pharmacology Dr. Mahmoud Taleb University of Al - Azhar Gaza Palestine Why Khaled Al Banna

1. Chapter I: Drugs Affecting theChapter I: Drugs Affecting the
Gastrointestinal SystemGastrointestinal System
Dr. Mahmoud H. Taleb
Assistant Professor of Pharmacology and Toxicology
Department of Pharmacology and Medical sciences
Faculty of Pharmacy- Al azhar University
1Dr. Mahmoud H. Taleb

2. Drugs Affecting theDrugs Affecting the
Gastrointestinal SystemGastrointestinal System
• Antiulcerants
• Digestives
• Antiemetics
• Antidiarrheals
• Laxatives
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3. Peptic UlcersPeptic Ulcers
• Common disease ， incidence rate: 10%~12%.
• Pathogenesis of ulcers
Aggressive Factors Defensive Factors
•Acid,pepsin
•Bile salts
•Drugs (NSAIDs)
•H.pylori
•Mucus,bicarbonate layer
•Blood flow,cell renewal
•Prostaglandins
•Phospholipid
•Free radical scavengers 3Dr. Mahmoud H. Taleb

4. Therapy Purpose ：
Therapy is directed at
enhancing host defense or
eliminating aggressive
factors; i.e., H. pylori.
Peptic UlcersPeptic Ulcers
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5. Drugs Used in Peptic UlcersDrugs Used in Peptic Ulcers
• Antacids
• Inhibitors of gastric acid production
H2-receptor antagonists
Proton pump inhibitors
Muscarinic antagonists
Gastrin receptor antagonist
• Mucosal Protectants
• Anti-Helicobacter pylori. drugs
Acid PumpAcid Pump
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7. Drugs Used in Peptic UlcersDrugs Used in Peptic Ulcers
Antacids ：
aluminum hydroxide
magnesium hydroxide
H2- receptor antagonists ：
cimetidine
ranitidine
Muscarinic antagonists ：
atropine 7Dr. Mahmoud H. Taleb

8. • Proton pump inhibitors ：
omeprazole
• Gastrin receptor antagonist ：
proglumide
• Mucosal Protectants ：
misoprostol
• Anti-Helicobacter pylori. Drugs
： antibiotics
Drugs Used in Peptic UlcersDrugs Used in Peptic Ulcers
8Dr. Mahmoud H. Taleb

9. AntacidsAntacids
General characteristics
• Antacids are weak bases that are taken orally
and that partially neutralize gastric acid and
reduce pepsin activity.
• Antacids reduce the pain associated with ulcers
and may promote healing. High doses are
required for healing: 40 mEq of base seven
times daily.
9Dr. Mahmoud H. Taleb

10. • Magnesium hydroxide
• Magnesium trisilicate
• Aluminum hydroxide
• Calcium carbonate
• Sodium bicarbonate
AntacidsAntacids
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11. HH22-receptor antagonists-receptor antagonists
Mechanism of action
• Competitively block the histamine (H2) receptor of
acid-producing parietal cells
rendering cells less responsive to not only histamine
but also to the stimulation of acetylcholine and
gastrin.
• Also up to 90% inhibition of vagal stimulated and
gastrin stimulated acid secretion.
complete inhibition has not been shown
11Dr. Mahmoud H. Taleb

12. HH22-receptor antagonists-receptor antagonists
Four FDA-approved:
Cimetidine （ Tagamet® ）
Ranitidine （ Zantac® , Randin ）
Famotidine （ Famodin® ）
Nizatidine （ Axid® ）
12Dr. Mahmoud H. Taleb

13. Therapeutic effects:
• Promote the healing of gastric and
duodenal ulcers
• Gastroesophageal reflux dz [GERD]
• Upper GI bleed [GIB]
• May be effective in stress ulcers &
peptic esophagitis
HH22-receptor antagonists-receptor antagonists
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14. Side effect:
• Overall low < 3%
• CNS: < 1% total
headache, lethargy ， confusion,
depression ， hallucinations
• ENDO ：
Impotence ， increased prolactin ， gynecomastia
• HEME:
Thrombocytopenia
Drug interaction
H2-receptor antagonistsH2-receptor antagonists
14Dr. Mahmoud H. Taleb

15. Muscarinic antagonistsMuscarinic antagonists
Atropine ：
• Block the M1 class receptors
• reduce acid production
• abolish gastrointestinal spasm
relatively unpopular as a first choice because of
high incidence of anticholinergic side effects
(dry mouth and blurred vision)
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16. • H+,K+-ATPase (Proton Pump) inhibitor
• Irreversible inhibition
Must synthesize new enzyme
Long duration
Omeprazole (Prilosec®)
Lansoprazole (Prevacid®)
Pantoprazole
Rabeprazole
Proton pump inhibitorsProton pump inhibitors
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17. Mechanism of ActionMechanism of Action
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18. OmeprazoleOmeprazole （（ loseclosec ））
• Irreversibly binds to H+/K+ ATPase
• Prevents H+ ion production & secrection
• Block all acid secretion = achlorhydria
to return to normal must synthesize new H+/K+
ATPase
• Inhibit H. pylori
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19. OmeprazoleOmeprazole （（ loseclosec ））
Therapeutic uses
• Gastroesophageal reflux dz [GERD]
• Peptic ulcer
• Infection with H. pylori plus(Hp)
• Upper GI bleed [GIB]
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20. Gastrin receptor antagonistGastrin receptor antagonist
Proglumide
It is gastrin and cholycytokinin inhibitors
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21. Mucosal Protective AgentsMucosal Protective Agents
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22. • A congener of prostaglandin E1
• PG’s:
 inhibit gastric acid secretion
 exhibit ‘cytoprotective’ activity
 enhance local production of mucus or
bicarbonate
 promote local cell regeneration
 help to maintain mucosal blood flow
MisoprostolMisoprostol
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23. • Misoprostol is approved
for use in patients taking
NASIDs who are at risk for
gastric ulcers
• Misoprostol produces
diarrhea and stimulation
of uterine contraction.
MisoprostolMisoprostol
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24. • Sucralfate
 cytoprotective agent
 stress ulcerations & PUD
 inhibit H. pylori
• Bismuth （ Pepto-Bismol® ）
 inhibit pepsin activity
 inhibit H. pylori
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25. Agents Used in infection ofAgents Used in infection of
Helicobacter PyloriHelicobacter Pylori
• Helicobacter pylori ， HP
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26. Aimed at eliminating H. pylori
Bismuth ( Pepto-Bismol®)
Amoxicillin (Amoxil ® )
Clarithromycin ( Klacid )
Tetracycline ( Terramycin®)
Metronidazole (Flagyl ® )
Agents Used in infection ofAgents Used in infection of
Helicobacter PyloriHelicobacter Pylori
26Dr. Mahmoud H. Taleb

27. 1990~
1970~
Before
1970
1980~
Antacids
H2-receptor antagonists
Proton pump inhibitors
Proton pump inhibitors
Agents Used in infection
of Helicobacter Pylori
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28. DigestivesDigestives
Pepsin
Pancreatin
Lactasin
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29. • Histamine1
-receptor antagonist , diphenhydramine
• Cholinergic antagonist, hyosine,
• Dopamine antagonists :
Metoclopramide Domperidone （ motilium ）
[Therapeutic uses]
[Side effects]
• 5-HT3
antagonists eg, ondasetron
•
Antiemetic DrugsAntiemetic Drugs
D2-receptor antagonist (periphery)
A weaker antiemetic, fewer extrapyramidal
effects.
Accelerates gastric emptying; has little effect
on the colon
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32. • Metoclopramide (Reglan)
• is a central dopaminergic (D2-receptor) and
serotonergic (5-HT3-receptor) antagonist.. It appears
to enhance coordi-nated transmission in cholinergic
nerve plexuses that finally release acetylcholine at
muscarinic M2-receptors on the muscle cells, since its
effect is abolished by atropine.. Since it is a dopa-
minergic neuron antagonist in the central nervous
system, it may possibly also have a direct influence
on dopaminergic or other innervation of
gastrointestinal smooth muscle.
Dr. Mahmoud H. Taleb 32

33. • In the upper gastrointestinal tract, metoclopramide
causes a dose-related rise in the lower esophageal
sphincter (LES) pressure (tone). It increases the
amplitude of peristaltic contractions in the
esophagus, slightly increases their duration and
speed of propa-gation,. It also does not influence
gas-tric acid secretion. Metoclopramide increases
gastric emptying in most people. It also has a good
antiemetic effect arising from its central D2- and 5-
HT3-blocking actions.
Dr. Mahmoud H. Taleb 33

34. Adverse effectsAdverse effects
• Metoclopramide has adverse side effects such as
• fa-tigue, dizziness, faintness, and various
extrapyramidal syndromes caused by its central
antidopaminergic activity In children, the major
extrapyramidal syndrome is an oculogyric crisis with
torticollis and neck pain. With chronic use,
metoclopramide may also cause in-creased serum
prolactin levels in adults, which may result in
gynecomastia,
Dr. Mahmoud H. Taleb 34

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IV. Antidiarrheals
Increased motility of the gastrointestinal
tract and decreased absorption of fluid are
major factors in diarrhea.
Antidiarrheal drugs include antimotility
agents, adsorbents, and drugs that modify
fluid and electrolyte transport

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A- Antimotility agents
Two drugs that are widely used to control diarrhea
are diphenoxylate and loperamide.
Both are analogs of meperidine and have opioid-
like actions on the gut, activating presynaptic
opioid receptors in the enteric nervous system to
inhibit acetylcholine release and decrease
peristalsis.

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At the usual doses, they lack analgesic
effects. Side effects include drowsiness, ,
and dizziness. Because these drugs can
contribute to toxic megacolon, they should
not be used in young children or in patients
with severe
colitis.

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B. Adsorbents
Adsorbent agents, such as bismuth
subsalicylate, methylcellulose analuminum
hydroxide are used to control diarrhea.
Presumably, these agents act by adsorbing
intestinal toxins or microorganisms and/or
by coating or protecting the intestinal
mucosa. They are much less effective than
antimotility agents. They can interfere with
the absorption of other drugs.

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Laxatives
Laxatives are commonly used to accelerate
the movement of food through the
gastrointestinal tract. These drugs
can be classified on the basis of their
mechanism of action as irritants or stimulants
of the gut, bulking agents, and
stool softeners.

41. Indications for Laxatives
• (1) to empty the bowel before elective colonic or
rectal surgery or radiological or endoscopic
examinations;
• (2) to minimize straining at stool in patients with
cardiovascular disease or with hernia; and
• (3) to prevent hard, abrasive bowel movements that
elicit pain.
• All laxatives must be avoided in persons with nausea,
vomiting, cramps, colic, or other unex­plained
abdominal discomfort
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A. Irritants and stimulants
Senna is a widely used stimulant laxative. Its
active ingredient is a group of sennosides, a
natural complex of anthraquinone glycosides.
Taken orally, it causes evacuation of the
bowels within 8 to 10 hours. It also causes
water and electrolyte secretion into the
bowel.

43. These agents appear to work by inhibiting
colonic mucosal (Na+
+ K+
)-ATPase, leading
to accumula-tion of salt and water in the
lumen. At higher doses they may stimulate
colonic myenteric nerve fibers.
• Anthraquinones, phenolphthalin. Rubarb, aloe,
cascara, caster oil, and biscodyl
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B. Bulk laxatives
The bulk laxatives include hydrophilic
colloids (from indigestible parts of fruits and
vegetables) or bran. They form gels in the
large intestine, causing water retention and
intestinal distension, thereby increasing
peristaltic activity. Similar actions are
produced by methylcellulose, psyllium seeds,
and bran.

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C. Saline and osmotic laxatives
Saline cathartics, such as magnesium citrate,
magnesium sulfate, sodium phosphate, and
nonabsorbable salts (anions and cations) that
hold water in the intestine by osmosis and
distend the bowel,
.

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D. Stool softeners (emollient laxatives or
surfactants)
Surface-active agents that become
emulsified with the stool produce softer
feces and ease passage. These include
docusate sodium, docusate calcium, and
docusate potassium. They may take days to
become effective. They should not be taken
together with mineral oil because of the
potential for absorption of the mineral oil.

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E. Lubricant laxatives
Mineral oil and glycerin suppositories are
considered to be lubricants. They facilitate
the passage of hard stools.
Mineral oil should be taken orally in an
upright position to avoid its aspiration and
potential for lipoid pneumonia.

48. Side Effects of Laxatives
• Cathartic colon syndrome (They all have a risk of
being habit-forming)
• They may cause electrolyte imbalances when used
chronically eg. Hypokalemia
• Malabsorption
• Liver abnormalities
• Increased loss of proteins through the intestine
• Laxatives also increase the potential of loss of
pharmacologic effect of poorly absorbed, delayed-
acting, and extended-release oral preparations by
accelerating their transit through the intestines.
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49. Dr. Mahmoud H. Taleb 49
DRUG TREATMENT OF
INFLAMMATORY BOWEL DISEASE
Sulfasalazine (Salazopyrin)
5­Aminosalicylic Acid (5­ASA) is the active compo-nent,
and the sulfonamide portion of sulfasalazine causes most
of the side effects, it seemed reasonable to link two
molecules of 5-ASA together via an azo bond and exclude
sulfapyridine altogether. This resulting drug is called
olsalazine

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Watery diarrhea is an adverse effect of
olsalazine; it occurs at higher doses and
with severe or more extensive disease.
The probable mechanism is promotion -of
ileal fluid secretion, which is not
reabsorbed by the inflamed right colon.
Olsalazine may cause renal toxicity,

51. Thank you!Thank you!
51Dr. Mahmoud H. Taleb