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CLINICAL PHARMACOLOGY OF GASTROINTESTINAL AGENTS

CLINICAL PHARMACOLOGY OF GASTROINTESTINAL AGENTS. Treatment of peptic ulcer. Antimicrobial agents (tetracycline, bismuth subsalicylate, and metronidazole) to eradicate H. pylori infection

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CLINICAL PHARMACOLOGY OF GASTROINTESTINAL AGENTS

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  1. CLINICAL PHARMACOLOGY OF GASTROINTESTINAL AGENTS

  2. Treatment of peptic ulcer • Antimicrobial agents (tetracycline, bismuth subsalicylate, and metronidazole) to eradicate H. pylori infection • Misoprostol (a prostaglandin analog) to inhibit gastric acid secretion and increase carbonate and mucus production, to protect the stomach lining • Antacids to neutralize acid gastric contents by elevating the gastric pH, thus protecting the mucosa and relieving pain • Avoidance of caffeine and alcohol to avoid stimulation of gastric acid secretion • Anticholinergic drugs to inhibit the effect of the vagal nerve on acid-secreting cells • H2 blockers to reduce acid secretion • Sucralfate, mucosal protectant to form an acid-impermeable membrane that adheres to the mucous membrane and also accelerates mucus production • Dietary therapy with small infrequent meals and avoidance of eating before bedtime to neutralize gastric contents • Insertion of a nasogastric tube (in instances of gastrointestinal bleeding) for gastric decompression and rest, and also to permit iced saline lavage that may also contain norepinephrine • Gastroscopy to allow visualization of the bleeding site and coagulation by laser or cautery to control bleeding • Surgery to repair perforation or treat unresponsiveness to conservative treatment, and suspected malignancy.

  3. Ranitidine (Ranitidin) Forms of production: 0,15 gand 0,3 g tablets and ampoules with 2 ml of 2,5 % solution.

  4. RECOMMENDATIONS OFHELICOBACTER PYLORI ERADICATION • omeprazole 20mg • amoxicillin 1000mg • clarithromycin 500mg, all twice daily for 7 days. • An alternative regimen with a similar eradication rate of around 90% is: • omeprazole 20mg • clarithromycin 250mg • metronidazole 400mg, again all twice daily for 7 days.

  5. A typical quadruple therapy • a PPI twice a day • bismuth 120 mg four times a day • metronidazole 400 mg three times a day • oxytetracycline 500 mg four times a day, all for 7 days.

  6. Ulcers associated with NSAIDs • omeprazole 20mg daily is preferable to ranitidine 150mg twice daily as the respective rates of healing are 80% and 63%. • H2RAs are slow to heal the ulcers if the offending drug is not stopped and so, under these conditions, a PPI is preferred. • H pylori eradication is no more effective than omeprazole alone to heal ulcers, but if the infection is present, then eradication will reduce the rate of relapse. • H pylori is not associated with an increased risk of ulcer with NSAIDs in the elderly but there is an increased risk of bleeding.

  7. Motilium Form of production: 0,01 g tablets

  8. LAXATIVES AND CATHARTICS

  9. Indications for Use • 1. To relieve constipation in pregnant women, elderlyclients whose abdominal and perineal muscles havebecome weak and atrophied, children with megacolon,and clients receiving drugs that decrease intestinalmotility (eg, opioid analgesics, drugs with anticholinergiceffects) • 2. To prevent straining at stool in clients with coronaryartery disease (eg, postmyocardial infarction), hypertension,cerebrovascular disease, and hemorrhoids andother rectal conditions • 3. To empty the bowel in preparation for bowel surgery ordiagnostic procedures (eg, colonoscopy, barium enema) • 4. To accelerate elimination of potentially toxic substancesfrom the GI tract (eg, orally ingested drugs or toxiccompounds) • 5. To prevent absorption of intestinal ammonia in clientswith hepatic encephalopathy • 6. To obtain a stool specimen for parasitologic examination • 7. To accelerate excretion of parasites after anthelminticdrugs have been administered • 8. To reduce serum cholesterol levels (psyllium products)

  10. Contraindications to Use Laxatives and cathartics should not be used in the presenceof undiagnosed abdominal pain. The danger is that the drugsmay cause an inflamed organ (eg, the appendix) to ruptureand spill GI contents into the abdominal cavity with subsequent peritonitis, a life-threatening condition. Oral drugsalso are contraindicated with intestinal obstruction and fecalimpaction.

  11. Antidiarrheals

  12. Antidiarrheal drugs are indicated in thefollowing circumstances: • 1. Severe or prolonged diarrhea (>2 to 3 days), to preventsevere fluid and electrolyte loss • 2. Relatively severe diarrhea in young children and olderadults. These groups are less able to adapt to fluid andelectrolyte losses. • 3. In chronic inflammatory diseases of the bowel (ulcerativecolitis and Crohn’s disease), to allow a more nearlynormal lifestyle • 4. In ileostomies or surgical excision of portions of theileum, to decrease fluidity and volume of stool • 5. HIV/AIDS-associated diarrhea • 6. When specific causes of diarrhea have been determined

  13. Contraindications to Use Contraindications to the use of antidiarrheal drugs include diarrheacaused by toxic materials, microorganisms that penetrateintestinal mucosa (eg, pathogenic E. coli, Salmonella,Shigella), or antibiotic-associated colitis. In these circumstances,antidiarrheal agents that slow peristalsis may aggravateand prolong diarrhea. Opiates (morphine, codeine) usuallyare contraindicated in chronic diarrhea because of possible opiatedependence. Difenoxin, diphenoxylate, and loperamide arecontraindicated in children younger than 2 years of age.

  14. Chronic pancreatitis • There is no cure for chronic pancreatitis. Once the pancreas is damaged, then it is not able to return to normal function and there is always the potential for further attacks. Treatment is, therefore, directed towards preventing attacks, controlling the pain and treating the complications.Preventing symptoms worseningPatients with chronic pancreatitis should avoid alcohol altogether. If the pancreatitis is due to excess alcohol consumption, then this is essential. If it is due to other causes, then it seems sensible to avoid a substance which is capable of damaging the pancreas.If an underlying cause has been identified then this should be treated. Disorders of calcium metabolism and of fat metabolism will be treated appropriately. Your doctor may recommend removal of the gall bladder if pancreatitis is thought to be caused by gall stones.

  15. Chronic pancreatitis • Preventing attacksThe long-standing principle has been to try and rest the pancreas. This involves giving pancreatic supplements such as Creon (which contain pancreatic enzymes in high concentration) together with drugs which reduce acid secretion by the stomach. Patients should also follow a low-fat diet. These measures reduce the presence of fat in the duodenum, reduce acid in the duodenum and reduce the need for pancreatic enzyme secretion. These measures are very successful in about a third of patients, moderately successful in a third and unhelpful in a third.Some eminent specialists have supported the use of antioxidants in the treatment of chronic pancreatitis. These antioxidants include selenium and vitamin C.

  16. Chronic pancreatitis • Control of painThis is a very important aspect of the treatment of chronic pancreatitis. Pancreatic pain varies in severity from mild (controllable with simple analgesics such as paracetamol (eg Panadol)) to severe (requiring morphine-like drugs for control).In addition to the preventive measures listed above, the basic principle is to use the drug lowest down the analgesic ladder which controls the pain. Since the pain is often worse at night and since both body and mind are at their lowest ebb in the early hours of the morning, the lowest rung of the analgesic ladder may be pethidine or morphine (eg MST continus tablets). Since the pain is chronic and severe, there is a fine line between adequate analgesia and addiction.

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