Efta Triastuti & Ema Pristi Yunita Program Studi Sarjana Farmasi Jurusan Farmasi FKUB Understand how to determine therapy and evaluation algorithm for patients with peptic ulcer symptoms Able to identify desired therapeutic outcomes Able to educate the patients about the important of therapeutic adherence in H. pylori eradication Able to conduct the monitoring plan in patient with peptic ulcer medications Helicobacter pylori
Hypersecretion of HCl Gastric pain
Stomach Gastric bleeding
Korticosteroids
NSAIDs
Basal Maximal Acid Acid Output Output During the Response to fasting state meals
Cephalic Follows a phase of acid circadian cycle secretion
Highest at Gastric phase night & lowest of acid in the morning secretion
Modulated by acetylcholine & histamine acting
Symptoms Signs
Weight loss may be associated with Mild epigastric pain nausea and vomiting
Complications bleeding, perforation, Nocturnal pain or obstruction
Anemia, tarry stools (melena) or “coffee- The severity of pain often fluctuates grounds” emesis (hematemesis)
Pain often occurs 1 to 3 hours after meals Alarm signs!!! Heartburn, belching, nausea, or vomiting Direct Cyclooxygenase- Cyclooxygenase- Systemic irritation Independent Toxicity Dependent Toxicity pharmacologic actions
Reduction in Denudation gastroduodenal mucosal (penggundulan) of surface epithelial cells prostaglandin concentrations
Increased mucosal permeability to luminal contents
Reduction of the phospholipid content and surface hydrophobicity COX-1 COX-2 activity? activity?
Setiap NSAID memiliki indeks selektivitas terhadap enzim COX Selektivitas terhadap hambatan kedua enzim COX, baik COX-1 maupun COX-2 dapat diukur dengan menghitung rasio hambatan COX-2/COX-1 Apabila nilai rasio semakin kecil, maka aktivitas hambatan terhadap enzim COX-1 semakin kecil dan menghasilkan efek samping akibat hambatan COX-1 semakin kecil No. Obat NSAID Selektivitas No. Obat NSAID Selektivitas 1. Aspirin COX-1 = COX-2 13. Meloksikam COX-2 > COX-1 2. Diflunisal Tidak ada data 14. Nabumeton COX-2 = COX-1 3. Indometasin COX-1 > COX-2 15. Celecoxib COX-2 >> COX-1 4. Sulindak Tidak ada data 5. Etodolak COX-2 > COX-1 6. Asam mefenamat Tidak ada data 7. Diklofenak COX-2 >> COX-1 8. Ketorolak Tidak ada data 9. Ibuprofen COX-1 > COX-2 10. Naproksen COX-1 > COX-2 11. Ketoprofen Tidak ada data 12. Piroksikam COX-1 > COX-2
Definite Possible
•Prior PUD •H. Pylori infection •Prior GI ulcer •Cigarette smoking complication •Advanced agea •Concomitant use of corticosteroids, anticoagulants, & ethanol •Comorbid disease
a > 65 years old in some studies; > 75 years old in others Inhibits cyclooxygenase irreversibly acetylation of cyclooxygenase
Capacity for PG synthesis does not return to normal for several days, until new Potent inhibitors of enzyme can be thromboxane synthesized •gastric PG do not synthesis fully recover for approximately 5-8 •in the platelet, PG days synthesis does not return to normal for 14 days Potent inhibitors of prostaglandin synthesis Co-therapy with synthetic Co-therapy with PPIs Stop NSAID if ulcer has prostaglandin E1 (PGE1) formed analogue (Misoprostol) during NSAID use then treatment with H2RAs or PPIs There are no placebo-controlled studies evaluating whether PPIs can Reduces NSAID-induced prevent the complications of If NSAIDs cannot be discontinued serious GI adverse events NSAID-induced ulcers use of a PPI will allow ulcer healing, even while NSAID use continues COX-2 Specific Inhibitors Older and Safer NSAIDs Phospholipid NSAIDs
Phosphatidylcholine- celecoxib diclofenac NSAID product combination
rofecoxib Salsalate Invasive Non-invasive (endoscopy biospy (endoscopy not based) required) •Biopsy urease test •Urea breath test (e.g., CLO test) •Serology (IgG) •Histology •Urine antibody •Culture •Fecal antigen PPI b.i.d + clarithromycin 500 mg b.i.d + amoxicillin 1000 mg b.i.d or metronidazole 500 mg b.i.d for a minimum of 7 days
In case of failure PPI b.i.d + bismuth subsalicylate/subcitrate 120 mg q.i.d + metronidazole 500 mg t.i.d + tetracycline 500 mg q.i.d for a minimum of 7 days (If bismuth is not available, PPI-based triple therapies should be used) Subsequent failures
Handled on a case-by-case basis should be referred, and culture and sensitivities of H. pylori (may help select the proper regimen) Eradication success rate Regimen Days of treatment (%)
PBMT 7 85
PCM 7 84
PCA 7 82
PMA 7 76
BMT 14 80
PC 14 65
BMA 14 62
PA 14 58 P (PPIs); B (bismuth); M (metronidazole); T (tetracycline); C (clarithromycin); A (amoxicillin)
Meta-analysis of H. pylori eradication regimens (119 studies, 6416 patients). Modi®ed from Taylor et al. (1997) Resolve symptoms
Reduce acid secretion
Promote epithelial healing
Prevent ulcer-related complications
Prevent ulcer recurrence
Eradication of HP* Avoid Avoid alcohol smoking consumption
Avoid Avoid stress NSAIDs
Avoid food & Vagotomy beverages exacerbate ulcer
Drug Common Side Effects Contraindications Considerations Cimetidine • Headache Hypersensitivity to Cimetidine reduces • Dizziness cimetidine metabolism of • Arthralgia certain drugs • Myalgia (theophylline, • Constipation warfarin, phenytoin, • Diarrhea lidocaine, & • Gynecomastia quinidine) • Galactorrhea • Loss of libido Ranitidine • Headache Hypersensitivity to Ranitidine can be Famotidine • Dizziness ranitidine or given IV to treat • Arthralgia famotidine patients who are not • Myalgia able to tolerate the • Constipation oral formulation • Diarrhea
Drug Common Side Effects Contraindications Considerations Omeprazole • Headache Hypersensitivity to • Drug interaction Esomeprazole • Diarrhea omeprazole, with ketoconazole Lansoprazole • Rash esomeprazole, or itraconazole due Pantoprazole • Gastrointestinal lansoprazole, or to the acid discomfort pantoprazole environment • Anorexia required for • Back pain absorption of these azole drugs • Pantoprazole can be given IV in patients who are not able to tolerate oral pantoprazole Drug Common Side Effects Contraindications Considerations Aluminum hydroxide • Constipation Hypersensitivity to All antacids can • Osteomalacia in aluminum hydroxide potentially ↑ or ↓ the patients with renal rate or extent of failure absorption of Magnesium • Diarrhea Hypersensitivity to concurrently hydroxide • Hypermagnesemia magnesium administered oral (in patients with hydroxide drugs by changing renal failure) transit time or by binding the drug Sodium bicarbonate • Abdominal cramps • Respiratory • Flatulence alkalosis • Alkalosis • Hypocalcemia • Vomiting • Hypochloremia Calcium carbonate • Hypercalcemia Severe renal • Nausea insufficiency • Vomiting • Anorexia Drug Common Side Effects Contraindications Considerations Sucralfate • Constipation Hypersensitivity to Decreased sucralfate effectiveness of quinolones (e.g., ciprofloxacin) because of chelation and decreased absorption Colloidal bismuth • Darkening of the Known allergy to Reduces absorption tongue and/or stool aspirin or other of tetracyclines, likely • Nausea nonaspirin salicylates through chelation or • Vomiting by reducing solubility as a result of increasing gastric pH Drug Common Side Effects Contraindications Considerations Misoprostol • Gastrointestinal Pregnancy Cytoprotective effects disturbance mediated by ↑ gastric mucus and bicarbonate production Drug Common Side Effects Contraindications Considerations Dicyclomine • Dry mouth • Age less than 6 Not as effective as • Blurred vision months H2RAs or PPIs for the • Tachycardia • Breastfeeding treatment of PUD • Urinary retention • Gastrointestinal • Constipation obstruction • Glaucoma Eradication therapy with a PPI-based 3-drug regimen should be considered for all patients who test positive for HP (decrease recurrent)
Different antibiotics should be used if a second course of HP eradication therapy is required
Selective COX-2 inhibitors have not been shown to be any more effective than the combination of PPI and a non-selective NSAID in reducing the incidence of ulcers, and questions remain regarding their long-term cardiovascular safety Obtain
CBC baseline
Creatinin serum baseline
Patients history of symptom
Alarm signs development
Potential drug interaction