Transcript GIT-Drugs.15.Feb.2011

Drugs used to treat GIT
disordes
Anton Kohút
Gastric ulcer
Pathogenesis of Ulcers
Therapy is directed at enhancing host defense or
eliminating aggressive factors; i.e., H. pylori.
Aggressive Factors
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Acid, pepsin
Bile salts
Drugs (NSAIDs)
H. pylori
Defensive Factors
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Mucus, bicarbonate layer
Blood flow, cell renewal
Prostaglandins
Phospholipid
Free radical scavengers
Gastric ulcer and NSAIDs
H. pylori
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infection
Drugs used to treat gastric ulcer
Regulation of gastric acid secretion
I. Antisecretory drugs
1. H2 – blockers: cimetidine,
ranitidine, famotidine
nisatidine
2. M1 – blockers: pirenzepine,
dicyclomine, propantheline
3. Antagonist of gastrin
receptors: somastatine
4. Agonists of PG receptors:
misoprostol, entprostyl
II. Antacids
-sodium bicarbonate,
-calcium carbonate,
-aluminium hydroxide,
-magnesium hydroxide
Control of gastric acid secretion
Antisecretory agents
1. H2 histamine blockers – cimetidine, ranitidine,
famotidine, nisatidine
2. Antimuscarinic agents –pirenzepine,
dicyclomine,
3.
Agonists of prostaglandine receptors misoprostol
4. Antagonist of gastrin receptors- somatostatin
5. Inhibitors of proton pump – omeprazole,
pantoprazole
H2 receptor antagonists
Therapeutic uses of H2 antagonists
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Acute stress ulcers:
in managing acute stress ulcers associated with major
physical trauma in high-risk patients in intensive care units.
They are usually injected intravenously.
Gastroesophageal reflux disease:
Low doses appear to be effective for prevention and
treatment of heartburn (gastroesophageal reflux).
However, about 50 percent of patients do not find benefit,
and PPIs are now used preferentially in the treatment of this
disorder.
they may not relieve symptoms for at least 45 minutes.
Antacids more efficiently, but temporarily, neutralize secreted
acid already in the stomach.
Finally, tolerance to the effects of H2 antagonists can be seen
within 2 weeks of therapy.
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All H2 antagonists are equally effective in
promoting healing of duodenal and gastric
ulcers. However, recurrence is common after
treatment with H2 antagonists is stopped (60–
100 percent per year).
The use of these agents has decreased with the
advent of the PPIs.
Patients with NSAID-induced ulcers should be
treated with PPIs, because these agents heal
and prevent future ulcers better than H2
antagonists.
Antacids
• Calcium containing
Calcium carbonate
• Magnesium containing
Magnesium hydroxide
• Aluminium containing
Aluminium hydroxide
Antacids may decrease absorption of other
drugs
• Cytoprotective
agents - misoprostol
(PGE1), sucralfate,
bismuth subsalicylate
• Antibacterial
agents colloidal
bismuth ATB:
ampicilline
tetracyclines,
metronidazole,
clarithromycin
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Sucralfate:
- This complex of aluminum hydroxide and
sulfated sucrose binds to positively charged groups
in proteins of both normal and necrotic mucosa.
- By forming complex gels with epithelial cells,
sucralfate creates a physical barrier.
- Effectively heals duodenal ulcers and is used in
long-term maintenance therapy.
- Because it requires an acidic pH for activation,
sucralfate should not be administered with H2
antagonists or antacids.
Bismuth subsalicylate:
Effectively heal peptic ulcers.
In addition to their antimicrobial actions,
They inhibit the activity of pepsin, increase
secretion of mucus, and interact with
glycoproteins in necrotic mucosal tissue to
coat and protect the ulcer crater.
Antibacterial agents
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Currently, either
triple therapy consisting of a PPI with either
metronidazole or amoxicillin plus
clarithromycin,
or quadruple therapy of bismuth
subsalicylate and metronidazole plus
tetracycline plus a PPI, are administered for
a 2-week course.
GIT motility disorders
GIT motility disorders
• Constipation means hard
stools, difficulty passing stools,
or the sense of incomplete
emptying after a bowel
movement.
• Diarrhoea is a watery stool
occurring more than three
times in one day. Prolonged
diarrhea can be a sign of other
problems and it can cause
dehydration.
Constipation
Some drugs causing constipation
• Analgesics (inhibitors of prostaglandin syntesis)
• Antacids (containing calcium carbobate or
aluminium hydroxide)
• Anticholinergics
• Antihistamines (H1 blockers)
• Corticosteroids
• Clonidine
• Ganglionic blocking agents
• Laxatives (used chronically)
• Myorelaxants
• Opioids
• Phenothiazines
• Tricyclic antidepresants
• Verapamil
Laxatives
I.
II.
Bulk forming laxatives: high fiber, absorbs
water to increase bulk, distends bowel to
initiate reflex bowel activity –
- polysaccharides and celluloses derived from
grains, psyllium, methylcellulose, and carboxymethylcellulose, synthetic resin polycarbophil
Emolients- surfactants: stool softeners and
lubricants, promote more water and fat in the
stools, lubricate the fecal material and
intestinal walls -stool softeners: docusate
salts, lubricants: mineral oil
Laxatives (cont.)
III.
Saline and osmotic laxatives: increase osmotic pressure
IV.
Stimulant laxatives (contact, iritant) –
within the intestinal tract, causing more water to enter the
intestines.
Result: bowel distention, increased peristalsis, and evacuation
magnesium sulfate, magnesium hydroxide, magnesium citrate,
sodium phosphate
the disaccharide lactulose; glycerin; sorbitol and mannitol;
and polyethylene glycol-electrolyte solutions.
increases peristalsis via intestinal nerve stimulation:
diphenylmethane phenolphthalein, bisacodyl, anthraquinone
laxatives, castor oil (ricin, ricinoleic acid)
V.
Prokinetic agents
Laxatives: Side Effects
Bulk-forming laxatives have few side effects and
minimal systemic effects:
allergic reactions (plant gums)
 flatulence
 systemic retention of Na+ and H2O (psyllium,
carboxymethylcellulose)
 dextrose should be avoided in diabetic patients
 cellulose can reduce the absorption of many drugs
(cardiac glycosides, salicylates, nitrofurantoin)
 psyllium may bind coumarin derivatives
Saline laxatives
 up to 20% of the salt is absorbed
 Mg2+ - toxicity in patients with impaired renal
function
 Na+ salts should not be used in patients with
congestive heart failure or renal disease
 phosphate laxatives can cause hyperphosphatemia
and a reduction of plasma Ca2+
 hypertonic salt solutions can produce significant
dehydration and must be administered with
sufficient water to ensure that no net loss of body
water occurs
Hyperosmotic
 lactulose: flatulence, cramps, abdominal discomfort
 excessive dosage can cause diarrhea, loss of fluid and
K+, hypernatremia, exacerbation of hepatic
encephalopathy
Contraindications
 patients requiring a galactose-free diet must not use
lactulose
 patients with diabetes must be cautious in using
lactulose
Stimulants
fluid and electrolyte deficits
(overdosage)
they can damage enterocytes
(inflammatory response in the colon)
allergic reactions, osteomalacia
protein- losing gastroenteropathy
possible pink coloring of the urine and
feces (phenolphthalein)
an excessive laxative effect and
abdominal pain (senna, cascara)
Prokinetic agents
 direct M-receptor agonists (bethanechol)
 AChE inhibitors (neostigmine)
 inhibitory presynaptic D2-receptor blockers
(metoclopramide)
 excitatory presynaptic 5-HT4-receptor agonists
(cisaprid)
 excitatory motilin receptor activators (erythromycin)
 prokinetic drugs increase gastric emptying
 they increase tone of the lower esophageal sphincter
 they exhibit antiemetic activity (metoclopramide)
 they improve coordination of gastroduodenal
contractions
Side effects
cholinergic agonists have variety of muscarinic
side effects (excess GI secretions, cramps,
salivation, sweating, urination, lacrimation,
defecation)
dopamine-receptor
dystonia,
antagonists
Parkinson´s
can
induce
disease-like
effects
hyperprolactinemia (gynecomastia, galactorhea
Diarrhoea
Diarrhoea
• Traveller’s diarrhoea is one of the most common illnesses for
tourists going to tropical climates. As many as 60% of all travellers
suffer some form of diarrhoea
Some drugs causing diarrhoea
• Adrenergic neuron blocking agents
(reserpine, quanethidine)
• Antimicrobials (e.g. sulfonamides,
tetracyclines, most broad spectrum ATB
• Cholinergic agonists and cholinesterase
inhibitors
• Procinetic agents (metoclopramide,
domperidone, cisapride)
• Prostaglandins
• Quinidine
Antidiarrhoeal drugs
I.
Opioids: diphenoxylate and loperamide free of
opiate – like CNS effect, opium tincture, codeine,
decrease bowel motility, decrease transit time through
the bowel, allowing more time for water and electrolytes
to be absorbed, opioids are effective in the treatment
of moderate-to-severe diarrhea!
III. Octreotide (the synthetic analog of somatostatin)
 inhibition of gastric acid and pepsinogen secretion,
inhibition of endocrine secretions (e.g., gastrin,
cholecystokinin, secretin, VIP, and motilin),
inhibition of intestinal fluid and bicarbonate secretion,
and diminution of smooth muscle contractility.
IV. Other Agents
a. Adsorbents: kaolin, pectin, bismuth subsalicylate,
activated charcoal
coat the walls of the GI tract, bind to the causative
bacteria or toxin, which is then eliminated through
the stool
b. Intestinal flora modifiers : lactobacili (supplying
missing bacteria to the GI tract, suppressing the
growth of diarrhea-causing bacteria),
c. Muscarinic antagonists
b. fiber supplements - adsorbents (psyllium,
polycarbophil, carboxymethylcellulose) - increase
the viscosity of feces
Antiemetics
Receptors involved in vomiting
Causes of vomiting
I. Drugs
• Anticancer drugs,
cardiac glycosides,
apomorphine,
levodopa,
bromocryptine,
cholinomimetics,
opiates, ergot alkaloids
II. Physiological
• Pregnancy, head
motion, weitghlesness
III. Pathophysiological
• Uremia,
endocrinopathies,
alcoholism, migraine,
allergies,
• gastric irritations
IV. Toxic
• Food poisons,
industrial poisons,
radiations, infections
Recomended antiemetic treatment