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What are the three common forms of PUD?
- Helicobacter pylori induced
- NSAID induced
- Stress induced
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What is the MOA for antacids?
- neutralize gastic acid by raising the intragastric pH
- inhibits conversion of pepsinogen to pepsin
- stimulate the production of mucosal prostaglandins
- increases LES tone
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Explain what antacids are used for and how they are taken
- Used for symptomatic relief
- NO healing power
- in suspensions (liquids), so absorped better
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What side effects must you watch our for when using antacids?
- Aluminum based = constipation
- Magnesium based = diarrhea
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What are some drug interactions for Antacids that cause chelation?
- tetracycline
- fluoroquinolone
- iron
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What is a drug interaction with antacids that cause inactivation
sucralfate
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What drug interactions with antacids cause decrease absorption?
- H2 antagonist
- Ketoconazole
- Ampicillin
- Phenytoin
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What are some antacid products?
- Aluminum + Magnesium
- Calcium carbonate
- sodium bicarb
- bismuth
- *quick onset, short duration, need many doses
- *may mask more serious problems
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What is the MAO for Histamine-2 Receptor antagonists (H2RA)?
- Inhibits histamine receptors on parietal cells
- Decreases the secretion of H+ ions
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When are H2RA indicated as 1st line treatment?
- PUD
- mild-moderate PUD or GERD
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What is the MAO of proton pump inhibitors?
- Irreversible inhibition of H+/K+ ATPase on parietal cells - decrease gastric acid
- Protonation in small bowel necessary for drug to be activated
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When is a PPI indicated as 1st line treatment?
- GERD
- Moderate-severe PUD or GERD
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H2RA's can also be used for...
- H. pylori
- Maintenance of remission
- treatment of NSAID ulcers
- erosive or non-erosive esophagitis
- treatment of DU/GU
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PPI can also be used for..
- Maintenance of remission
- treatment of H. pylori
- treatment of NSAID ulcers
- treatment of DU/GU
- treatment of erosive esophagitis only
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What is the duration of treatment for DU, GU, and GERD for both PPIs and H2RA?
- H2RA - DU 4-8wks, GU 8wks, GERD 8wks
- PPI - DU 4-8wks, GU 4-8wks, GERD 8wks
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When is the best time to take an H2RA?
Take a larger dose before bedtime
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When is the best time to take a PPI?
- Take 30-60 minutes before a meal
- done to maximize inhibition of proton pump
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What are the PPI drugs?
- Lansoprazole
- Omeprazole
- Rabeprazole
- Pantoprazole
- Esomeprazole
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What are the adverse effects and drug interactions of lansoprazole?
- AE-Nausea, HA
- Interactions - Theophylline, ketoconazole, iron, ampicillin, sucralfate
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What are the adverse effects and drug interactions of Omeprazole?
- AE-nause, HA, diarrhea
- interactions - warfarin, phenytoin, diazepam, ketoconazole, sucralfate, clopidogrel
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What are the adverse effects and drug interactions of Rabeprazole?
- AE - Nausea, HA, diarrhea
- interactions - Ketoconazole, iron, ampicillin
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What are the adverse effects and drug interactions of pantoprazole?
- AE-HA, diarrhea
- interactions - ketoconazole, iron, ampicillin
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What are the adverse effects and drug interactions of esomeprazole?
- AE - HA and diarrhea
- interactions - Ketoconazole, iron, ampicillin, clopidogrel
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What is sucralfate and how does it work?
- Promotes mucosal defenses by forming reacting with hydrochloric acid to form a paste like substance and and binds to surface of ulcer
- barrier allows ulcer to heal
- NO acid reducing capacity
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How does the inhibition of COX-1 in nonspecific NSAIDS work?
- Inhibits cyclo oxygenase which decreases prostaglandins and decreases inflammation
- BUT by decreasing prostaglandins it decreases the protecting in GI tract
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Where are COX-1 inhibitors found?
GI tract & Kidney
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Where are COX-2 inhibitors found?
in sites of inflammation
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What is the TX of NSAID induced ulcers?
- D/C NSAIDS if possible
- start a PPI or H2RA
- *if you have to continue NSAID - use a PPI
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How can you prevent NSAID induced ulcers and when is it indicated?
- Use Misoprostol which causes bad diarrhea
- Use in HIGH RISK pt w/ prior history, >60yo, high does NSAID therapy, receiving anticoag. corticosteriods
- deal w/diarrhea with high risk patients
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What is the MAO of Misoprostol?
- Prostaglandins E 1 analog
- Stimulates production of mucous and HCO3-
- Cytoprotection
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What are the adverse effects of Misoprostol?
- Diarrhea
- abdominal pain
- spontaneous abortions
- postmenopausal women-bleeding
-
What is the one contraindication for Misoprostol use?
Women of childbearing age!
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What is the treatment of NSAID induced ulcers?
- stop NSAID therapy when ulcer occurs
- PPI - agent of choice when NSAIDS must be continued
- Tx H.pylori when pt. taking NSAIDS who have ulcers and are infected with the organism
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How do you treat H. pylori?
- Combine 2 antibiotics plus a PPI or H2RA
- Bismuth + metro + tetracycline x 2 weeks
- Lansoprazole + clarithro + amoxicillin x 10 days
- Omeprazole + clarithro + amoxi x 10 days
- Esomeprazole + clarithro + amoxi x 10 days
- Rabeprazole + clarithro + amoxi x 10 days
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What is the duration of treatment for H. pylori?
- The 2 antibiotics should be continued for 7-14 days
- The PPI or H2RA should be continued for 2-5 weeks after anbx stops
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What is bismuth based quadruple therapy?
- Special therapy for H. pylori
- uses a PPI or H2RA with bismuth, metro, and tetra for 10-14 days
-
What are the combination products used to treat H. pylori?
- Ranitidine bismuth citrate - Tritec
- lansoprazole, amoxicillin - Prevpac
- Bismuth subsalicylate, metro, tetracycline - Helidac
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What are four complications of GERD?
- Esophagitis
- Barrets
- Adenocarcinoma
- Strictures
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What is the Non-Pharm treatment of GERD?
- Diet, avoid exercise, tight clothing, smoking
- pregnancy
- Avoid nicotine, iron, potassium, alcohol, and narcotics
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What is the empiric treatment of GERD?
- OTC antacids - OTC H2blockers or OTC PPI
- Rx H2 blockers or PPI
- Metoclopramide
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When do you use an antacid for GERD?
- infrequent mild sx
- adjunctive therapy
-
What is H2RA's role in treatment of GERD?
- 1st line for chronic, mild-moderate GERD
- Non-erosive esophagitis
must monitor sx and AE's
-
What is PPI's role in the treatment of GERD?
- 1st line in moderate to severe GERD
- when other agents fail
- must not chew, take 30-60 minutes before meal
most monitor for sx and AE's
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What is the MAO for metoclopramide?
- Stimulates motility in upper GI
- considered prokinetic
- Increases LES tone
- increases antral contractions
- increases perstalsis
-
What are the AE's for Metoclopramide?
- Galactorrhea
- Diarrhea
- extrapyramidal symptoms
- depression
- drowsiness
-
When is Metoclopramide contraindicated?
- Parkinson's disease
- obstruction
-
What are some drug interactions with Metoclopramide?
- Anticholinergics
- MAO inhibitors
- Levodopa
-
What should you monitor Metoclopramide for?
- Renal fucntion
- adverse effects
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What drug classes are used in the treatment of Ulcerative Colitis (UC) and Crohns?
- Aminoglycosides
- Corticosteriods
- Immunosupressants
- misc. antibiotics
- monoclonal antibodies
-
What is the MAO for aminosalicylates (ASA)?
- 1st line for UC and Crohns
- reduce prostaglandin & leukotriene production
- inhibits bacteria-induced chemotaxis
-
What are the agents classified as Aminosalicylates?
- Sulfasalazine
- mesalamine
- olsalazine
- balsalazide
-
What do all Aminosalicylates do?
- They are cleaved into products that provide anti-inflammatory activity in the colon/rectum
- effects are primarily topical
- Split products include 5-aminosalicyclic acid (5-ASA)
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When are Corticosteriods used and what is a contraindiction?
- Used for short-term use
- Contra - LT use see cushing-like condition
-
What are the corticosteriods used in the treatment of IBD?
Prednisone, methyprednisone, hydrocortisone
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What is the specific agent used in the treatment of UC and IBD?
- Budesonide -
- high oral potency in UC use
- Low bioavailabity - released in ileum for disease affecting ileum or ascending colon
-
What is the dosing of corticosteriods?
- for MODERATE acute exacer - 40-60mg q24h
- *prednisone is drug of choice
- for SEVERE exacer - IV therapy
- *Methylprednisone is drug of choice
- taper does when withdrawing
-
Hydrocortisone is used in the treatment of UC and IBD
- Oral or topical use
- enema is more effective than suppository or foam
- Foam - greater system absorption
-
What is Budesonide and how does it work?
- Enteric coated oral product that allows drug to be released in the ileum and ascending colon
- exerts local anti-inflammatory effect
- Induces remission in mild-moderate Crohns disease of ileum and ascending colon
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What are some AE's of corticosteriod use?
- Hyperglycemia
- HTN
- electrolyte imbalance
- Increased apetite
- insomnia
- psychosis
- anxiety, tremors
- Increased fluid retention
-
What do we need to monitor corticosteriods for when treating IBD?
- Acute- BP and Glucose
- Chronic - Lipids, fasting glucose, Electrolytes, Bone density
-
What are the pros and cons of using Immunsuppresives to treat IBD?
- Pros - maintain remission, reduce steriod use
- Cons - very slow onset (3-12 months), Lots of AE's, Cost
-
What are the immunosuppresive agents used for treating IBD?
- Azathioprine
- 6-Mercaptopurine
- Methotrexate
- Cyclosporine
-
what is the MAO for Azathioprine/6-Mercaptopurine?
- Inhibits purine synthesis
- Inhibits DNA synthesis
- Decreases cell replication
-
What is the time of onset for Azathioprine/6-Mercaptopurine and was are some side effects?
- Time of onset - 3-6 months
- SE's - lots of hemotologic effects 'penias', pancreatitis
-
What are some contraindications for the use of Azathioprine/6-mercaptopurine?
-
What are contraindictions to the use of Azathioprine/6-Mercaptopurine?
- Active liver disease
- Pregnancy
- Caution with severe renal impairment
-
What is the MAO for Methotrexate?
- Inhibits dihydrofolate - important in folic acide production
- Decreases further cell replication
-
What is the time of onset for Methotrexate?
time of onset - 12-16 weeks
-
What are the adverse effects of Methotrexate?
- Most serious are hemotological
- Anemia
- leukopenia
- N/V/D
- Heptatoxicity
- Renal dysfunction
- Folic acid def.
- *Contraindicated in Pregnacy
-
What is the MAO for cyclosporine?
- Binds to cyclophilin receptor
- inhibits T-cell activation
- decreases cytokine production
-
What is the time of onset for cyclosporine?
time of onset - 2-3 days IV
-
What are some AE's of Cyclosporine?
- Nephrotoxicity **
- Tremor
- HTN
- Pancreatitis
- Heptatoxicity
- Seizure
- infection
-
When are antibiotics used to treat IBD?
- Used in Crohns disease only
- used when microorganisms is suspected but not proven
-
What are the antibiotics used to treat Crohns disease?
- Ciprofloxacin
- Metronidazole
- rifaxamin
-
What are the Monoclonal antibodies used in treating IBD?
- Infliximab
- Adalimumab
- Natalizumab
-
What is the MAO for infliximab?
- Neutralizes activity of soluble TNF alpha by binding to TNF alpha receptors and inhibit receptor binding
- Reduces infiltration of inflammatory cells and TNF alpha production
- Reduces mononuclear cell ability to express TNF alpha and interfero
-
How is infliximab dosed?
- Given every week or every 2 weeks and slowly progress to give it every 8 or 9 weeks as maintenance
- this treatment continues forever
-
What are some AE's to infliximab?
- Sepsis
- Serum-sickness
- HA
- N/V/D
- liver toxicity
- Arthalgia, myalgia
- dyspepsia
- rash
- lymphomas
-
What can infliximab produce if used inproperly?
- TB
- Histoplasmosis
- Listeriosis
- Pneumocystosis
- Pneumonia
- Hep B
-
Information about other Monclonal antibodies
- Adal - TNF alpha blocker, similar AE to inflix
- Nata - leukocyte blocker for pt. who cant tolerate TNF blocker, careful of JC virus may lead to death
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