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What are the three common forms of PUD?
- Helicobacter pylori induced
- NSAID induced
- Stress induced
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
Explain what antacids are used for and how they are taken
- Used for symptomatic relief
- NO healing power
- in suspensions (liquids), so absorped better
What side effects must you watch our for when using antacids?
- Aluminum based = constipation
- Magnesium based = diarrhea
What are some drug interactions for Antacids that cause chelation?
What is a drug interaction with antacids that cause inactivation
What drug interactions with antacids cause decrease absorption?
- H2 antagonist
What are some antacid products?
- Aluminum + Magnesium
- Calcium carbonate
- sodium bicarb
- *quick onset, short duration, need many doses
- *may mask more serious problems
What is the MAO for Histamine-2 Receptor antagonists (H2RA)?
- Inhibits histamine receptors on parietal cells
- Decreases the secretion of H+ ions
When are H2RA indicated as 1st line treatment?
- mild-moderate PUD or GERD
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
When is a PPI indicated as 1st line treatment?
- Moderate-severe PUD or GERD
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
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
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
When is the best time to take an H2RA?
Take a larger dose before bedtime
When is the best time to take a PPI?
- Take 30-60 minutes before a meal
- done to maximize inhibition of proton pump
What are the PPI drugs?
What are the adverse effects and drug interactions of lansoprazole?
- AE-Nausea, HA
- Interactions - Theophylline, ketoconazole, iron, ampicillin, sucralfate
What are the adverse effects and drug interactions of Omeprazole?
- AE-nause, HA, diarrhea
- interactions - warfarin, phenytoin, diazepam, ketoconazole, sucralfate, clopidogrel
What are the adverse effects and drug interactions of Rabeprazole?
- AE - Nausea, HA, diarrhea
- interactions - Ketoconazole, iron, ampicillin
What are the adverse effects and drug interactions of pantoprazole?
- AE-HA, diarrhea
- interactions - ketoconazole, iron, ampicillin
What are the adverse effects and drug interactions of esomeprazole?
- AE - HA and diarrhea
- interactions - Ketoconazole, iron, ampicillin, clopidogrel
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
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
Where are COX-1 inhibitors found?
GI tract & Kidney
Where are COX-2 inhibitors found?
in sites of inflammation
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
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
What is the MAO of Misoprostol?
- Prostaglandins E 1 analog
- Stimulates production of mucous and HCO3-
What are the adverse effects of Misoprostol?
- abdominal pain
- spontaneous abortions
- postmenopausal women-bleeding
What is the one contraindication for Misoprostol use?
Women of childbearing age!
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
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
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
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
What are four complications of GERD?
What is the Non-Pharm treatment of GERD?
- Diet, avoid exercise, tight clothing, smoking
- Avoid nicotine, iron, potassium, alcohol, and narcotics
What is the empiric treatment of GERD?
- OTC antacids - OTC H2blockers or OTC PPI
- Rx H2 blockers or PPI
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
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?
- extrapyramidal symptoms
When is Metoclopramide contraindicated?
- Parkinson's disease
What are some drug interactions with Metoclopramide?
- MAO inhibitors
What should you monitor Metoclopramide for?
- Renal fucntion
- adverse effects
What drug classes are used in the treatment of Ulcerative Colitis (UC) and Crohns?
- 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?
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)
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
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
What are some AE's of corticosteriod use?
- electrolyte imbalance
- Increased apetite
- 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?
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
- 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
- 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 **
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?
What are the Monoclonal antibodies used in treating IBD?
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?
- liver toxicity
- Arthalgia, myalgia
What can infliximab produce if used inproperly?
- 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