Term
| what is the etiology of peptic ulcer disease? |
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Definition
| primary: helicobacter pylori. also: NSAIDs, increase of destructive factors (HCl, pepsin, bile), and decrease in defensive factors (mucus, HCO3, blood flow/NO, regeneration or growth factors) or increase in aggravating factors (ethanol, diet, smoking, stress, steroids, NSAIDs) |
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Term
| what % of GI ulcers is helicobacter responsible for? |
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Definition
| 70% however - many pts with helicobacter pylori infections also have cachexia - so they never get an ulcer, just accompanying gastritis |
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Term
| why is stress a contributing factor to peptic ulcer formation? |
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Definition
| b/c stress increases HCl secretion and decreases immune function |
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Term
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Definition
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Term
| what generally characterizes the antihistamine H2 blockers? are their effects dose-dependent? what kind of acid secretions do they inhibit? what location ulcers are they effective against? do they have an effect on GI motility/emptying time? what is their healing rate? |
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Definition
| the H2 blockers such as *cimetidine are competitive receptor antagonists, they have dose-dependent effects, inhibit basal/food-stimulated/nocturnal acid secretions, effective for duodenal > gastric ulcers, have little effect on GI motility/emptying time and have a healing rate of > 70% are completely healed w/in 6-8 wks |
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Term
| what was the first H2 blocker? |
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Definition
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Term
| how is cimetidine metabolized? does it interact with other drugs? how does it affect hormones? can pregnant women use it? |
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Definition
| cimetidine undergoes 1st pass metabolism and will inhibit the P450 enzyme system - therefore it interacts with diazapems, anticoagulants, etc. cimetidine also blocks the androgen receptor and decreases the metabolism of estradiol/increases prolactin levels, leading to gynecomastia and impotency in men and galactorrhea in women. it is not recommended during pregnancy. |
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Term
| other than cimeditine, what are the other H2 blockers and any particular characteristics? |
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Definition
| ranitidine (minimal P450 inhibition), famotidine (negligible P450 inhibition), and nizatidine (negligible P450 inhibition) |
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Term
| what are the ADRs for H2 blockers? |
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Definition
| H2 blockers are generally safe, w/only moderate, reversible ADRs including: rash, GI disturbances, diarrhea, CNS (drowsiness, confusion, *headache*, malaise, dizziness), bradycardia/hypotension w/ rapid IV admin, alteration of liver function/enzyme productio, and hormonal effects *only for cimetidine*:impotency, gynecomastia, and galactorrhea |
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Term
| what is the level of drug-drug interaction with H2 blockers? |
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Definition
| drug interaction w/H2 blockers is mostly relegated to cimetidine b/c of its P-450 activity (esp w/benzos, phenytoin, warfarin), but also decreased absorption of drugs which require GI acidity (ketoconazole/itraconazole), and antacids - which decrease absorption of H2 blockers. |
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Term
| what drugs are the most effective in reducing HCl secretion? what is their mechanism of action? |
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Definition
| proton pump inhibitors which *irreversibly inhibit H+/K+ ATPase* such as omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprozole |
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Term
| what conditions are proton pump inhibitors used for? |
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Definition
| zollinger-ellison syndrome (gastrin-tumors), gastric/duodenal ulcers, and GERD |
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Term
| what ADRs are associated with proton pump inhibitors? |
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Definition
| P450 inhibition (w/omeprazole), headache, rash, increased liver enzymes (like cimetidine), GI disturbances like diarrhea, hypergastronemia, rat carcinoid tumors, reduced Ca++ absorption (*risk of osteoporosis), and colonic cell hyperplasia |
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Term
| how should proton pump inhibitors be administered? |
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Definition
| on an empty stomach and all undergo 1st pass metabolism |
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Term
| what are long term risks of GI acid suppression (hypochlorhydria)? |
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Definition
| increased gastric CA, helicobacter pylori overgrowth, gastronemia, rebound hyperacidity, polyps, and decreased B12 and iron absorption |
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Term
| how do H2 blockers compare with PPIs? |
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Definition
| PPIs are *better with H. pylori infection, *hemorrhagic ulcers/bleeding - maintain clot better w/pt on NSAIDs. H2 blockers have a lower incidence of ADRs, they are *cheaper, *safer in pregnancy (except cimetidine), cause *less hypergastrinemia and *potential for gastric carcinoid tumors |
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Term
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Definition
| a cytoprotective salt of sucrose complexed to sulfated aluminum hydroxide which interacts with HCl to form a viscous paste that binds to proteins in ulcers or erosions. it is also supposed to increase mucosal prostavglandin synthesis |
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Term
| what ADRs are associated with sucralfate? |
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Definition
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Term
| does sucralfate interact with other drugs? |
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Definition
| sucralfate interacts (esp during absorption) with digoxin, anticoagulants, phenytoin, and quinolones and *SHOULD NOT* be administrated with antacids, H2 blockers or PPIs |
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Term
| what is misoprostol? what does it do? when is it used? |
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Definition
| misoprostol is a synthetic prostaglandin E1 analog that replaces the protective prostaglandins consumed with prostaglandin-inhibiting therapies such as NSAIDs. misoprostol increases mucus/NO/HCO3, increases cell proliferation, decreases acid secretion, preserves microcirculation, and stabilizes lysosomes. |
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Term
| what ADRs are associated with misoprostol? |
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Definition
| diarrhea, gas, cramps, stimulation of GI and uterine smooth muscle - *contraindicated in pregnancy* |
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Term
| what is bismuth subsalicylate? |
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Definition
| peptobismol is a colloidal preparation of bismuth (heavy metal - not absorbed) and salicylate (absorbed) |
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Term
| how does bismuth subsalicylate work? |
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Definition
| bismuth subsalicylate binds mucus glycoproteins, coats/protects GI from pepsin/bile acids, increases mucus/HCO3, PG synthesis, decreases intestinal secretions, and is bacteriocidal to E. coli, H. pylori, C. difficle, and B. fragilis |
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Term
| what ADRs are associated with bismuth subsalicylate? |
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Definition
| bismuth subsalicylate may stain teeth, GI mucosa, and blacken stools due to bacterial interaction to form bisulfide. w/overusage, bismuth toxicity (encepthalopathy) and salicylate toxicity are possible |
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Term
| if H. pylori is confirmed/suspected in conjunction with a peptic ulcer, what antibx are effective? are there any drugs that increase the efficacy of these antibx? |
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Definition
| pepto-bismol, metronidazole, tetracycline, amoxicillin, clarithromycin. PPIs will increase intragastric pH which then increases the action of these antibx - esp amoxicillin |
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Term
| what are the options for tx of GERD (gastro-esophageal reflux disease)? |
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Definition
| lifestyle modification, prokinetic agents, acid suppression, and antireflux sx |
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Term
| what is the main prokinetic drug used for tx of GERD? |
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Definition
| metoclopramide, which *blocks the enteric GI presynaptic dopamine-D2 receptors. metoclopramide increases ACh activity (cholinomimetic), increases upper GI tone/mobility and also has anti-emetic effects via CNS activity |
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Term
| what ADRs are associated with metoclopramide? |
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Definition
| increased GI motility (possible diarrhea), and dopamine receptor antagonism in the CNS leading to extrapyramidal effects (like parkinson's): seizures, increased prolactin, galactorrhea, and menstrual irregularities |
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Term
| what are the other prokinetic drugs used for tx of GERD? |
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Definition
| *bethanechol which has muscarinic (M3) actions which increase LES pressure and GI motility and *erythromycin which is a motilin agonist that increases GI motility |
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Term
| what acid suppressors are useful in treating GERD? |
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Definition
| proton pump inhibitors are preferred (esp for more serious cases w/esophageal erosion), H2 blockers hasten healing w/excessive heartburn, and antacids/sulcrafate can provide some relief in milder conditions |
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Term
| what kind of disease is IBS? |
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Definition
| a nonorganic functional disturbance with an etiology that includes pyschosocial, altered motility (increased gastrocolonic response), and incresed GI sensory response (volume/distension) |
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Term
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Definition
| when symptoms occur: increased dietary fiber, antidiarrheals, antispasmodics, avoidance of excacerbating foods, and adminstration of drugs that block serotonin receptor activity |
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Term
| how do drugs that block serotonin receptor activity help with IBS? |
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Definition
| GI 5-HT3 receptors activate visceral afferents, resulting in nausea/bloating/pain/inhibtion of L colonic motility. drugs such as *alosetron* are 5-HT3 receptor antagonists used to treat women when diarrhea is their main complaint via decreasing GI motility |
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Term
| what ADRs are associated with alosetron? |
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Definition
| severe constipation and life-threatening acute ischemic colitis - bad enough that drs have to enroll pts in a special progam to prescribe it |
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Term
| what are the 2 kinds of inflammatory bowel disease? |
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Definition
| ulcerative colitis and crohn's disease |
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Term
| what drugs are used to treat inflammatory bowel disease? |
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Definition
| 5-aminosalicylic acid (5-ASA) drugs: sulfasalazine/balsalazide/olsalazine/mesalamine, antimicrobials (metronidazole, ciprofloxacin), corticosteroids for acute flares, immunosuppressives: azathioprine, mercaptopurine - anti-TNF drugs, and experimentally: methotrexate/cyclosporine |
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Term
| how do the 5-aminosalicylic acid (5-ASA) drugs help with IBD? |
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Definition
| *topical distribution in the GI, not systemic bc the colonic bacteria break the azo bond and release the ASA with sulfasalazine/balsalazide/olsalazine and with mesalamine, the acrylic coating dissolves at the ph 7 found in the terminal ileum/colon (ASACOL), ethylcellulose coated-time release throughout the GI (PENTASA), or mesalamine enema (ROWAWA and CANASA) |
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Term
| what ADRs are associated with 5-aminosalicylic acid (5-ASA) drugs? |
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Definition
| rash, fever, flu-like symptoms, GI disturbances/diarrhea, salicylate toxicity at higher doses, and sulfasalazine can form sulfapyridine which when absorbed can cause allergy/rash/hemolytic anemia/folic acid absorption interference |
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Term
| what are the anti TNF drugs? what are they indicated for? |
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Definition
| infliximab, adalimuma, and certolizumab are indicated for acute/chronic chron's disease (remission/maintenance) and act by preventing TNF binding to receptores. they are used in pts w/inadequate response to mesalamine/steroids |
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Term
| what ADRs are associated with infliximab, adalimuma, and certolizumab? |
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Definition
| infection, antibody development, infusion rx, and autoimmune rxs |
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Term
| what is considered ulcerative proctitis/distal colitis? how is it generally treated? |
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Definition
| < 40 cm - generally treated with mesalamine suppositories or steroids such as budesonide (formulated to release in the intestines) |
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Term
| what is considered ulcerative colitis? how is it generally treated? |
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Definition
| > 40 cm, oral mesalamine/sulfasalamine, steroids, mercaptopurine/azathioprine for steroid-dependent/cyclosporine-dependent remissions and antibx if acute infection present |
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