1. Clinical pharmacy in gastroenterology

2. The structure of digestive or alimentary tract

3. Digestion is the first stage of metabolism
This system does secretory, motor, absorption, excretion and immune functions

4. Anatomico-physiological bases
Secretory function
- formation and exudation of digestive juices into intestinal lumen
Daily secretion:
1,5 l saliva,
2,5 l gastric juice,
1,0 l pancreas juice,
1,2 l bile,
2,5 l intestinal juice

5. Anatomico-physiological bases
Motor function
- food movement into intestinal pipe and its permanent mixing with digestive juices
Absorbtion
- absorption of some ingredients from undigested food and indigestible material

6. Anatomico-physiological bases
Excretion
- moving off undigested food remainders and also some matters picked out in intestinal lumen
Immune function
In wall of large intestine there are accumulations of lymphoid tissue - “Peyer’s plaques”, where ripening of lymphocytes takes place

7. Anatomico-physiological bases
Stomach
Duodenum
Small intestine
Large intestine

8. Anatomico-physiological bases
Basic stomach functions:
physical and chemical processing of food, his depositing and evacuation;
participation in metabolism;
participation in hemostasis (synthesis of gastromucoprotein by parietal cells etc.);
participation in water-salt metabolism;
Synthesis of prostaglandines and gastrointestinal hormones

9. Клиническая фармация в гастроэнтерологии
Factors that play the great role of the development of inflammation diseases in the gastroduodenal area
Protective factors
mucus
Ionic gradient
bicarbonates
prostaglandins
Epithelial cells
Mucus membrane blood supply
Aggression factors
Drugs and medicines (NSAIDs)
hydrochloric acid
Pepsin
Helicobacter pylori
Клиническая фармация в гастроэнтерологии

10. Ways of examination: questioning
The main complaints of GIT impairment:
Pain (in epigastric area)
Appetite disorders
Dysgeusia
Eructation
Heartburn
Nausea
Vomitting
Constipation
Diarrhea
Meteorism
Fatigue
Клиническая фармация в гастроэнтерологии

11. Laboratory and instrumental methods of examination
Fiber-optic gastroduodenoscopy
Клиническая фармация в гастроэнтерологии

12. Laboratory and instrumental methods of examination
Colonoscopy and biopsy
Клиническая фармация в гастроэнтерологии

13. Laboratory and instrumental methods of examination
X-ray examination of GIT
Клиническая фармация в гастроэнтерологии

14. Laboratory and instrumental methods of examination
Bacteriologic, histologic and fast urea test of Н. Pylori
Клиническая фармация в гастроэнтерологии

15. Laboratory and instrumental methods of examination
Non-invasive test : Breath test with urea
Клиническая фармация в гастроэнтерологии

16. An algorithm approach to the diagnosis of GIT disorders
Клиническая фармация в гастроэнтерологии

17. Laboratory and instrumental methods of examination
Hematology
Клиническая фармация в гастроэнтерологии

18. Laboratory and instrumental methods of examination
Urinalysis and blood biochemistry tests
Клиническая фармация в гастроэнтерологии

19. Laboratory and instrumental methods of examination
Faeces analysis
Клиническая фармация в гастроэнтерологии

20. Main syndromes in gastroenterology:
Gastric dyspepsia
Intestinal dyspepsia
Maldigestion and malabsorption
Hypovitaminosis
Gastrointestinal bleeding
Asthenoneurotic syndrome
Anemic syndromes
Pain syndrome

21. Syndromes in GIT disorders
Hypovitaminosis: skin dryness,
angular cheilosis, stomatitis, hair loss,
trophic changes of nails

22. Basic stomach diseases
Chronic gastritis - chronic inflammatory-dystrophyc process in stomach mucous, being attended with violation of cells regeneration processes and progressing atrophy of glandular epithelium

23. Basic stomach diseases
Chronic gastritis
Chronic autoimmune gastritis (type A)
Chronic gastritis (type B)
In accordance with dominant etiologic factor…

24. Basic stomach diseases
Chronic autoimmune gastritis (type A) - variant of chronic gastritis, conditioned by appearance of antibodies to parietal (acid-secretory) cells of stomach mucous

25. Basic stomach diseases
Etiology
At the beginning of this disease there is fundamental importance of combination of the exogenic and endogenic factors
Pathogeny
Along of antibodies making to parietal cells of mucous stomach takes place her damage.
Hereinafter develops diffuse atrophy of stomach mucous, his secretory function lowers, up to significant secretory insufficiency.
In part of cases there is a produce of auto-antibodies to gastromucoprotein (internal Castle’s factor) then which lead to the development of В12-deficiency anemia.

26. Chronic autoimmune gastritis (type A)
Clinical manifestations/ syndromes
1.Pain syndrome: pain in epigastric area, temporary aching after food. Patients complaints about heaviness or sense of stomach enlargement, pressure in epigastric area and left subcostal area.
2.Syndrome of gastric dyspepsia: lowering of appetite, disagreeable taste in mouth, eructation, nausea with possible vomiting.
3.Syndrome of intestinal dyspepsia: rumbling sounds in abdomen, flatulency, leaning to diarrhea.

27. Chronic autoimmune gastritis (type A)
Clinical manifestations/ syndromes
4.Maldigestion and malabsorption: dehydration due to diarrhea, hypovitaminosis, weight loss.
5.Neurotic (asthenoneurotic) syndrome: weakness, irritability, paresthesias, cold sensations in the extremities, neurogenic, cardiogenic, vascular symptoms (angina like pains, hypotension).

28. Chronic autoimmune gastritis (type A)
Diagnostic criteria of chronic gastritis type А
Clinical manifestations
Special methods of investigation
Complaints - blunt pains in epigastrium, appetite loss, disagreeable taste in mouth, nausea, heaviness after food, belch rotten, diarrheas.
Examination - coated tongue, symptoms hypovitaminosis (skin dryness, hair loss, stomatitis and etc.), flatulency.
X-ray examination- tone and peristalsis is weak, forced stomach evacuation.
Gastroscopy faded mucous.
Biopsy - stomach mucous atrophy and inflammation signs

29. Chronic autoimmune gastritis (type A) Principles of medicinal therapy
correction of gastric secretion violations (substitution therapy, forcing of gastric secretion).
forcing of mucous regeneration process (anabolic hormones, biologic stimulants).
correction of metabolic disturbances (aminoacids, vitamins, anabolic hormones).
correction of motored violations (prokinetics).
correction of intestinal digestion violations (polyenzymatic medications: festal, panzynormum).

30. Basic stomach diseases
Chronic gastritis (type B) - variant of chronic gastritis, induced by bacterium Нelicobacter pylori.

31. Basic stomach diseases Etiologic factors may be
Endogenous
Exogenous

32. Basic stomach diseases
Endogenous factors
Genetic predisposition:
augmentation of parietal cells;
surplus gastrin liberation;
rise of pepsinogen level in blood;
Violation in gastroduodenal movements;
lack of pepsin inhibitors;
violation of Ig A structure;
blood group 0 (I);
positive Rh-factor;
Presence of antigenes HLA В5, В15, В35.

33. Basic stomach diseases
Exogenous factors
violation of nutrition;
harmful habits (smoking, alcohol, abuse of coffee);
professional influences and mode of life;
damaging action of medicinal preparations (anti-inflammatory drugs, corticosteroids, some antibiotics, iron preparations, potassium).
To be infected by Helicobacter pylori

34. Basic stomach diseases Clinical manifestations
Pain syndrome: “hungry” pain (nighttime pain) in epigastric area, which can stop after food intake;
Neurotic syndrome: irritability, fatiguability, bad sleep;
Syndrome of gastric dyspepsia: heartburn, nausea, sour belch;
Syndrome of intestinal dyspepsia: constipations.

35. Basic stomach diseases
Diagnostic criterions of chronic gastritis type В
Clinical manifestations
Special methods of investigation
Complaints - hungry epigastric pains, vomiting on pains height, heart-burn, belch sour, constipation.
Examination - sickliness attached to epigastral palpation
X-ray exam- raised tonus of stomach antral area, peristalsis is weakened, hypersecretion signs.
Gastroscopy - edema and hyperemia of mucous, folds hypertrophy mucous stomach.
Biopsy - signs of chronic inflamma-tion and hyperplasia mucous of stomach antral area.

36. Symptoms of Dyspepsia Ulcer-like Dominant Dysmotility-like Dominant
Nocturnal pain
Localized epigastric burning
Better with food
Heartburn
Retrosternal
burning
Nausea
Bloating
Early satiety
Worse with food

37. Major Causes of Dyspepsia
Williams 1988 Stanghellini 1996 Heikkinen (n=1386) (n=1057) (n=766)
% of Patients with Diagnosis
Gastric Cancer Peptic Ulcer Esophagitis/ Functional

39. Helicobacter pylori
A spiral shaped, Gram-negative, microaerophilic, and flagellated bacterium, living in the stomach and duodenum
About 3 microns long with a diameter of about 0.5 micron
Causing up to 80% of peptic ulcers, more than 90% of duodenal ulcers, and some types of gastritis
Rediscovered in 1982 by the laureates and made connection with stomach ulcers and gastritis
Helicobacter pylori (blue bars, curved, 2-4 microns) localized in the mucus on the mucous surface, at the intercellular lines. Photo: tangential section of the gastric mucous

40. Epidemiology
Approximately two-thirds of the world's population is infected with H. pylori.
70% - 90% in developing countries
25% - 50% in developed countries
Over half the population is infected in early childhood in China.
Most of those infected never have symptoms.
The bacteria are most likely spread from person to person through fecal-oral or oral-oral routes.
Possible environmental reservoirs include contaminated water sources.
The source of H.pylori is unknown yet .

41. H. pylori Epidemiology

42. Pathogenicity Stomach acid Gastric epithelium
H.pylori lives in the mucus lining to escape from the highly acidic gastric juice. (Its helical shape facilitates its penetration of the mucus layer.)
It can fight the acid by excreting an enzyme called urease.
The immune system responds to the infection by sending white cells, killer T cells, and other infection fighting agents.
However, they cannot easily get through stomach lining to reach the infection.
As the immune response grows, immune cells die and release destructive compounds on the stomach lining cells.
Within a few days, gastritis and perhaps eventually a peptic ulcer results.
Gastric epithelium

45. Symptoms
The most common ulcer symptom is burning pain in the epigastrium (the upper middle region of the abdomen). The pain typically occurs when the stomach is empty.
Less common symptoms include nausea, vomiting, and loss of appetite.
Bleeding can also occur.
Recent studies have shown an association between long-term infection and the development of gastric cancer, which is the most common cancer in China.

46. Testing for H. pylori Test Sensitivity Specificity Cost Comments
C13 or C14 90% to 100% 96% to 100% ++ Limited - requires urease breath nuclear medicine test department
Serology 91% to 98% 75% to 80% + Widely available commercial labs
Capillary % to 90% 75% to 80% + Office test, must purchased by doctor admin
Endoscopic 99% 99% ++++ Requires biopsy specialist Invasive
(Cutler A. Gastro 1995;109:136. Megraud F. Scand J Gastro 1996;215:57)

47. Fundamental rules of anti-ulcer therapy
Steady lowering of acid reaction (рН > 3 not less h/day):
Proton pump ihibitors
Н2-histaminoblockers
Antacids
Eradication of Helicobacter pylori:
Antibiotics
Bismuth
Derivative nitromidazole
Rise cytoprotection (peculiarly attached to gastric ulcers ):
Sucralfate
Colloid bismuth
Synthetic analogues prostaglandins
Reparants
Use of medications with minimum side effects
Optimum compliance (observance by treatment program)

48. H. pylori Eradication (All given for one week)
Treatments of choice
Regimen PPI Antibiotics
PPI - AC BID Amoxicillin 1 g bid Clarithromycin 500 mg bid
PPI - MC BID Metronidazole 500 mg bid Clarithromycin 250 mg bid
Alternate
PPI - BMT BID Bismuth 2 tabs qid Metronidazole 250 mg qid Tetracycline 500 mg qid

49. H. pylori Eradication cure by one medication does not adapt
First line therapy:“triple therapy”: proton pump inhibitor (omeprazolum 20 mg twice/day or pantoprazolum 40 mg/ day) + antibiotics against Н. pylori (amoxicillin 1 g or metronidazol mg twice/day and clarithromycin (500 mg twice/day))
First/Second line therapy: “cure standard” - “quadrotherapy therapy”
proton pump inhibitor (omeprazolum 20 mg twice/day or pantoprazolum 40 mg/ day)
metronidazol (500 mg triplicate/day)
tetracycline (500 mg quadruplicate/day)
bismuth (120 mg quadruplicate/day)
Course of treatment -10 days
Second line therapy:«tripletherapy» includes
proton pump inhibitor (omeprazolum 20 mg twice/day or pantoprazolum 40 mg/day) from first to tenth day
clarithromycin (500 mg twice/day)
levofloxacin (500 mg once/day)

50. Acid Suppression Therapy for Ulcer-like Functional Dyspepsia
H2-receptor antagonist for 4 weeks OR
Proton pump inhibitor for 2 weeks

51. Receptor stimulation of acid secretion

52. Fundamental rules antihelicobacter therapy
In the same patient it is not allowed to repeat the previously used therapy which turned to be ineffective one
If two types of treatment regimens are not effective , and there id no significant eradication, then it is necessary to determine the sensitivity of Н.рylori strain to the whole spectrum of used antibiotics
Administration of back up “quadritherapy” regimen is desirable only after complete clarification of the failure of the different variants of “triple therapy”
The presence of Н. рylori up to year after conducted therapy should be considered as an infection set-back, but and not einfection
“Quadrotherapy” regimen must be used in case of infection set-back

53. Management of Ulcer-like Functional Dyspepsia
Ulcer-like Symptoms Dominant
Education/lifestyle modification
Test Hp + -
Trial of acid suppression
Eradicate Hp
Reassess
Success
Failure
Investigate
Trial of prokinetic

54. Lifestyle Modification for Patients with Functional Dyspepsia
Small frequent meals
Stop smoking
Reduce alcohol
Reduce caffeine
Avoid irritating foodstuffs
Maintain an ideal weight
Review medications

55. Risk Factors for Stomach Cancer
Helicobacter pylori was the first bacterium to be officially recognized as a cancer-causing agent.
Helicobacter pylori infection. Nitrates and nitrites are substances commonly found in cured meats, some drinking water, and certain vegetables, that can be converted by Helicobacter pylori, into compounds that have been found to cause stomach cancer in animals.

56. Helicobacter pylori: associated pathology
Gastritis B %
Ulceration %
Gastric Ca <1%
Lymphoma (MALT) <1%
De todas las patologías asociadas a la infección por Hp, la UGD es la que ha visto mas substancialmente modificado su manejo clínico por la irrupción de esta bacteria

57. Gastro-oesophageal reflux disease
chronic symptom of mucosal damage caused by stomach acid coming up from the stomach into the esophagus.
GERD is usually caused by changes in the barrier between the stomach and the esophagus, including abnormal relaxation of the lower esophageal sphincter, which normally holds the top of the stomach closed, impaired expulsion of gastric reflux from the esophagus, or a hiatal hernia.

58. Alginate-containing antacid
Gastro-oesophageal reflux disease
Endoscopic image of peptic stricture, or narrowing of the esophagus near the junction with the stomach: This is a complication of chronic gastroesophageal reflux disease and can be a cause of dysphagia or difficulty swallowing.
Barrett’s oesophagus
Alginate-containing antacid

59. Undiagnosed dyspeptic patient
Alginate-containing antacid
Heart burn without “alarm symptoms”
If symptoms persist after
1 week of regular treatment then H2 antagonist
If symptoms persist after
2 weeks of regular treatment the patient should be referred to the general practitioner

60. THE END