Anti ulcer drugs

It includes the description for ulcer and drugs used in the traetment for the ulcer

1. ANTI-ULCER DRUGS M.ASIYABI M.PHARM – 1 st YEAR DEPARTMENT OF PHARMACOLOGY Hey, Don’t worry…. Ulcer is easily curable with proper medications…We got anti-ulcer Drugs for you…

2. INTRODUCTION From ancient time stomach ulcer has been recognised and also therapy established according to their knowledge. A Roman emperor Marcus Aurelius was died due to perforated ulcer. More than 12 centuries ago, Paulus Aeginata recognised the acid neutralisation was the effective treatment. Later on 19 th century, lot of research has been developed for treatment of ulcer.

3. Cont….. After period of time it has been identified that bacteria can cause the ulcer. (Mainly Helicobacter pylori ) The main goal of Anti-ulcer drug is that to decreasing the level of gastric acidity or enhancing mucosal protection. For infectious agent new approach was found to prevent or to kill micro organisms.

4. ULCER Stomach ulcers are painful sores that can be found in the stomach lining or small intestine. They occur when the thick layer of mucus that protects your stomach from digestive juices is reduced, thus enabling the digestive acids to eat away at the lining tissues of the stomach . A stomach or gastric ulcer is a break in the tissue lining the stomach.

5. CAUSES An infection with the bacterium Helicobacter pylori (H. pylori) Long-term use of nonsteroidal anti-inflammatory drugs, such as aspirin and ibuprofen. Many people take NSAIDs without having any side effects, but there's always a risk the medication could cause problems, such as  stomach ulcer s, particularly if taken for a long time or at high doses. Cancer: stomach cancer can present as an ulcer, particularly in older people.

6. CAUSES BY LIFESTYLE FACTORS Not eating food on time (Eating Late) Too much of spicy foods Stress Drink too much of alcohol Ciggarette smoking.

7. SIGNS AND SYMPTOMS Burning sensation Abdominal pain just below the ribcage Bloating Bright or altered blood present in vomit or bowel motions Burping or acid reflux Dark blood in stools or stools that are black or tarry Heartburn (burning sensation in the chest)

8. Cont…. Indigestion Nausea Loss of appetite Symptoms  of anemia, such as light-headedness The vomiting of blood — which may appear red or black Shock due to blood loss which require medical attention (medical emergency). Weight loss

9. Gastric secretions of the stomach strive to keep a pH of 2 to 5. Pepsin-a digestive enzyme is activated at a pH of 2, the acid-pepsin complex of gastric secretions can cause mucosal damage If the pH inc. to 5 - the activity of pepsin declines Gastric Mucusal Barrier (GMB) - thick, viscous, mucous material that provides a barrier between the mucosal lining & the acidic gastric secretions - defense against corrosive substances, maintains integrity of the gastric mucosal lining

10. Possible areas of ulcer in Stomach

11. SPINCHTER MUSCLES Two sphincter muscles: - Cardiac - located at the upper portion of the stomach - prevents reflux of acid into the esophagus - pyloric - located at the lower portion of the stomach - prevents reflux of acid into the duodenum

12. TYPES OF ULCER * Esophageal ulcers  reflux of acidic gastric secretion into the esophagus d/t a defective or incompetent cardiac sphincter * Duodenal ulcers  hypersecretion of acid from the stomach that passes to the duodenum * Gastric ulcer  breakdown of GMB (gastric mucosal barrier) * Pyloric ulcer

13. PATHOPHYSIOLOGY There is imbalance between aggressive factors (acid & pepsin ) and defensive factors (e.g. prostaglandins, mucus & bicarbonate layer ).

14. Cont… Hydrochloric acid and pepsin destroy gastric and duodenal mucosa . Mucus and bicarbonate ion secretions protect mucosa Prostaglandins protect mucosa by enhancing mucus and bicarbonate production and by enhancing mucosal blood flow

15. Regulation of gastric secretions Parietal cells secrete acid in response to: Histamine (local hormone): H 2 receptors Gastrin (hormone): CCK 2 receptors Ach (neurotransmitter): M 3 receptors Proton pump (H + / K + ATPase )

16. TREATMENT Eradication of H. pylori infections Hyposecretory drugs. H 2 receptor blockers Antimuscarinic drugs Proton pump inhibitors Mucosal cytoprotective agents. Prostaglandin analogues Sucralfate ( Carafate R ) Neutralizing agents (antacids).

17. Gastric hyposecretory drugs Include: H 2 receptor blockers Proton pump inhibitors Antimuscarinic drugs Hyposecretory drugs decrease gastric acid secretion  Promote healing & relieve pain.

18. Proton pump inhibitors (PPI’S) Ome prazole – Lanso prazole Panto prazole - Ra prazole Acts by irreversible inhibition of proton pump (H+/ K+ ATPase ) that is responsible for final step in gastric acid secretion from the parietal cell.

19. PHARMACODYNAMICS They are the most potent inhibitors of acid secretion available today. Produce marked inhibition of basal & meal stimulated-acid secretion (90-98%). Reduce pepsin activity. Promote mucosal healing & decrease pain Proton pump inhibitors heal faster the ulcers than H-2 blockers, and have H.pylori inhibitory properties How?.

20. PHARMACODYNAMICS They are the most potent inhibitors of acid secretion available today. Produce marked inhibition of basal & meal stimulated-acid secretion (90-98%). Reduce pepsin activity. Promote mucosal healing & decrease pain Proton pump inhibitors heal faster the ulcers than H-2 blockers, and have H.pylori inhibitory property.

21. PHARMACOKINETICS Given orally as enteric coated capsules (unstable in acidic medium in stomach). Are pro-drugs rapidly absorbed from the intestine. Activated in the acidic medium of parietal cell canaliculi . Therefore, Should not be combined with H 2 blockers or antacids. Inactivated if at neutral pH.

22. Cont…. Have long duration of action (> 12 h-24 h). Once daily dose is sufficient Given 1 h before meal. Bioavailability is reduced by food. metabolized in the liver by Cyt-P450. Dose reduction is required in severe liver failure.

23. USES Eradication of H. pylori (combined with antimicrobial drugs). Resistant severe peptic ulcer ( 4-8 weeks). Reflux esophagitis . Hypersecretory conditions as Zollinger Ellison syndrome and gastrinoma (First choice).

24. ADVERSE EFFECTS Headache, diarrhea & abdominal pain. Achlorhydria Hypergastrinaemia . Gastric mucosal hyperplasia. Increased bacterial flora increased risk of community-acquired respiratory infections & nosocomial pneumonia Long term use: Vitamin B 12 deficiency increased risk of hip fractures

25. H2 receptor blockers - Cime tidine - Rani tidine - Famo tidine - Niza tidine Mechanism of action They competitively and reversibly block H 2 receptors on the parietal cells.

26. PHARMACOKINETICS Good oral absorption Given before meals. Famotidine is the most potent drug. Exposed to first pass metabolism (except nizatidine that has 100 % bioavailability). Duration of action (4-12 h). Metabolized by liver. Excreted mainly in urine. Cross placenta & excreted in milk (should not be given in pregnancy unless it is necessary).

27. PHARMACODYNAMICS Reduce basal and food stimulated-acid secretion Block 90% of nocturnal acid secretion (which depend largely on histamine) & 60-70% of total 24 hr acid secretion. Therefore, it is better to be given before night sleep . Reduce pepsin activity. Promote mucosal healing & decrease pain

28. USES GERD ((heartburn/ dyspepsia). Acute ulcer healing in moderate cases Duodenal Ulcer (6-8 weeks). Benign gastric ulcer (8-12 weeks). Pre-anesthetic medication (to prevent aspiration pneumonitis ). Prevention of bleeding from stress-related gastritis. Post–ulcer healing maintenance therapy. Together with NSAIDs to prevent ulcers

29. ADVERSE EFFECTS GIT disturbances (Nausea & Vomiting). CNS effects: Headache - confusion (elderly, hepatic dysfunction, renal dysfunction). Bradycardia and hypotension (rapid I.V.) CYT-P450 inhibition (Only Cimetidine ) decrease metabolism of warfarin , phenytoin , benzodiazepines.

30. Cont… Endocrine effects (Only Cimetidine ) Galactorrhea ( Hyperprolactinemia ) Antiandrogenic actions ( gynecomasteia –impotence) due to inhibition of dihydrotestosterone binding to androgen receptors . Precautions Dose reduction of H 2 RAs in severe renal or hepatic failure and elderly.

31. ANTACIDS These drugs are mainly inorganic salts e.g.: NaHCO 3 ; Ca CO 3 ; Al (OH) 3 ; Mg (OH) 2 acts by direct chemical neutralization of HCL and as a result may decrease pepsin activity. used to relief pain of peptic ulcer & for dyspepsia. All antacids  absorption of some drugs as tetracycline, fluoroquinolones , iron.

32. Cont…. NaHCO3: Systemic alkalosis; CaCO3 : milk alkali syndrome ( hypercalcemia , renal failure ) Al (OH)3 : constipation; Mg (OH)2 : Diarrhea Therefore , combination of Mg (OH) 2 plus Al (OH)3 commonly used.

33. MISOPROSTOL Prostaglandin analogues (PGE1 )  HCL secretion.  protective measures (  mucous/bicarbonate & gastric mucosal blood flow). Orally, must be taken 3-4 times/day. Used for NSAIDS-induced peptic ulcer but H2 blockers or proton pump inhibition are better. Adverse effects: Abdominal cramps; diarrhea Uterine contraction ( dysmenorrhea or abortion); Vaginal bleeding .

34. If  H. pylori  infection is diagnosed in the presence of peptic ulcer disease Eradication with most commonly "triple therapy" with a PPI,  clarithromycin , and  amoxicillin +/-  metronidazole for 7-14 days (Cure rates of 70% to 90% ). Pentaprazole 40 mg BID Amoxicillin 1000 mg BID Clarithromycin 500 mg BID

35. SUCRALFATE Is a sucrose sulfate- aliminium complex works as an oral cytoprotective agent via binding to the duedenal mucosa and thus creating physical barrier. Also, may stimulate bicarbonate secretion USES : Mainly as an addition for resistance gastritis or GERD

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