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Transcript
Clinical pharmacology of
gastrointestinal agents
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.
Gastritis
Gastritis means inflamation of the stomach. It means that white blood
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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 inflammation–either 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.
Gastritis
Aspirin & NSAID Gastritis

NSAID stands for non-steroidal anti-inflammatory drug.
These are arthritis and pain relievers and include the overthe-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.
Gastritis (cont’d)
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.
Gastritis (cont’d)
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.
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
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.
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.
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 acidreducing 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
Treatment of peptic ulcer

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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 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.
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.
Motilium
Form of production: 0,01 g tablets
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.
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.
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)
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.
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.
Diet
The 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.
Antidiarrheals
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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 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 antibioticassociated 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.