Selamat

Datang
Peserta
Lokakarya
 Paulus Kurnia
Bagian Farmakologi FKUH
UNIVERSITAS HASANUDDIN
ANATOMI SALURAN
CERNA
MEKANISME SEKRESI
ASAM LAMBUNG
HISTOLOGI LAMBUNG
Faktor Faktor
FaktorDefensif
FaktorAgresif
Agresif Defensif
Ulcus Pepticum
Ketidakseimbangan antara faktor AGRESIF &
DEFENSIF

Faktor Defensif Faktor Agresif

-Mukus - Asam lambung
-Bicarbonate - H Pylori
-Aliran darah - OAINS
-Prostaglandin - Merokok
- Nitric oxide
Kelompok Obat Ulcus
Pepticum
1. Antasida
2. H2-Receptor Antagonists (Ranitidin)
3. Proton Pump Inhibitors (Omeprazole)
4. M1 Blocker (Pirenzipine)
5. PGE1 Analogs (Misoprostol)
6. Cytoprotectans ( Sucralfate)
7. Antibiotics (Triple combination)
1. Antasida
Sodium bicarbonate
CaCO3
Al3+ hydroxides
Mg2+ hydroxide
Mg Trisilicate
 Antasida

Diberikan oral 1-3 jam setelah makan /

sebelum makan
Preparat Mg+2 meningkatkan motilitas usus
(laksatif)
ES : Diare
Preparat Al+3 merelaksasi otot polos usus
ES : Konstipasi
Preparat Ca+2 menghasilkan gas CO2
ES : perut kembung, mual, flatulence,acid
rebound, konstipasi
Efek Samping
Toksisitas Aluminum yang berhub.
dengan Peny.Ginjal
Osteoporosis, enchephalopathy, myopathy
Hypercalcemia
Phosphate retention
Calcium precipitation in the kidney
Mengganggu absorpsi beberapa obat
Take 2 hrs before or after other drugs
2.H2RAs
Menghambat secara kompetitif dan
reversibel terhadap reseptor H2 yang
terdapat pada membran sel parietal
basolateral lambung
Kurang potent dibandingkan PPIs tetapi
tetap menekan asam lambung 70% dalam
waktu 24 Jam
As
H2 receptor blockers

Cimetidine (200 ; 400 mg)

H2-blocker I yg tersedia
Menghambat enzim P450 =>
Interaksi obat
Ranitidine (150 ; 300 mg)
Enzim P450 => Efek smping
minimal
Nizatidine (300 mg)
Famotidine ( 20 ; 40 mg )
 Farmakokineti
kdiabsorpsi
Cepat : setelah pemberian
Konsentrasi serum mencapai puncak 1-3 jam
Level Terapeutik dipertahankan sampai 12 jam
Ikatan protein plasmanya hanya 20 %
Dimetabolisme di hati 10% s/d 35 %
Obat dan metabolitx diekskresikan oleh ginjal
(**kurangi dosis pada gangguan faal ginjal)
Efek Samping H2RAs
All less than 3%
Diarrhea
Headache
Drowsiness
Fatigue
Muscular pain
Constipation
Much less common
Confusion, delirium in the elderly
Associated with thrombocytopenia
Cimetidine anti-androgen effects
 3.PPIs
Penekan sekresi asam lambung yang paling poten
Efek penekan asam bekerja 24-48 Jam
Penghambat pompa proton Irreversibel, memblokade
98% sekresi asam pada berbagai bentuk ulkus dan
sindroma zollinger-Ellison hipersekresi.
Obat ini diberikan dalam bentuk kapsul yang dilapisi
gelatin, untuk mencegah pemecahan oleh asam
lambung, sehingga bisa mencapai usus halus, absorpsi
baik, mencapai peredaran darah dan bisa sampai ke sel
parietal.
 PPIs
Penghambat secara ireversibel
H+/K+ATPase dengan tujuan :
Blok sekresi asam lambung
Menurunkan konsentrasi Pepsin
Meningkatkan pH gastric

Sekresi asam hanya bisa tercapai bila

pompa proton baru ada
Steady-state inhibition (affecting 70% of
pumps) bisa sampai 2 5 hari
Farmakologi PPI
Obat bekerja ketika pH dibawah 4
setelah diabsorpsi,masuk ke sirkulasi
sistemik,kmdn akan berdifusi ke sel parietal
lambung
Biovailabilitas menurun dengan makanan
Sangat efektif bekerja setelah puasa lama ketika
sejumlah pompa proton aktif (mis : ketika seblum
sarapan)
 Sediaan PPI yg Ada
saat ini
Esomeprazole 20;40mg (1x1)
Lansoprazole 15;30 mg(1x1)
Omeprazole 10 mg; 20 mg (1x1)
Pantoprazole 20;40 mg (1x1)
Rabeprazole 10; 20 mg (1x1)
Metabolisme PPI
Cepat diserap
Ikatan protein kuat
Dimetabolisme dihati oleh sitokrom P450
(CYP2C19 and CYP3A4)
Sisa metabolites sulfat diekskresikan
lewat feces dan urin
Penyakit hati mengurangi clearance dari
lansoprazole( kurangi dosis )
 Menghambat reseptor kolinergik
muskarinik selektif di reseptor M1 di
lambung
Bisa menghambat produksi asam
basal 40 50 %
Afinitas sgt rendah pd reseptor di otot
jantung& otot polos
Dosis 50 mg (2x1)
Sediaan 25 mg/tab
Jarang digunakan sekarang
5. PGE1 Analogs ( Misoprostol)
PGE2,1 and PGI2 Disintesis mukosa lambung
Acid-reducing effects
Bind to EP3 receptors on parietal cells
Decrease acid production
Efek sitoprotective
Stimulation of mucin and bicarbonate
Increase mucosal blood flow
Contrast with NSAIDS which diminish prostaglan
formation by inhibition of cycloxygenase and lea
ulcer formation
Farmakokinetik
Cepat diserap
Efek terapeutik mencapai puncak dalam
waktu 60-90 minutes
Bertahan hanya sampai 3 jam (qid dose
required)
Samping :
Diarrhea abdominal cramps as high as
30%
Begins within 2 weeks and often resolves
spontaneously in 1 week
Can exacerbate inflammatory bowel
disease
Contraindicated during pregnancy
trimester 1 (uterotrofik)
Dosis :
Misoprostol 200 microgram (4x1)
Terutama sebagai profilakasis tukak peptik
pada pasien beresiko tinggi (lansia, Nsaid
induced)
6.Cytoprotectans
(Sucralfate)
Sulfated polysaccharide
Acid activated (pH 4)
Administered on an empty stomach 1 hr
before meals
Stimulates local prostaglandin synthesis,
adsorbs pepsin
Binds bile acids
Not absorbed => essentially free of side
effects
Indikasi dan Dosis
Tukak lambung dan duodenum
1 gr 4x sehari 1 jam sebelum makan
 Efek Samping

Constipation (2 %)
Avoid in renal failure
May impair absorption of other drugs (inhibit
absorption phenytoin, digoxin, cimetidine,
ketoconazole, fluroquinolone antibiotics)
 7. Antibiotic for Peptic Ulcer
Antibiotic ulcer therapy:
Combinations must be used:
-Bismuth disrupts cell wall of H. pylori
-Clarithromycin inhibits protein synthesis
-Amoxicillin disrupts cell wall
-Tetracyclin inhibits protein synthesis
-Metronidazole used often due to bacterial resistance to
amoxicillin and tetracyclin, or due to intolerance by
the patient

Standard treatment regimen for peptic ulcer:

PPI + Clarithromycin 500 mg + Amoxicilln 500 mg
Terima Kasih
Constipation
Abnormally infrequent and difficult passage of
feces through the lower GI tract
Symptom, not a disease
Disorder of movement through the colon
and/or rectum
Can be caused by many diseases
or
drugs(opium,anticholinergics,antacid,clonidine
)
Laxatives:
Mechanism
Bulk forming of Action
High fiber
Absorbs water to increase bulk
Distends bowel to initiate reflex bowel activity
Examples:
psyllium (plantago)
methylcellulose
Calsium polycarbophil
Agar(hydrophilic colloid)
Laxatives:
Mechanism
Emollient
of Action
Stool softeners and lubricants
Promote more water and fat in the stools
Lubricate the fecal material and intestinal
walls
Examples:
Dioktilnatrium sulfosuksinat
Parafin cair
Minyak zaitun
 Laxatives:
Mechanism
Stimulant cathartics
of Action
Increases peristalsis via intestinal
nerve stimulation
Examples:
minyak jarak
sena
cascara
bisacodyl
fenolftalein
Laxatives: Side Effects
Bulk forming
Impaction
Fluid overload
Emollient
Skin rashes
Decreased absorption of vitamin
Stimulant
Nutrient malabsorption
Skin rashes
Gastric irritation
Rectal irritation
Antidiarrheals
Causes of Diarrhea
Acute Diarrhea Chronic Diarrhea
Bacterial Tumors
Viral Diabetes
Drug induced Hyperthyroidism
Nutritional/Alergy Irritable bowel
Protozoal syndrome
Food Intoxication Psychogenic
Antidiarrheals
Drugs that decrease peristalsis,
thereby allowing fluid absorption from
the intestinal contents
Examples:
Anticholinergics
Protectants/adsorbents
Opiate-related agents
Probiotics
Antibiotics
Antidiarrheals
Anticholinergics are used to treat tenemus
and vomiting
Examples:
Atropine
Ekst Belladona

Hiosin N - butilbromida

Propantheline bromida

Scopolamin metil - bromida

Side effects include dry mucous

membranes, urine retention, tachycardia,
and constipation
Antidiarrheals
Protectants/adsorbents coat inflamed
intestinal mucosa with a protective layer
(protectants) or bind bacteria and/or digestive
enzymes and/or toxins to protect intestinal
mucosa from damaging effects (adsorbents)
Examples:
Bismuth subsalicylate (bismuth + aspirin-like
product)
Kaolin/pectin

Attapulgite

simethicone

Side effects include constipation

Antidiarrheals
Opiate-related agents control diarrhea.
MOA : effects on intestinal motility (
receptors), intestinal secretion (
receptors), or absorption ( & receptors)
Examples:
Diphenoxylate
Loperamide

Side effects include CNS depression, ileus,

urine retention, bloat, and constipation
SP: < 2years, pregnancy, lactation
Antidiarrheals
Probiotics seed the GI tract with beneficial
bacteria; use is based on the theory that
some forms of diarrhea are caused by
disruption of the normal bacterial flora of
the GI tract
Must be refrigerated to maintain the
viability of the bacteria
Examples:
Plain yogurt with active cultures
Variety of trade-name products Eg : L-Bio, Bio GI,

Lacbon
Antibiotic
A theory regarding the development of
diarrhea is that anaerobic bacteria may
increase due to disruption of normal GI
flora
One way to treat this is to use an
antibiotic effective against anaerobic
bacteria
Metronidazole is an example of an
antibiotic used to treat diarrhea.
GIT Regulator
Antagonist dopamine:(cholinergic effect)
-metoclopramide
-domperidone
Cholinomimetic indirect: cisapride
 Antibiotic
Quinolone
Chloramphenicol
Tetracycline
Cotrimoxazole
Metronidazole
 Antiviral
Lamivudine
Adefovir dipivoxil
Telbivudine
Interferon/pegylated interferon
kasus
1. Seorang wanita, 26 tahun, karyawati, belum
menikah, datang dengan keluhan nyeri ulu hati
yang hilang timbul sejak 5 hari yg lalu. Juga
disertai rasa mual,, kadang sendawa, kembung
dan nanfsu makan berkurang. Keluhan tersebut
dirasakan baik pada waktu perut kosong
maupun setelah makan. PF : KU baik, semua :
dbn, kec adanya nyeri tekan epigastrium.
Bila saudara memilik terapi empirik, obat apa
saja yang akan saudara berikan?tuliskan
resepx1