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83 Cards in this Set
- Front
- Back
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What are the forms of PUD? (4)
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Differs from gastritis-ulcers extend into muscularis mucosa
Helicobacter pylori-associated (mostly in stomach and duodenum) NSAID-induced (mostly in stomach and duodenum) Stress-related mucosal damage – ICU |
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What are the risk factors for stress induced mucosal damage?
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-mechanical ventilation for more than 48 hours
-coagulopathies -renal failure -sepsis/shock -high dose corticosteroids -brain or spinal cord injury -significant burn injury |
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Etiology of PUD?
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-H. pylori
-NSAIDS -Critical illness -Zollinger-Ellison syndrome -Viral infection (CMV) -Vascular insufficiency |
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Epidemiology of PUD
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-Equal prevalence male female
-Older women increasing (likely due to NSAID use) -Gastric ulcer higher mortality |
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What is H. pylori strongly associated with?
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PUD
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What do most patients with gastric or duodenal ulcers not on NSAIDS have?
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H. pylori
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What % of the population is colonized w/ H. pylori?
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50% (15% will develop clinical symptoms of an ulcer)
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How is H. pylori transmitted?
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-fecal-oral
-oral-oral -iatrogenic |
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Injury from NSAIDs
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-subclinical gastric hemorrhage w/ even 1 dose!
-gastric ulceration/bleeding |
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Which are more common, gastric or duodenal ulcers?
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gastric ulcers
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What are the risk factors for NSAID-induced serious GI complications?
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-Age > 60 years
-Previous PUD -Previous NSAID-related GI effects -Previous upper GI bleed -Concomitant corticosteroid use -High-dose and multiple NSAID use -Concomitant anticoagulant use or coagulopathy -Chronic major organ impairment |
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What is the mechanism of NSAID induced GI mucosal damage?
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-direct topical irritation
-inhibition of endogenous GI mucosal prostaglandin synthesis (cyclooxygenase (COX) is rate limiting step in conversion of arachidonic acid to PG and is inhibited by NSAIDs) |
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What does arachindonic formed by?
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COX 1 and COX 2 enzymes
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What is COX 1 involved with?
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-GI mucosal integrity
-PLT aggregation -renal function |
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What is COX 2 involved with?
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-pain and inflammation
-mitosis and growth -bone formation |
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What do the non-selective NSAIDs target?
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COX 1 and COX 2
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What are the least ulcerogenic of the non-selective NSAIDs?
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-Oxaprozin (Daypro)
-Nabumetone (Relafon) -Etodolac (Lodine) |
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Which NSAIDs have the greatest potential for harm?
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-Piroxican (Feldene)
-Indomethacin (Indocin) -Ketorolac (Toradol) |
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Which NSAIDs are intermediate risk?
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-Naproxen (Naprosyn)
-Ketoprofen (Orudis) -Diclofenac (Voltaren) |
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What are 3 complications of PUD?
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-UGI bleeding (6-10% mortality)
-Perforation-into peritoneal cavity -Obstruction-scarring or edema of the duodenal bulb or pyloric channel |
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Tx of NSAID induced ulcer
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-stop NSAID (if possible)
-use a COX-2 inhibitor or decrease the dose of the current NSAID |
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If NSAID stopped, what should be administered?
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-H2 blockers
-PPIs -sucralfate |
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If NSAID continued, what should be administered?
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-PPIs
-H2A NOT effective |
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After ulcer is healed and NSAID continued, what should be administered?
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misoprostil or PPI
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Misoprostil
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-Synthetic cytoprotective prostaglandin
-Category X -Major adverse effect is diarrhea -Dose: 200mcg po qid -Guidelines list misoprostil as option but very difficult to adhere to. |
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Do patients tolerate misoprostil well?
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NO!
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How are COX 2 inhibitors superior to COX 1?
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have been shown to cause fewer endoscopic ulcers than nonselective NSAIDs
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Which COX 2 has been shown to decrease incidence of serious GI events?
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Rofecoxib (but was pulled from market for CV risk)
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What are 2 COX 2 inhibitors?
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Celecoxib and meloxicam
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Why is there a huge controversy surrounding COX 2 inhibitors?
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Huge controversy exists regarding how differently Cox-2 inhibitors should be viewed from traditional NSAIDs and which patients should not receive COX2 inh b/c of CV risk
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What does selection of a regimen for eradication of H. pylori depend on?
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Efficacy
Tolerability Drug interaction potential Antibiotic resistance Cost Compliance |
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What is regimen of choice for eradicating H. pylori?
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3 drug regimen including a PPI
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Resistance to what ab is increasing?
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metronidazole
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What is the typical length of tx for eradication of H. pylori?
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10-14 days
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What do most drugs that treat PUD target?
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parietal cells in gut mucosa
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Why are antacids prescribed in PUD?
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-neutralization of gastric acid
-inhibit the conversion of pepsinogen to pepsin -some mucosal protection -primarily used for symptomatic relief on an as needed basis |
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What is the recommended dosing for antacids in PUD?
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1 and 3 hours after meals and at bedtime
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Antacids adverse reactions: aluminum
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-encephalopathy
-anemia -anorexia -constipation -phosphate depletion |
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Antacids adverse reactions: magnesium
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-CNS depression
-nausea -vomiting -diarrhea |
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Antacids adverse reactions: calcium
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-alkalosis
-renal insufficiency -constipation |
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Antacids adverse reactions: sodium
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-edema
-CHF -HTN |
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H2 receptor antagonists
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-inhibition of acid secretion
-competitive and selective inhibition of the action of histamine thus reducing the basal and stimulated secretion of gastric acid |
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4 H2 receptor antagonists
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-Cimetidine (Tagamet)
-Famotidine (Pepcid) -Nizatidine (Axid) -Ranitidine (Zantac) |
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What is the healing rate for H2 receptor antagonists?
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70-95% after 4-8 weeks, respectively
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What should be done when prescribing H2 antagonists for patients with poor renal function?
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dose adjusted (down)
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What does cimetidine increase concentration of?
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-carbamazepine (Tegretol)
-warfarin (Coumadin) -phenytoin (Dilantin) -diazepam (Valium) |
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What do ALL H2 receptor antagonists inhibit absorption of?
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-ketoconazole (Nizoral)
-itraconazole (Sporanox) -calcium carbonate |
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What are the adverse effects of H2 receptor antagonists?
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-Headache
-Diarrhea -Constipation -Dizziness -Drowsiness -Fatigue -Alteration in LFT’s -Reversible confusional states -Gynecomastia – cimetidine only |
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PPIs
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Omeprazole (Prilosec) – available OTC
Lansoprazole (Prevacid) Pantoprazole (Protonix) – available IV Rabeprazole (Aciphex) Esomeprazole (Nexium)-available IV |
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PPI mechanism of action
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-Irreversibly bind to the Na/K – ATP-ase proton pump, thus inhibiting gastric acid secretion
-Inhibit >90% of acid secretion in 24 hours -Relieve symptoms earlier and heal ulcers faster than the H2 blockers -Generally stronger than H2 receptor antagonists |
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What does omeprazole cause increased concentrations of?
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-diazepam
-cyclosporine -carbamazepine -phenytoin -warfarin |
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What do all PPIs inhibit absorption of?
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-ketoconazole
-itraconazole -calcium carbonate |
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What are the adverse effects of PPIs?
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(overall, well-tolerated)
-headache -dizziness -nausea -diarrhea -constipation -skin rash |
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Sucralfate
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-protects GI mucosa
-forms a "band-aid" over the ulcer -less than 5% of drug is absorbed -aluminum hydroxide salt of a sulfated disaccharide that forms an ulcer adherent complex with exudates from the ulcer, thereby protecting it from further damage from acid |
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What does sucralfate prevent absorption of?
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-quinolone antibiotics (Cipro, Levaquin, etc)
-digoxin (Lanoxin) -levothyroxine (Synthroid) -phenytoin (Dilantin) -tetracycline and warfarin (Coumadin) |
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How can you avoid drug interactions with sucralfate?
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give drug 2 hours before and 4 hours after carafate
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Complications of GERD
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-strictures
-hemorrhage -perforation -aspiration -Barrett's esophagus |
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What is the mechanism of GERD?
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-transient relaxation of LES
-low resting LES pressure -transient increase in abdominal pressure |
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Sx of GERD
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Substernal burning pain (true concern...pts think they are having an MI)
Cough Wheeze Aggravated by foods, body position, or drugs |
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What is the key to tx of GERD?
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prolonged suppression of gastric acid secretion
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H2 receptor antagonists in tx of GERD
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-The more severe the presentation, the more difficult to treat
-Prolonged therapy (>12 weeks) often necessary |
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PPIs in tx of GERD
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-Highly effective
-Effective in H2 antagonist-resistant disease |
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Metaclopramide
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-pro-kinetic agent (increases gastric emptying)
-dopamine antagonist – selectively increases gastric emptying -dose related increase in LES tone |
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What are adverse effects of Metaclopramide?
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restlessness, drowsiness, fatigue, diarrhea, abdominal pain and nausea
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What patient population should not be prescribed Metaclopramide and why?
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patients with Parkinson’s disease, can induce a Parkinson-like syndrome
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Cisapride
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-Available by “compassionate use” (delivery system between FDA and manufacturer--> only sent to particular patients and strict monitoring)
-Selective cholinergic agent devoid of dopaminergic activity -Increases LES tone, improves esophageal peristalsis, promotes gastric emptying |
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What are drugs that can increase cisapride levels? What can result?
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Inhibitors of CPY3A4 –
-clarithromycin -erythromycin -ketoconazole -fluconazole -grapefruit juice TORSADES DE POINTES CAN RESULT!! |
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What are adverse effects of cisapride?
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Torsades–de-Point – drug interactions
Diarrhea Abdominal pain Flatulence Headache Fatigue Depression Dizziness Seizures Urinary problems |
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Sucralfate in tx of GERD
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-Similar healing rates to the H2 antagonists
-Less effective in severe disease -Must be given as the suspension -Not widely used due to 4x a day dosing and drug interactions |
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What is the MC GI disorder?
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IBS
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IBS general information
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-Incidence in women is 3 times greater than in men
-Etiology is unknown -Diagnosis of exclusion -Hypersensitive and hyper-responsive bowel |
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What does Serotonin 5-hydroxytryptamine (5-HT) do?
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plays a major role in regulation of intestinal motility, secretion, and visceral sensitivity
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Alosetron
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-selective 5-HT3 blocker
-approved, withdrawn, then re-approved -strict risk-management program -TIGHT control due to severe GI side effects and reported deaths |
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What is Alosetron approved for?
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-only approved for treating women with severe, diarrhea-predominant IBS that has lasted for 6 months or more and has not responded to conventional treatment
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What does Alosetron do?
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-decreases abdominal pain, increases colonic transit time, increases stool firmness and decreases fecal urgency and frequency
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What is the sx pattern in Alosetron use?
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-symptoms decline 1-4 weeks into therapy and will return within 1 week of drug discontinuation
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What is Alosetron metabolized by?
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-metabolized in the liver by cytochrome P450 enzymes 3A4, 2C9, 1A2
-may have levels affected by drugs known to induce or inhibit these enzymes |
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What are the adverse effects of Alosetron?
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-Constipation (29%)
-Impaction -Bowel obstruction -Perforation -Ischemic colitis (84 cases as of 3/2002 --> reason why FDA withdrew it from the market) |
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What must patients do to take Alosetron?
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must sign patient-physician agreement outlining side effects etc. so they are aware of risks
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Tegaserod
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-Serotonin analog
-Approved for short-term therapy of constipation-predominant IBS in women |
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What are the adverse effects of Tegaserod?
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Diarrhea
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What are the contraindications for Tegaserod?
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Contraindicated in:
-severe renal impairment -moderate or severe liver impairment -history of bowel obstruction -gallbladder disease -abdominal adhesions |
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What are 3 other meds that can be used to treat IBS?
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-laxatives
-antidiarrheals -antidepressants |
