DRUGS USED IN

GASTROINTESTINAL DISEASES
Dr. Francisca Diana A,M.Sc

Outline
Drugs used in acid-peptic diseases
Prokinetic agent
Antiemetic
Antidiarrheals
Laxatives
Antispasmodic
Drug used for miscellaneous GI disorder

DRUG USED IN ACID-PEPTIC

Acid neutralizing agents

DISEASE
Acid production inhibitor
H2 antagonist
Proton-pump inhibitors
Mucosal protective agents
Other acid suppressant

GASTER
Terdiri atas
Bodi
Kardia

Fundus
Korpus
Pilorus

Cekungan
Kurvatura minor
Kurvatura mayor

Mukosa lambung dibagi menjadi tiga

daerah ekskresi:
Area glandula kardia mensekresi

mukus dan pepsinogen.

Area glandula oksintik (parietal)
mensekresi ion H, pepsinogen dan
bikarbonat.
Area glandula pilorik mensekresi
gastrin dan mukus.

Pepsinogen dikatalisis oleh HCl jadi pepsin,

yaitu enzim proteolitik

Ulkus peptik di esofagus, lambung dan
duodenum terjadi apabila produksi asam
lambung dan pepsin tidak berimbang dgn
sietem pertahanan gastroduodenal

Schematic model for physiologic control of hydrogen ion (acid)

secretion by the parietal cells of the gastric fundic glands

Acid neutralizing agents:

Antacids

Antacid tidak mengurangi volume HCl yang

dikeluarkan lambung tetapi peninggian Ph

akan menurunkan aktivitas pepsin.
Antasid dibagi dlm 2 golongan :
a.Antasid sistemik : Natrium bikarbonat
(NaHCO3) diabsorpsi di dlm usus halus
sehingga menyebabkan urin bersifat alkalis.
b.Antasid nonsistemik : Al(OH)3, Mg(OH)2,
CaCO3 hampir tidak diabsorpsi dlm usus sehingga
tidak menimbulkan alkalosis metabolik.

Acid neutralizing agents:

Antacids
Combination of Al(OH) , Mg(OH) , CaCO
3

(+simethicone)
Pharmacodynamics:
Form salt and water
Promote mucosal defense by stimulation of PG

production

Drug interaction:
Inhibit absorption of digoxin, phenytoin, cimetidine,
fluoroquinolone
Some Al can be absorbed

Acid neutralizing agents:

Antacids

H2 receptor antagonists
Cimetidine, ranitidine, nizatidine, famotidine
Pharmacodynamic:
Reduce acid secretion in 2 ways: competitive

inhibition H2 receptor & modulate PCs

response to gastrin & Ach
Reduce 90% (at night) and 60-80% (daytime)

H2 receptor antagonists
Pharmacokinetic:
rapidly absorbed in intestinal lumen
Undergo 1st pass metabolism F = 50%
T1/2: 1-4 hrs, and d.o.a depend on dose, 10 hrs in
recommended dose
Elimination: hepatic metab., glomerular filtration
filtration & renal tubular secretion
Cross the placenta, secreted into breast milk

H2 receptor antagonists
Safety:
Extremely safe
SE:

diarrhea, constipation, headache, fatigue, myalgia

Gynaecomastia
Blood dyscrasi
Avoid from pregnant and nursing women

Drug interaction:
cimetidine prolong half-lives drugs that are substrate for CYP:

warfarin, theophylline, phenitoin, lidocaine, quinidine, bblockers, Ca-channel blockers, benzodiazepines

Compete with procainamide for renal tubular secretion

H2 receptor antagonists

Proton-pump inhibitors
Omeprazole, esomeprazole, lansoprazole,
pantoprazole, rabeprazole
Pharmacodynamic:
Protonated & concentrated in PC canaliculi
The reactive cation binds covalently with H/K

ATPase
Reduce 80-95%, needs 3-4 days to return

Proton-pump inhibitors
Pharmacokinetic: absorbed in intestinal lumen
(available in enteric coated)
An acid-labile lipophylic prodrug: need acid

environment to be activated easily diffuse into

acidified compartment (PC canaliculi)
To be administered 1 hour before meal
Highly protein bound
Undergo 1st pass & hepatic metabolism
T1/2: 1,5 hr but acid inhibition last up to 24 hr
No renal elimination

Proton-pump inhibitors
Safety:
Extremely safe
SE: due to highly reduction acid
Reduction in cyanocobalamin
absorption
Food-bound minerals (?)
Increase risk of enteric infections

 Drug interaction
Alter absorption of certain drugs
Hanya omeprazol yg dpt menghambat aktivitas
enzim CYP2C19 serta menginduksi CYP1A2
(meningkatkan klirens beberapa obat
antipsikotik, takrin dan teofilin)

Proton-pump inhibitors
OBAT

OMEPRAZOL

BIOAVAILABILI T
TAS
(JAM)
(%)

Dosis lazim untuk

peptic ulcer atau
GERD

40-65

0,5 1,5

20-40 mg 1 kali sehari

ESOMEPRAZOL

> 80

1,2 1,5

20 40 mg 1 kali
sehari

LANZOPRAZOL

80

1,5

30 mg 1 kali sehari

PANTOPRAZOL

77

1,0 1,9

40 mg 1 kali sehari

RABEPRAZOL

52

1-2

20 mg 1 kali sehari

Mucosal protective agents

Sucralfate: A complex of sucrose salt + sulfated AlOH
forms a paste that selectively cover ulcers/erosions
Pharmacokinetic:
Almost unabsorbed
Breaking down into sucrose sulfate & Al salt
Pharmacodynamic:
Forming physical barrier so that prevent further caustic
damage stimulate mucosal PG & HCO3 secretion
Enhancing mucosal repair
Drug interaction:
Inhibit absorption of digoxin, phenytoin, cimetidine,
fluoroquinolone
Some Al can be absorbed

Mucosal defense enhancing

agents
Bismuth
compounds
Pharmacodynamic: = sucralfate
Stimulate PG, mucus, bicarbonat secretion

Prostaglandin analog: misoprostol

A methyl analog of PGE1
Pharmacokinetic:
T1/2: 30 mnts 3-4 times daily
Pharmacodynamic: stimulates mucus and bicarbonat secretion
SE: diarrhea, abdominal cramp (10-20%), stimulate
uterine contraction
Dosis : oral, dewasa 200 mg 4 kali/sehari atau 400 mg 2
kali/hari.
Indikasi : usia lanjut atau perdarahan saluran cerna akibat
AINS

Mechanism of action of drug used in acid peptic disease

PROKINETIC AGENTS
Agents that enhance coordinated GI motility and transits
material in the GI tract
Cholinomimetic
Bethanechol
Neostigmin methylsulfate
Dopamine receptor antagonist
Metoclopramide
domperidon
Serotonin (5-HT4) receptor agonist
Cisapride, prucalopride
Motilin agonist
Macrolides: erythromycin

PROKINETIC AGENTS
Side effects:
Metoclopramide
Extrapyramidal effect
Elevated prolactin level galactorrhea, gynaecomastia,

menstrual disorder
methaemoglobinemia
Domperidone
No extrapyramidal effect

Cisaprid
Fatal cardiac arrythmia (occasionally) torsades de

pointes due to induced EAD

PROKINETIC AGENTS
Therapeutic use:
GERD
Impaired gastric emptying
Postvagotomy
Diabetic gastroparesis
NGT-ed patients

Dyspepsia syndrome (non-ulcers)

Antiemetic
Persistent hiccup (metoclopramide)

LAXATIVES

Stimulant laxatives
Merangsang mukosa, saraf intramural atau otot

polos usus sehingga meningkatkan peristaltik dan

sekresi lendir usus.
Castor oil
Kerjanya pada usus halus sehingga efek terlihat setelah 3 jam

ES : kolik, dehidrasi yg disertai gangguan elektrolit

Dianjurkan untuk diberikan pada pagi hari waktu perut

kosong.
Dosis : dewasa : 15-60 mL, Anak : 5 -15 mL
Dosis lebih besar tidak menambah efek pencahar

Stimulant laxatives
Diphenylmethane derivatives:
a. bisacodyl
Dosis : supp 10 mg, oral : dewasa 10-15 mg; anak 5 10 mg
ES : kolik usus, perasaan terbakar pd penggunaan rektal
Efek pencahar terlihat setelah 6 -12 jam pd pemberian oral
Pada pemberian rektal efek setelah - 1 jam
Anthraquinone derivatives: Aloe, senna, cascara
Efek pencahar golongan ini bergantung pada antrakinon yg
dilepaskan dari ikatan glikosidanya.
Efek muncul setelah 6 jam
Zat aktif bisa ditemukan pada ASI (cascara)
ES : pigmentasi kolon, penggunaan kronis menyebabkan kerusan
neuron mesenterik

Bulk forming laxatives

Pembentuk massa tinja
Bekerja dengan meningkatkan massa tinja, karena

kemampuannya menarik air dan ion dalam lumen

kolon, sehingga membentuk hidrogel.
Contoh : sediaan semi sintetik : metilselulosa
dan natrium karboksimetilselulosa; sedangkan
sediaan alami : agar-agar, biji psyllium dan kulit
padi

PELEMBEK TINJA
Bekerja dengan meningkatkan ukuran tinja

dan melembekkan tinja tanpa merangsang

peristaltik usus baik langsung maupun
tidak langsung sehingga mudah
dikeluarkan.
Contoh : Parafin cair, Na dokusat , glycerin

supp, parafin cair (mineral oil)

Osmotic laxatives
Osmolalitas lumen usus

meningkat dan pergerakan cairan

terjadi karena tekanan osmotik.
Terbagi 2 Jenis :
saline laxatives:
unabsorbable sugars: sorbitol,

lactulose

SALINE LAXATIVES
Merupakan garam non organik yang

mengandung kation atau anion dan tidak segera

diabsorpsi mukosa usus karena cenderung
bertahan di saluran cerna.
Peristaltik usus meningkat disebabkan pengaruh
tdk langsung karena daya osmotiknya.
Air ditarik ke dlm lumen usus dan tinja menjadi
lembek setelah 3 6 jam.
Absorpsi pencahar garam melalui usus
berlangsung lambat dan tidak sempurna.
Contoh : magnesium citrate, sodium phosphate

Mechanism of action of laxatives

ANTIEMETIC
1. Serotonin (5-HT3) receptors antagonist
Ondansetron, granisetron, ramosetron, palanosetron,
dolasetron
2. Dopamine antagonist: Metoklopramide, domperidon
3. H1-antagonist : Cyclizine, Promethazine,

prochlorperazine, CPZ
4. Antikolinergics: Scopolamine
5. Cannabioid antagonist: Dronabinol

ANTIDIARRHEA
1. Opioid agonist
2. Colloidal bismuth compound
3. Kaolin (hydrated Mg-Al silicate) & pectin

(indigestible KH)
4. Bile salt-binding resin
5. Octreotide

Pharmacodynamic

antidiare

Side effects

Opioid
(Loperamide,
Diphenoxylate,
codein)

Inhibit presynaptic
cholinergic nerve, reduce
peristaltic activity
Increase transit time
Decrease mass colonic
movements

constipation, cramps,
drowsiness, paralytic ileus,
abdominal bloating.
Diphenoxylate, but not
loperamide, produce euphoria
dan respiratory depression

Colloidal bismuth
compound

direct antimicrobial
effects and binds
enterotoxins

Dark stools, black staining of

the tounge

Kaolin & pectin

adsorbents of bacterial
toxins and fluid, thereby
decreasing stool liquidity
and number.

Have no significant adverse

effect except constipation.
Should not be taken within 2
hours of other medication

Bile salt-binding resin binds bile salts and

(Cholestiramine,
increases fecal excretion of
Colestipol,
bile acids
colesevalam)

Bloating, flatulence,
constipation
Fat malabsorption
Should not be taken within 2
hours of other medication

Somatostatin-like
(Octreotide)

Steatorrhea, nausea,
bloating
Fat-soluble vitamin
deficiency

reduces intestinal fluid

secretion & pancreatic
secretion
slows GI motility, inhibit

ANTIPASMODIC
1. Anticholinergic

Hyoscyamine, Dicyclomine
2. Serotonin (5-HT3) receptor antagonist
Alosetron

Indication:
to prevent the pain and fecal urgency
in
patient with IBS
treatment of diarrhea-predominant IBS

Drug used for miscellaneous GI

1. Pancreatic enzymes: pancreatin,
disorder
pancrelipase

Chronic pancreatitis

Malabsorption
2. Bile acids: ursodeoxycholic

Gallstone dissolution
3. Antiflatulance: simethicone, herbal prep.
(antifoaming agent)

References
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Goodman & Gilmans the pharmacological basis of
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pancreatic disease. In: Goodman & Gilmans the
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