Obat-obat sistem

gastrointestinal

Devi Usdiana Rosyidah, dr., M. Sc

Pharmacology Department
Medical Faculty of UMS
2017
Formularium nasional
 Antasida/antiulkus : antasida, esomeprazol,
lansoprazol, omeprazol, ranitidin, sukralfat,
 Antiemetik : deksametason, dimenhidrinat,
domperidon, klorpromazin, metoklopramid,
ondansetron,
 Antihemoroid : kombinasi
 Antispasmodik : atropin, hiosina butilbromid,
 Obat diare : atapulgit, garam oralit, kaolin pektin,
loperamid, zinc
 Katartik : bisakodil, gliserin, parafin, fenoftalein,
laktulosa, natrium fosfat, polietilen glikol
 Lain-lain : asam ursodeoksikolat
Antasida/antiulkus
 Antasida
- Kombinasi : aluminium hidroksida 200
mg+magnesium hidroksida 200 mg  tab
kunyah atau suspensi
ANTASID
 Basa lemah : Al OH3, Mg OH2, Ca CO3
 MK : Mengubah pH lambung, menghambat
pepsin
 Dibagi 2 :
a. Sistemik : NaHCO3/Ca
CO3+HClNaCl+H2O+CO2
b. Lokal : AlOH3, MgOH2
 ANTASID
 ES Antasid sistemik :
- Alkalosis metabolik
- Retensi Na
- Edema
 NaHCO3 : alkalinisasi urin, pengobatan pruritus lokal
- Sediaan 500-1000 mg
- Dosis 1-4 gram
 Milk alkali syndrom ? NaHCO3/CaCO3 + susu  sakit
kepala, iritabel, lemah , mual muntah, K >>>, alkalosis,
kalsifikasi batu di ginjal.
ANTASID
 Antasid non sitemik :
- Bersifat demulcen dan adsorben
- Al OH3 : konstipasi
- Indikasi : tuksk peptik, nefrolitiasis fosfat,
adsorben racun
- Sediaan : suspensi, tablet
- Mg OH2 : katartik
ANTASID
 CaCoO3: konstipasi, muntah, perdarahan
sal cerna, disfungsi ginjal, fenomena acid
rebound—(sel prietal sekresi
gastrin)sekresi asam lambung saat
malam hari tinggi
 Mg2Si3O8nH2O : pembentuk batu
silikatpenggunaan kronik
 Sediaan : 500 mg
ANTASID
 Ex : NaHCO3, CaCO3distensi abd +
sendawa (pelepasan CO2 dan karbonat)
 Mg2+&Al3+abs <<<
 Alrelaksasi ot.polos gastrikpenundaan
pengosongan, konstipasi
 Mg
 Simetikonmenurunkan pembusaan,
turunkan refluk esofagus
 Makanan me++ PH jd 5 dlm 1 jam
ANTASID
 Mengadsorbsi obat lain
 ES :
- Sindrom susu alkali
- Batu ginjal
- Osteomalasia/osteoporosis
- Neurotoksisitas
- Diare
- Na >>>kardiovaskuler disease
- Interaksi : kurangi adsorbsi obat INH, penisilin,
tetrasiklin, nitrofurantoin, as nalidiksat, sulfonamid,
fenilbutazon
ANTASID
 Sediaan : 1 produk gabung antara Al OH,
Mg OH dan simetikon
 Sering self medication
 Hati2 sistemik jangka panjang
 suspensi lbh cepat
AH2 : Ranitidin tab 150 mg, injeksi 25
mg/mL

 Ex : cimetidin, ranitidin, famotidin,po, iv ;

nizatidin
 MK : kompetisi reversibel dg histamin berik. dg
(R) H2X sekresi as.basal, supresi prod. as
o/k makanan, gastrin, hipoglikemia, stimulasi
vagust.u. Nokturnalfrek. 1x/hari sblm
tidur
AH2
 FK : abs cepat p.o-ik.prot <<<-ekskresi :
filtrasi, sekresi tub. Ginjal
 Durasi kerja iv : cimetidin 4-5 jam, ranitidin
6-8 jam, famotidin 10-12 jam
 ES : ringan diare, sakit kepala, mengantuk,
kelelahan, nyeri otot, konstipasi, halusinasi,
delirium, ginekomastia (lk)-ik cimetidin dg
(R) androgen, galaktorea (pr)-X hidroksilasi
estradiol, jml sperma turun/impotensi-
reversibel
 Jk panjang ES : sitopenia
AH2
 Melalui plasenta, ekskresi ASI(+)
 I : ulkus gaster, ulkus duodenal, GERD,
tanpa komplikasi, profilaksis ulkus stress
AH2
SUKRALFAT : tab 500 mg,
suspensi 500 mg/5mL
 Td : sukrosa oktasulfat + AlOH2+ Asgel
kental, lengket melekat kuat di sel epitel
selama 6 jam stlh penggunaan
 Stimulasi prod PG lokal&EGF
 Ikat garam empeduu/esofagitis, gastritis
refluk
 Profilaksis ulkus stress
 Pemberian saat perut kosong/1 jam sblm
makan, no antasid 30 menit setelah sukralfat
SUKRALFAT
 ES : konstipasi , ggn ginjalAl >>>, antasid
(Alumunium/Al), hambat absorbsi obat
lain (oleh karena itu diberikan 2 jam
setelah obat lain)
Anti ulkus : PPI
 Esomeprazol serb injeksi 40 mg (iv)
 Lansoprazol
a. kaps 30 mgtx jangka pendek tukak lambung,
tukak duodenum, GERD, berikan 1 jam sblm
makan.
b. serb injeksi 30 mgpasien IGD atau rawat inap
dengan riw. Perdarahan sal. cerna
 Omeprazol
a. Kaps 20 mgtx jangka pendek tukak lambung,
tukak duodenum, GERD, berikan 1 jam sblm
makan.
b. serb injeksi 40 mgpasien IGD atau rawat inap
dengan riw. Perdarahan sal. cerna
PPI
 Paling efektif
 Ex : omeprazol 20 mg, esomeprazol,
lansoprazol, rabeprazol, pantoprazol
(tab/iv)
 Prodrugaktif (lingk. asam)
 Sifat : basa lemah
 MK : katalisasi protonberikatan dg
sistein 813ireversibel (24-48 jam/>)
HCl ditekan sd 80-95%
PPI
 FK : abs cepat-ik.prot>>>
granul/tablet salut enterik, metab : hati, ekskresi
sulfat : urin, feses, T1/2 1-2 jam, durasi kerja
panjang
 Diminum bersamaan/sebelum makan,
interaksi dg antagonis H2
 Frek : 1-2x/hari selama 2-5 hari (steady
state)
 ES : mual, nyeri abdomen, konstipasi,
flatulensi, diare, atralgia, sakit kepala, ruam,
hipergastronemiahiperplasia sel ECL?
PPI
 G T1ok, no teratogenik
 Berikan 30 menit sblm makan
 I : ulkus gaster, ulkus duodenum, GERD,
sindrom ZE
Antiemetik
 Deksametason injeksi 5mg/mL hanya untuk
menyertai terapi antineoplastik
 Dimenhidrinat tab 50 mg
 Domperidon tab 10 mg, syr 5mg/5mL, drops 5mg/mL
- Modest prokinetic activity in doses of 10-20 mg three
times a day.
- Although it does not readily cross the blood-brain
barrier to cause extrapyramidal side effects,
domperidone exerts effects in the parts of the CNS
that lack this barrier, such as those regulating emesis,
temperature, and prolactin release.
- As is the case with metoclopramide, domperidone
does not appear to have any significant effects on
lower GI motility
Antiemetik
 Klorpromazin tab sal 25 mg, injeksi 5
mg/mL (im), injeksi 25 mg/mL (im)
 Metoklopramid tab 5 mg, tab 10 mg, syr
5 mg/5 mL, drops 2 mg/mL, injeksi 5
mg/mL
 ondansetron tab 4 mg, tab 8 mg, injeksi
2 mg/mL
- Indikasi ondansetron : tab pencegahan
muah dan muntah pd kemoterapi dan
radioterapi, injeksi idem tab yang highly
emetogenik
Antiemetik
 Metoclopramide and domperidone are dopamine D 2 -
receptor antagonists.
 Within the gastrointestinal tract activation of
dopamine receptors inhibits cholinergic smooth
muscle stimulation; blockade of this effect is believed to
be the primary prokinetic mechanism of action of
these agents.
 These agents increase esophageal peristaltic amplitude,
increase lower esophageal sphincter pressure, and
enhance gastric emptying but have no effect on small
intestine or colonic motility.
 Metoclopramide and domperidone also block
dopamine D 2 receptors in the chemoreceptor trigger
zone of the medulla (area postrema), resulting in
potent antinausea and antiemetic action
 Antiemetik
 The most common adverse effects of
metoclopramide involve the central nervous system.
Restlessness, drowsiness, insomnia, anxiety, and
agitation occur in 10–20% of patients, especially the
elderly.
 Extrapyramidal effects (dystonias, akathisia,
parkinsonian features) due to central dopamine
receptor blockade occur acutely in 25% of patients
given high doses and in 5% of patients receiving
longterm therapy.
 Tardive dyskinesia, sometimes irreversible, has
developed in patients treated for a prolonged period
with metoclopramide.
Antiemetik
 For this reason, long-term use should be
avoided unless absolutely necessary,
especially in the elderly.
 Elevated prolactin levels (caused by both
metoclopramide and domperidone) can
cause galactorrhea, gynecomastia, impotence,
and menstrual disorders.
 Domperidone is extremely well tolerated.
Because it does not cross the blood-brain
barrier to a significant degree,
neuropsychiatric and extrapyramidal effects
are rare
Simeticone
 Simethicone is an inert, non-toxic insoluble liquid.
 Because of its ability to collapse bubbles by forming a
thin layer on their surface, it is an effective anti-foaming
agent. Although it may be effective in diminishing gas
volumes in the GI tract, it is not clear whether this
accomplishes a therapeutic effect.
 Simethicone is available in chewable tablets, liquid-filled
capsules, suspensions, and orally disintegrating strips,
either by itself or in combination with other overthe-
counter medications including antacids and other
digestants.
 The usual dosage in adults is 40-25 mg four times daily.
Activated charcoal may also be used alone or in
combination with simethicone, but has not been shown
conclusively to have much benefit
Antiemetik
Antihemoroid
 Kombinasi bx supositoria anal : bismut
subgalat, heksaklorofen lidokain, seng
oksida,
 Produk lain :
- Baca MIMS/ISO
Antispasmodik
 Atropin tab 0,5 mg, injeksi 0,25 mg/mL
(im,iv,sc)
 hiosina butilbromid tab 10 mg, injeksi 20
mg/mL
Obat diare
 Atapulgit tab
 garam oralit
 kaolin pektinkaolin 550mg+pektin
20mg
 Loperamid tab sal selaput 2 mgtidak
untuk anak-anak
 Zinc tab dispersal 20 mg, syr 20mg/5mL,
serb 10 mgdiberikan bersama oralit
selama 10 hari
 Obat diare
 Pharmacotherapy of diarrhea in adults should be reserved
for patients with significant or persistent symptoms.
 Nonspecific anti-diarrheal agents typically do not address
the underlying pathophysiology responsible for the diarrhea;
their principal utility is to provide symptomatic relief in
mild cases of acute diarrhea.
 Many of these agents act by decreasing intestinal motility
and should be avoided as much as possible in acute
diarrheal illnesses caused by invasive organisms.
 In such cases, these agents may mask the clinical picture,
delay clearance of organisms, and increase the risk of
systemic invasion by the infectious organisms; they also may
induce local complications such as toxic megacolon
 Obat diare
 Some of these agents also may bind bacterial toxins
and bile salts. Clays such as kaolin (a hydrated
aluminum silicate) and other silicates such as
attapulgite (magnesium aluminum disilicate;
DIASORB, others) bind water avidly (attapulgite
absorbs eight times its weight in water) and also may
bind enterotoxins.
 However, binding is not selective and may involve
other drugs and nutrients; hence these agents are
best avoided within 2-3 hours of taking other
medications.
 A mixture of kaolin and pectin (a plant
polysaccharide) is a popular over-the-counter
remedy (KAOPECTOLIN, others) and may provide
useful symptomatic relief of mild diarrhea
 Loperamid
 Loperamide (IMODIUM,IMODIUM A-D, others), a
piperidine butyramide derivative with μreceptor
activity, is an orally active anti-diarrheal agent.
 The drug is 40-50 times more potent than
morphine as an anti-diarrheal agent and
penetrates the CNS poorly. It increases small
intestinal and mouth-to-cecum transit times.
 Loperamide also increases anal sphincter tone, an
effect that may be of therapeutic value in some
patients who suffer from anal incontinence.
Loperamid
 In addition, loperamide has anti-secretory
activity against cholera toxin and some
forms of Escherichia colitoxin, presumably
by acting on Gi-linked receptors and
countering the increase in cellular cyclic
AMP generated in response to the toxins
 Overdosage, however, can result in CNS
depression (especially in children) and
paralytic ileus.
Katartik
 Bisakodil tab sal 5 mg, susp 5 mg, supositoria
10 mg
 Gliserin drops 10mg/mL, cairan obat luar
100mg/mL
 Kombinasi : Parafin+gliserin+Fenoftalein
 Laktulosa syr 3,335 g/5mL
 natrium fosfat lar oral hanya untuk
colonoscopy
 polietilen glikol serbuk
Obat konstipasi/pencahar
 Pencahar rangsang : minyak jarak,
bisakodil, dll
 Pencahar garam : mg sulfat, Na sulfat, dll
 Pencahar pembentuk masa : metilselulosa,
agar
 Pencahar emolien : parafin cair, minyak
zaitun, dll
Obat konstipasi/pencahar
Obat konstipasi/pencahar
Lain-lain : asam ursodeoksikolat

 Cholic acid, chenodeoxycholic acid, and

deoxycholic acid constitute 95% of bile acids;
lithocholic acid and ursodeoxycholic acid are
minor constituents.
 Bile acids and their conjugates are essential
components of bile that are synthesized from
cholesterol in the liver.
Lain-lain : asam
ursodeoksikolat
 Bile acids were first used therapeutically
for gallstone dissolution; use for this
indication requires a functional gallbladder
because the modified bile must enter the
gallbladder to interact with gallstones. To
be amenable to dissolution, the gallstones
must be composed of cholesterol
monohydrate crystals and generally must
be <15 mm in diameter to provide a
favorable ratio of surface to size.
Lain-lain : asam
ursodeoksikolat
 For these reasons, the overall efficacy of
litholytic bile acids in the treatment of
gallstones has been disappointing (partial
dissolution occurs in 40-60% of patients
completing therapy and is complete in only
33-50% of these).
 Although a combination of chenodiol and
ursodiol probably is better than either agent
alone, ursodiol is preferred as a single agent
because of its greater efficacy and
lessfrequent side effects (e.g., hepatotoxicity)
Buku rujukan
 Formularium nasional tahun 2015
 FK UI, 2016. Farmakologi dan terapi.
Jakarta : departemen farmakologi dan
terapi FK UI
 Goodman & Gilman’s. 2011. The
Pharmacological Basis of Therapeutics.
twelfth edition. New York : Mc-Graw Hill
 Katzung, 2012. Basic and clinical
pharmacology. 12th edition. Mc-Graw Hill