Acid Supressive Therapy

Diagnosa Terapi Keterangan Terapi Permasalahan pd px

HM ec SH Omeprazol 2x1 ampul Liver failure, melena, mual

Antasida syr 3 x CII +, nyeri perut -, perut penuh
+, SCr: 1,3
CKD st V+ anemia+Obs Omeprazol 2x1 ampul Melena, mual +,
melena Sukralfat 3x CI Hemodialisa reguler
(pasien PP)

Gastritis erosive + Omeprazol 2x1 ampul Nyeri perut kuadran kiri

duodenitis + post TB paru Sukralfat 4 x CI bawah, panas hilang timbul
DM ND st V + sepsis + Ranitidin 2x1 ampul Mual
asidosis metabolic+ edema lama GFR: 7,6 ml/menit (SCr:
paru 16,2),
CKD st 5 + hipokalemia Ranitidin 2x1 ampul Gagal ginjal, mual, muntah
lama +, kembung +, SCr: 17,5,
HD reguler
DM ND st 2 + obs. febris Omeprazol 3x1 ampul ND st 2, nyeri perut +, nyeri
sukralfat 3xCI ulu hati +, muntah +,
hemodialisa
SH + ascites + gastritis Omeprazol 2x1 ampul Melena +, nyeri perut +
+EH Sukralfat 4xCII
SH+Hematesis melena Omeprazol 2x1 ampul Melena
+DM sukralfat 4xCI
Drug used in acid peptic disease
Drug used in acid peptic disease
Drug used in acid peptic
H2 Receptor Antagonist
 Drug used in acid peptic disease
H2 Receptor Antagonist

binds 4-10 times less avidly

than cimetidine to cyt P450
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 ClCr :15-30 ClCr <50 ClCr <10 ClCr 20-50
impairment mL/min: mL/min: mL/min: mL/min :
600mg/day; PO 150 mg/day 20 mg/day 150 mg/day;
or IM/IV or 20 mg
ClCr<15 50 mg every ClCr <20
mL/min: q 12-24 hr other day mL/min: 150
300-400 mg every
mg/day other day
Hepatic No dosage adjustment is needed
impairment
 Dose-reducing H2 receptor antagonists in the
presence of low glomerular filtration rate:
a systematic review of the evidence
Results:

With declining GFR, there was a significant increase in

the area under the curve (AUC) and elimination half-life
(t1/2) of the serum drug concentration of H2RAs (P<0.001).
Compared with a GFR >80 ml/min/1.73m2, drug AUC increased by 200%
when the GFR was 30 ml/min/1.73m2, and by 300% when the GFR was
20 ml/min/1.73m2. In hospitalized patients with low GFR, reducing the
interval dose of intravenous H2RA was associated with fewer adverse
reactions.
The gastro-protective effects of H2RAs were similar with
reduced and unadjusted doses.

Manlucu, J.,Tonelli, M., Ray, J.G., Papaioannou, A., Youssef, G.,Thiessen-Philbrook, H.R., Holbrook, A., Garg, A.X. 2005.
Dose-reducing H2 receptor antagonists in the presence of low glomerular filtration rate: a systematic review of the evidence.
Nephrol Dial Transplant. 20; 2376-2384.
Risk of adverse drug reactions among hospitalized patients
when H2 receptor antagonist dose was unadjusted
vs appropriate for GFR
 Journal of clinical gastroenterology

On-demand treatment of acute heartburn with the

antacid hydrotalcite(Mg6Al2(CO3)(OH)16 4H2O):
compared with famotidine and placebo: randomized
double-blind cross-over study .
.Holtmeier , Holtmann, Caspary, Weingrtner, 2007,

: comparing to famotidine and placebo,

hidrotalcite is relieving the symptom
significantly faster and more effective in 3
hours after administering,
 Drug used in acid peptic disease

omeprazole esomeprazole

lanzoprazole

pantoprazole Rabeprazole
Drug used in acid peptic disease
proton pump inhibitor

and feces
 Use of proton pump inhibitors and risk of
osteoporosis related
fractures
Results: exposure of 7 or more years was associated with increased risk of an
osteoporosisrelated fracture (adjusted OR 1.92, 95% confidence interval
[CI] 1.163.18, p = 0.011). We also found an increased risk of hip fracture after 5 or more
years of exposure (adjusted OR 1.62, 95% CI 1.022.58, p = 0.04), with even higher risk
after 7 or more years exposure (adjusted OR 4.55, 95% CI 1.6812.29, p = 0.002).

Conclusion:
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.
Further study is required to determine the clinical importance of this finding and to
determine the value of osteoprotective medications for patients with long-term use of
proton pump inhibitors

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 Lansoprazo Pantoprazole Rabeprazole Esomeprazole
le
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%); Urine (33%) Urine (71%); Urine (90%); Urine (80%); feces
feces Feces (67%) feces(18%) feces (20%)
Renal impairment No dosage adjustment is needed (no significant changes)
Hepatic No Severe No No No dosage
impairment dosage decreased dosage dosage adjustment is needed
Adjustmet dose Adjustmet Adjustmet For patients with
is needed (prolonged is needed is needed severe liver
t) impairment (Child
Pugh class C), do not
exceed a dose of 20
mg.
Factors that affect Food Antacids none Food not Food
absorption food studied
PPI used 30-60 minutes before meals, recommended in the morning
Esomeprazole Versus Other Proton Pump Inhibitors in Erosive
Esophagitis: A Meta-Analysis of Randomized Clinical Trials

Results: Meta-analysis was performed on 10 studies (n 15,316). At 8

weeks, there was a 5% (RR, 1.05; 95% confidence interval, 1.021.08)
relative increase in the probability of healing of EE with esomeprazole,
yielding an absolute risk reduction of 4% and NNT of 25. The calculated
NNTs by Los Angeles grade of EE (grades AD) were 50, 33, 14, and 8,
respectively. Last, esomeprazole conferred an 8% (RR, 1.08; 95%
confidence interval, 1.051.11) relative increase in the probability of GERD
symptom relief at 4 weeks.

Conclusions: As compared with other PPIs, esomeprazole

confers a statistically significant improvement, yet,
clinically, only a modest overall benefit in 8-week healing
and symptom relief in all-comers with EE. The clinical
benefit of esomeprazole appears negligible in less severe
erosive disease but might be important in more severe
disease.
Gralnek, I.M., Dulai, G.S., Fennerty, M.B.,Brennan M. Spiegel, R. 2006. Esomeprazole Versus Other Proton Pump Inhibitors in
Erosive Esophagitis: A Meta-Analysis of Randomized Clinical Trials. Clinical Gastroenterology and Hepatology. 4; 1452-
1458.
Meta-analysis: Comparing the Efficacy of Proton Pump
Inhibitors in Short-term Use

Results: Two significant differences were found in the PPIs compared. In

to omeprazole 20 mg (RR 1.18; 95%CI: gastroesophageal reflux
disease esomeprazole 40 mg was superior 1.14-1.23). In
peptic ulcer disease pantoprazole 40 mg was superior to
omeprazole 20 mg (RR 1.07; 95%CI: 1.02-1.13). In Helicobacter pylori
eradication no significant differences were found.

Conclusions: Both significant differences found were in favour of the

highest dose of PPI on a milligram basis. This indicates that the difference
may be dose dependent and not proton pump inhibitor specific. Therefore,
when prescribing PPIs, other arguments than clinical efficacy, such as
those related to pharmacoeconomics, may be considered.

Klok, R.M., Postma, M.J., van Hout, B.A, Brouwers, JRBJ.2003. Comparing Efficacy of Proton
Pump Inhibitors in Short-term use; a meta-analysis of available clinical trials. Alimentary
Pharmacology & Therapeutics. 17(10):1237-45
 Drug used in acid peptic disease

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)
 Administration
Take recommended dose with water on:
an empty stomach, 1 hour before or 2
hours after meals.
Take any other medications at least 2
hours before taking sucralfate.
Do not take antacids (if prescribed) within
30 minutes of taking sucralfate. May cause
constipation (increased exercise, fluids,
fruit, or fiber may help).
 cimetidine, ranitidine,
digoxin, Interactions
fluoroquinolone
antibacterials,
tetracycline,
ketoconazole,
Antacid
levothyroxine,
Phenytoin
quinidine,
The recommended interval
Theophylline is 30 minutes. .
Warfarin

should be an interval of
2 hours between giving
sucralfate
 DOSAGE
Children:
Dose not established, doses of 40-80 mg/kg/day divided
every 6 hours have been used
Stomatitis (unlabeled use): 2.5-5 mL (1 g/10 mL
suspension), swish and spit or swish and swallow 4
times/day
Adults:
Stress ulcer prophylaxis: 1 g 4 times/day
Stress ulcer treatment: 1 g every 4 hours
Duodenal ulcer:
Treatment: 1 g 4 times/day on an empty stomach and at
bedtime for 4-8 weeks, or alternatively 2 g twice daily;
treatment is recommended for 4-8 weeks in adults, the
elderly may require 12 weeks
Maintenance: Prophylaxis: 1 g twice daily
Stomatitis (unlabeled use): 1 g/10 mL suspension, swish
and spit or swish and swallow 4 times/day
 Dosis pada keadaan gangguan ginjal

Toksisitas aluminium pada orang normal tanpa

gangguan ginjal tidak muncul,
Pada orang dengan gangguan ginjal kondisi end
stage akan muncul kejang, otot lemas, nyeri pada
tulang, dan encephalopathy aluminium berat.

Sucralfate harus dengan perhatian khusus apabila

digunakan pada pasien dengan gangguan ginjal,
dengan adanya monitoring dari kadar aluminium
toksisitas
(Martidale, 2007).
 Acid Suppresive Therapy
To maintain high intragastric pH in patients with
peptic ulcer bleeding
Prevention of rebleeding
Stress Ulcer
 Efficacy of primed infusions with high dose ranitidine and
omeprazole to maintain high intragastric pH in patients with peptic
ulcer bleeding: a prospective randomised controlled study

Method: prospective randomized studies

Aim: Ranitidin vs Omeprazole to maintain intragastric pH in
patients with peptic ulcer bleeding.
Protocol:

Ranitidine: initial: 50 mg 0,25 mg/kg BB for 24 hr (iv)

Omeprazole: initial: 80 mg 8 mg/hr for 24 hr (iv)
 Efficacy of primed infusions with high dose ranitidine and
omeprazole to maintain high intragastric pH in patients with peptic
ulcer bleeding: a prospective randomised controlled study

Result:

Conclusions:
Primed infusions of omeprazole after a bolus produced
consistently high intragastric pH values in patients with bleeding peptic
ulcers, whereas primed infusions with ranitidine were less effective
during the second half of a 24 hour treatment course. This loss of
effectiveness may be due to tolerance.
Labenz, J., Peitz, U., Leusing, C., Tillenburg, B., Blum, A.L., Borsch, G. 1997. Efficacy of primed infusions with high
dose ranitidine and omeprazole to maintain high intragastric pH in patients with peptic ulcer bleeding: a prospective
randomised controlled study. Gut 1997; 40: 36-41. pp. 36-40.
 Proton Pump Inhibitors for the Prevention of Stress-Related Mucosal Disease in Critically-Ill
Patients: A Meta-Analysis
Supot Pongprasobchai MD*, Samruay Kridkratoke MD*, Cherdchai Nopmaneejumruslers MD**

Material and Meta-analysis of the randomized controlled trials

Method comparing PPI versus H2RA for SRMD prophylaxis
Parameter Gastrointestinal bleeding and nosocomial pneumonia

Results Three studies involving 569 patients were included in

the meta-analysis.
The overall incidence of clinically important bleeding
was significantly lower in the PPI group (3.5%) as
compared to H2RA (8%), odds ratio (OR) 0.42 (95%
CI 0.20-0.91). The incidences of nosocomial
pneumonia were not different (10.2% versus 10.1%,
OR 1.02, 95% CI 0.59-1.75) between the two groups.

Conclusion PPI is superior to H2RA in the prevention of clinically

important bleeding from SRMD with a similar rate of
nosocomial pneumonia.

(J Med Assoc Thai Vol. 92 No. 5 2009)

 Intravenous pantoprazole versus ranitidine for prevention of rebleeding
after endoscopic hemostasis of bleeding peptic ulcers

Method: prospective randomized study

Aim: Pantoprazole vs Ranitidine treatment after endoscopic hemostatic for
prevention rebleeding.
Method:

Dose: Pantoprazole: i.v. 40 mg/12 hr for 3 days 40 mg/day orally

Ranitidine: i.v. 50 mg/8 hr for 3 days 150 mg/12 hr orally
 Intravenous pantoprazole versus ranitidine for
prevention of rebleeding after endoscopic hemostasis
of bleeding peptic ulcers

Result:
 Intravenous pantoprazole versus ranitidine for
prevention of rebleeding after endoscopic hemostasis
of bleeding peptic ulcers

Conclusions:
After endoscopic injection, treatment of rebleeding peptic ulcers,
intravenous pantoprozole is more effective than ranitidine for the
prevention of rebleeding.

No significant differences between the pantoprazole and

ranitidine groups with regard to the need for emergency surgery,
transfusion requirements, hospital stay or mortality.

Ping, I., Gin, H.L., Ching, C.L., Chiun, K.L., Hoi, H.C., Chung, J.W., Chang, B.S., Pei,M.T., Deng,
C.W., Wen, M.W., Kwok, H.L. 2004. Intravenous pantoprazole versus ranitidine for prevention
of rebleeding after endoscopic hemostasis of bleeding peptic ulcers. World J Gastroenterol.
10(24). Pp. 3666-
 Intravenous pantoprazole versus ranitidine for
prevention of rebleeding after endoscopic hemostasis
of bleeding peptic ulcers

Result:
STRESS ULCER
JOURNAL TITLE COMMENTS / SUMMARY WEB LINK

Crit Care. Science PPIs achieve a more rapid and sustained http://www.nc
2005 review: The increase in gastric pH and arenot associated bi.nlm.nih.gov
Feb;9(1):45 use with the rapid tachyphylaxis seen with H2RAs. /entrez/query.
- of proton As a result, and after the introduction of fcgi?db=pub
50. Epub pump intravenous formulations, PPIs are beginning to med&cmd=R
2004 Oct 8 inhibitors be used for the prophylaxis of SRMD in etrieve&dopt=
for gastric critically ill adults. AbstractPlus
acid &list_uids=15
suppression 693983&quer
in critical y_hl=14&itool
illness. =pubmed_do
csum
Curr Treat Stress- The available PPIs significantly increase http://www.nc
Options related gastric pH for up to 24 hours after one dose. bi.nlm.nih.gov
Gastroente Mucosal Preliminary studies have demonstrated a /entrez/query.
rol Disease significant reduction in SRMD bleeding for fcgi?db=pub
. 2003 patients receiving PPI prophylaxis. PPIs may med&cmd=R
Apr;6(2):13 become an effective tool for reducing the etrieve&dopt=
5- incidence of SRMD in critically ill patients. AbstractPlus
145 &list_uids=12
628072&quer
y_hl=14&itool
=pubmed_Do
cSum
(Vanderbilt Medical Center, 2005)
JOURNA TITLE COMMENTS / SUMMARY WEB LINK
L
Ann Proton-pump Available data indicate that PPIs are safe and http://www.nc
Pharmaco inhibitors efficacious for elevating intragastric pH in critically ill bi.nlm.nih.gov
the for stress ulcer patients. PPIs should be used only as an /entrez/query.
r. 2002 prophylaxis in alternative to H(2)RAs or sucralfate since the fcgi?db=pub
Dec;36(12 critically ill superiority of PPIs over these agents for med&cmd=R
):1 patients. etrieve&dopt=
929-37
preventing SRMD associated gastrointestinal AbstractPlus
bleeding has not been established. Additional &list_uids=12
comparative studies with adequate patient numbers 452757&quer
and pharmacoeconomic analyses are needed before y_hl=2&itool=
PPIs are considered the agents of choice for stress pubmed_doc
ulcer prophylaxis. PMID: 12452757 [PubMed - indexed sum
for MEDLINE]

Crit Care Randomized, Immediate-release omeprazole suspension is effective http://www.nc

Med. double-blind in preventing upper gastrointestinal bleeding and more bi.nlm.nih.gov
2005 comparison of effective than intravenous cimetidine in maintaining /entrez/query.
Apr;33(4): immediaterelease gastric pH of >4 in critically ill patients. fcgi?itool=abs
76 omeprazole oral tractplus&db=
0-5 suspension pubmed&cmd
versus =Retrieve&do
intravenous pt=abstractpl
cimetidine for us&list_uids=
the prevention of 15818102
upper
gastrointestinal
bleeding
in critically ill (Vanderbilt Medical Center, 2005)
Recommendations

Penggunaan Ranitidin Penyesuaian

dosis pada GFR<10 ml/menit
DISCUSSION
 ANTACIDS
Pharmacokinetics:
Work locally in the stomach by neutralizing
gastric acid.
Distributed throughout the GI tract;
eliminated primarily in the feces.
Pharmacodynamics:
Reduces the total amount of acid in the GI
tract.
 ANTACIDS
Pharmacotherapeutics:
Prescribed to relieve pain and promote
healing in peptic ulcer disease.
Also used to relieve symptoms of acid
indigestion, heart-burn, dyspepsia, or
GERD.
Also used to prevent stress ulcers, GI
bleeding, and hyperphosphatemia in
kidney failure.
 ANTACIDS
Drug interactions:
All antacids can interfere with the
absorption of oral drugs given at the same
time.
Adverse reactions:
Diarrhea, constipation, electrolyte
imbalances
 H2-RECEPTOR
ANTAGONISTS
Commonly prescribed anti-ulcer drugs
include:
Cimetidine (Tagamet)
Nizatidine (Axid)
Ranitidine (Zantac)
Famotidine (Pepcid)
 H2-RECEPTOR
ANTAGONISTS
Pharmacokinetics:
Absorbed rapidly and completely except
for famotidine; food and antiacids may
reduce absorption; distributed widely
throughout the body; metabolized by the
liver; excreted primarily in the urine.
Pharmacodynamics:
Block histamine from stimulating the acid-
secreting parietal cells of the stomach.
 H2-RECEPTOR
ANTAGONISTS
Pharmacotherapeutics:
Used therapeutically to:
Promote healing of duodenal and gastric
ulcers.
Provide long-term treatment of
pathological GI hypersecretory conditions.
Reduce gastric acid production and
prevent stress ulcers.
 H2-RECEPTOR
ANTAGONISTS
Drug interactions:
Cimetidine inhibits metabolism of ethyl
alcohol in the stomach resulting in higher
blood alcohol levels.
Adverse reactions:
Headache, diarrhea, and rash
 PROTON PUMP INHIBITORS
Disrupt chemical binding in stomach cells
to reduce acid production, lessening
irritation and allowing peptic ulcers to heal.
These drugs include:
Rabeprazole (Aciphex)
Pantoprazole (Protonix)
Omenprazole (Prilosec)
Lansoprazole (Previcid)
 PROTON PUMP INHIBITORS
Pharmacokinetics:
Given orally in enteric-coated form to
bypass the stomach and are dissolved and
absorbed in the small intestine.
Highly protein-bound and are extensively
metabolized by the liver; eliminated in the
urine.
 PROTON PUMP INHIBITORS
Pharmacodynamics:
Block the last step in the secretion of
gastric acid by combining with hydrogen,
potassium, and adenosine triphosphate in
the parietal cells of the stomach.
 PROTON PUMP INHIBITORS
Pharmacotherapeutics:
Indicated for:
Short term treatment of gastric ulcers
Active duodenal ulcers and peptic ulcers
(H. pylori)
Erosive esophagitis
GERD
Hypersecretory states
 PROTON PUMP INHIBITORS
Drug interactions:
May interfere with the metabolism of
diazepam, phenytoin, and warfarin.
May also interfere with drugs that depend
on gastric pH for absorption.
Adverse reactions:
Abdominal pain, diarrhea, nausea, and
vomiting
 OTHER PEPTIC ULCER
DRUGS
Misoprostol (Cytotec) - Protects against
peptic ulcers caused by NSAIDs by
reducing the secretion of gastric acid and
by boosting the production of gastric
mucus.
Sucralfate (Carafate) - Works locally in the
stomach by rapidly reacting with
hydrochloric acid to form a thick, paste-like
substance that adheres to the gastric
mucosa.
 ADSORBENT DRUGS
Prescribed as antidotes for the ingestion of
toxins which are substances that can lead
to poisoning or overdose.
Most commonly used adsorbent drug is
activated charcoal.
Pharmacokinetics:
Must be given soon after toxic ingestion;
not absorbed or metabolized; excreted
unchanged in feces.
 ADSORBENT DRUGS
Pharmacodynamics:
Inhibits toxins from being absorbed in the
GI tract by attracting and binding with
them.
Pharmacotherapeutics:
A general purpose antidote used for many
types of acute oral poisoning.
 ADSORBENT DRUGS
Drug interactions:
Drugs to induce vomiting that had been
given before administration, now are
discouraged so administration is not
delayed.
Adverse reactions:
Black stools and constipation.
 ANTIFLATULANT DRUGS
Disperse gas pockets in the GI tract.
Simethicone is the major drug currently
used.
Pharmacokinetics:
Not absorbed in the GI tract; distributed to
the intestinal lumen; eliminated in the
feces.
 ANTIFLATULANT DRUGS
Pharmacodynamics:
Provide de-foaming action in the GI tract.
Pharmacotherapeutics:
Used to treat conditions in which excess
gas is a problem such as: functional
gastric bloating, postop gaseous bloating,
diverticular disease, spastic or irritable
colon, and air swallowing.
 ANTIFLATULANT DRUGS
Drug interactions:
Dont interact significantly with other
drugs.
Adverse reactions:
None known.
 DIGESTIVE DRUGS
Aid digestion in patients who are missing
enzymes or other substances needed to
digest food.
Include:
Dehydrocholic acid
Pancreatin and pancrelipse.
 DIGESTIVE DRUGS
Pharmacokinetics:
Arent absorbed; act locally in the GI tract;
excreted in the feces.
Pharmacodynamics:
The action of digestants resembles the
action of the body substances they
replace.
Dehydrocholic acid - bile
Pancreatin and pancrelipase - pancreatic
 DIGESTIVE DRUGS
These drugs contain:
Trypsin to digest proteins
Amylase to digest carbohydrates
Lipase to digest fats
 DIGESTIVE DRUGS
Pharmacotherapeutics:
Each digestant has its own indication:
Dehydrocholic acid provides temporary
relief of constipation.
Pancreatic enzymes are given to patients
with pancreatitis, cystic fibrosis, and
steatorrhea.
 DIGESTIVE DRUGS
Drug interactions:
Antacids reduce the effects of pancreatic
enzymes.
Adverse reactions:
Diarrhea
Mechanism of gastric acid secreation
Regulation of Gastric Secreation of HCl
 Preparat Bahan Kemampuan Volume Kandungan Na
netralisasi untuk (mg/dosis)
asam netralisasi
(mEq/ml) 140 mEq
(ml)
Alternagel Al(OH)3 3,2 44 17
Amphojel Al(OH)3 1,3 107 150
Gelusil Al(OH)3, 4,8 29 7,5
Mg(OH)2,
Simetikon
Maalox Al(OH)3, 2,7 52 14
Mg(OH)2
Maalox Al(OH)3, 5,7 25 4
HRF Mg(OH)2
Mylanta Al(OH)3, 5,1 27 6,2
DS Mg(OH)2,
Simetikon
 Drug used in acid peptic disease
proton pump inhibitor

Title: COMPARISON OF INHIBITORY EFFECTS OF THE

PROTON PUMP-INHIBITING DRUGS OMEPRAZOLE,
ESOMEPRAZOLE, LANSOPRAZOLE, PANTOPRAZOLE, AND
RABEPRAZOLE ON HUMAN CYTOCHROME P450 ACTIVITIES

Methods: we performed in vitro studies using human liver

microsomal preparations and recombinant CYP2C19.

Conclusion:Our data suggest that, although the inhibitory profiles of

the five studied PPIs were similar, lansoprazole and pantoprazole
are the most potent in vitro inhibitors of CYP2C19 and CYP2C9,
respectively. Esomeprazole showed less inhibitory potency
compared with omeprazole and its R-enantiomer. The inhibitory
potency of rabeprazole was relatively lower than the other PPIs, but
its thioether analog showed potent inhibition on the P450 enzymes
investigated, which may be clinically significant.
Drug used in acid peptic disease
RCT STRESS ULCER
PROPHYLAXIS
Acute Risk Factors for Stress Ulceration

Mechanical ventilation (>48 hours)

Coagulopathy
Renal failure
Hypoperfusion (sepsis, shock, or organ
dysfunction)
High-dose corticosteroids (>250 mg/day
hydrocortisone or equivalent)
Brain/spinal cord injury
Significant burn injury (total body surface area
>35%)
 Proton Pump Inhibitors (PPIs)

Levy MJ, Seelig CB, Robinson NJ, et al. Comparison of omeprazole and ranitidine
for stress ulcer prophylaxis. Dig Dis Sci 1997; 42:1255-9.
REFERENCES
1. American Society of Health-System Pharmacists. ASHP therapeutic guidelines on stress ulcer
prophylaxis. Am J Health-Sys Pharm 1999; 56:347-79.
2. Cook D, Heyland D, Griffith L, et al. Risk factors for clinically important upper gastrointestinal
bleeding in patients requiring mechanical ventilation. Crit Care Med 1999; 27:2821-7.
3. Cook DJ, Fuller HD, Guyatt GH, et al. Risk factors for gastrointestinal bleeding in critically ill patients.
N Engl J Med 1994; 330:377-81.
4. Metz CA, Livingston DH, Smith S, et al. Impact of multiple risk factors and ranitidine prophylaxis on
the development of stress-related upper gastrointestinal bleeding: A prospective, multicenter, doubleblind,
randomized trial. Crit Care Med 1993; 21:1844-9.
5. Phillips JO, Metzler MH, Palmieri TL, et al. A prospective study of simplified omeprazole suspension
for the prophylaxis of stress-related mucosal damage. Crit Care Med 1996; 24:1793-1800.
6. Lasky MR, Metzler MH, Phillips JO. A prospective study of omeprazole suspension to prevent
clinically significant gastrointestinal bleeding from stress ulcers in mechanically ventilated trauma
patients. J Trauma 1998; 44:527-33.
7. Levy MJ, Seelig CB, Robinson NJ, et al. Comparison of omeprazole and ranitidine for stress ulcer
prophylaxis. Dig Dis Sci 1997; 42:1255-9.
8. Phillips JO, Metzler MH, Huckfeldt RE, et al. A multicenter, prospective, randomized clinical trial of
continuous infusion I.V. ranitidine vs. omeprazole suspension in the prophylaxis of stress ulcers. Crit
Care Med 1998; 26:101A.
9. Azevedo JR, Soares MG, Silva G, et al. Prevention of stress ulcer bleeding in high risk patients.
Comparison of three drugs. Crit Care Med 1999; 27:A145.
10. Roberts KW, Pitcher D, Cryer B. Effect of lansoprazole suspension versus continuous intravenous
ranitidine infusion on gastric pH of mechanically ventilated intensive care unit patients. Pharmacother
2000; 20:342.
11. Allen ME, Kopp BJ, Erstad BL. Stress ulcer prophylaxis in the postoperative period. Am J Health-
Syst Pharm 2004; 61:588-96.
Major Constituents of some Antacids

Hypercalcemia, Acid
rebound, nephrolithiasis
Gastric ulcer

Induced by drugs
 Usefulness of anti-ulcer drugs for the
prevention&treatment of peptic ulcers
induced by low doses of aspirin
METHODS: The patients were randomly classified into the proton
pump inhibitor (PPI)-treated group and the H2 receptor antagonist
(H2RA)-treated group. The administration of low-dose aspirin was
continued concomitantly, and endoscopic examinations were
performed 8 wk later.
RESULTS: Endoscopic examinations revealed that the tissue in the
region of the gastro-mucosal lesions had reverted to normal in all
patients in the PPI-treated group and in 12 patients(92%) in the
H2RA-treated group; no significant differences were observed
between the groups.
CONCLUSION: H2RA therapy was effective for both the
prevention and treatment of low-dose aspirininduced peptic ulcer,
similar to the effects of PPIs, while cytoprotective anti-ulcer drugs
were ineffective in preventing ulceration.

Nakashima, et al., 2009. World J Gastroenterol February 14; 15(6): 727-731

 Systematic review and meta-analysis of proton
pump inhibitor therapy in peptic ulcer bleeding
Review methods Included randomised controlled trials compared proton pump
inhibitor with placebo or H2 receptor antagonist in endoscopically proved
bleeding ulcer and reported at least one of mortality, rebleeding, or surgical
intervention. Trials were graded for methodological quality. Two assessors
independently reviewed each trial, and disagreements were resolved by
consensus.
Results We included 21 randomised controlled trials comprising 2915 patients.
Proton pump inhibitor treatment had no significant effect on mortality (odds ratio
1.11, 95% confidence interval 0.79 to 1.57; number needed to treat (NNT)
incalculable) but reduced rebleeding (0.46, 0.33 to 0.64; NNT 12) and surgery
(0.59, 0.46 to 0.76; NNT 20). Results were similar when the meta-analysis was
restricted to the 10 trials with the highest methodological quality: 0.96, 0.46 to
2.01, for mortality; 0.41, 0.25 to 0.68, NNT 10, for rebleeding; 0.62, 0.46 to 0.83,
NNT 25, for surgery.
Conclusions Treatment with a proton pump inhibitor reduces the risk of
rebleeding and the requirement for surgery after ulcer bleeding but has no benefit
on overall mortality.

(Leontiadis, G.I.,Sharma,V.K., Howden, C.W., 2005, Systematic review and meta-

analysis of proton pump inhibitor therapy in peptic ulcer bleeding, BMJ
2005;330;568, Available at: http://bmj.com/cgi/content/full/330/7491/568 ,
Downloaded from bmj.com on 28 June 2009)
 Are proton pump inhibitors the first choice for acute
treatment of gastric ulcers? A meta analysis of
randomized clinical trials

Methods: A literature search was conducted to identify randomized, controlled clinical

trials that included a PPI in at least one treatment arm and assessed the gastric ulcer
healing rates endoscopically. The healing rates were estimated for each treatment at
specific time points, and Rate Ratios (RR) and 95% confidence intervals (CI) were
estimated for each trial.
Results: Sixteen trials met the inclusion criteria: four compared a PPI versus placebo,
nine compared a PPI versus ranitidine (no trials of rabeprazole versus ranitidine met the
inclusion criteria), and three compared a newer PPI (lansoprazole, pantoprazole or
rabeprazole) versus omeprazole. In relation to ranitidine, the pooled RR of PPIs
(lansoprazole, omeprazole and pantoprazole) was 1.33 (95% CI 1.24 to 1.42) at four
weeks. In each trial, greater improvement in the studied clinical symptoms was found
with the newer PPIs (rabeprazole, pantoprazole and lansoprazole) when compared to
omeprazole.
Conclusion: In this study treatment with PPIs resulted in higher healing rates than
ranitidine or placebo. This evidence suggests that the first choice for gastric ulcer
treatment for the greater relief of symptoms is one of the newer PPIs.

Salas, M., Ward, A.,Caro, J. 2002, Are proton pump inhibitors the first choice for acute treatment of
gastric ulcers? A meta analysis of randomized clinical trials, BMC Gastroenterology, 2:17.
 LANSOPRAZOLE FOR THE PREVENTION OF
RECURRENCES OF ULCER
COMPLICATIONS FROM LONG-TERM LOW-DOSE
ASPIRIN USE
Conclusions
In patients who had ulcer complications related
to the long-term use of low-dose aspirin,
treatment with lansoprazole in addition to the
eradication of H. pylori infection significantly
reduced the rate of recurrence of ulcer
complications.

(N Engl J Med 2002;346:2033-8.)

 PENELITIAN

Pada penelitian evaluasi sucralfate dalam

mengatasi GERD tingkat keberhasilannya
17%-67%

(Michael Pettit, 2005. Treatment of gastroesophageal reflux disease. Pharm

World Sci. Springer).
 PENELITIAN
Gastritis yang muncul akibat infeksi H.
pylori dapat dikombinasi dengan PPI
dan antibiotik dengen cure rate 90 %.
Antibiotik yang biasa digunakan adalah
amoxicillin, clarithromycin, metronidazole
dan tetracycline digunakan dengan
konbinasi beberapa PPI selama 10-14 hari
(EBM, 2004).
Head-to-head comparison of H2-receptor antagonists and
proton pump inhibitors in the treatment of erosive
esophagitis: A meta-analysis
Results: RRs of cumulative healing rates for each comparison at 8 wk were: high dose vs
standard dose H2RAs, 1.17 (95%CI, 1.02-1.33); standard dose proton pump inhibitors vs
standard dose H2RAs, 1.59 (95%CI, 1.44-1.75); standard dose other proton pump inhibitors
vs standard dose omeprazole, 1.06 (95%CI, 0.98-1.06). Proton pump inhibitors produced
consistently greater healing rates than H2RAs of all doses across all grades of esophagitis,
including patients refractory to H2RAs. Healing rates achieved with standard dose
omeprazole were similar to those with other proton pump inhibitors in all grades of
esophagitis.

Conclusion: H2RAs are less effective for treating patients with

erosive esophagitis, especially in those with severe forms of
esophagitis. Standard dose proton pump inhibitors are
significantly more effective than H2RAs in healing esophagitis
of all grades. Proton pump inhibitors given at the
recommended dose are equally effective for healing
esophagitis
Wang, W.H., Huang, J.Q., Zheng, G.F., Xia, H.H.X., Wong, W.M., Lam, S.K., Wong, B.C.Y. 2005. Head-to-head
comparison of H2-receptor antagonists and proton pump inhibitors in the treatment of erosive esophagitis: A meta-
analysis World Journal of Gastroenterology. 11(26):4067-4077