GASTROINTESTINAL

NOOR WIJAYAHADI
Ulkus Lambung / Peptikum

Faktor Pelindung
vs
Faktor Perusak
 Peptic ulcer

Common causative factors for ulceration:

1. H. pylori
2. too much gastric acid
3. too much pepsin
4. breakdown of the protective mucus
5. use of non-steroidal anti-inflammatory
drugs (NSAID)
6. stress-related damage
7. radiation
8. chemotherapy
 H. pylori treatment
Helicobacter pylori  etiologic agent of
 peptic ulcers and gastritis
 major risk factor for gastric adenocarcinoma and mucosa-
associated lymphoid tissue lymphoma (MALT).

14 days regimens triple therapy regimens:

 1) a proton pump inhibitor (PPI)
 2) two anti-microbial (clarithromycin and amoxycillin)

14 days regimens Quadruple therapy:

1) proton pump inhibitor (PPI)
2) bismuth subcitrate
3) tetracycline
4) metronidazol
 Triple Therapy

 The BEST among all the Triple therapy regimen is

Omeprazole / Lansoprazole - 20 / 30 mg bd
Clarithromycin - 500 mg bd
Amoxycillin / Metronidazole - 1gm / 500 mg bd

 Given for 14 days followed by P.P.I for 4 – 6 weeks

 Short regimens for 7 – 10 days not very effective

 Triple Therapy – cont …
Some other Triple Therapy Regimens are

 Bismuth subsalicylate – 2 tab qid

Metronidazole - 250 mg qid
Tetracycline - 500 mg qid

 Ranitidine Bismuth citrate - 400 mg bd

Tetracycline - 500 mg bd
Clarithromycin / Metronidazole - 500 mg bd
 Quadruple Therapy

 Given when Triple Therapy fails

 Omeprazole / Lansoprazole - 20 / 30 mg bd
Bismuth subsalycilate - 2 tabs qid
Metronidazole - 250 mg qid
Tetracycline - 500 mg qid
 Bismuth compounds
effects :
1. anti-microbial activity against Helicobacter pylori
2. stimulation of prostaglandin synthesis 
increasing mucosal protection
3. chelation with exposed ulcer proteins and
protecting the ulcer base.
 Monotherapy  not very effective in eradicating
H. pylori.
 Combined with other agents (anti-microbials,
PPI's or H2 antagonists) 90% eradicated.
 Also used to treat nausea, diarrhea, and
indigestion.
 Darkening the tongue and stool
 Prolonged use encephalopathy
 ANTASIDA

penetral atau pengikat HCl lambung.

 Antacids

Duration of action :
 30 min when taken in empty stomach
 2 hrs when taken after a meal
Side effects :
 Al3+ antacids – constipation (As they relax gastric
smooth muscle & delay gastric emptying)
 Mg2+ antacids – Osmotic diarrhoea .
 In renal failure Al3+ antacid – Aluminium toxicity
&
Encephalopathy
 Antacids – Common additives

 Simethicone – Decrease surface tension ,thereby

reduce bubble formation
Added to prevent reflux .
 Alginates - Form a layer of foam on top of
gastric contents & reduce reflux
 Oxethazaine – Surface anaesthetic
 Antacid - Interactions

 Adsorb drugs and form insoluble complexes

that are not absorbed .

Clinical importance :
Interactions can be avoided by taking
antacids 2 hrs before or after ingestion of other
drugs .
 1. NaHCO3
 Sekarang sudah tdk dianjurkan
 Netralisasi terlalu cepat  CO2
banyak
 kembung
 Absorbsi Na+ sempurna  alkalosis
sistemik
 2. CaCO3

 CO2 yg terbtk lebih sedikit.

 Pemakaian jangka panjang
menyebabkan hiperkalsemia dan
nefrokalsinosis.
 Dapat menyebabkan acid rebound
krn meningkatkan gastrin dan
stimulasi sel parietal oleh Ca2+
 Sedikit menyebabkan obstipasi.
 3. Mg(OH)3
 Cukup baik sbg antasida.
 Tidak dianjurkan utk terapi jangka
panjang pd pasien dg gangguan
fungsi ginjal  dapat
hipermagnesia.
 Punya efek laksan (laxative).
 4. Al(OH)3
 Menetralkan & mengadsorpsi HCl.
 Mbtk Al2(PO4)3 yg tdk larut dlm usus
halus.
 Menguntungkan utk pasien insufi-
siensi ginjal krn tdk hiperfosfatemi.
 Pd pasien dg ginjal sehat justru
menjadi kekurangan PO4
 Interaksi obat : mekan absorbsi grm
besi, tetrasiklin & asam empedu krn
adsopsi / pbtkn komplek.
 Sebabkan konstipasi.
Pengatur Keasaman
Lambung
 H2-antagonists
 very effective and relatively safe agents for
the treatment of ulcer disease Mostly
basal (nocturnal) & post-prandial acid
secretions are reduced  reduce ulcer pain
and promote healing of the mucosa.
 short half-life and duration of action more
than once daily administration is required
 metabolized and unmetabolised product is
excreted into the urine  dosage
adjustments are required in renal
insufficiency.
 H2-receptor antagonists ( cimetidine) 
inhibit hepatic cytochrome P-450 enzymes
 1. Antihistaminika H2
(H2-bloker)
 Scr kompetitif memblok reseptor H2
histamin.
 Menghambat sekresi asam basal & yg
diinduksi histamin.
 Menekan sekresi asam yg diinduksi gastrin
& vagus krn scr nonkompetitif m’pengaruhi
sistem reseptor-efektor ACh & gastrin.
 Preparat : simetidin, ranitidin (durasi lbh
panjang, daya lbh besar shg dosis lbh
kecil)
 Pemberian : pd malam hari
 ESO jarang : sakit kepala, pusing,
nausea, diare, obstipasi, nyeri otot &
sendi.
Simetidin :
 kerja antiandrogen : gangguan
potensi & ginekomasti.
 krn mrpkn inhibitor sit-P450 maka
akan memperpanjang kerja BDZ,
antikoagulan, lidokain, fenitoin &
teofilin.
 Cimetidine Ranitidine Famotidine Nizatidine

Bioavailability 80 50 40 >90
Relative Potency 1 5 -10 32 5 -10
Half life (hrs) 1.5 - 2.3 1.6 - 2.4 2.5 - 4 1.1 -1.6
Duration of 6 8 12 8
action (hrs)
Inhibition of 1 0.1 0 0
CYP 450
Dose mg(bd) 400 150 20 150
H2 Blockers–Side effects & Interactions

 Cimetidine causes gynecomastia, galactorrhea

(as it is antiandrogenic & increases orolactin level)
 Cimetidine inhibits CYP450 & increases conc.
of Warfarin, Theophylline, Phenytoin, Ethanol.
 2. Pirenzepin
(antagonis kolinergik)

 Aksi selektif pd reseptor muskarinik

di sel parietal  sekresi asam .
(daya inhibisi sekresi asam < H2 anta-
gonis).
 Parasimpatolitik lain spt atropin
(antagonis non selektif)  tdk efektif
pd dosis yg diperbolehkan.
 ESO jarang : mulut kering, mata
kabur, gangguan buang air seni.
 3. Proton Pump Inhibitors

 Most effective drugs in antiulcer therapy

 Irreversible inhibitor of H+ K+ ATPase

 Prodrugs requiring activation in acid environment
 Weakly basic drugs & so accumulate in canaliculi
of parietal cell
 Activated in canaliculi & binds covalently to
extracellular domain of H+ K+ ATPase
 Acid secretion resumes only after synthesis of
new molecules
 P.P.I. – Side effects & Interactions

 Causes hypergastrinemia which leads to

carcinod tumor in rats
 But no evidence of such tumors in man

 Inhibit CYP 450 & hence metabolsim of

warfarin, phenytoin, etc
 Pantoprazole & Rabeprazole have no significant
interactions
 Mucosal Protective Agents

 Sucralfate

 Misoprostol

 Colloidal Bismuth compounds

 4. Sukralfat
 Mrpkn basa Al-sakarosa-sulfat
 M’percepat penyembuhan ulkus dg
mbtk komplek dg prot di perm
ulkus mbtk lapisan pelindung dr
faktor agresif.
 ESO : obstipasi
 KI : gangguan fungsi ginjal yg
berat  bahaya sistemik krn Al
yg diabsorbsi.
 5. Bismut kelat
 Aksinya sama dengan sukralfat.
 Diberikan sblm makan (lambung kosong).
6. Karbenoksolon
 Bekerja m’perbaiki faktor protektif dg cara :
stimulasi pbtkn mukus, m’perpan- jang umur
sel mukosa lambung  m’percepat
penyembuhan ulkus.
 ESO : spt mineralokortikoid  retensi air &
Na+  hipertensi, hipokalemi, m’perburuk
insufisiensi miokard.
 KI : insuf. hati, jtg, ginjal, hipertensi.
 Interaksi dg diuretika penahan K+ 
menghentikan aksi karbenoksolon.
 7. Prostaglandin
• Bekerja m’perbaiki faktor protektif dg cara
: stimulasi pbtkn mukus, mempertahankan
/meningkatkan aliran darah mukosa lambung,
mempertahankan barier mukosa terhadap
difusi kembali H  m’percepat penyembuhan
ulkus.
• Menghambat faktor agresif  mengurangi
sekresi asam.
• Contoh : misoprostol
 efektif dalam pencegahan ulkus yang
disebabkan OAINS / NSAID
 Misoprostol

 PGE1 analogue

 Modest acid inhibition

 Stimulate mucus & bicarbonate secretion

 Enhance mucusal blood flow

 Approved for prevention of NSAID induced ulcer

 Diarrhoea & cramping abd. pain – 20 %

 Not so popular as P.P.I are more effective & better

tolerated
 M1-inhibitors

 Pirenzepine
 rarely used clinically  poor reduction
gastric acid secretion.
 the mechanism is less specific than the
proton pump inhibitors.
 Gastro-esophageal Reflux

The common factors :

 a lack of saliva
 poor peristaltic movement
 decreased lower esophageal sphincter (LES)
pressure
 transient episodes of LES relaxation
 delayed gastric emptying
 increased gastric acid

Therapy  decreasing gastrointestinal gastric acid,

increasing gastric motility or increasing LES tone.
 5-HT4-agonists

 cisapride (Prepulsid) may increase the

efficacy of therapy in reflux disease when
combined with PPI's or H2-receptor
antagonists  increases LES pressure,
improves esophageal body motility and
accelerates gastric emptying.
 no effect on colonic motility  not used as
a laxative
 prolongs the QT interval and may cause
cardiac dysrhythmias when given with other
CP450 inhibiting agents (i.e. erythromycin)
 is restricted
 MOTILITAS GI
- Motilitas Gastrointestinal diatur oleh:
1. Hormon gastrointestinal
2. Sistem Saraf: intrinsik (enteral)
ekstrinsik (sentral)

- Saraf Intrinsik  paling dominan

 target pengobatan mual, muntah,
konstipasi, diare
 Sistem Saraf Intrinsik
Gerak usus dirangsang via reseptor kolinergik

 Direk  rangsangan pada reseptor kolinergik
 Indirek  rangsang pleksus myenterikus 
rangsang reseptor kolinergik

Pleksus Myenterikus dapat dirangsang oleh:

- neurotransmiter (serotonin, dopamine)
- neurokrin (subst P, motilin, kolesistokinin)
- GI peptides (gastrin, VIP).
 Sistem Saraf Ekstrinsik
1) Extrinsik parasimpatis (n. vagus & n.
pelvikus)  umumnya eksitasi

2) Extrinsik simpatis  inhibisi

Antiemetik
 Pathophysiology of Emesis

Cancer chemotherapy
Cerebral cortex
Opioids Smell
Sight Anticipatory emesis
Thought
Chemoreceptor Vestibular
Vomiting Centre
Trigger Zone (medulla)
Motion nuclei
(CTZ) sickness
Muscarinic, 5 HT3 & Muscarinic
(Outside BBB) Histaminic H1 Histaminic H1
Dopamine D2
5 HT3,,Opioid Chemo & radio therapy
Receptors
Gastroenteritis

Pharynx & GIT

5 HT3 receptors
 Emesis and anti-emetics
 Beda dengan peristalsis (saraf intrinsik dominan),
SSP paling dominan dalam nausea & vomiting
 Pusat Muntah dapat dirangsang oleh:
1) Obat (mis. Kemoterapi)
2) Aferen n. vagus
3) Gangguan vestibular
dehidrasi & gangguan elektrolit
 Anti-emetik  blok reseptor pusat muntah:
- antagonis dopamin D2
- antagonis serotonin
- antikolinergik (antimuskarinik)
- antihistamin H1
- kanabinoid
 Antagonis Dopamin D2

metoklopramid & domperidon

 blok reseptor Dopamin D2 (inhibitory) di Pleksus
Myenterikus  pelepasan asetilkolin meningkat
 rangsang reseptor muskarinik  rangsang
peristalsis
 Antagonis reseptor Dopamin D2 di Chemoreceptor
Trigger Zone (CTZ)  anti-emesis.

Domperidone tidak lewat blood-brain-barrier 

jarang timbul Efek Samping extrapyramidal (CTZ
di luar BBB).
Metoclompramide juga aktivasi reseptor serotonin
 Phenothiazines & Butyrophenones
 - Phenothiazines  antipsikotik
Prochlorperazine
Promethazine
 - Butyrophenone
Droperidol
 Droperidol used for postop. nausea & vomiting,
but cause QT prolongation.
 Antagonis Serotonin

Ondasetron & granisetron

- SSP  anti-emetik karena kemoterapi
- N. vagus  pelepasan asetilkon naik 
peristalsis meningkat
 H1 Antihistaminics

 - Efektif untuk motion sickness

 - Drugs available
Meclizine
Cyclizine
Dimenhydrinate
Diphenydramine
Promethazine – Used in pregnancy, used by
NASA for space motion sickness
 antikolinergik (antimuskarinik)

- SSP  antiemetik
- Gastrointestinal  hambat peristalsis

- Scopolamine (hyoscine) – transdermal

patch untuk motion sickness
 Cannabinoids

 Dronabinol – sebagai ajuvan pada kemoterapi

yang merangsang muntah
 Nabilone
Antiemetik mana yang lebih baik, Metoclopramide
atau Domperidone ?

 CTZ di luar BBB

 Metoclopramide dapat lewat BBB
 ESO ekstrapiramidal
 LAKSATIF / KATARTIK

1. Bulk Katartik (pembentuk massa)

2. Osmotic Laxatives
3. Stool Surfactant Agents (Softeners)
4. Stimulant Laxatives
 Konstipasi

 Penyebab :
1. overstimulasi sistem simpatis
2. inhibisi sistem parasimpatis
3. resobsi air di kolon adekuat
4. sisa makanan di rektum kurang

 Karena penyakit atau pemakaian obat
 Karena kurang gerak dan intake air
 Bulk Katartik (pembentuk massa)

Polisakarida tak tercernakan :

- Natural  psyllium, methylcellulose
- Sintetis  polycarbophil

- Bakteri usus dapat mencerna serat 

ESO: kembung dan flatus

-  vol intestinal   menstimulasi gerak

peristaltik
 Osmotic Laxatives
Garam / ion sulit diabsorbsi air tertarik ke
lumen usus  volume feses banyak

Magnesium oxide
 Hati2 pada renal insufisiensi
Sorbitol& laktulosa
Dicerna kuman usus
 flatus and kram

Dosis tinggi  diare dalam 1-3 jam 

gangguan elektrolit
 Stool Surfactant Agents (Softeners)

 Dioktil sulfosuksinat  melunakkan

feses
 Parafin liquidum  melicinkan dinding
usus  penggunaan kronik akan
mengganggu abs vit larut lemak
 Dokusate, Gliserin  supp.
 Stimulant Laxatives
 Meningkatkan motilitas lambung & usus
 Tdk utk jangka panjang  menyababkan
kram abdominal

1. Derivat Antrakinon  Bisakodil

Aloe, senna, cascara
2. Derivat Difenilmetan
phenolphthalein  kardiotoksis
3. Castor Oil
OBAT DIARE
 Diarrhea

 Penyebab:
1. over-stimulation saraf parasimpatis
2. inhibisi saraf simpatis
3. bakteria atau virus
4. iritasi  over-secresi air & electrolytes

Karena penyakit atau Obat

 Umumnya self-limiting  tidak perlu obat
Gangguan elektrolit  perlu rehidrasi
 OBAT DIARE
 REHIDRASI

1. Antibiotik
 utk infeksi spec ( tifes, disentri )
2. Zat Pengabsorbsi
 mengabsorbsi toxin bakteri : kaolin
3. Obat sejenis morfin
 mengurangi garakan peristaltik, me-
ningkatkan reabsorbsi air
 Opiate receptors

 opioid m-receptor  located on the

myenteric neurons.
 agonists  inhibit acetylcholine release
from the neuron  resulting in a decrease
in GI motility.
 This effect occurs at dosages lower than
that required for analgesia.
 Opiate agonists in GI

 markedly reduce peristaltic and propulsive motor

activity
 increasing pyloric, ileocolic and anal sphincter tone.
increase segmental contractions + prolonging transit
and increasing the resistance to flow through the
lumen.

Natural opioids (morphine and codeine)  very

effective anti-diarrheal drugs.
Loperamide (synthetic opioid) :
 does not penetrate the blood brain barrier
 for acute diarrhea and chronic diarrhea associated
with irritable bowel disease.