intestine
Appendix: Hand form the cecum(sometime inflamed , appendicitis)
Colon : Ascending , Traverse , Descending , Sigmoid
Rectum
Anus : external body opening
Goblet cells produce mucus to act as a lubricant

12. The Stomach
•The stomach lies between theoesophagusand theduodenum
•Cardiac sphincterand thePyloric sphincterkeep the contents of
the stomach contained.

13. The Stomach
The stomach is divided into four sections
Cardia This is the area where the esophagus meets with the stomach
Fundus This is the uppermost area of the stomach that lies just under the
diaphragm
Body This is the largest part of the stomach between the fundus and pylorus.
Pylorus It is divided into thepyloric antrumwhich lies next to the body and
thepyloric canalwhich lies next to the duodenum.

14. The Stomach
Functions
Acts as storage tank for food
Breaking down the food into a liquidly mixture called chyme
Mixing enzymes which is are chemicals that break down
food.
Delivers chyme to the small intestine
The stomach uses pepsin and peptidase to break down
proteins in your food

15. Glands of the Stomach
Cardiac
Pyloric
Gastric*
*The cells of the gastric gland are the
largest in number and of primary
importance when discussing acid control

16. Parietal cells
Produce and secrete HCl
Primary site of action for many acid-controller drugs
Chief cells
Secrete pepsinogen,
Pepsinogen becomes pepsin when exposure to acid
Pepsin breaks down proteins
Mucoid cells
Mucus-secreting cells (surface epithelial cells)
Provide a protective mucous coat
Protect against self-digestion by HCl
Cells of the Gastric Gland

17. Three faces of Gastric Secretion
Cephalic face
by the taste or smell of food tactile sensation in the
mouth secrete HCL & pepsin in the stomach
Gastric face
Food has entered to the stomach continue secretion
of HCL & pepsin
Intestinal face
Chyme has entered to duodenum, so gastric secretion
no longer needed , decrease gastric secretion

18. Parietal cell (Oxyntic cells)
Parietal cells, are thestomachepitheliumcellsthat
secretegastric acid
The parietal cell contains receptors for gastrin,
histamine(H2), & acetylcholine(M3) ,
When acetylcholine, histamine or gastrin (released from G
cells into the blood)bind to the parietal cell receptors,
that stimulate acid secretion from a H+,K+ATPase
(the proton pump) on the canalicular surface.

19. Parietal cell

20. Gastric Acid Production
H
2CO
3 : Carbonic acid
CA : Carbon Anhydrase

21. Gastric Acid Production
1.CO
2defused to parietal cell
2.In the parietal cell you get H
2O, With Help of Carbon
Anhydrase CO
2 & H
2O formed H
2CO
3
3.Which is not stable inside to parietal cell & It breakdown
to H
+
& HCO
3
-
4.HCO
3-goes to blood stream to balance Cl
-
will come to
Parietal cell
5.Through Proton pump H
+
goes to caniliculus with the help
of ATP
6.To balance that from the canaliculus K
+
goes to parietal
cell then to blood stream
7.Cl
-
goes to canaliculus with effects
8.In the canaliculus lumen HCL will Produced

22. Types of
Acid-Controlling Agents
Antacids
H2 antagonists
Proton pump inhibitors

23. Antacids : Mechanism of Action
Promote gastric mucosal defense mechanisms
DO NOT prevent the over-production of acid
DO neutralize the acid once it’s in the stomach
Aluminum Salts (carbonate, hydroxide)
Magnesium Salts (carbonate, hydroxide)
Calcium Salts (carbonate)
Side Effects
Aluminum and calcium :Constipation
Magnesium :Diarrhea
Calciumcarbonate :Produces gas and belching

24. Histamine Type 2 (H2) Antagonists
Cimetidine
Famotidine
Ranitidine
Mechanism of Action
Block histamine (H
2) at the receptors of parietal cells
thereby production of H+ is reduced, resulting in
decreased production of HCl

25. Proton Pump Inhibitors
Mechanism of Action
Irreversibly bind to H
+
/K
+
ATPase enzyme
Result: ALL gastric acid secretion is blocked
Lansoprazole
Omeprazole
Rabeprazole
Pantoprazole
Esomeprazole

26. Mechanism of Action
Esomeprazoleworks by binding irreversibly
to the H+/K+ ATPasein the proton pump.
Inhibition dramatically decrease the secretion of
hydrochloric acid into the stomach

27. Pharmacokinetic data of Esomeprazole
Bioavailability 90%
Protein binding 97%
Metabolism Hepatic(CYP2C19,CYP3A4)
Half-life 1-1.5 h
Excretion 80%Renal
20%Faecal
C-max (peak plasma level) 1.5 h

28. Esomeprazole
Esomeprazole is theS-isomerofomeprazole
Esome capsules are formulated as a "multiple
unit pellet system" thecapsuleconsists o
small enteric-coated granules (pellets) of the
esomeprazole formulation inside an outer
shell.

29. Therapeutic Indications & Dosage of
Esome
Gastroesophageal Reflux (GERD)
NSAID-associated gastropathies
H-Pylori eradication
Symptomatic GERD (heartburn) in patients
ENRD
Empiric therapyis amedicalterm referring to the initiation
of treatment prior to determination of a firmdiagnosis

31. Dosage Schedule
GERD Esome 40mg
Once daily
For 4 to 8 weeks
Symptomatic GERD Esome 20mg
Once daily
For 4 week
NSAIDs induced
gastropathies
Esome 20mg
or
Esome 40mg
Once daily
H.Pylori eradication
Amoxicillin
Clarithromycin
Esome 40mg
1000mg
500mg
OD for 10 days
OD for 10 days
BD for 10 days

32. EsomeIV Administration
Esome IV Injection
Esome IV injection is prepared by dissolving the
lyophilized (freeze & dried ) powder (40mg) in 5ml of
0.9% NaCl solution
Reconstituted solution must be administered as an IV
injection over no less than 3 min.
The reconstitute solution should be Stored at room
temperature up to 30
O
C & administered within 12h

33. EsomeprazoleIV Administration
EsomeprazoleIV infusion 40mg
A solution for IV infusion is prepared by first reconstituting
the contents of one vial with 5 mLof 0.9% Sodium Chloride
Injection, Lactated Ringer’s Injection, or 5% Dextrose
Injection,
further diluting the solution to a final volume of 50 mL
The solution (admixture) should be administered as an IV
infusion over a period of 10 to 30 minutes.
Should be administered within the designated time period as below.
The admixture should be stored at room temperature up to 30°C
0.9% Sodium Chloride Injection, 12h
Lactated Ringer’s Injection 12h
5% Dextrose Injection 6h

34. Itraconazole, ketoconazole, (anti-fungal )
Bioavailability of itraconazole and ketoconazole may
be reduced. Due to decreased intragastric acidity
Drug metabolize in CYP2C19
Benzodiazepines (diazepam, cilalopram) plasma
concentrations maybe increased
Drug Interactions

35. Adverse Reactions
Common Uncommon
Headache Dermatitis
abdominal pain Pruritus :
Flatulence
(localizedorgeneralizeditchingduetoi
rritationofsensory nerveendings )
diarrhea Urticaria
constipation dizziness/vertigo
Nausea dry mouth
Vomiting

36. Contraindication
Known hypersensitivity to esomeprazole,
any ingredient in the formulation, or other
substituted benzimidazoles
(e.g. lansoprazole, omeprazole, pantoprazole,
rabeprazole).

37. Pediatric : below 18 yrs not established
Hepatic insufficiency
mild/ moderate : no dose adjustment required
Severe : 20mg once daily should not exceed
Renal insufficiency
Pharmacokinetics of esomeprazole in patient with renal
impairments are not expected to be altered relatively
to healthy volunteers.Less than 1% excrete in
unchanged in urine
Special Population