Department of Pharmacology and Therapy

Medical School Lampung University

 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

 Cimetidine:

400 mg, 200mg

2x400mg for 4-6 weeks

Ranitidine: 150 mg (tab), 25mg &50mg(inj)

Peptic ulcer: 2x 150mg or 1x300mg (night)

Zollinger ellison: 3x150mg
Famotidine: acute duodenal ulcer 1x40mg or
2x20mg. maintenance: 1x20mg
Nizatidine: duodenal ulcer 1x300mg or 2x150mg
8 weeks
maintenance:1x150mg
GERD: 2x150mg-300mg for 12 weeks

 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)
- Antacid can impair the absorption of other
drugs and shouldnt 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 ; shouldnt be

administered simultaneously with antacids, H2-receptor
antagonist , or proton pump inhibitors

 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 = 12 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

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.

 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

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Laxative Effect and latency in Usual Clinical

Dosage
________________________________________________
Softening of feces,

evacuation,

Soft or semifluid stool,

Watery

1-3 days
6-8 hours
1-3 hours
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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
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