ANISYAH ACHMAD, S.Si., Apt., Sp.FRSDepartement of Clinical Pharmacy, Major of Pharmacy,

FKIK- UNSOED

GASTROENTEROLOGY

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

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

Effek Gastrin Merangsang 1. Peningkatan gerak lambung2. Pengosongan lambung3. Relaksasi sfingter ileosekal4. Gerak mass5. Sekresi getah lambung6. Sekresi getah pankreas

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

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

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

4. Enzim Pepsin

di sekresi : sel utama (Chief Cell)

Pepsinogen pepsinHCL ( pH : 1,5 – 3,5)

Protein (terutama daging) polipeptidapepsin

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

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)

Faktor perangsang sekresi lambung :

- Asetilkolin / parasimpatis / vagus - Hormon Gastrin - Asam amino, alcohol, nikotin, kafein- Stress emosi

Fase Sekresi- Fase cephalic- Fase gastric- Fase intestinal

GIT DISEASE

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

Barrett esophagus

• Normal epithelium: squamous type• Barrett: becomes columnar with many Goblet

cells• Precursor for adenocarcinoma of the

esophagus

Barrett esophagus

Barrett esophagus

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

Cancer of the esophagus

Congenital pyloric stenosis

• Hypertrophy of the circular muscle layer of the pylorus

• Projectile vomiting in 1st 2 weeks of life

• Palpable mass

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

Acute Gastritis

Peptic ulcers

• Common locations:lesser curvatureantrumprepyloric areas

• Causes: H.pylori infection bile-induced gastritis

• Not a precursor lesion of carcinoma of the stomach

Benign Gastric Ulcers

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

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

Cancer of the stomach

DRUG USED

ANTACIDS SUCRALFATE

H2 RECEPTOR ANTAGONIST PROTON PUMP INHIBITOR

1. Antacids2. H2 RA 3. Proton Pump

Inhibitor4. Sucralfat5. Antimicrobials

(Triple combination)

4

5

ANTACIDS

Katzung, B.G., 2006. Basic and Clinical Pharmacology, 10thEd. New York: McGraw-Hill.

Commonly used in antacid products

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

• 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

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)

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]

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.

Katzung, B.G., 2006. Basic and Clinical Pharmacology, 10thEd. New York: McGraw-Hill.

effect

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

• In renal impairment, H2RA agents need dose adjustment

• Cimetidin should be avoided to use, because it is highly bound to cytochrome P450

PRECAUTION

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

proton pump inhibitorPROTON PUMP INHIBITOR

and feces

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.

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.

Profile of Pharmacokinetics(linear and non-linear)

• 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)

ACID PEPTIC DRUG USE

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)

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

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.

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

PPI & H2RA (except Cimetidin)

due to the less adverse effect on CNS

DRUG OF CHOICE ON LOSS CONSCIOUSNESS PATIENT

THANK YOU FOR ALL