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Transcript of Gastro 2012
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ANISYAH ACHMAD, S.Si., Apt., Sp.FRSDepartement of Clinical Pharmacy, Major of Pharmacy,
FKIK- UNSOED
GASTROENTEROLOGY
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Meliputi : 1. Mulut + Kelenjar Saliva2. Pharynx3. Esophagus 4. Lambung5. Usus Halus (Duodenum,jejunum,ileum)6. Colon – Sigmoid – Rectum – Anus 7. Pancreas (Fungsi Eksokrin)8. Hepar9. Kandung Empedu
ORGAN SISTEM PENCERNAAN
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Hormon pencernaan
1. H.Gastrin : ~ disekresi di antrum (sel G) ~ rangs sekresi : - bila ada makanan masuk lambung ( t.u daging) - asetilkolin, parasimpatis, vagus - regangan dinding lambung
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Effek Gastrin Merangsang 1. Peningkatan gerak lambung2. Pengosongan lambung3. Relaksasi sfingter ileosekal4. Gerak mass5. Sekresi getah lambung6. Sekresi getah pankreas
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Hormon Sekretin
~ sekresi di duodenum (sel S)~ rangs sekresi : bila isi duodenum asam~ effek : - menghambat pengosongan lambung - menghambat gerak usus - merangs sekresi elektrolit pankreas - merangs sekresi getah empedu
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LAMBUNG
Fungsi : 1. Tempat menyimpan makanan2. Tempat mencampur makanan dg getah lambung chyme3. Tempat mengosongkan makanan 4. Mencegah masuknya sebagian kuman 5. Tempat absorbsi alkohol + obat-obatan
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Getah lambung
- 1,5 – 2 liter / hari ( pH 1,5 – 3,4 ) - mengandung: 1. Elektrolit : H+, Cl, K+, Na+ 2. Mucus : sel mucus - melindungi mukosa (penderita gastritis : Tx antasida) 3. Lipase dan Amilase : sedikit sekali
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4. Enzim Pepsin
di sekresi : sel utama (Chief Cell)
Pepsinogen pepsinHCL ( pH : 1,5 – 3,5)
Protein (terutama daging) polipeptidapepsin
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5. Rennin - Hanya pada masa bayi
- menggumpalkan susu
Casein susu para casein
Rennin + Ca pepsin
6. Faktor intrinsik - disekresi oleh sel parietal - membantu absorbsi vit B12
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7. Histamin - reseptor H2 merangs sekresi HCl (gastritis : obat H2 Bloker - cimetidine)
8. HCL - disekresi : sel parietal Ion H+ dipompa ke lumen canaliculi (pompa proton) Terapi gastritis :
obat gol Proton Pump Inhibitor (PPI)
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Faktor perangsang sekresi lambung :
- Asetilkolin / parasimpatis / vagus - Hormon Gastrin - Asam amino, alcohol, nikotin, kafein- Stress emosi
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Fase Sekresi- Fase cephalic- Fase gastric- Fase intestinal
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GIT DISEASE
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Gastroesophageal reflux
• Reflux of gastric contents into the esophagus• Heartburn, substernal pain, burning sensation• Predisposing factors: alcohol, smoking,
pregnancy• May lead to: esophagitis, strictures, Barrett
esophagus
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Barrett esophagus
• Normal epithelium: squamous type• Barrett: becomes columnar with many Goblet
cells• Precursor for adenocarcinoma of the
esophagus
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Barrett esophagus
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Barrett esophagus
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Cancer of the esophagus
• Most frequent type: squamous cell carcinoma• Dysphagia, weight loss, anorexia• Upper and middle thirds of the esophagus• Adenocarcinoma type : lower third of the
esophagus
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Cancer of the esophagus
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Congenital pyloric stenosis
• Hypertrophy of the circular muscle layer of the pylorus
• Projectile vomiting in 1st 2 weeks of life
• Palpable mass
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Gastritis
• Acute gastritis• Causes:
NSAIDSsmokingalcholic drinksburns :
Curlings ulcerCushings ulcer
• Chronic gastritis• Chronic inflammation, atrophy of the mucosa• Helicobacter pylori gastritis: most common
form• Increases risk of gastric cancer
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Acute Gastritis
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Peptic ulcers
• Common locations:lesser curvatureantrumprepyloric areas
• Causes: H.pylori infection bile-induced gastritis
• Not a precursor lesion of carcinoma of the stomach
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Benign Gastric Ulcers
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Cancer of the Stomach
• Common: more than 50 years old, men, Blood group A
• Predisposing factors:H. pylori infectionNitrosaminesexcessive salt intakelow fresh fruits, vegetables dietachlorhydiachronic gastritis
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Cancer of the stomach• Most common type: adenocarcinoma• Rare in the fundus• Aggressive spread to adjacent organs• Virchow node: large supraclavicular node• Krukenberg tumors: bilateral, enlarged ovaries,
“signet ring” cells• Two types:• 1. intestinal type: fungating mass; ulcer with
irregular necrotic base and firm, raised margins• 2. infiltrating or diffuse type: linitis plastica
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Cancer of the stomach
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DRUG USED
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ANTACIDS SUCRALFATE
H2 RECEPTOR ANTAGONIST PROTON PUMP INHIBITOR
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1. Antacids2. H2 RA 3. Proton Pump
Inhibitor4. Sucralfat5. Antimicrobials
(Triple combination)
4
5
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ANTACIDS
Katzung, B.G., 2006. Basic and Clinical Pharmacology, 10thEd. New York: McGraw-Hill.
Commonly used in antacid products
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PHARMACODYNAMICS/KINETICS Onset of action: Paste formation and ulcer adhesion: 1-2 hours Duration : Up to 6 hours Absorption : Oral: <5% Distribution : Acts locally at ulcer sites; unbound in GI tract to aluminum and sucrose octasulfate Metabolism : None Excretion : Urine (small amounts as unchanged compounds)
Katzung, B.G., 2006. Basic and Clinical Pharmacology, 10thEd. New York: McGraw-Hill. Lacy, C.F., Armstrong, L., Goldman, M., Lance, L., 2006. Drug Information Handbook, 14th Edition, USA: Lexi-Comp’s.
SUCRALFAT
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• It works on pH less than 4 due to paste like formation
Neal, M.J., 2005. Medical Pharmacology At a Glance, Fifth Edition, Oxford: Blackwell Publishing Comp.
SUCRALFAT
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INTERACTIONS
• digoxin• fluoroquinolone
antibacterials• tetracycline• ketoconazole • levothyroxine • Phenytoin• quinidine • Theophylline• Warfarin
should be an interval of 2 hours before giving
sucralfate
AntacidH2RA
PPI
The recommended interval is 1 hour after sucralfate
(Anderson, 2007. Handbook clinical Drug Data)
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In patients with renal failure, aluminum may accumulate to toxic levels
the signs of aluminum toxicity :seizures, muscle weakness, bone pain, and severe aluminium
encephalopathy have been reported in patients with end-stage renal disease requiring dialysis
monitored for potential signs of aluminum toxicity
Hemstreet, 2001. Use of sucralfate in renal failure. The Annals of Pharmacotherapy: Vol. 35, No. 3, pp. 360-364);( Martindale, 2007); (Anderson, 2007. Handbook clinical Drug Data)
Precautions For[Al(OH)3) and Sucralfate]
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Cimetidine interferes with several Important hepatic cytochrome P450pathway.Ranitidine binds 4-10 times less to Cytochrome P450
H2 RECEPTOR ANTAGONIST
Katzung, B.G., 2006. Basic and Clinical Pharmacology, 10thEd. New York: McGraw-Hill.
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Katzung, B.G., 2006. Basic and Clinical Pharmacology, 10thEd. New York: McGraw-Hill.
effect
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CHARACTERISTIC CIMETIDINE RANITIDINE FAMOTIDINE NIZATIDINE
OoA 1 hour 1 hour 30 minutes
DoA 4-5 hours 8-12 hours 10-12 hours 8-12 hours
Bioavailability 60 20% 5525% 414% 955%75% in renal failure
Protein binding 206% 15% 16% 305%
Half-life 1.90.4hr 20.4hr 30.5hr 1.40.2hr
Excretion urine urine urine Urine
RENAL IMPAIRMENT
po iv po iv po iv po iv
ClCr > 50 ml/min 300 mg 6 h400 mg 6 h800 mg12 h
300 mg 6 h
300 mg 12 h
50 mg 12 h
20 mg 12 h40 mg 12 h
20 mg 300 mg 24 h
-
ClCr : 10-50 300 mg 8-12 h
300 mg 8-12 h
150 mg 24 h
50 mg 12-24 h
20 mg 24 h
20 mg 24 h
150 mg 24 h
-
ClCr < 10 300 mg 12 h
300 mg 12 h
150 mg 24 h
50 mg 24 h
20 mg 48 h
20 mg 48 h
150 mg 48 h
-
Hepatic impairment
No dosage adjustment is needed but monitor
COMPARISON OF H2 RECEPTOR ANTAGONIST AGENT
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• In renal impairment, H2RA agents need dose adjustment
• Cimetidin should be avoided to use, because it is highly bound to cytochrome P450
PRECAUTION
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H2RAinjection should be given over 30 minutes
or slow injection over 5 minutes
Rapid intravenous infusion may cause bradycardia and hypotension through blockade of cardiac H2 receptors; therefore, intravenousinjection should be given over 30 minutes
ADMINISTRATION
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proton pump inhibitorPROTON PUMP INHIBITOR
and feces
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Use of proton pump inhibitors and risk of osteoporosis related fractures
a retrospective, matched cohort study • Use of proton pump inhibitors for 7 or more years is associated with a significantly increased risk of an osteoporosis-related fracture.
• There is an increased risk of hip fracture after 5 or more years exposure.
Targownik, E., Lix, L.M., Metge, C.J., Prior H.J., Leung, S., Leslie, W.D. 2008. Use of proton pump inhibitors and risk of osteoporosis related Fractures. CAMJ. 179 (4); 319-26.
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Characteristic Omeprazole Lansoprazole Pantoprazole Rabeprazole Esomeprazole
OoA 1hr 1hr 1,75 hr 1,75 hr 1,5hr
DoA 72hr >1day >1 day 24 hours
Bioavailability 30-40% 80-85% 77% 52% 64%
Protein binding 95% 98% 97% 94,8-97,5% 97%
Half-life 0,5-1hr 1hr 2hr 1-2hr 1-1,5 hr
Excretion Urine(77%); feces
Urine (33%)Feces (67%)
Urine (71%);feces(18%)
Urine (90%); feces
Urine (80%); feces (20%)
Renal impairment No dosage adjustment is needed (no significant changes)
Hepatic impairment
No dosageAdjustmet is needed
Severe decreased dose (prolonged t½)
No dosageAdjustmet is needed
No dosageAdjustmet is needed
No dosageadjustment is needed For patients withsevere liverimpairment (ChildPugh class C), do notexceed a dose of 20mg.
Factors that affect absorption
Food Antacids food
none Food not studied
Food
Pharmacokinetic Non linear linear linear linear Non linear
PPI used 30-60 minutes before meals.
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Profile of Pharmacokinetics(linear and non-linear)
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• ivOmeprazol infusion diluted on100 ml in NaCl 0,9% or dextrose 5% in water administered 20-30 minute due to thrombophlebitis and abcess
• po- 30 minutes before meal.
- the tablet should not be chewed due to enteric coated formulation
ADMINISTRATION PPI
(AHFS Drug Information, 2007)
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ACID PEPTIC DRUG USE
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IN RENAL IMPAIRMENTIncrease the risk of osteoporosis (due to the risk of
osteodystrophy renal on patient with CKD)
Monitor the worsening of renal failure because PPI is drug induced of tubulo-interstitial nephritis (3%)
PRECAUTION FOR PPI
(Torpey N, nephrology dialysis transplantation (2004). P: 14441-1446)
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No Indication and possible etiology Use for Drug and Dose
1.. Dyspepsia- Peptic Ulcer- Gastroparesis(in DM)- Endoscopy, chronic
Helicobacter pylori
Upper abdominal or eoigastric symptom
-H2 reseptor Antagonis placebo (ranitidine, famotidine)-cicapride, metochlopramide, as prokinetic- PPI for Helicobacter pylori
2. GERD -Mild Intermitten symptom-Moderate symtoms-Severe or refractory symtomps
-Antacids are the mainstay for rapid relief of occasional heartburn. (Maalox, Mylanta)-H2 reseptor antagonis 2 x 1, or promotility agent.-PPI 1 x before breakfast
3. GI Bleeleding/upper GI bleding- Peptic ulcer- Portal HT, oesephageal
varices- Erosive gastritis
-Bleeding (stabilization of Blood Pressure, heart rate, splanchnic blood flow- Acute drug therapy : octreotide continous IV infusion.Vasopressin ( ↓splanchnic blood flow & portal Blood pressure)
-H2 reseptor antagonis no benefit in stopping acute bleeding or reducing the incidence of rebleeding.(not recommended).-PPI high dose of omeprazole, lansoprazole, 2 x1 for 5 days have been shown reduce the risk of rebleeding in patient with peptic ulcer
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4. Erosive gastritis ProphylaxisTherapy
-Sucralfat or H2 Antagonist reseptor (ranitidine,famotidin, infusion over 24 h), check pH after 4 h of infusion.-PPI in ICU should not be use due to unpredictable oral absorption
5. Spesific type of gastritis-Peptic ulcer, cause of: -NSAID -H. Pylori -acid hypersecretory (zolinger Ellison)
-acid antisecretary-mucosal defence
-PPI-H2 antagonis reseptor.-sucralfat-BismuthProstaglandin analog-Antacid-H pylori eradication (t.antibiotic)
Current Medical, Diagnosis & Treatment, by Lawrence M. Tierney,Jr, Stephen J McPhee, Maxine A Papadakis, 2008.
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PPI Pantoprazole AND Lanzoprazole- linier pharmacokinetic no dose adjustment- less interaction with others drugs less binding
with CYP450- Bioavailability greater than others - T1/2 pharmacodynamic (<49,5 hr) >>
DRUG OF CHOICE IN RENAL AND HEPATIC FAILURE PATIENT
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PPI & H2RA (except Cimetidin)
due to the less adverse effect on CNS
DRUG OF CHOICE ON LOSS CONSCIOUSNESS PATIENT
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THANK YOU FOR ALL