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Transcript of 1 H2 Blockers, PPIs, & H. pylori Treatment Betty Golightly, B.Sc.Pharmacy Clinical Pharmacist...
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H2 Blockers, PPIs, & H. pylori Treatment
Betty Golightly, B.Sc.PharmacyClinical Pharmacist
Foundation in Travel Medicine (SCIEH)
Certificate in Travel Health® (ISTM)
September 2010
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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.
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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.
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BackgroundStatisticsEpidemiologyAnatomy & physiology of the GI tract
PharmacologyH2 Receptor AntagonistsProton Pump Inhibitors
Helicobacter pyloriSignificanceTreatments
Q & A
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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 lansoprazole 36th ranitidine 50th
Gareau, M and Campeau, L. Rx Chart Toppers: The top prescription drugs in Canada. Retrieved from http://www.canadianhealthcarenetwork.ca/pharmacists/clinical/drug-info/rx-chart-toppers-the-top-prescription-drugs-in-canada-3414
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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
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Tortora, G. Principles of Human Anatomy 4th Edition. Harper & Row, Publishers. New York, NY. 1986. p 582 Figure 23-1
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Tortora, G. Principles of Human Anatomy 4th Edition. Harper & Row, Publishers. New York, NY. 1986. p 596/ figure 23-10
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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 5812 Ibid p. 599
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Parietal cells hydrochloric acid (HCl) 1
activates pepsinogen ->pepsin Intrinsic factor (Vit B12 absorption!)
Acidic environment?Protein breakdown Iron absorptionFirst-line of defence against microbes
1 Tortora, G. Principles of Human Anatomy 4th Edition. Harper & Row, Publishers. New York, NY. 1986. p 599-600
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Tortora, G. Principles of Human Anatomy 4th Edition. Harper & Row, Publishers. New York, NY. 1986.p599. Figure 23-11 (c).
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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 Williams & Wilkins.USA. 2000. p.521
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Zantac®-Aug/99 1; generic Apotex-Dec/87 2 ???
Available-tabs(150 &300mg); injection(25mg/ml); oral solution (15mg/ml)LCA is 0.1800 for 150mg tabs 3
Indications & Dosages (DU & GU benign) 4Tabs or solution=300mg qd or 150mg bid x
4wks then maintenance dose of 150mg qhs1 PHAC Drug Product Database. Retrieved from http://webprod.hc-sc.gc.ca/dpd-bdpp/info.do?lang=eng&code=430922 PHAC Drug Product Database. Retrieved from http://webprod.hc-sc.gc.ca/dpd-bdpp/info.do?lang=eng&code=74273 AHW Drug Benefit List. Retrieved from https://idbl.ab.bluecross.ca/idbl/search.do;jsessionid=bc77d69ab3f98d04d1a76811dd21f15fae5ee2e96afdccdd0f054382408eee1a.e34Rc3qTchyKbi0LbhqObhyQchqMe04 Repchinsky C. CPS. The Canadian Drug Reference for Health Care Professionals. Canadian Pharmacists Association: Ottawa, Canada, 2007. p2689
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Contraindications Sensitivity to ranitidine
Drug interactions May affect bioavailability of ketoconazole Elderly pt on both hypoglycemics & theophylline
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 Association: Ottawa, Canada, 2007. p 2688-9
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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 & Dosages 4
DU 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=70882 PHAC Drug Product Database. Retrieved from http://webprod.hc-sc.gc.ca/dpd-bdpp/info.do?lang=eng&code=135833 AHW Drug Benefit List. Retrieved from https://idbl.ab.bluecross.ca/idbl/search.do;jsessionid=0f15f636777b4c0088a159982ac6e12a37d00b0108798255f7983b33abb18a67.e34Rc3qTchyKbi0LbhqObhyQchuQe04 Repchinsky C. CPS. The Canadian Drug Reference for Health Care Professionals. Canadian Pharmacists Association: Ottawa, Canada, 2007. p1784
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Contraindicationshypersensitivity to H2 receptor blockers
Drug interactionsNone listed
Side-effects-top 4Headache (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
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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 infectionGERDHypersecretory conditions
ExamplesPantoprazole, rabeprazole, lansoprazole
Herfindal E and Gourley D (Eds.). Textbook of Therapeutics: Drug and Disease Management. 7th Edition. Lippincott Williams & Wilkins.USA. 2000. p.523
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Pantoloc ®-May/001; generic Ranbaxy-Feb/082
Available as 20 & 40mg enteric-coated tabletsLCA 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=654692 PHAC Drug Product Database. Retrieved from http://webprod.hc-sc.gc.ca/dpd-bdpp/info.do?lang=eng&code=790403 AHW Drug Benefit List. Retrieved from https://idbl.ab.bluecross.ca/idbl/search.do;jsessionid=2416adae22ef476bdf89f30066d8f5da3d5256f6868cb53e2674560ee83a5c99.e34Rc3qTchyKbi0LbhqObhyQchqMe04 Repchinsky C. CPS. The Canadian Drug Reference for Health Care Professionals. Canadian Pharmacists Association: Ottawa, Canada, 2007. p1721-2
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ContraindicationsSensitivity to any of the ingredients
Drug interactionsWarfarin? Isolated cases of INR changes-monitor
INRFalse (+) urine screening THC tests!>3ys use=malabsorption of cyanocobalamin
Side-effects-top 3Headache (2.1%)Diarrhea (1.6%)Nausea (1.2%)
1 Repchinsky C. CPS. The Canadian Drug Reference for Health Care Professionals. Canadian Pharmacists Association: Ottawa, Canada, 2007. p1721-2
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Pariet ™ April/02 1; generic Novo Nov/07 2
Available as 10 & 20mg enteric-coated tabsLCA 20mg= 0.7826 (Pariet=1.3975) 3
Indications & 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 1000mg1 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=782003 AHW Drug Benefit List. Retrieved from https://idbl.ab.bluecross.ca/idbl/search.do;jsessionid=2416adae22ef476bdf89f30066d8f5da3d5256f6868cb53e2674560ee83a5c99.e34Rc3qTchyKbi0LbhqObhyQchqMe04 Repchinsky C. CPS. The Canadian Drug Reference for Health Care Professionals. Canadian Pharmacists Association: Ottawa, Canada, 2007. p1726
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ContraindicationsSensitivity to any of the ingredients
Drug interactionsCo-administration decreases ketoconazole
absorptionCo-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 2Headache (2.8%)Diarrhea (2.6%)
1 Repchinsky C. CPS. The Canadian Drug Reference for Health Care Professionals. Canadian Pharmacists Association: Ottawa, Canada, 2007. p1726-8
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Prevacid®-Dec/951; generic Apotex-June/092
Available as 15 & 30mg delayed-release cap and FasTabPrevacid 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) 5Duodenal 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=185162 PHAC Drugse. Retrieved from http://webprod.hc-sc.gc.ca/dpd-bdpp/info.do?lang=eng&code=779193 PHAC Drug Product Database. Retrieved from http://webprod.hc-sc.gc.ca/dpd-bdpp/info.do?lang=eng&code=734294 AHW Drug Benefit List. Retrieved from https://idbl.ab.bluecross.ca/idbl/search.do;jsessionid=2416adae22ef476bdf89f30066d8f5da3d5256f6868cb53e2674560ee83a5c99.e34Rc3qTchyKbi0LbhqObhyQchqMe0Repchinsky C. CPS. The Canadian Drug Reference for Health Care Professionals. Canadian Pharmacists Association: Ottawa, Canada, 2007. p1863-7
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ContraindicationsSensitivity to any of the ingredients
Drug interactionsProlonged inhibition of gastric acid secretion=theory
ketoconazole, ampicillin esters, iron salts, digoxin absorptionCo-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!HeadacheDiarrheaAbdominal pain
1 Repchinsky C. CPS. The Canadian Drug Reference for Health Care Professionals. Canadian Pharmacists Association: Ottawa, Canada, 2007. p1863-7
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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
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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. p10882 PHAC Drug Product Database. Retrieved from http://webprod.hc-sc.gc.ca/dpd-bdpp/info.do?lang=eng&code=619483 AHW Drug Benefit List. Retrieved from https://idbl.ab.bluecross.ca/idbl/search.do;jsessionid=2416adae22ef476bdf89f30066d8f5da3d5256f6868cb53e2674560ee83a5c99.e34Rc3qTchyKbi0LbhqObhyQchqMe0
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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-tops-for-h-pylori-infection-5258
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