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91 Cards in this Set
- Front
- Back
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Name the aggressive factors of PUD(3)
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-parietal cells:: secrete HCl
-chief cells::secrete proteolytic enzyme pepsin -gastric infection by H.Pylori |
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Name the defensive factors of the gastric mucosa(4)
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-secretion of mucus and bicarbonate forms barrier
-abundant microcirculation -rapid, continuous cell regeneration -prostaglandins:: cytoprotective effects |
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discuss the phases of secretion by the parietal cells
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-basal acid secretion in circadian pattern(low in am)
-cephalic phase and basal circadian rhythm mediated by vagal n. -ACh released during cephalic phase -gastrin is major stimulaus for acid secretion during gastric phase |
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discuss the cytoprotective effects of prostaglandins
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-PGE2 directly inhibits acid secretion
-stimulate mucus and bicarbonate secretion -enhance mucosal capillary blood flow -reduce back-diffusion of hydrogen ions -enhance cell turnover |
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what is the pathogenesis of PUD?
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-most mucosal damage happens at night when there are no protective food effects
-most common cuase is H pylori -chronic use of NSAIDs is second most common cause |
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what are the possible risk factors for PUD?
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H.pylori, chronic use of NSAIDs, smoking, corticosteroids, gastric acid hypersecretion, acute EtOH ingestion, stress and possible certain foods
(no conclusive evidence on EtOH, stress, and foods) |
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What is the occurrence of h. Pylori associated with ulcers?
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found in:
-75% gastric ulcers -95% duodenal ulcers |
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What are the characteristics of a H. Pylori infection?
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-antral colonization
-local inflammatory response -chronic active gastritis |
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what does H pylori secrete? (4)
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-urease::generates free ammonia
-protease::degrades glycoproteinsin mucus decreasing its viscosity -platelet-activating factor(PAF)::promotes thrombotic occlusion of surface capillaries -lipopolysaccharide::recruits inflammatory cells |
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what is the role of neutrophil secretions in H pylori infection?
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action of myeloperoxidases results in production of hypochlorous acid (HOCl) which reacts with ammonia to form monochloramine:: both HOCl and monochloramine are cytotoxic
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what conditions increase the risk factorsfor chronic NSAID users (nonselective COX inhibitors) for PUD?
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age >60, prior hx of PUD,high dose NSAIDs, concurrent use of steroids, anticoagulants, or antipatelets
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what should be done for NSAID users with significant risk factors for PUD?
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prophylactic use of a PPI or misoprostol
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spicy foods and caffeine cause?
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dyspepsia
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what are the three categories of nonulcer dyspepsias?
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(1)structural disease-induced::gastric motillity disorder
(2)functional ::40-60% cases with "alarm" symptoms (3)drug-induced |
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describe the urea breath test for H pylori
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-noninvasive test used toidentify presenceof active infectionand to confirm eradication one month later
-H pylori urease metabolizes urea to ammonia and CO2; this activity is not present in normal stomach |
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tx for h pylori
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-positive test indicates 7-14 day regimen of antimicrobials and acid-suppressive therapy
-triple therapy most common and successful -quadruple therapy is option if triple therapy unlikely to work -sequential therapy if triple and quadruple are unsuccessful |
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describe triple therapy for tx of H. pylori
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-combo of a PPI, amoxicillin, and clarithromycin for 7-14 days
-due to increasing resistance to clarithromycin, avoid triple therapy if local failure rates are high or if pt has recently used a macrolide or metronidazole |
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all successful tx regimens for h pylori include?
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clarithromycin, metronidazole, or both
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describe the quadruple therapy for h pylori
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PPI, bismuth, metronidazole, and tetracylcline for 10-14 days
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prophylaxis for NSAID induced ulcer?
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PPIs have equal efficacy to misoprostol and are more effective than H2RA
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how should you take antacids?
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-do not take on empty stomach/duration is only 20-40 min
-take one hour after meals because delayed gastric emptying allows duration to last up to 3hrs |
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what is the most frequent and dose-limiting side effect of the antacid magnesium hydroxide?
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diarrhea
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Magnesium hydroxide can accumulate and cause significant CNS depression in pts with?
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renal dysfunction
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what is the most frequent and dose-limiting side effect of the antacid aluminum hydroxide?
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constipation
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What does aluminum hydroxide benefit in pts with chronic kidney disease?
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decreases hyperphosphatemia:: aluminum hydroxide binds GI phosphate, decreases phosphate absorption, and lowers elevated plasma levels of phophate
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what is referred to as "acid rebound" in pts taking calcium crbonate(antacid)?
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-increased gastric acid secretion may occur after high doses of 4-8g, but has also occurred at lower doses such as 500mg
-due to stimulatory effects on calcium cation on mucosal cells and hypergastrinemia -no evidence of clinical significance and does not affect healing rates |
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Sodium bicarbonate contraindicated for?
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chronic use--should only be used for short-term relief of indigestion
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"milk alkali syndrome" due to use of sodium bicarbonate with calcium
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-metabolic alkalosis occurs when high calcium intake is combined with any factor the produces alkalosis
-hypercalcemia metabolic alkalosis, neurologic symptoms, and renal impairment |
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"sodium overload" cautioned in use of sodium bicarbonate in pts with?
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HTN, CHF, CKD, and cirrhosis
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drug interactions that result in complexation interactions of aluminum/magnesium hydroxide(3)
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(1)fluoroquinolones
(2)tetracyclines (3)H2 antagonists |
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DI of aluminum/magnesium hydroxide antacid and fluoroquinolones?
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complexation interaction
--admin of "oxacins" and antacids should be separated by 4-6 hrs or give fluoroquinolone first followed by the antacid 2hr later |
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DI of aluminum/magnesium hydroxide antacid and tetracycline?
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complexation reaction::
--tetracycline chelation by divalent(Ca, Mg, Zn) and trivalent(Al, Fe, Bi)metal cations; do not take antacids or dairy products for at least 2hr after tetracycline admin |
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DI of aluminum/magnesium hydroxide antacid and H2 antagonists?
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complexation reaction
--take the antacid 2hrs before or 2hrs after the H2 antagonist |
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There is decreased bioavailability of drugs(such as ketoconazole) requiring __________ for dissolution and absorption in pts taking antacids
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an acidic medium
(--antacids increase the intragastric pH) |
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what is sucralfate?
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nonabsorbed, locally acting agent that binds to, and protects, ulcerated tissue from acid, pepsin, and bile salts
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MOA of sucralfate
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binds to damaged(proteinaceous exudate) and ulcerated tissue
-forms physical barrier to hydrogen diffusion -inhibition of pepsin proteolysis -adsorbs bile salts |
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effectiveness of sucralfate in the treatment of duodenal and gastric ulcers?
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as safe and effective as H2RA
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MOA of H2RA?
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-selectively and competitively inhibit the actions of histamine at the H2 rec
-inhibit fasting secretions(basal acid secretion) -reduce meal stimulated secretion -potent inhibitors of all phases of gastric acid secretion -inhibit nocturnal secretion by more than 90% |
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approved H2RA drugs (4)
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cimetidine, ranitidine, famotidine, nizatidine
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H2RA agents relative efficacy and potency?
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-all are indicated for duodenal and gastric ulcers
-all comparable in healing capacities -famotidine has highest potency |
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what is the effect of cimetidine on the P450 system?
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-significant broad spectrum inhibition
-blocks metabolism of many drugs metabolized by P450 -beware in narrow therapeutic index drugs such as theophylline, warfarin, and phenytoin |
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what H2RA meds do not bind to P450?
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famotidine and nizatidine
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what is the drug interaction between cimetidine and ketoconazole?
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-cimetidine alters the gastric pH--(increases it)--thereby slowing the dissolution of ketoconazole and decreasing its absorption
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what have clinical studies shown to be the most important factor in healing duodenal ulcers?
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-suppression of nocturnal acid
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how should H2RA meds be administrated?
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once daily at bedtime
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MOA of PPIs
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-irreversibly binds to the H-K ATPase and inhibits basal and stimulated gastric acid secretion
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PPIs
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-weakly basic prodrugs that exist mainly in the lipid soluble nonionized form at the pH of the duodenum
-absorption occurs at the GI mucosa into the portal circulation and then into systemic blood |
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describe absorption of PPIs into parietal cells
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-PPIs diffuse through basolateral membranes into the intracellular compartment of parietal cells
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what happens to the PPIs once inside the parietal cells?
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-concentration gradient favors passive diffusion through the apical membrane into the secretory canaliculi
-due to the large amts of acid in the canaliculi, the PPIs are immediately protonated and "trapped" there |
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describe what happens to the PPIs once they are "trapped" in the canaliculi
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the protonated forms undergo chemical rearrangement to the active species which covalently binds to sulfhydryl groups in the H-K ATPase
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Why must oral dosage forms of PPIs be enteric-coated?
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to protect the drug from being protonated by the gastric acid and undergoing the irreversible chemical change in the gastric lumen; making absorption from the duodenum minimal to none
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__________are the most potent of the acid suppressors since inhibition is noncompetitive and irreversible.
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PPIs
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Maximal acid suppression occurs when a PPI is taken_______________.
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0.5-1.0 hr before a meal
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PPIs are the DOC for?
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PUD, GERD, and ZES
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____________ may be used concurrrently with PPIs.
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antacids
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omeprazole(Prilosec)
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PPI--racemic mixture of R and S isomers
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lansoprazoleDR capsule/naproxen tablets (Prevacid Napra-Pac) indicated for?
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-to decrease risk of gastric ulcers associated with the use of NSAIDs in pts in who have had a hx of a GU and have to be on an NSAID to tx RA, OA, or AS
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esomeprazole (Nexium)
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S-isomer of omeprazole; metabolized more slowly producing higher and more prolonged plasma levels--therefore increased bioavailability compared to omeprazole
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which PPI has DI due to inhibition of P450?
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omeprazole(Prilosec)
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which PPI does not show any clinical evidence of DI due to P450 inhibition?
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lansoprazole (Prevacid)
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What is the DI between omeprazole and clopidogrel?
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-both Rx and OTC omeprazole products should not be used due to reduced antiplatelet effects of clopidogrel
-esomeprazole shouldalso not be used in combo -this DI can occur if given concurrently or 12hr apart |
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Is there a DI between clopidogrel and H2RAs and/or antacids?
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-no evidence of a DI (except cimetidine) causing reduction of antiplatelet activity
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Describe a PPIs effect on intragastric pH
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-raises pH
-decreases absorption of drugs which require an acidicmedium for dissolution (ex:ketoconazole) |
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First line regimen in primary therapy of H pylori infection?
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-PPI BID(all PPIs effective)
-clarithromycin 500mg BID -amoxicillin 1000mg BID (if PCN allergy give metronidazole 500mg BID for full 14 days) |
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Second line regimen in primary therapy of H pylori infection?
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-PPI
-bismuth -metronidazole -tetracycline (all for 10-14 days) |
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_________is more effective than H2RAs in preventing recurrences in pts with healed duodenal or gastric ulcers.
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Sucralfate 1g BID or 2g hs
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risk factors for NSAID-associated ulcer and GI complications?
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high-dose NSAIDs, low-dose ASA, H pylori, hx of ulcer related GI complication, age>65, chronicdebilitation(esp CV dz), and concurrent use of steroids, anticoagulants, or antiplatelets
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What can be used to prevent NSAID-induced ulcers?
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misoprostol(Cytotec)-start with low doses and titrate up till diarrhea becomes dose-limiting
DOC is PPI-similar to misoprostol for healing, better maintenance, and better tolerated |
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what is the occurrence of diarrhea in Zollinger-Ellison syndrome?
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-diarrhea present in >50%
-may also have steatorrhea |
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Describe the differences in the PUD related to ZES
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-more persistent and unresponsive to standard therapy
-usually in 1st part of duodenum and solitary -multiple ulcers in 10-20% -up to 67% may have severe esophagitis |
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what is the lab test for ZES?
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secretin provocation test:
in ZES IV secretin causes a marked increase in serum gastrin by stimulating secretin receptors found only in gastrinoma cells |
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What is the treatment for ZES?
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-PPI DOC due to marked potency, prolonged duration of action, and safety profile
-PPI may be the only tx for resolution of all Sx -higher doses, BID dosing, and long term tx may be needed -omeprazole BID may provide better suppression of gastric acid output |
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Pathogenesis of GERD
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-dysfunction of the LES
-caused by relaxation of LES, increased abdominal pressure, failure of mechanism to clear acid |
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what are two examples of failure of mechanisms to clear acid causing potential for GERD?
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(1)Scleroderma-loss of esophageal peristalsis
(2)Sjorgren's syndrome-salivary hyposecretion |
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Atypical and "alarm" S and Sx of GERD
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-atypical Sx: laryngitis, eroded dental enamel
-alarm Sx: dysphagia, bleeding, weight loss, anemia |
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Tx of GERD
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-antacids
-alginic acid -PPIs for acid suppression -prokinetic agents |
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Effects of antacids on GERD
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-neutralize gastric acid and increase intragastric pH
-increases LES pressure -increased PG release, mucus production, and mucosal blood flow |
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Effects of alginic acid on GERD
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-reacts with sodium bicarbonate and H2O to form viscous solution of sodium alginate to provide mechanical barrier to gastric contents
-chew tablets thoroughly and take with plenty of H2O -only effective in the upright position(due to floatation) |
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Effects of PPIs in tx of GERD
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-considered superior to any other class for reducing Sx, healing esophagitis, and maintaining remission
-give 30-60 min before meals(usually breakfast) -if higher doses divide BID with 2nd dose at evening meal(not bedtime) |
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Effects of prokinetic agents on tx of GERD
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-stimulate motility of upper GIT by enhancing actions of ACh
-increase tone and amplitude of gastric contractions, relax the pyloric sphincter, and increase peristalsis of the duodenum and jejunum -increase resting tone of the LES |
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metclopramide(Reglan)
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prokinetic agent
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ADR of metoclopramide (Reglan)
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-extrapyramidal Sx: acute dystonias, tardive dyskinesia
-caused by blockade of central dopamine receptors |
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Use of meoclopramide(Reglan) is contraindicated in ______________
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Parkinson's Dz--antagonizes effects of levodopa
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_______are the DOC for moderate and severe GERD
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PPIs
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Maintenance therapy for GERD
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-continuous therapy is usually necessary with a daily PPI
-PPIs are DOC for maintenance of esophagitis -the full standard dose or even increased doses may be required |
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Stress Ulcers
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-occur in clinical settings of severe physiologic stress
-multiple, superficial erosive lesions in proximal stomach -continuous bleeding and clinically significant bleeding may develop within 3-7 days of the initial insult |
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pathogenesis of stress ulcers
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-alteration of defense mech:
ischemia and hypoxia in shock decrease mucosal blood flow, decreased oxygen/nutrient delivery, inability to remove/neutralize gastric acid, back diffusion of acid from gastric lumen -decreased rate of turnover and cellular proliferation -lack of PG synthesis and mucus formation |
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risk factors for stress ulcers
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-prolonged mechanical ventilation and coagulopathy
-risk increases with number of days of ventilation and length of ICU stay |
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guidelines for stress ulcer prophylaxis
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-recommended only for ICU pts who:
--mechanical ventilation >48 hrs --have a hx of GI ulceration or bleeding within 1yr before admin --have coagulopathy |
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Goals of treatment of stress ulcers
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-for prophylaxis, an intragastric pH >3.5 decrease frequency of bleeding in pts at risk for stress-related mucosal dz
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Treatment of Stress ulcers
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-H2RA (cimetidine) for prevention of UGI bleeding; 50 mg/hr by continuous IV infusion
-immediate release omeprazole/bicarbonate suspension as effective as cimetidine infusion for SUP -the only PPI is omeprazole(Zegerid 40mg UD) approved for prevention of UGI bleeding critically ill pts |
