1. Drugs used to treat GIT disordes
Anton Kohút

2. Gastric ulcer

5. Pathogenesis of Ulcers
Therapy is directed at enhancing host defense or
eliminating aggressive factors; i.e., H. pylori.
Aggressive Factors
Acid, pepsin
Bile salts
Drugs (NSAIDs)
H. pylori
Defensive Factors
Mucus, bicarbonate layer
Blood flow, cell renewal
Prostaglandins
Phospholipid
Free radical scavengers

6. Gastric ulcer and NSAIDs
H. pylori infection

8. Drugs used to treat gastric ulcer Regulation of gastric acid secretion
I. Antisecretory drugs
1. H2 – blockers: cimetidine, ranitidine, famotidine nisatidine
2. M1 – blockers: pirenzepine, dicyclomine, propantheline
3. Antagonist of gastrin receptors: somastatine
4. Agonists of PG receptors: misoprostol, entprostyl
II. Antacids
-sodium bicarbonate,
-calcium carbonate,
-aluminium hydroxide,
-magnesium hydroxide

9. Control of gastric acid secretion

11. Antisecretory agents 4. Antagonist of gastrin receptors- somatostatin
H2 histamine blockers – cimetidine, ranitidine, famotidine, nisatidine
Antimuscarinic agents –pirenzepine, dicyclomine,
Agonists of prostaglandine receptors - misoprostol
4. Antagonist of gastrin receptors- somatostatin
5. Inhibitors of proton pump – omeprazole, pantoprazole

12. H2 receptor antagonists

13. Therapeutic uses of H2 antagonists
Acute stress ulcers:
in managing acute stress ulcers associated with major physical trauma in high-risk patients in intensive care units. They are usually injected intravenously.
Gastroesophageal reflux disease:
Low doses appear to be effective for prevention and treatment of heartburn (gastroesophageal reflux).
However, about 50 percent of patients do not find benefit, and PPIs are now used preferentially in the treatment of this disorder.
they may not relieve symptoms for at least 45 minutes.
Antacids more efficiently, but temporarily, neutralize secreted acid already in the stomach.
Finally, tolerance to the effects of H2 antagonists can be seen within 2 weeks of therapy.

15. All H2 antagonists are equally effective in promoting healing of duodenal and gastric ulcers. However, recurrence is common after treatment with H2 antagonists is stopped (60–100 percent per year).
The use of these agents has decreased with the advent of the PPIs.
Patients with NSAID-induced ulcers should be treated with PPIs, because these agents heal and prevent future ulcers better than H2 antagonists.

16. Antacids Magnesium hydroxide Calcium containing Calcium carbonate
Magnesium containing
Magnesium hydroxide
Aluminium containing Aluminium hydroxide
Antacids may decrease absorption of other drugs

18. Antibacterial agents colloidal bismuth ATB: ampicilline
Cytoprotective agents - misoprostol (PGE1), sucralfate, bismuth subsalicylate
Antibacterial agents colloidal bismuth ATB: ampicilline
tetracyclines, metronidazole, clarithromycin

19. 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.
- Effectively heals duodenal ulcers and is used in long-term maintenance therapy.
- Because it requires an acidic pH for activation, sucralfate should not be administered with H2 antagonists or antacids.

20. Bismuth subsalicylate:
Effectively heal peptic ulcers.
In addition to their antimicrobial actions,
They inhibit the activity of pepsin, increase secretion of mucus, and interact with glycoproteins in necrotic mucosal tissue to coat and protect the ulcer crater.

21. Antibacterial 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, are administered for a 2-week course.

22. GIT motility disorders

23. GIT motility disorders
Constipation means hard stools, difficulty passing stools, or the sense of incomplete emptying after a bowel movement.
Diarrhoea is a watery stool occurring more than three times in one day. Prolonged diarrhea can be a sign of other problems and it can cause dehydration.

24. Constipation

25. Some drugs causing constipation
Analgesics (inhibitors of prostaglandin syntesis)
Antacids (containing calcium carbobate or aluminium hydroxide)
Anticholinergics
Antihistamines (H1 blockers)
Corticosteroids
Clonidine
Ganglionic blocking agents
Laxatives (used chronically)
Myorelaxants
Opioids
Phenothiazines
Tricyclic antidepresants
Verapamil

26. Laxatives
Bulk forming laxatives: high fiber, absorbs water to increase bulk, distends bowel to initiate reflex bowel activity –
- polysaccharides and celluloses derived from grains, psyllium, methylcellulose, and carboxy-methylcellulose, synthetic resin polycarbophil
II. Emolients- surfactants: stool softeners and lubricants, promote more water and fat in the stools, lubricate the fecal material and intestinal walls -stool softeners: docusate salts, lubricants: mineral oil

27. Laxatives (cont.)
Saline and osmotic laxatives: increase osmotic pressure within the intestinal tract, causing more water to enter the intestines.
Result: bowel distention, increased peristalsis, and evacuation
magnesium sulfate, magnesium hydroxide, magnesium citrate, sodium phosphate
the disaccharide lactulose; glycerin; sorbitol and mannitol; and polyethylene glycol-electrolyte solutions.
Stimulant laxatives (contact, iritant) –
increases peristalsis via intestinal nerve stimulation:
diphenylmethane phenolphthalein, bisacodyl, anthraquinone laxatives, castor oil (ricin, ricinoleic acid)
V Prokinetic agents

28. Laxatives: Side Effects
Bulk-forming laxatives have few side effects and minimal systemic effects:
 allergic reactions (plant gums)
flatulence
systemic retention of Na+ and H2O (psyllium, carboxymethylcellulose)
dextrose should be avoided in diabetic patients
cellulose can reduce the absorption of many drugs
(cardiac glycosides, salicylates, nitrofurantoin)
psyllium may bind coumarin derivatives

29. Saline laxatives
up to 20% of the salt is absorbed
Mg2+ - toxicity in patients with impaired renal function
Na+ salts should not be used in patients with congestive heart failure or renal disease
phosphate laxatives can cause hyperphosphatemia and a reduction of plasma Ca2+
hypertonic salt solutions can produce significant dehydration and must be administered with sufficient water to ensure that no net loss of body water occurs

30. Hyperosmotic
lactulose: flatulence, cramps, abdominal discomfort
excessive dosage can cause diarrhea, loss of fluid and K+, hypernatremia, exacerbation of hepatic encephalopathy
Contraindications
 patients requiring a galactose-free diet must not use lactulose
 patients with diabetes must be cautious in using lactulose

31. Stimulants
fluid and electrolyte deficits (overdosage)
they can damage enterocytes (inflammatory response in the colon)
allergic reactions, osteomalacia
protein- losing gastroenteropathy
possible pink coloring of the urine and feces (phenolphthalein)
an excessive laxative effect and abdominal pain (senna, cascara)

32. Prokinetic agents

33. direct M-receptor agonists (bethanechol)
AChE inhibitors (neostigmine)
inhibitory presynaptic D2-receptor blockers (metoclopramide)
excitatory presynaptic 5-HT4-receptor agonists (cisaprid)
excitatory motilin receptor activators (erythromycin)
prokinetic drugs increase gastric emptying
they increase tone of the lower esophageal sphincter
they exhibit antiemetic activity (metoclopramide)
they improve coordination of gastroduodenal contractions

34. Side effects
cholinergic agonists have variety of muscarinic side effects (excess GI secretions, cramps, salivation, sweating, urination, lacrimation, defecation)
dopamine-receptor antagonists can induce dystonia, Parkinson´s disease-like effects hyperprolactinemia (gynecomastia, galactorhea

36. Diarrhoea

37. Diarrhoea
Traveller’s diarrhoea is one of the most common illnesses for tourists going to tropical climates. As many as 60% of all travellers suffer some form of diarrhoea

40. Some drugs causing diarrhoea
Adrenergic neuron blocking agents (reserpine, quanethidine)
Antimicrobials (e.g. sulfonamides, tetracyclines, most broad spectrum ATB
Cholinergic agonists and cholinesterase inhibitors
Procinetic agents (metoclopramide, domperidone, cisapride)
Prostaglandins
Quinidine

41. Antidiarrhoeal drugs
Opioids: diphenoxylate and loperamide free of opiate – like CNS effect, opium tincture, codeine,
decrease bowel motility, decrease transit time through the bowel, allowing more time for water and electrolytes to be absorbed, opioids are effective in the treatment of moderate-to-severe diarrhea!
III. Octreotide (the synthetic analog of somatostatin)
 inhibition of gastric acid and pepsinogen secretion,
inhibition of endocrine secretions (e.g., gastrin, cholecystokinin, secretin, VIP, and motilin),
inhibition of intestinal fluid and bicarbonate secretion, and diminution of smooth muscle contractility.

42. IV. Other Agents
Adsorbents: kaolin, pectin, bismuth subsalicylate, activated charcoal
coat the walls of the GI tract, bind to the causative bacteria or toxin, which is then eliminated through the stool
b. Intestinal flora modifiers : lactobacili (supplying missing bacteria to the GI tract, suppressing the growth of diarrhea-causing bacteria),
c. Muscarinic antagonists
b. fiber supplements - adsorbents (psyllium, polycarbophil, carboxymethylcellulose) - increase the viscosity of feces

44. Antiemetics

45. Receptors involved in vomiting

47. Causes of vomiting I. Drugs
Anticancer drugs, cardiac glycosides, apomorphine, levodopa, bromocryptine, cholinomimetics, opiates, ergot alkaloids
II. Physiological
Pregnancy, head motion, weitghlesness
III. Pathophysiological
Uremia, endocrinopathies, alcoholism, migraine, allergies,
gastric irritations
IV. Toxic
Food poisons, industrial poisons, radiations, infections

48. Recomended antiemetic treatment