FARMAKOTERAPI GANGGUAN / PENYAKIT GASTROINTESTINAL : OBAT ANTI ULCUS

Oleh Wiwik Kusumawati

 Apakah penyakit atau gangguan pada

saluran cerna ?
Apa obatnya (farmakoterapi) untuk

penyakit atau gangguan tersebut ?

Tujuan
Pada akhir pembelajaran mahasiswa akan dapat
1.

2.
3. 4.

5.

Menjelaskan prinsip farmakoterapi penyakit ulkus peptik Menyebutkan penggolongan obat antiulkus Menjelaskan mekanisme aksi obat antiulkus Menjelaskan efek samping obat antiulkus Menentukan pemilihan obat anti ulkus yang tepat pada px dg ulkus peptikum

CASE

A 62 years old man who present to the emergency department on Sunday evening complaining of intermittent burning epigastric pain for more than 2 months. His pain is not radiating and occurs to the right of his epigastrium. This pain change in intensity and is worse with meals. He also has noticed intermittent belching, being bloated, being weak when walking, and complains of nausea after eating. Since last Friday, he has been having black, tarry bowel movements. He does not have any history of PUD or GI bleeding and has not experienced anorexia or vomiting.

Pendahuluan
Pemberian obat Per Oral (PO) Efek samping obat PO :

Erosi lambung/gastriris (40-50 %) Ulkus (10-25 %) Diare

Ulkus peptikum
Penyakit dengan dampak kerusakan pada

mukosa sampai tunika muskularis saluran cerna Ulkus duodenum (duodenal ulcer) Ulkus lambung (gastric ulcer)

Etiologi ulkus peptikum

Infeksi helicobacter pylori (80 % - 95 %) Ketidakseimbangan faktor agresif

(ulserogenik) dan faktor defensif (protektif) Efek samping NSAIDs

Al-Baqarqh (168) & Al-A`Raf (160)

Hai manusia makanlah apa-apa yang ada di

bumi yang halal lagi baik.

..makanlah yang baik-baik, di antara

rizki yang Kami anugerahkan kapadamu.

Obat anti ulkus

Antacid dan antisekretori Obat sitoprotektif Kombinasi

Antacid
Bufer mukosa Menurunkan PH lambung dengan

menetralisir asam lambung Efek samping diare Aluminium hidroksida dan magnesium karbonat (efektif untuk ulkus duodenum)

Antisekretori
Antagonis reseptor H2 (cimetidin, ranitidin,

famotidin, dll) Antagonis reseptor muskarinik/M1 (piranzepin) Inhibitor pompa proton (omeprazole)

Antagonis reseptor H2
Efektif menghambat sekresi asam lambung

karena histamin, makanan, pentagastrin, insulin, dll Efektif untuk ulkus lambung maupun duodenum (ranitidin) PO atau IV Ikatan dengan sitokrom P450

CIMETIDIN

RANITIDIN

efektif untuk terapi ulkus lambung dan duodenum efek samping: pusing, mual, muntah, kemerahan. Impotensi, gynecomasti

inhibitor poten sekresi asam lambung lebih aktif 5-8x durasi lebih lama ikatan sitokromP450 kurang reseptor androgenik kurang efektif profilaksis u.duodenum (NSAIDs)

 Dosis :

Cimetidin 400 mg 2x/hari atau 800 mg/malam Ranitidin 150 mg 2x/hari atau 300 mg/malam
Lama terapi 4-8 minggu

Piranzepin
Antagonis reseptor M1 (efek samping) Efektif untuk terapi dan preventif ulkus

duodenum rekuren Kurang dapat diterima dibandingkan H2 antagonis Dosis 50 mg 2x/hari atau 100 mg /malam (4-6 minggu)

Omeprazole
Inhibitor pompa proton Menghambat enzim H+/ K+ ATPase Potensi lebih besar dibandingkan H2

antagonis (respon 2 minggu = 4 minggu H2 antagonis) Penyembuhan ulkus duodenum lebih cepat

 Monoterapi dapat menekan H pylori Kombinasi dengan antibiotik dapat untuk

eradikasi H pylori Efek samping diare, headache, nausea, dll Dosis 20-40 mg / pagi (2-8 minggu)

Obat sitoprotektif
Prostaglandin analog (misoprostole) Sukralfat Senyawa bismuth

Misoprostole
Analog prostaglandin Efektivitas sebanding dengan H2 antagonis Efek sitoprotektif pada dosis rendah Efek samping kolik, nausea, diare,

dispepsia, headache, perdarahan uterus Kontra indikasi ibu hamil Dosis 200 mikrogram 4x/hari (4-8 minggu)

Lumen stomach

Mucus Parietal cell Vagus

H+
K+
Cl-

K+
cAMP M1 Paracrine cell

ClATP

H2

Histamine

G-cells

Eradikasi Infeksi H pylori

* Bismuth chelate * Amoxycillin Metronidazole 70-80 % 2 minggu
Omeprazole Clarithromycin Metronidazole

95-100 %
1 minggu

Eradikasi Infeksi H pylori (revisi, Neal, 2005)

Omeprazole Clarithromycin Amoxicillin Kesembuhan pd 90 % px 1 minggu

An Aspirin Tablet and a Gastric Ulcer, 2000

A 76-year-old woman had iron-deficiency anemia, a hematocrit of 24 percent, and a positive test for occult blood in stool. For several years, she had been taking 400 mg of etodolac twice a day for rheumatoid arthritis; one tablet of enteric-coated, regularstrength aspirin a day; and 1 mg of warfarin sodium a day for severe peripheral vascular disease. Her international normalized ratio was 1.15. After receiving a transfusion, she underwent upper gastrointestinal endoscopy, which revealed an aspirin tablet, with the enteric coating still intact, within an ulcer of the gastric antrum. The tablet was removed with a forceps. Treatment with etodolac and aspirin was stopped, and the patient was given 30 mg of lansoprazole twice a day. Two months later, a second endoscopic examination showed complete healing of the ulcer.

A Comparison of Omeprazole with Ranitidine for Ulcers Associated with Nonsteroidal Antiinflammatory Drugs,1998

Background Suppressing acid secretion is thought to reduce the risk of ulcers associated with regular use of nonsteroidal antiinflammatory drugs (NSAIDs), but the best means of accomplishing this is uncertain. Methods We studied 541 patients who required continuous treatment with NSAIDs and who had ulcers or more than 10 erosions in either the stomach or duodenum. Patients were randomly assigned to doubleblind treatment with omeprazole, 20 mg or 40 mg orally per day, or ranitidine, 150 mg orally twice a day, for four or eight weeks, depending on when treatment was successful (defined as the resolution of ulcer and the presence of fewer than five erosions in the stomach and fewer than five erosions in the duodenum, and not more than mild dyspepsia). We randomly assigned 432

A Comparison of Omeprazole with Ranitidine for Ulcers Associated with Nonsteroidal Antiinflammatory Drugs

Results At eight weeks, treatment was successful in 80 percent (140 of 174) of the patients in the group given 20 mg of omeprazole per day, 79 percent (148 of 187) of those given 40 mg of omeprazole per day, and 63 percent (110 of 174) of those given ranitidine (P<0.001 for the comparison with 20 mg of omeprazole and P = 0.001 for the comparison with 40 mg of omeprazole). The rates of healing of all types of lesions were higher with omeprazole than with ranitidine. During maintenance therapy, the estimated proportion of patients in remission at the end of six months was 72 percent in the omeprazole group and 59 percent in the ranitidine group. The rates of adverse events were similar between groups during both phases. Both medications were well tolerated.

A Comparison of Omeprazole with Ranitidine for Ulcers Associated with Nonsteroidal Antiinflammatory Drugs

Conclusions In patients who use NSAIDs regularly, omeprazole healed and prevented ulcers more effectively than did ranitidine.

Preventing Recurrent Upper Gastrointestinal Bleeding in Patients with Helicobacter pylori Infection Who Are Taking Low-Dose Aspirin or Naproxen,2001
Background

Many patients who have had upper gastrointestinal bleeding continue to take low-dose aspirin for cardiovascular prophylaxis or other nonsteroidal antiinflammatory drugs (NSAIDs) for musculoskeletal pain. It is uncertain whether infection with Helicobacter pylori is a risk factor for bleeding in such patients.

Preventing Recurrent Upper Gastrointestinal Bleeding in Patients with Helicobacter pylori Infection Who Are Taking Low-Dose Aspirin or Naproxen,2001

Methods We studied patients with a history of upper gastrointestinal bleeding who were infected with H. pylori and who were taking lowdose aspirin or other NSAIDs. We evaluated whether eradication of the infection or omeprazole treatment was more effective in preventing recurrent bleeding. We recruited patients who presented with upper gastrointestinal bleeding that was confirmed by endoscopy. Their ulcers were healed by daily treatment with 20 mg of omeprazole for eight weeks or longer. Then, those who had been taking aspirin were given 80 mg of aspirin daily, and those who had been taking other NSAIDs were given 500 mg of naproxen twice daily for six months. The patients in each group were then randomly assigned separately to receive 20 mg of omeprazole daily for six months or one week of eradication therapy, consisting of 120 mg of bismuth subcitrate, 500 mg of tetracycline, and 400 mg of metronidazole, all given four times daily, followed by placebo for six months.

Preventing Recurrent Upper Gastrointestinal Bleeding in Patients with Helicobacter pylori Infection Who Are Taking Low-Dose Aspirin or Naproxen, 2001

Results We enrolled 400 patients (250 of whom were taking aspirin and 150 of whom were taking other NSAIDs). Among those taking aspirin, the probability of recurrent bleeding during the six-month period was 1.9 percent for patients who received eradication therapy and 0.9 percent for patients who received omeprazole (absolute difference, 1.0 percent; 95 percent confidence interval for the difference, 1.9 to 3.9 percent). Among users of other NSAIDs, the probability of recurrent bleeding was 18.8 percent for patients receiving eradication therapy and 4.4 percent for those treated with omeprazole (absolute difference, 14.4 percent; 95 percent confidence interval for the difference, 4.4 to 24.4 percent; P=0.005).

Preventing Recurrent Upper Gastrointestinal Bleeding in Patients with Helicobacter pylori Infection Who Are Taking Low-Dose Aspirin or Naproxen, 2001

Conclusions Among patients with H. pylori infection and a history of upper gastrointestinal bleeding who are taking low-dose aspirin, the eradication of H. pylori is equivalent to treatment with omeprazole in preventing recurrent bleeding. Omeprazole is superior to the eradication of H. pylori in preventing recurrent bleeding in patients who are taking other NSAIDs, such as naproxen.

Helicobacter pylori Infection and the Development of Gastric Cancer, 2001

Conclusions Gastric cancer develops in persons infected with H. pylori but not in uninfected persons. Those with histologic findings of severe gastric atrophy, corpuspredominant gastritis, or intestinal metaplasia are at increased risk. Persons with H. pylori infection and nonulcer dyspepsia, gastric ulcers, or gastric hyperplastic polyps are also at risk, but those with duodenal ulcers are not.

Helicobacter pylori Infection and the Development of Gastric Cancer, 2002

The authors enrolled 1526 patients, of whom 1246 had H. pylori infection. Of the H. pyloripositive patients, 297 had gastric ulcers and 275 had duodenal ulcers. Hence, 572 patients had a condition for which treatment to eradicate the H. pylori infection is indicated. The remaining H. pyloripositive patients had gastric polyps and nonulcer dyspepsia, conditions for which eradication treatment is not currently indicated. Eradication treatment was administered to 253 patients, but the authors do not specify whether these patients were among the 572 who had gastric ulcers or duodenal ulcers. Assuming that they were, there remained at least 319 patients who had a clinical indication for eradication therapy yet did not receive this treatment. More important, it appears that these remaining patients were not offered this therapy.

Helicobacter pylori Infection and the Development of Gastric Cancer, 2002

No gastric cancer developed after the eradication of H. pylori in the 253 infected patients who received this treatment. Therefore, at least 319 patients were exposed to an increased risk of gastric cancer even though they had an indication for eradication therapy that, if successful, would have eliminated the risk.

Komplikasi
Faktor host Lokasi ulkus Komplikasi

Tx Komplikasi

U duodenum

U lambung
Tx obat gagal, operasi/reseksi

Omeprazole Sucralfat

Profilaksis
Antagonis H-2 1/2 dosis Sucralfat 1 g 2x/hr Indikasi:

px kumat-kumatan, ada komplikasi tidak perlu reseksi

Asy-Syura (78-80)
Allah yang menciptakan saya dan Dia pula

yang memberi petunjuk, memberi makan dan minum dan bila saya sakit Dia yang menyembuhkan saya.

Wassalamualaikum wr.wb.