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128 Cards in this Set
- Front
- Back
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What are some acid-related diseases?
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1. GERD
2. Peptic ulcer disease (PUD) 3. NSAID-induced ulcers 4. Stress-related ulceration |
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What are the 3 main factors in acid stimulation?
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1. Neuronal - ACh
2. Endocrine - gastrin 3. Paracrine - histamine |
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What are the cells of the stomach?
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1. Parietal cells (body & fundus) -- secrete HCl
2. ECL -- secrete histamine 3. G cells (antrum) -- secrete gastrin 4. Superficial epithelial cells -- secrete bicarb and mucus 5. D cells (antrum) -- secrete somatostatin --> inhibits gastrin secretion |
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How does acid secretion occur at the receptor level?
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ACh neural input + gastrin hormonal input (from G cell) --> act on ECL cell --> ECL cell releases histamine --> histamine binds to parietal cell --> HCl secreted
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What are the different phases of gastric secretion?
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1. Cephalic phase (initiated by thoughts of food)
2. Gastric phase (initiated in response to ingestion of food) |
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What are the receptors involved in promoting digestion?
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Parasympathetic
-Muscarinic *Increase motility & tone *Relax sphincters *Stimulate acid secretion |
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What are the receptors in inhibiting digestion?
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Sympathetic
-alpha 1, alpha 2, beta 2 *Decrease motility & tone -alpha 1 *Constrict sphincters -alpha 2 *Inhibit acid secretion |
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What is the normal function of the lower esophageal sphincter?
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Constricted until the movement of peristaltic wave causes it to relax to allow passage of food
Constricts after food passes through, to protect lower esophagus and "trap" food |
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What do peptic and mucous cells secrete?
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Pepsinogen
In acidic stomach, pepsinogen --> pepsin |
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When does feedback inhibition occur?
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pH 3-4
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What factors provide intrinsic protection to the GI mucosa?
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1. Mucus/bicarb -- barrier/neutralize
2. Gastric blood flow -- "pulls" acid away 3. Cell turnover -- continuous "replacement" 4. Prostaglanding E2 -- inhibits acid secretion (secreted by mucosal cells at pH < 3) |
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What diagnostic testing is available for gastric disease detection?
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1. Upper GI series/barium swallow
2. Esophageal pH monitoring 3. Endoscopy 4. Hemacult 5. Hgb/Hct; BUN/sCr 6. Empiric treatment 7. Urea breath test; stool Ag; urease via endoscopic biopsy (H. pylori) |
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If there is an acute GI bleed, what lab value might indicate so?
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Elevated BUN
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What is GERD?
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Reflux of stomach contents into the esophagus
--> can be associated with laryngitis, cough, asthma, and dental erosions |
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What is the pathogenesis of GERD?
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1. Altered motility +/- altered tone +/- decreased epithelial defense
2. Esophageal mucosa exposure to gastric acid contents, bile acids, pepsin 3. Prolonged esophageal transit times 4. Decreased resting pressure of lower esophageal sphincter |
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What are the s/s of GERD?
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1. Irritation, scarring, stricture (most common)
2. Occult blood loss, anemia 3. Tooth discoloration 4. Failure to thrive, anorexia 5. Progressive obstruction 6. Hemorrhage 7. Barrett's esophagitis (increased risk for cancer) |
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What are the non-pharmacologic tx options for GERD?
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1. Position -- avoid slouching; sleep with HOB elevated
2. Weight reduction 3. Smoking cessation 4. Diet restrictions -- a) no snacks < 3 hrs before lying down; b) avoid large meals; c) avoid caffeine, choc, fatty and spicy foods |
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How does peptic ulcer disease develop?
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Imbalance of aggressive and protective factors
Protective: prostaglandins, mucus, bicarb, mucosal blood flow Aggressive: acid, pepsin, NSAID, H. pylori |
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What types of peptic ulcers are possible?
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1. Duodenal
2. Gastric |
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Under what circumstances does gastric acid cause ulceration?
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Ulceration ONLY in the presence of pepsin
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How do stress ulcers form?
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Usually because of decreased mucosal blood flow
-"superficial gastritis"/mucosal erosion vs. craters -Stomach > duodenum -Risk factors: mechanical ventilation, coagulopathy |
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How do NSAID-induced ulcers form?
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NSAIDs cause inhibition of COX-1 activity --> decrease in release of protective prostaglandin E2 (=inhibits acid secretion when released)
Incidence 0.8% unless risk factors present |
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What are risk factors for PUD?
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1. NSAID use
2. Smoking cigarettes 3. Zollinger-Ellison syndrome (gastrinoma) 4. Family history 5. H. pylori infection |
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What factors are possibly associated with PUD?
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1. Corticosteroids (COX 1 inhibitor)
2. Blood group O 3. Stress 4. Poverty |
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What is the clinical presentation of PUD?
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1. Epigastric pain: duodenal 1-3 hrs post-meal; gastric worse after food & at night
2. Dyspepsia; N/V; anorexia; weight loss 3. Blood-streaked emesis/stool in 20% 4. Hemorrhage |
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What are some non-pharmacologic tx options?
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1. Similar to GERD therapies
2. Stress reduction |
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What are treatment goals for PUD?
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1. Relief of symptoms
2. Promotion of ulcer healing 3. Prevention of ulcer recurrence and complications 4. Cost-effective therapy |
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How do we accomplish tx goals for PUD?
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1. Eliminate H. pylori (if present)
2. Reduce gastric acidity 3. Enhance mucosal defenses |
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What are the pharmacologic classes for drugs that inhibit acid production?
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1. H-2 receptor antagonists (H2RAs)
2. Proton pump inhibitors (PPIs) |
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What is the MOA of histamine-2 antagonist receptors (H2RAs)
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Reversibly inhibit gastric acid secretion by competitively antagonizing H2 receptors on parietal cells
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What is the therapeutic effect of H2RAs?
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1. Decreased acid production
2. Inhibition of gastric acid 3. Diminished parietal cell responsiveness to other stimulants (e.g., gastrin) |
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What are the names of some H2RAs?
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1. Cimetidine (IV, PO)
2. Famotidine (IV, PO) 3. Ranitidine (IV, PO) 4. Nizatidine (PO) |
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Which H2RAs undergo extensive first-pass metabolism in PO form?
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Cimetidine, famotidine, ranitidine --> bioavailability ~50%
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Which H2RA has very good bioavailability?
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nizatidine
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What is important in considering prescribing cimetidine?
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Has to be dosed more frequently and has more adverse effects than other H2RAs
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Which H2RAs are eliminated primarily hepatically?
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cimetidine and ranitidine
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Which H2RAs are eliminated primarily renally?
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famotidine and nizatidine
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How should H2RAs be adjusted for renal insufficiency?
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Decrease dose for ClCr < 50 ml/min
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Which patient population should you use caution with when prescribing H2RAs?
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Pregnancy -- cross the placenta and are secreted in breast milk but have not been a/w with major teratogenic risk
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Is it possible for H2RAs to lose effectiveness?
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Yes, tachyphylaxis is possible
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What are the most common adverse effects of H2RAs?
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-CNS: confusion, hallucinations, headache, drowsiness
-Skin: rash -GI: N/V/D, flatulence, dry mouth, constipation -Heme: thrombocytopenia |
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Which H2RA affects CYP450 enzymes?
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Cimetidine inhibits CYP 2C9, 2D6, 3A4
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Which drugs are affected by H2RAs?
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1. Drugs requiring gastric acid (i.e., acidic environment) for absorpiton
2. Ketoconazole and itraconazole (antifungals) 3. Alcohol: All H2RAs may inhibit the action of alcohol dehydrogenase --> potentiates effects of alcohol |
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What is the healing time for tx of duodenal and gastric ulcers with H2RAs?
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Overall healing of 70-95% after 4-8 weeks
All H2RAs are equally effective and tolerated |
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How do H2RAs differ in dosing?
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Famotidine is most potent and possesses longest duration of action
Cimetidine has to be dosed more frequently |
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In what case is H2RA most effective?
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Nocturnal acid secretion
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In what cases are H2RAs less effective?
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1. Not effective against H. pylori-associated PUD
2. Not as effective for chronic PUD or GERD |
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In what form do proton pump inhibitors (PPIs) come?
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Enteric coated capsule or pellets within a capsule
--> acid-labile medication |
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Where in the GI tract are PPIs absorbed?
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Intestines
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PPIs are pro-drugs -- how are they converted to their active state?
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PPIs travel through the blood and enter parietal cells where they are converted to active state by sulfenic acid
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Once PPIs are active, what is their MOA?
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Irreversibly bind to and inhibit the parietal cell's active proton pump
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How quickly do PPIs work?
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Within 24 hours, inhibit >90% secretion of acid
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What is rebound acid secretion?
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Increased gastrin secretion seen in 5-10% of long-term PPI users
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Why must PPIs be continued long-term?
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Proton pumps regenerate in the parietal cell, requiring more PPIs
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How should PPIs be administered?
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1 hr before a meal (breakfast/1st meal)
Bioavailability decreased ~50% by food Must be administered before meal because it must be present in the parietal cell when the proton pump starts working |
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What is the half-life and duration of action of PPIs?
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Short half-life (1.5-2 hrs)
Duration: ~24 hrs --> can inhibit acid secretion for 1-2 days after single dose |
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How are PPIs excreted?
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Renally as primarily inactive metabolite
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How can PPIs be administered for acute situations?
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IV
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What adverse effects are a/w PPIs?
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-GI: N/V/D, constipation, flatulence, dark feces, increased LFT
-CNS: dizziness, headache, insomnia -GU: pyuria, hematuria -Long-term: hip fracture? -Rebound hypersecretion |
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Can PPIs be used by pregnant women?
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Caution in first trimester
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What are some potential adverse effects?
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1. Gastric tumors (rare)
2. Increases in gastric bacterial concentrations 3. Increased risk of enteric infections (e.g., C. diff colitis) |
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What significant drug interactions do PPIs cause?
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1. All PPIs are substrates of CYP 2C19, some 3A4
2. All inhibit CYP2C9/2C19 to varying degrees --> citalopram, phenytoin, propranolol, sertraline 3. PPI + clopidogrel --> suboptimal effect of clopidogrel |
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How do PPIs affect nutrition?
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1. Interfere with gastric absorption of B12
2. Reduced calcium absorption --> increased risk hip fracture 3. Magnesium absorption affected |
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What can be done to allow for calcium absorption when PPIs are being used?
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Calcium citrate -- citrate breaks off and creates temporary acidic environment for calcium absorption
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How efficacious are PPIs?
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Relieve symptoms and heal duodenal/gastric ulcers more quickly than H2RAs
2-4 wks witih absolute healing rates comparable (>90%) |
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What GI conditions benefit most from PPIs?
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1. Non-erosive and erosive reflux disease
2. Esophageal complications of reflux disease 3. Extraesophageal manifestations |
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What are the names of drugs within the PPI class?
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Omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole
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What is the MOA of antacids?
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Neutralization
Antacids are weak bases that react with gastric acid to form water and a salt |
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What is the secondary MOA of antacids?
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Stimulate mucosal prostaglandin synthesis --> protective feature
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When should antacids be taken?
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Between meals
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Which antacids are non-absorbable?
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1. Aluminum hydroxide: Maalox, Mylanta, Gaviscon
2. Magnesium hydroxide: Maalox, Mylanta, Gaviscon With alkaline pancreatic secretion in the duodenum, the antacid precipitates again and is largely excreted in feces |
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Which antacids are absorbable?
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1. Sodium bicarbonate: Alka-seltzer
2. Calcium bicarbonate: Tums, Rolaids With alkaline pancreatic secretion in duodenum, it is precipitated again and subject to reabsorption (sodium > calcium) |
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What are the common therapeutic uses for antacids?
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Symptomatic tx in patients with GERD --> OTC for heartburn and dyspepsia
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What should antacids NOT be used for?
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Tx of active peptic ulcer disease
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What are some administration considerations for antacids?
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1. Multiple daily doses due to short duration of action (4-7/day)
2. Empty stomach 3. Liquid formulations have more rapid onset than tablets 4. Some formulations contain sugar -- caution with DM |
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What are adverse effects of sodium bicarbonate?
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1. Formation of CO2 --> bloating, belching
2. Sodium may be reabsorbed --> exacerbate fluid retention, HTN, kidney disease, HF |
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What are the adverse effects of calcium bicarbonate?
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1. Formation of CO2 --> belching, bloating
2. Constipation 3. Potential for hypercalcemia 4. May induce rebound acid secretion --> calcium stimulates muscle contraction and can promote gastric secretion |
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What are the adverse effects of magnesium compounds?
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1. Diarrhea
2. Magnesium can be absorbed --> sedation, N/V (avoid in patients with severe renal disease) |
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What are the adverse effects of aluminum antacids?
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1. Constipation
2. Aluminum can be absorbed --> avoid in patients with severe renal disease |
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How might the adverse effects of diarrhea/constipation be controlled?
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Antacid product that combines magnesium and aluminum
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How do antacids affect other drugs?
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1. Increase gastric pH
--> digoxin, phenytoin, ketoconazole, itraconazole --> enteric-coated drugs may be released prematurely 2. Reduce absorption of other drugs due to their adsorption to the surface of antacid 3. Complexation (chelation) --> fluoroquinolones (administer 2 hrs before or 2 hrs after) --> tetracyclines (administer 2-3 hrs before antacids) |
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How efficacious are antacids?
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Healing after 4 weeks is 46-88% for duodenal ulcers
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What is Gaviscon?
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Barrier plus antacid
--> sodium bicarb + alum. hydroxide + magnesium trisilicate + alginic acid |
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What is the MOA of Gaviscon?
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-Antacid neutralizes acid
-Rxn between alginic acid and salivary bicarb --> foam floats on top of gastric contents so the antacid solution is refluxed (protects esophagus) |
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What is the MOA of sucralfate?
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Undergoes cross-linking in gastric juice, fomring a viscous gel/paste that adheres to mucoasal defects and exposed deeper layers
"band-aid" |
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What are the therapeutic uses of sucralfate?
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1. Tx of gastric/duodenal ulcers (less effective)
2. Prevention of stress ulcers for patients at risk |
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How should sucralfate be taken?
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4x/day on an empty stomach, 1 hr before meals
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What are the adverse effects of sucralfate?
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Diarrhea; aluminum ions can cause constipation, caution with renal impairment
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What are the drug interactions a/w sucralfate?
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Altered absorption of other PO meds
--> take otehr meds 1 hr before or 2 hrs after |
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What is misoprostol?
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Semisynthetic prostaglandin
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What are the effects of misoprostol?
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1. Inhibits gastric acid secretion
2. Increase mucus and bicarb secretion |
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How is misoprostol a cytoprotective drug?
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Prophylaxis for drug-induced peptic ulcer caused by long-term NSAID and corticosteroid use
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What are the adverse effects of misoprostol?
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Frequent diarrhea, cramps
--> seen after ~ 2 wks, resolves spontaneously after 1 week |
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Are there any contraindications to misoprostol use?
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Pregnancy --> increases uterine contractility
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What is the MOA of Pepto-bismol?
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1. Coats ulcers and erosions --> protective layer against acid and pepsin
2. May stimulate prostaglandin, mucus, and bicarb secretion |
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What are the other uses of Pepto-Bismol?
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1. Anti-diarrheal
2. Antimicrobial activity --> bismuth activity against H. pylori |
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How is Pepto-Bismol excreted?
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-Bismuth: feces (dark feces)
-Salicylate: slow renal excretion |
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What are the adverse effects of Pepto-Bismol?
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1. Blackening of stool
2. Darkening of tongue 3. Encephalopathy -- use short term and not with renal failure 4. Salicylate toxicity in high doses |
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What precautions should be taken with Pepto-Bismol?
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1. Patients on aspirin
2. Contraindicated with warfarin 3. Contraindicated with salicylate (aspirin) allergy |
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What are the effects of prokinetic agents?
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1. Increased resting esophageal sphincter tone
2. Improved gastric tone and peristalsis 3. Relaxes pyloric sphincter 4 Augmented duodenal peristalsis |
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What are the clinical uses for prokinetic agents?
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1. GERD
2. Nausea/vomiting 3. Gastroparesis |
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What is the MOA of Reglan (prokinetic agent)?
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1. Blocks dopamine receptors --> prevents relaxation of GI smooth muscle
2. Increase lower esophageal sphincter tone and enhance gastric emptying |
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What are the pharmacokinetics of Reglan?
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PO or IV administration
-Absorption: rapidly from GI -Metabolism: hepatic -Excretion: renal |
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What are the adverse effects of Reglan?
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-CNS: sedation, confusion, insomnia, anxiety, extrapyramidal effects, seizures
-GI: diarrhea -Increased prolactin levels --> galactorrhea, gynecomastia, impotence |
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When is Reglan contraindicated?
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Obstruction of GI tract
--> muscle constriction will make GI obstruction worse |
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What is the MOA of erythromycin (prokinetic agent)?
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Acts as a motilin agonist by directly stimulating the motilin receptors --> effects:
1. Improves/increases gastric emptying 2. Improves duodenal ctx |
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In which patients is erythromycin useful?
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Patients with diabetic/neuropathic gastroparesis
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What drug interactions occur with erythromycin use?
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1. Decreased clearance of protease inhibitors, phenytoin, cyclosporine, carbamazepine, astemizole, BZs, statins
2. Potentiate the effects of warfarin (from effect on GI flora, which do not produce vit. K) |
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What are the rates of H. pylori infection in N. America in patients with dyspepsia?
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30%
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How does H. pylori exert pathogenicity?
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1. Cytotoxin release (inflammation)
2. Breaks mucosal defense 3. Adherence |
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What percentage of ulcers are a/w H. pylori infection?
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Duodenal 90%
Gastric 70% |
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How does family hx relate to H. pylori infection?
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Familial but not necessarily genetic
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How can a diagnosis of H. pylori infection be made?
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1. Urea breath test
2. Stool antigen 3. Biopsy via endoscopy 4. Serology for IgG -- caution, may be elevated because of another microbe |
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What antibiotic can be subbed if amoxicillin or clarithromycin are not tolerated?
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Metronidazole (Flagyl)
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What is the ideal combination therapy for H. pylori infection?
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PPI (preferably omeprazole) + antibiotic(s) + bismuth
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What are the adverse effects of multi-drug regimen for H. pylori?
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1. N/V/D
2. Bitter or metallic taste in mouth (clarithromycin therapy) 3. Bismuth may cause darkening of stool |
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What is the chemoreceptor trigger zone?
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Area within the medulla (outside the BBB) tha treceives inputs from drugs, NTs, hormones, and communicates with vomiting center to initiate vomiting
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What NTs are implicated in N/V?
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1. ACh
2. Histamine 3. Substance P 4. Serotonin 5. Dopamine |
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What drugs are in the class of serotonin 5-HT3 antagonists?
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1. Dolasetron
2. Granisetron 3. Ondansetron 4. Palonsetron (dosed once weekly) |
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What is the MOA of serotonin antagonists?
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Competitively block 5-HT3 receptors in the chemoreceptor trigger zone and GI tract
--> blocker peripheral and central stimulation of vomiting |
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What are the clinical uses for serotonin antagonists?
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1. Chemotherapy-induced N/V --> most effective administered IV 30 min before
2. Post-operative N/V |
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What are the adverse effects of serotonin antagonists?
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Headache; dizziness; constipation; QT prolongation
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What are phenothiazines?
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Antipsychotic drugs that can be used for antiemetic and sedative properties
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What is the MOA of phenothiazines?
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Inhibit dopamine and muscarinic receptors (chemoreceptor trigger zone)
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What drugs fall under phenothiazines?
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1. Promethazine
2. Prochlorperazine both in PO, IV, PR, IM |
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What are the adverse effects of phenothiazines?
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Sedation; hypotension; extrapyramidal effects; anticholinergic effects
Anticholinergics impair SLUD (= salivation, lacrimation, urination, defecation) |
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What corticosteroid may be used to provide moderate antiemetic activity?
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Dexamethasone
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What are the adverse effects of corticosteroids?
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Euphoria; anxiety; insomnia; fluid retention; mood changes; hyperglycemia; increased appetite
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