Clinical pharmacology of gastrointestinal agents

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Clinical pharmacology of gastrointestinal agents
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Digestive diseases

• All diseases that pertain to the
  gastrointestinal tract are labelled as digestive
  diseases. This includes diseases of the
  esophagus, stomach, first, second and third part
  of the duodenum, jejunum, ileum, the ileo-cecal
  complex, large intestine (ascending, transverse
  and descending colon) sigmoid colon and rectum.

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Gastritis

• Gastritis means inflamation of the stomach. It
  means that white blood cells move into the wall
  of the stomach as a response to some type of
  injury. Gastritis does not mean that there is an
  ulcer or cancer. It is simply inflammationeither
  acute or chronic. What are the causes of
  gastritis?Helicobacter Pylori
• This is the name of a bacteria that has learned
  to live in the thick mucous lining of the
  stomach. Although it doesn't actually infect the
  underlying tissue, it does result in acute and
  chronic inflammation. It probably occurs early in
  childhood and remains throughout life unless
  antibiotics cure it. The infection can lead to
  ulcers and, in later life, even to stomach cancer
  in some people. Fortunately, there are now ways
  to make the diagnosis and treat this
  disorder.Autoimmune Gastritis - Pernicious
  Anemia
• The stomach lining also may be attacked by the
  immune system leading to loss of the stomach
  cells. This causes acute and chronic inflammation
  which can result in a condition called pernicious
  anemia. The anemia occurs because the body no
  longer can absorb vitamin B12 due to a lack of a
  key stomach factor, destroyed by the chronic
  inflammation. Stomach cancer can even occur later
  in life.

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Gastritis

• Aspirin NSAID Gastritis
• NSAID stands for non-steroidal anti-inflammatory
  drug. These are arthritis and pain relievers and
  include the over-the-counter drugs Advil,
  Naprosyn, Motrin and ibuprofen as well as many
  prescription arthritis medicines such as
  Voltaren, Feldene, Lodine and Relafen. Along with
  aspirin, they reduce a protective substance in
  the stomach called prostaglandin. These drugs
  usually cause no problems when taken for the
  short-term. However, regular use can lead to a
  gastritis as well as a more serious ulcer
  condition.
• Alcohol
• Alcohol and certain other chemicals can cause
  inflammation and injury to the stomach. This is
  strictly dose related in that a lot of alcohol is
  usually needed to cause gastritis. Social or
  occasional alcohol use is not damaging to the
  stomach although alcohol does stimulate the
  stomach to make acid.

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Gastritis (contd)

• Hypertrophic Gastritis
• At times, the folds in the stomach will become
  enlarged and swollen along with the inflammation.
  There is not a great deal known about why this
  occurs. A variation of this type of gastritis is
  called Ménétrier's disease where the gastric
  folds become gigantic. With this condition, there
  is often protein loss into the stomach from these
  weeping folds.

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Gastritis (contd)

• Symptoms
• The symptoms of gastritis depend on how acute it
  is and how long it has been present. In the acute
  phase, there may be pain or gnawing in the upper
  abdomen, nausea and vomiting. In the chronic
  phase, the pain may be dull and there may be loss
  of appetite with a feeling of fullness after
  several bites of food. Very often, there are no
  symptoms at all. If the pain is severe, there may
  be an ulcer as well as gastritis.
• Treatment
• The treatment of gastritis will depend on its
  cause. For most types of gastritis, reduction of
  stomach acid by medication is often helpful.
  Beyond that, a specific diagnosis needs to be
  made. Antibiotics are used for infection.
  Elimination of aspirin, NSAIDs or alcohol is
  indicated when one of these is the problem. For
  the more unusual types of gastritis, other
  treatments may be needed.

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Peptic ulcer disease (PUD) is a very common
ailment, affecting one out of eight persons in
the United States. The causes of PUD have
gradually become clear. With this understanding
have come new and better ways to treat ulcers and
even cure them
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PEPTIC ULCER DISEASE

• Helicobacter pylori (H. pylori)
• This funny-sounding name identifies the basic
  cause of most peptic ulcers, excluding those
  caused by aspirin or arthritis drugs. This
  bacteria has a twisted spiral shape and infects
  the mucous layer lining of the stomach. This
  infection produces an inflammation in the stomach
  wall called gastritis. The body even develops a
  protein antibody in the blood against it. The
  bacteria is probably acquired from contaminated
  food or from a drinking glass. It ims only after
  H. pylori bacteria injure the protective mucous
  layer of the stomach, allowing damage by stomach
  acid, that an ulcer develops.
• Arthritis medications include ibuprofen (Advil),
  Feldene, Naprosyn, Voltaren, Indocin, Aleve,
  Lodine, and many others. As with aspirin, they
  can damage the mucous layer of the stomach, after
  which the stomach acid causes the final injury.
  So, H. pylori and certain drugs are the two
  major factors that cause ulcers. In rare cases, a
  patient will produce very large amounts of acid
  and develop ulcers. This condition is called
  Zollinger -Ellison syndrome. Finally, some people
  get ulcers for unknown reasons.

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PEPTIC ULCER DISEASE Symptoms

• Ulcers cause gnawing, burning pain in the upper
  abdomen. These symptoms frequently occur several
  hours following a meal, after the food leaves the
  stomach but while acid production is still high.
  The burning sensation can occur during the night
  and be so extreme as to wake the patient. Instead
  of pain, some patients experience intense hunger
  or bloating. Antacids and milk usually give
  temporary relief. Other patients have no pain but
  have black stools, indicating that the ulcer is
  bleeding. Bleeding is a very serious complication
  of ulcers.

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PEPTIC ULCER DISEASE

• Therapy of PUD has undergone profound changes.
  There are now available very effective
  medications to supress and almost eliminate the
  outpouring of stomach acid. These
  acid-suppresssing drugs have been dramatically
  effective in relieving symptoms and allowing
  ulcers to heal. If an ulcer has been caused by
  aspirin or an arthritis drug, then no subsequent
  treatment is usually needed. Avoiding these
  latter drugs, should prevent ulcer recurrence.
  The second major change in PUD treatment has
  been the discovery of the H. pylori infection.
  When this infection is treated with antibiotics,
  the infection, and the ulcer, do not come back.
  Increasingly, physicians are not just suppressing
  the ulcer with acid-reducing drugs, but they are
  also curing the underlying ulcer problem by
  getting rid of the bacterial infection. If this
  infection is not treated, the ulcers invariably
  recur. There are a number of antibiotic
  programs available to treat H. pylori and cure
  ulcers. Working with the patient, the physician
  will select the best treatment program available

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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.

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

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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.

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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.

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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.

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• Motilium
• Form of production 0,01 g tablets

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LAXATIVES AND CATHARTICS

• Constipation can be defined as infrequent or
  hard pellet stools, or difficulty in evacuating
  stool. Passing one or more soft, bulky stools
  every day is a desirable goal. While troublesome,
  constipation is not usually a serious disorder.
  However, there may be other underlying problems
  causing constipation and, therefore, testing is
  often recommended.

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Constipation

• Constipation is often caused by a lazy colon that
  does not contract properly and fails to move the
  stool to the rectum. The colon also can become
  spastic and remain contracted for a prolonged
  time. In this case, stool cannot move along. Too
  much water is absorbed and hard pellet-like stool
  develops. Constipation also can result from a
  mechanical obstruction, such as tumors or
  advanced diverticulosis, a disorder which can
  distort and narrow the lower-left colon. Other
  conditions that can produce a sluggish, poorly
  contracting bowel include pregnancy, certain
  drugs, thyroid hormone deficiency, the chronic
  abuse of laxatives, travel, and stress.

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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)

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Laxatives

• There are two main types of laxatives
  stimulants (chemical) and saline (liquid or
  salt). They occasionally help temporary
  constipation problems. However, chronic use of
  laxatives, especially stimulant laxatives is
  discouraged because the bowel becomes dependent
  upon them. Bowel regularity should occur without
  laxatives. An occasional enema is preferrable
  over the chronic use of laxatives.

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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.

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DietThe following foods should be eaten daily in
adequate amounts

• Whole grain breads (whole wheat)
• Bran cereals
• Vegetables -- Root (potatoes, carrots, turnips),
  leafy green (lettuce, celery, spinach), or cooked
  high residue (cabbage)
• Fruit -- Cooked or stewed (prunes, applesauce) or
  fresh fruit (skin and pulp)
• Bulking Agents -- Fiber is the undigested part of
  plant food that passes into the colon. Certain
  types of fiber can absorb and hold large amounts
  of water. This, in turn, results in a larger,
  bulkier stool which is soft and easier to pass.
  Adequate fiber in food or from supplements is
  recommended daily. This type of water-retaining
  fiber generally is easily obtained each day by
  one of the following
• Food bran -- This is available as wheat, oat or
  rice bran. Processing of wheat and other grains
  removes this valuable fiberous part of the food
  so these processed products should be avoided.
• Psyllium bran -- The psyllium plant is remarkable
  because its ground seeds can retain so much
  water. This product is available as Metamucil,
  Konsyl, Effersyllium, Per Diem Fiber, or the less
  expensive generic preparation in drug and health
  food stores. Although labeled a laxative, it
  really is not a laxative.
• Methylcellulose -- This is another fiber derived
  from wood which also retains water. It is
  available as Citrucel.

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Antidiarrheals
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• Antidiarrheal drugs are indicated in the
  following circumstances
• 1. Severe or prolonged diarrhea (gt2 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 Crohns 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

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Contraindications to Use

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