dr. Dwi Indria Anggraini, M.Kes.

, SpKK
Dr.dr. Asep Sukohar, M.Kes
Department of Pharmacology and Therapy
Medical School Lampung University
I. Drugs used to treat peptic ulcer disease
Phatogenesis :

3 major factors :
- Infection Helicobacter pylori
- HCl secretion 
- Inadequate mucosal defense against gastric
acid
Treatment :
- Eradicating H. pylori infection
- Reducing secretion of gastric acid /
neutralization
- Providing agents to protect gastric mucosa
 Drugs used to treat peptic ulcer disease
(continued)

V. Antimuscarinic agents
-Hyoscyamine - Pirenzepine
-Mepenzolate

VI. Antacids
-Aluminum hydroxide -Magnesium hydroxide
-Calcium carbonate -Sodium bicarbonate

VII. Mucosal protective agents

-Colloidal bismuth
-Sucralfate
 Eradication H. pylori  rapid healing &
low recurrence rates

Regimen of choice base on efficacy & cost

• Two week, triple therapy :
• bismuth - metronidazole - tetracycline / +
antisecretory drugs

Second-line regimen
• Two AM :
• Metronidazole - amoxicillin or clarithromycin +
antisecretory agent (omeprazole)

Single AM :
• Less effective
 Secretion of acid by gastric parietal cells
 regulated by
- Histamine
- Acetylcholine
- Gastrin
- Prostaglandin E2 & I2

 Histamine / ACh / Gastrin + Receptors 

activation H+ / K+-ATPase proton pump 
secretes HCl into the lumen of stomach
 Prostaglandin E2 and I2  gastric acid
production 
Competitively blocking binding histamin to H2-receptors

Chief clinical use  inhibitors of gastric acid secretion

Drugs :

• Cimetidine (prototype) - Famotidine

• Ranitidine - Nizatidine

Capable of over 90% reduction in basal, food-stimulated, and

nocturnal secretion of gastric acid after a single dose

Promoting the healing of duodenal and gastric ulcers and

preventing their recurrence
Actions :

• Act on H2-receptors in the stomach, blood vessel, etc

• Reversible competitive antagonist
• Completely inhibit gastric acid secretion induced by
histamine or gastrin
• Only partially inhibit gastric acid secretion induced by
ACh or bethanechol

Therapeutic uses :

• Peptic ulcers
• Zollinger-Ellison syndrome
• Acute stress ulcers
• Gastroesophageal reflux disease (heartburn)
 Cimetidine & other H2- DOA > , Potency 5-10 x

Ranitidine
Cimetidine

antagonist : > than cimetidine

Given orally  Minimal SE , ≠ produce
distributed widely in antiandrogenic or
the body ( breast milk, prolactin-stimulating
placenta)  E : Urine effects of cimetidine
Short serum half-life  ≠ inhibit the mixed
increased in renal function oxygenase
failure system liver 
Slowly inactivated by ≠ affect the
the liver’s microsomal concentration of other
mixed function drugs
oxygenase system
 • Similar ranitidine in its
pharmacologic action
Famotidine • 20-160 x > potent than cimetidine
• 3-20 x > potent than ranitidine

• Similar ranitidine in its

pharmacologic action & potency
Nizatidine • Eliminated principally by the kidney
• Bioavailability ~ 100 %
PGE2 & PGI2  inhibit secretion HCl & stimulate
secretion of mucus & bicarbonate (cytoprotective
effect)

Pathogenesis peptic ulcer  deficiency PG

Less effective than H2-antagonist

Produces uterine constractions  CI in pregnancy

SE : Diarrhea , nausea (dose-related )

▪ Omeprazole
▪ Lansoprazole
- Inhibition of gastric acid secretion
- Do not affect gastric motility
- Absorption : rapidly
- Bioavailability : 70%
- 95% bound to plasma protein
- Metabolism : hepatic
- Exc : urine & feces
- Adverse effects - gastrointestinal
- C.N.S
 Hyoscyamine
 Adjuncts in the management of peptic ulcer disease
and Zollinger-Ellison syndrome

 Pirenzepine
 Relatively specific muscarinic M1-receptor
antagonist
 SE <
 Weak bases that react with gastric acid  Water + salt
 Reduction H.pylori colonization & stimulation PG
synthesis
 E.g. -Aluminum hydroxide -Magnesium hydroxide
-Calcium carbonate -Sodium bicarbonate
 MOA :
Pepsin is inactive in solution above pH 4.0
Once antacids administered, they will chemically reduce/neutralize
gastric acidity

 peptic activity

Relieve symptoms of peptic ulcer disease
 Sodium Bicarbonat  systemic antacid
NaHCO3 + HCl  NaCl + H2O + CO2
- Active ingredient in backing soda
- Highly soluble
 absorbed rapidly from the gut

promote systemic alkalosis and fluid retention

Not recommended for long-term use

CO2 release  belching, nausea, abdominal

distention, flatulence
Calcium Carbonate
Ca C03 + 2 HCl  CaCl2 + H2O + C02
- More slowly than sodium bicarbonate
- Very effective in neutralizing in gastric acid
- 10% produced is absorbed
 potential
- hypercalcemia
- milk alkali syndrome
- acid rebound

not recommended for long term use
Note : NaHCO3 or CaCO3  adm. with milk or cream 
“milk-alkali syndrome”
Aluminum Hydroxide
Al(OH)3 + 3 HCl → AlCl3 + H2O

- Onset of action : Late

- Duration of action : Long
- Often causes constipation
- Binds certain drugs : eg, tetracycline, vitamin
Magnesium Hydroxide
= Milk of Magnesia
Mg(OH)2 + 2 HCl  MgCl2 + 2 H2O
- Prolonging its neutralizing effect
- Magnesium salts  cathartic effect
- A small  absorbed  renal insufficiency

Clinical uses of antacids :

- Taken as tablets or suspension either acutely or just before
symptoms expected (usually between meals & at bedtime)
- Nor recommended for the treatment of active peptic ulcer
- Antacid can impair the absorption of other drugs and
shouldn’t taken concurrently
 Cytoprotective Enhance mucosal protection
mechanism
 Preventing mucosal injury
 Reducing inflammation
 Healing existing ulcers
 MOA :
Is though to involve polymeration and selective binding to
necrotic ulcer tissue

Act as a barrier to acid, pepsin, and bile

 Require an acid pH to be activated ; shouldn’t be

administered simultaneously with antacids, H2-receptor
antagonist , or proton pump inhibitors
Sitokrom P450 sistem oksidase
4 sub-famili utama: CYP1,CYP2, CYP3, dan CYP4 6 isoform
(CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, dan
CYP3A4)
Aktivitas dimodulasi oleh genetik dan faktor lain (umur, etnik,
jenis kelamin, diet, konsumsi alkohol atau tembakau) juga
kondisi patologis
 Anti diarrheal drugs include :
 anti motility agents
 adsorbents
 drugs that modify fluid and electrolyte
transport
 Loperamide
 an orally active antidiarrheal agent
 40-50 x > potent than morphine as an
antidiarrheal agents and penetrates the CNS
poorly
 has antisecretory activity against cholera toxin
and some forms of E.coli toxin
 effective and safe → marketed for OTC
distribution and is available in capsule, solution,
chewable forms
 Pharmacokinetic :
 its act quickly following an oral use, Tmax = 3-5 hours,
t1/2 = 11 hours, extensive hepatic metabolism

 Therapeutic uses :
 effective against traveler's diarrhea, used either alone or in
combination with antimicrobial agents (trimethoprim,
cotrimoxazole , fluoroquinolone).
 If clinical improvement in acute diarrhea does not occur
within 48 hours, loperamide should be discontinued.
 adjunct treatment in almost all forms of chronic diarrheal
disease.
 should not be used in children younger than 2 years of age
 lacks significant abuse potential
 overdosage → CNS depression and paralytic ileus
 children > sensitive than adults to the CNS-
depressants effects of loperamide
 in patients with active inflammatory disease of the
colon, loperamide should be used with great caution
to prevent development of toxic megacolon.
 structurally related to meperidine
 difenoxin is the active metabolite of diphenoxylate and also
is used as such to treat diarrhea
 as antidiarrheal agents, diphenoxylate and difenoxin >
potent than morphine
 Pharmacokinetic :
- extensively absorbed after oral administration, Tmax = 1-2 hours
deesterified
diphenoxylate -----------------> difenoxin , t1/2=12 hours
- higher doses (40-60 mg per day) → CNS effects →
potential for abuse and/or addiction
- available in preparations containing small doses of
atropine to discourage abuse and deliberate overdosage
Adsorbent agents such as kaolin, pectin,
methylcellulose and activated attapulgite, magnesium
aluminum silicate  widely used to control diarrhea.

These agents act by adsorbing intestinal toxins or

microorganisms, or by coating or protecting the
intestinal mucosa.

Less effective than antimotility agents and can interfere

with absorption of other drugs.
NSAIDs :
 Acetosal and indomethacin are effective in
controlling diarrhea  This antidiarrheal
action is probably due to inhibition of
prostaglandin synthesis.
 Antisecretory, antiinflammatory, and
antimicrobial effects, nausea and abdominal
cramps also may be relieved.

 effectively for the prevention and treatment

of traveler's diarrhea , but it also may be
effective in other forms of nonsyndromic,
episodic diarrhea.
Laxation :
• Evacuation of formed fecal material from the rectum

Catharsis :
• Evacuation of unformed, usually watery fecal
material from the entire colon

Classified on the basis of their MOA as :

• Irritants and stimulants
• Bulking agents
• Stool softeners
 Castor oil  ricinoleic acid  very irritating
 peristalsis 
 Cascara, senna, aloe contain emodin which
stimulates colonic activity
OOA delayed 6-8 hours
Pass into breast milk
 Phenolphthalein & bisacodyl  potent
stimulant of the colon
 SE :
 Abdominal cramps, potential for atonic colon with
prolonged use
Classification and Comparison of Representative Laxative
_________________________________________
Laxative Effect and latency in Usual Clinical Dosage
________________________________________________
Softening of feces, Soft or semifluid stool, Watery evacuation,
1-3 days 6-8 hours 1-3 hours
__________________________________________________________
Bulk-forming laxatives Stimulant laxatives Osmotic laxatives
Bran Diphenylmethane Sod.phosphates
Psyllium prep. derivates MgSO4
Methylcellulose Bisacodyl Milk of magnesia
Calcium polycarbophyl Mg Citrate
Surfactant laxatives Anthraquinone der. Castor oil
Docusates Senna
Poloxamers Cascara sagrada
Lactulose
__________________________________________________________