CLINICAL CLINICAL PHARMACOLOGY OF PHARMACOLOGY OF GASTROINTESTINAL GASTROINTESTINAL

AGENTSAGENTS

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.

Ranitidine (Ranitidin) Forms of production: 0,15 g and 0,3 g tablets and ampoules with 2 ml of

2,5 % solution.

RECOMMENDATIONS OF

HELICOBACTER 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.

A typical quadruple therapyA typical quadruple therapy

a PPI twice a day a PPI twice a day bismuth 120 mg four times a day bismuth 120 mg four times a day metronidazole 400 mg three times a metronidazole 400 mg three times a

day day oxytetracyclineoxytetracycline 500 mg four times a 500 mg four times a

day, all for 7 days. day, all for 7 days.

Ulcers associated with NSAIDsUlcers associated with NSAIDs

omeprazole 20mg daily is preferable to omeprazole 20mg daily is preferable to ranitidineranitidine 150mg 150mg twice daily as the respective rates of healing are 80% twice daily as the respective rates of healing are 80% and 63%. and 63%.

H2RAs are slow to heal the ulcers if the offending drug H2RAs are slow to heal the ulcers if the offending drug is not stopped and so, under these conditions, a PPI is is not stopped and so, under these conditions, a PPI is preferred. preferred.

H pylori eradication is no more effective than H pylori eradication is no more effective than omeprazole alone to heal ulcers, but if the infection is omeprazole alone to heal ulcers, but if the infection is present, then eradication will reduce the rate of relapse. present, then eradication will reduce the rate of relapse.

H pylori is not associated with an increased risk of ulcer H pylori is not associated with an increased risk of ulcer with NSAIDs in the elderly but there is an increased risk with NSAIDs in the elderly but there is an increased risk of bleeding. of bleeding.

MotiliumMotiliumForm of production: Form of production: 0,0,001 1 g tabletsg tablets

LAXATIVES AND CATHARTICSLAXATIVES AND CATHARTICS

Indications for Use• 1. To relieve constipation in pregnant women, elderly clients whose

abdominal and perineal muscles have become weak and atrophied, children with megacolon, and clients receiving drugs that decrease intestinal motility (eg, opioid analgesics, drugs with anticholinergic effects)

• 2. To prevent straining at stool in clients with coronary artery disease (eg, postmyocardial infarction), hypertension, cerebrovascular disease, and hemorrhoids and other rectal conditions

• 3. To empty the bowel in preparation for bowel surgery or diagnostic procedures (eg, colonoscopy, barium enema)

• 4. To accelerate elimination of potentially toxic substances from the GI tract (eg, orally ingested drugs or toxic compounds)

• 5. To prevent absorption of intestinal ammonia in clients with hepatic encephalopathy

• 6. To obtain a stool specimen for parasitologic examination• 7. To accelerate excretion of parasites after anthelmintic drugs have

been administered• 8. To reduce serum cholesterol levels (psyllium products)

Contraindications to Use

Laxatives and cathartics should not be used in the presence of undiagnosed abdominal pain. The danger is that the drugs may cause an inflamed organ (eg, the appendix) to rupture and spill GI contents into the abdominal cavity with subsequent peritonitis, a life-threatening condition. Oral drugs also are contraindicated with intestinal obstruction and fecal impaction.

Antidiarrheals

Antidiarrheal drugs are indicated in the following circumstances:

• 1. Severe or prolonged diarrhea (>2 to 3 days), to prevent severe fluid and electrolyte loss

• 2. Relatively severe diarrhea in young children and older adults. These groups are less able to adapt to fluid and electrolyte losses.

• 3. In chronic inflammatory diseases of the bowel (ulcerative colitis and Crohn’s disease), to allow a more nearly normal lifestyle

• 4. In ileostomies or surgical excision of portions of the ileum, to decrease fluidity and volume of stool

• 5. HIV/AIDS-associated diarrhea• 6. When specific causes of diarrhea have been determined

Contraindications to UseContraindications to Use

Contraindications to the use of antidiarrheal drugs Contraindications to the use of antidiarrheal drugs include diarrheainclude diarrhea caused by toxic materials, caused by toxic materials, microorganisms that penetratemicroorganisms that penetrate intestinal mucosa (eg, intestinal mucosa (eg, pathogenic pathogenic E. coli, Salmonella,E. coli, Salmonella, ShigellaShigella), or antibiotic-), or antibiotic-associated colitis. In these circumstances,associated colitis. In these circumstances, antidiarrheal antidiarrheal agents that slow peristalsis may aggravateagents that slow peristalsis may aggravate and prolong and prolong diarrhea. Opiates (morphine, codeine) usuallydiarrhea. Opiates (morphine, codeine) usually are are contraindicated in chronic diarrhea because of possible contraindicated in chronic diarrhea because of possible opiateopiate dependence. Difenoxin, diphenoxylate, and dependence. Difenoxin, diphenoxylate, and loperamide areloperamide are contraindicated in children younger than contraindicated in children younger than 2 years of age.2 years of age.

CChronic pancreatitishronic pancreatitis There is no cure for chronic pancreatitis. Once the pancreas There is no cure for chronic pancreatitis. Once the pancreas

is damaged, then it is not able to return to normal function is damaged, then it is not able to return to normal function and there is always the potential for further attacks. and there is always the potential for further attacks. Treatment is, therefore, directed towards preventing attacks, Treatment is, therefore, directed towards preventing attacks, controlling the pain and treating the complications.controlling the pain and treating the complications.

Preventing symptoms worseningPreventing symptoms worsening

Patients with chronic pancreatitis should avoid alcohol Patients with chronic pancreatitis should avoid alcohol altogether. If the pancreatitis is due to excess alcohol altogether. If the pancreatitis is due to excess alcohol consumption, then this is essential. If it is due to other consumption, then this is essential. If it is due to other causes, then it seems sensible to avoid a substance which is causes, then it seems sensible to avoid a substance which is capable of damaging the pancreas.capable of damaging the pancreas.

If an underlying cause has been identified then this should be If an underlying cause has been identified then this should be treated. Disorders of calcium metabolism and of fat treated. Disorders of calcium metabolism and of fat metabolism will be treated appropriately. Your doctor may metabolism will be treated appropriately. Your doctor may recommend removal of the gall bladder if pancreatitis is recommend removal of the gall bladder if pancreatitis is thought to be caused by gall stones.thought to be caused by gall stones.

CChronic pancreatitishronic pancreatitis

Preventing attacksPreventing attacks

The long-standing principle has been to try and rest the The long-standing principle has been to try and rest the pancreas. This involves giving pancreatic supplements such as pancreas. This involves giving pancreatic supplements such as Creon (which contain pancreatic enzymes in high concentration) Creon (which contain pancreatic enzymes in high concentration) together with drugs which reduce acid secretion by the stomach. together with drugs which reduce acid secretion by the stomach. Patients should also follow a low-fat diet. Patients should also follow a low-fat diet.

These measures reduce the presence of fat in the duodenum, These measures reduce the presence of fat in the duodenum, reduce acid in the duodenum and reduce the need for pancreatic reduce acid in the duodenum and reduce the need for pancreatic enzyme secretion. These measures are very successful in about enzyme secretion. These measures are very successful in about a third of patients, moderately successful in a third and unhelpful a third of patients, moderately successful in a third and unhelpful in a third.in a third.

Some eminent specialists have supported the use of antioxidants Some eminent specialists have supported the use of antioxidants in the treatment of chronic pancreatitis. These antioxidants in the treatment of chronic pancreatitis. These antioxidants include selenium and vitamin C. include selenium and vitamin C.

CChronic pancreatitishronic pancreatitis Control of painControl of pain

This is a very important aspect of the treatment of chronic This is a very important aspect of the treatment of chronic pancreatitis. Pancreatic pain varies in severity from mild pancreatitis. Pancreatic pain varies in severity from mild (controllable with simple analgesics such as paracetamol (controllable with simple analgesics such as paracetamol (eg Panadol)) to severe (requiring morphine-like drugs for (eg Panadol)) to severe (requiring morphine-like drugs for control).control).

In addition to the preventive measures listed above, the In addition to the preventive measures listed above, the basic principle is to use the drug lowest down the analgesic basic principle is to use the drug lowest down the analgesic ladder which controls the pain. Since the pain is often worse ladder which controls the pain. Since the pain is often worse at night and since both body and mind are at their lowest at night and since both body and mind are at their lowest ebb in the early hours of the morning, the lowest rung of ebb in the early hours of the morning, the lowest rung of the analgesic ladder may be pethidine or morphine (eg MST the analgesic ladder may be pethidine or morphine (eg MST continus tablets). Since the pain is chronic and severe, continus tablets). Since the pain is chronic and severe, there is a fine line between adequate analgesia and there is a fine line between adequate analgesia and addiction.addiction.