Download Phar 236 gastrointestinal drugs

H2 Blockers, PPIs, &
H. pylori Treatment
Betty Golightly, B.Sc.Pharmacy
Clinical Pharmacist
Foundation in Travel Medicine (SCIEH)
Certificate in Travel Health® (ISTM)
September 2010
1
As
per the definition regarding bias or
conflict of interest put forth in the
Guidelines and Criteria for CCCEP
Accreditation & as per Section 10.3, I
am declaring that I have no real or
potential conflict to disclose.
My
views and opinions are my own and do
not necessarily reflect those of PTSA.
2
Review
anatomy & physiology of the
Gastrointestinal Tract.
Recognize the pharmacology of
H2 Receptor Antagonists (H2 Blockers)
& Proton Pump Inhibitors (PPIs)
Identify the treatments available for
Helicobacter pylori infection.
3
Background
 Statistics
 Epidemiology
 Anatomy
& physiology of the GI tract
Pharmacology
 H2 Receptor
Antagonists
 Proton Pump Inhibitors
 Helicobacter
pylori
 Significance
 Treatments
Q
&A
4
 478
million rxs dispensed in 12mnths ending Oct/09
 GI/genitourinary therapeutic class rank 3rd
 GI anti-ulcerants



23,584,000 rxs
7.8% increase from previous yr.
~$1.4 billion
 Top






100 Drugs (by generic name)
pantoprazole 11th
rabeprazole 20th
esomeprazole 25th
omeprazole 28th
M and Campeau, L. Rx Chart Toppers: The top prescription drugs in
lansoprazole 36th Gareau,
Canada. Retrieved from
http://www.canadianhealthcarenetwork.ca/pharmacists/clinical/drug-info/rx-chartth
toppers-the-top-prescription-drugs-in-canada-3414
ranitidine 50
5
 Peptic

ulcer disease (PUD)
Chronic inflammatory condition characterized by
ulceration of the upper GI tract where parietal cells
secrete pepsin and hydrochloric acid






Especially stomach & duodenum->Gastric and Duodenal Ulcers
5-10% will experience in lifetime
Highest b/w 50-70 y.o.
Often recurrent disease
 Likely due to infection with Helicobacter pylori
Signs/symptoms
 Anorexia, n/v, belching, bloating, heartburn, epigastric pain
 DU-better with food intake; GU-worse with food intake
Risks Factors?
Adapted from Section 6-Gastrointestinal Diseases. Herfindal E and Gourley D (Eds.). Textbook of Therapeutics: Drug and Disease
Management. 7th Edition. Lippincott Williams & Wilkins.USA. 2000. p.515-8
6
Tortora, G. Principles of
Human Anatomy 4th Edition.
Harper & Row, Publishers.
New York, NY. 1986. p 582
Figure 23-1
7
Tortora, G. Principles of Human Anatomy 4th Edition. Harper & Row, Publishers.
New York, NY. 1986. p 596/ figure 23-10
8
 Digestion 1





Ingestion-eating
Peristalsis-movement of food
Digestion-chemical/mechanical breakdown of food
Absorption-digested food from digestive tract
Defecation-indigestible substances
 Stomach 2

Made up of gastric glands (gastric pits)



Mucous cells-mucus
Parietal cells-hydrochloric acid
Chief (zymogenic) cells-pepsinogen
1 Tortora, G. Principles of Human Anatomy 4th Edition. Harper & Row, Publishers.
New York, NY. 1986. p 581
2 Ibid p. 599
9
 Parietal


activates pepsinogen ->pepsin
Intrinsic factor (Vit B12 absorption!)
 Acidic



cells hydrochloric acid (HCl) 1
environment?
Protein breakdown
Iron absorption
First-line of defence against microbes
1 Tortora, G. Principles of Human Anatomy 4th Edition. Harper & Row, Publishers.
New York, NY. 1986. p 599-600
10
Tortora, G. Principles of Human Anatomy 4th Edition. Harper & Row, Publishers.
New York, NY. 1986.p599. Figure 23-11 (c).
11

Competitively/reversibly bind H2Receptor of parietal cell


Dose-dependant inhibition of gastric acid secretion
Useful in treatment of:





DU
Benign GU
Hypersecretory conditions
GERD
Not in H. pylori
Watch for drug interactions and adverse effects
 Examples



famotidine>nizatidine>ranitidine>cimetidine (potency)
Some available OTC
Herfindal E and Gourley D (Eds.). Textbook of Therapeutics: Drug and Disease Management. 7 th Edition. Lippincott
12
Williams & Wilkins.USA. 2000. p.521
generic Apotex-Dec/87 2 ???
 Available-tabs(150 &300mg);
injection(25mg/ml); oral solution (15mg/ml)
 Zantac®-Aug/99 1;

LCA is 0.1800 for 150mg tabs
 Indications

3
& Dosages (DU & GU benign)
4
Tabs or solution=300mg qd or 150mg bid x 4wks then
maintenance dose of 150mg qhs
1 PHAC Drug Product Database. Retrieved from http://webprod.hc-sc.gc.ca/dpd-bdpp/info.do?lang=eng&code=43092
2 PHAC Drug Product Database. Retrieved from http://webprod.hc-sc.gc.ca/dpd-bdpp/info.do?lang=eng&code=7427
3 AHW Drug Benefit List. Retrieved from
https://idbl.ab.bluecross.ca/idbl/search.do;jsessionid=bc77d69ab3f98d04d1a76811dd21f15fae5ee2e96afdccdd0f054382408eee1a.e34Rc3qT
chyKbi0LbhqObhyQchqMe0
4 Repchinsky C. CPS. The Canadian Drug Reference for Health Care Professionals. Canadian Pharmacists Association: Ottawa, Canada,
2007. p2689
13
 Contraindications

Sensitivity to ranitidine
 Drug


May affect bioavailability of ketoconazole
Elderly pt on both hypoglycemics & theophylline


interactions
sporadic drug interactions with ranitidine?
sucralfate (>2grams) decreases absorption of ranitidine
 Side-effects



Constipation
Diarrhea
Headache (sometimes severe)
1 Repchinsky C. CPS. The Canadian Drug Reference for Health Care Professionals. Canadian Pharmacists
14
Association: Ottawa, Canada, 2007. p 2688-9
 Pepcid®-Dec/861;
generic Apotex-Dec/932
 Available-tabs (20 &40mg); I.V. (10mg/ml)

LCA is 0.5896 for 20mg tabs (Pepcid 1.0632) 3
 OTC
Combos
 Indications

4
DU



& Dosages
Acute tx-40mg qhs x 4-8wks
Maintenance tx-20m qhs x 6-12mnths
GU (benign)

Acute Tx- 40mg qhs x 4-8wks
1 PHAC Drug Product Database. Retrieved from http://webprod.hc-sc.gc.ca/dpd-bdpp/info.do?lang=eng&code=7088
2 PHAC Drug Product Database. Retrieved from http://webprod.hc-sc.gc.ca/dpd-bdpp/info.do?lang=eng&code=13583
3 AHW Drug Benefit List. Retrieved from
https://idbl.ab.bluecross.ca/idbl/search.do;jsessionid=0f15f636777b4c0088a159982ac6e12a37d00b0108798255f7983b33abb18a67.e34Rc3qT
chyKbi0LbhqObhyQchuQe0
4 Repchinsky C. CPS. The Canadian Drug Reference for Health Care Professionals. Canadian Pharmacists Association: Ottawa, Canada,
15
2007. p1784
 Contraindications

hypersensitivity to H2 receptor blockers
 Drug

interactions
None listed
 Side-effects-top




4
Headache (4.6%)
Diarrhea (1.6%)
Dizziness (1.2%)
constipation(1.2%)
1 Repchinsky C. CPS. The Canadian Drug Reference for Health Care Professionals. Canadian
Pharmacists Association: Ottawa, Canada, 2007. p 1784
16
 Irreversibly
bind to & inhibit H+/K+ ATPase
(hydrogen/potassium adenosine triphosphatase enzyme)


aka the gastric proton pump of the parietal cell.
this is final phase in acid secretion
 Useful



in treatment of:
PUD-GU,DU, including H. pylori infection
GERD
Hypersecretory conditions
 Examples

Pantoprazole, rabeprazole, lansoprazole
Herfindal E and Gourley D (Eds.). Textbook of Therapeutics: Drug and Disease Management. 7th Edition. Lippincott Williams & Wilkins.USA.
2000. p.523
17
 Pantoloc ®-May/001;
generic Ranbaxy-Feb/082
 Available as 20 & 40mg enteric-coated tablets
LCA 40mg tabs 1.2135 (Pantoloc =2.1733)3
 Indications & Dosages (DU, GU, H.pylori) 4




Duodenal Ulcers =40mg qam x 2 wks (+2wks)
Gastric Ulcers=40mg qam x 4wks (+4wks)
H. pylori associated duodenal ulcer =40mg bid x 7days


+ clarithromycin 500mg + amoxicillin 1000mg
+ clarithromycin 500mg + metronidazole 500mg
1 PHAC Drug Product Database. Retrieved from http://webprod.hc-sc.gc.ca/dpd-bdpp/info.do?lang=eng&code=65469
2 PHAC Drug Product Database. Retrieved from http://webprod.hc-sc.gc.ca/dpd-bdpp/info.do?lang=eng&code=79040
3 AHW Drug Benefit List. Retrieved from
https://idbl.ab.bluecross.ca/idbl/search.do;jsessionid=2416adae22ef476bdf89f30066d8f5da3d5256f6868cb53e2674560ee83a5c99.e3
4Rc3qTchyKbi0LbhqObhyQchqMe0
4 Repchinsky C. CPS. The Canadian Drug Reference for Health Care Professionals. Canadian Pharmacists Association: Ottawa,
Canada, 2007. p1721-2
18
 Contraindications

Sensitivity to any of the ingredients
 Drug



interactions
Warfarin? Isolated cases of INR changes-monitor INR
False (+) urine screening THC tests!
>3ys use=malabsorption of cyanocobalamin
 Side-effects-top



3
Headache (2.1%)
Diarrhea (1.6%)
Nausea (1.2%)
1 Repchinsky C. CPS. The Canadian Drug Reference for Health Care Professionals. Canadian
19
Pharmacists Association: Ottawa, Canada, 2007. p1721-2
 Pariet
™ April/02 1; generic Novo Nov/07 2
 Available as 10 & 20mg enteric-coated tabs

LCA 20mg= 0.7826 (Pariet=1.3975)
 Indications



3
& Dosages (DU, GU, H.pylori)
4
Duodenal Ulcers=20mg qd up to 4 wks (+additional tx)
Gastric Ulcers=20mg qd up to 6wks (+4wks)
H. pylori associated duodenal ulcer=20mg bid x 7 days

+ clarithromycin 500mg + amoxicillin 1000mg
1 PHAC Drug Product Database. Retrieved from http://webprod.hc-sc.gc.ca/dpd-bdpp/info.do?lang=eng&code=67735
2 PHAC Drug Product Database. Retrieved from http://webprod.hc-sc.gc.ca/dpd-bdpp/info.do?lang=eng&code=78200
3 AHW Drug Benefit List. Retrieved from
https://idbl.ab.bluecross.ca/idbl/search.do;jsessionid=2416adae22ef476bdf89f30066d8f5da3d5256f6868cb53e2674560ee83a5c99.e34Rc3qTc
hyKbi0LbhqObhyQchqMe0
4 Repchinsky C. CPS. The Canadian Drug Reference for Health Care Professionals. Canadian Pharmacists Association: Ottawa, Canada,
2007. p1726
20
 Contraindications

Sensitivity to any of the ingredients
 Drug
interactions

Co-administration decreases ketoconazole absorption
Co-administration increases digoxin levels

Combination tx + clarithromycin + amoxicillin



Increased rabeprazole & 14-hydroxyclarithromycin plasma levels
Active against most strains of H.pylori (in vitro)
 Side-effects-top


2
Headache (2.8%)
Diarrhea (2.6%)
1 Repchinsky C. CPS. The Canadian Drug Reference for Health Care Professionals. Canadian
21
Pharmacists Association: Ottawa, Canada, 2007. p1726-8
Prevacid®-Dec/951; generic Apotex-June/092
 Available as 15 & 30mg delayed-release cap and FasTab
 Prevacid Fastab Nov/06 (not a benefit on the DBL) 3
 LCA *15 or 30mg 1.1200 (Prevacid 2.0000)4


Indications & Dosages (DU, GU, H.pylori) 5
 Duodenal Ulcers =15mg qd before breakfast x 2-4 wks
(+1yr for recurrent DU)
 Gastric Ulcers=15mg qd before breakfast x 4-8 wks
 H. pylori associated duodenal ulcer=30mg bid ac x
7,10,14 days

+ clarithromycin 500mg + amoxicillin 1000mg
1 PHAC Drug Product Database. Retrieved from http://webprod.hc-sc.gc.ca/dpd-bdpp/info.do?lang=eng&code=18516
2 PHAC Drugse. Retrieved from http://webprod.hc-sc.gc.ca/dpd-bdpp/info.do?lang=eng&code=77919
3 PHAC Drug Product Database. Retrieved from http://webprod.hc-sc.gc.ca/dpd-bdpp/info.do?lang=eng&code=73429
4 AHW Drug Benefit List. Retrieved from
https://idbl.ab.bluecross.ca/idbl/search.do;jsessionid=2416adae22ef476bdf89f30066d8f5da3d5256f6868cb53e2674560ee83a5c99.e34Rc3qTc
hyKbi0LbhqObhyQchqMe0
Repchinsky C. CPS. The Canadian Drug Reference for Health Care Professionals. Canadian Pharmacists Association: Ottawa, Canada, 2007.
22
p1863-7
 Contraindications

Sensitivity to any of the ingredients
 Drug

Prolonged inhibition of gastric acid secretion=theory




interactions
ketoconazole, ampicillin esters, iron salts, digoxin absorption
Co-administration->monitor theophylline levels
>2gms sucralfate decreases lansoprazole bioavailability
+food=50-70% decrease in extent of absorption

qam prior to breakfast
 Side-effects-depends



on study!
Headache
Diarrhea
Abdominal pain
1 Repchinsky C. CPS. The Canadian Drug Reference for Health Care Professionals. Canadian Pharmacists Association: Ottawa,
Canada, 2007. p1863-7
23
24
 Spiral
shaped, Gram (-), & flagellated bacteria
 Found b/w gastric cell surface & overlying
mucus gel layer
 Produces an enzyme-> urease


changes urea into ammonium & bicarbonate (protective)
basis for non-invasive diagnostic test

Ingestion of urea labelled with carbon 13 or 14 followed by a
breath test of urease activity (90-95% sensitivity)
 Human-to-human

transmission (fecal-oral)
Lower socioeconomic class & crowding=increased rates.
1 Herfindal E and Gourley D (Eds.). Textbook of Therapeutics: Drug and Disease Management. 7th
Edition. Lippincott Williams & Wilkins.USA. 2000. p.518-9
25
 Hp-PAC->bid


x 7,10, or 14 days
1
lansoprazole 30mg+clarithromycin 500mg+amoxicillin 1g
Aug/98 2; DBL (kit) 82.20003
 Other
PPI combinations previously sited
 Always remember drug interactions/side-effects of
clarithromycin & amoxicillin
 Success rates?
1 Repchinsky C. CPS. The Canadian Drug Reference for Health Care Professionals. Canadian Pharmacists Association: Ottawa, Canada,
2007. p1088
2 PHAC Drug Product Database. Retrieved from http://webprod.hc-sc.gc.ca/dpd-bdpp/info.do?lang=eng&code=61948
3 AHW Drug Benefit List. Retrieved from
https://idbl.ab.bluecross.ca/idbl/search.do;jsessionid=2416adae22ef476bdf89f30066d8f5da3d5256f6868cb53e2674560ee83a5c99.e34Rc3qTc
hyKbi0LbhqObhyQchqMe0
26

Recent study looking at Hybrid Therapy

1
Combination of sequential & concomitant treatments
 Esomeprazole 40mg + amoxicillin 1000mg (EA) bid x 7 days....
 EA+ clarithromycin 500mg + metronidazole 500mg bid x 7days
 97.4% eradications rates (vs. 91.9% for sequential tx)
1 Helwick, C. Hybrid therapy tops for H. Pylori infection. Retrieved from
http://www.canadianhealthcarenetwork.ca/pharmacists/clinical/health-index-therapeutics/gastroenterology/hybrid-therapy-topsfor-h-pylori-infection-5258
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