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DEMS: Unit 1 > Upper GI Pharmacology > Flashcards

Flashcards in Upper GI Pharmacology Deck (37):
1

Antibiotics role in peptic ulcers

  • critical role in eradicating H. pylori infection (associated w/many ulcers)
  • use: reduce rate of recurrence of gastric and duodenal ulcers
  • one component of "triple" or "quadruple" therapy

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Triple therapy drugs/use

  • use: tx of H. pylori-associated ulcers
  • PPI
  • Clarithromycin
  • Amoxicilin
  • OR Metronidazole

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Quadruple therapy drugs

  • Bismuth subsalicylate
  • Metronidazole
  • Tetracycline 
  • PPI or H2 antagonist

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Sequentioal therapy drugs

  • Amoxicillin + PPI (5 days)
  • then Clarithromycin + Tinidazole + PPI (5 days)

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Proton Pump Inhibitors: MOA

  • administered as prodrug ==> systemic circulation ==> parietal cells ==> active sulfenamide
  • covalent linkage to H+-K+-ATPase irreversible inactivates enzymes
    • 18 hours req. for synthesis of new enzyme

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Examples of PPIs

  • Omeprazole (Prilosec)
  • Lansoprazole (Prevacid)

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Clinical uses of PPIs

  • GERD
  • Peptic Ulcer Disease
  • NSAID-induced ulcers
  • Zollinger-Ellison syndrome (symptom relief/ulcer healing)

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H2 Receptor Antagonists examples

  • Ranitidine [Zantac]
  • Cimetidine [Tagamet]
  • Famotidine [Pepcid]
  • Nizatidine [Axid]

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H2 Receptor Antagonist: MOA

  • reversible, competitive block at parietal cell H2 receptors on basolateral membrane
    • better @ blocking nocturnal acid secretion (H2-mediated) vs. meal-stimulated (ACh/gastrin)
  • Less efficacious than PPIs but still suppress 24 hour acid secretion by 70%.

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PPIs: Pharmacokinetics/Dosing

  • rapidly absorbed
  • good oral availabilty w/enteric coating
  • dosing: empty stomach 1 hour before meals
  • metabolism: CYP450

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H2 Antagonists: Pharmacokinetics/Dosing

  • rapidly absorbed from GI tract
    • some enhancement w/food
  • dosing: BID
  • metabolism: mostly renal ==> dosage adjustment w/impaired renal fxn

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H2 antagonists: clinical uses

  • GERD
    • PPIs preferred in severe erosive esophagitis
  • Peptic Ulcer Disease
    • used at bedtime for noctural acid secretion
  • Stress-related gastritis

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PPIs: Side effects/drug interactions

  • mild SE (headache, ab pain, naseau) 
    • chronic use ==>
      • hypergastrinemia
      • rebound gastric acidity after discontinuation
  • drug-drug interactions
    • CYP450 metabolism ==>
    • omeprazole ==> inhibits conversion of clopidogrel (antiplatet agent) to active form

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H2 antagonists: Side effects/drug interactions

  • Side effects
    • rare and mild (dizzy, diarhea/constipation, HA)
    • some rare CNS/endocrine effects
  • drug-drug interactions
    • Cimetidine inhibits cytochrome P450 oxidative metabolism ==>

    • increase the effects or toxicity of number of drugs (theophylline, warfarin, phenytoin, carbamazepine, ketoconazole, itraconazole, benzodiazepines).

  • All antisecretory agents can decrease ketoconazole absorption by causing an increase in gastric pH.

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Sucralfate [Carafate]: MOA

  • = sulfated disaccharide aluminum salt
  • MOA: binds to necrotic ulcer tissue form protective barrier
  • used infrequently or an adjunct therapy

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Misoprostol (Cytotec): MOA

  • Prostaglandin (PGE1) analog
  • MOA: 
    • PGs ==> inhibition of cAMP formation @ parietal cells ==> decreased H+ secretion
    • AND stimulate HCO3- & mucous formation

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Misoprostol (Cytotec): Clinical Use

  • major indication = NSAID-induced GI ulceration
  • rarely used b/c 4x/day dosing + adverse effects

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Antacids: MOA, pharmacokinetics

  • MOA:
    • rapidly raise pH of stomach ==> 4-5
  • Pharmacokinetics
    • nonabsorbable
    • long-acting
  • Dosing
    • usually titrated to symptom relief
    • ~1-3 hours after meals (food ==> increased duration)

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Antacids: primary neutralizing ingredients

  • calcium
  • aluminum
  • magnesium
  • sodium bicarbonate

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Calcium (Tums): general characteristics

  • MOA: rapid, prolonged neutralization of acid
  • Safe, generally non-systemic, not recommended for chronic use 
  • SE:
    • Constipation
    • hypercalcemia / renal calculi (w/chronic use)
    • rebound secretion due to Ca++ effect on gastrin release

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Aluminum: general characteristics

  • MOA:
    • antacid
    • binds phosphate in gut

  • Widely used
  • SE
    • constipation
    • Chronic intake ==> CNS toxicity (encephalopathy)

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Magnesium (Milk of Magnesia): general characteristics 

  • MOA: antacid
  • Use: often combined w/Al or Ca antacids to counteract constipation
  • SE
    • osmotic diarrhea
    • Avoid use if renal disease present 

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Sodium bicarbonate (baking soda): general characteristics

  • MOA: antacid
    • Potent and effective
    • evolution of CO2
  • SE
    • Contraindicated for prolonged therapy due to systemic effects: Na+ overload and alkalosis
  • Avoid if:  Pregnant, CHF, hypertension, edema, renal failure (i.e., conditions exacerbated by fluid retention)

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Prokinetic agents: Clinical Use

  • empiric and symptoms-based treatment for various disorders of bowel motility [achalasia of esophagus, gastroparesis]
  • symptom relief of esophagitis associated with gastroesophageal reflux disease (GERD).

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Prokinetic agents: examples

  • Metoclopramide (Reglan)
  • Tegaserod (Zelnorm)
  • Cisapride (Propulsid)

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Metoclopramide: MOA & SE

  • MOA: antagonist (-) at presynaptic dopamine (DA) receptors (D2) that inhibit the release of acetycholine
  • SE:
    • somnolence
    • dystonic reactions
    • tardive dyskinesia

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Tegaserod (zelnorm) & Cisapride: MOA & SE

  • MOA: agonists at postsynaptic 5HT4 receptors to directly increase ACh release
    • Stimulates motility and increases transit in esophagus, stomach, small intestine and ascending colon
    • Reduces bloating associated with irritable bowel syndrome
  • SE 
    • Some severe SEs (e.g. MIs, CVAs & arrhythmias) ==> severely restricted use
    • back on market for IBS

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Erythromycin: MOA

  • promotility agent
  • MOA: (+) is an agonist at excitatory (+) at neural and smooth muscle motilin receptors

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Therapeutic targets of anti-emetic agents

  • vomiting center/solitary tract nucleus
  • afferent inputs to vomiting center:
    • chemoreceptor trigger zone/area postrema
      • dopamine, 5-HT3, muscarinic, and mu opioid receptors
    • vestibular apparatus
      • muscarinic and H1 receptors
    • vagal/eneteric afferents
      • 5-HT3
    • higher CNS centers

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Ondansetron [Zofran]: MOA, efficacy, SE

  • MOA: Block of serotonin (5-HT3) receptors at chemoreceptor trigger zone (CTZ in CNS), solitary tract nucleus, and on visceral afferents (GI tract
  • Clinical use:
    • vomiting assoc. w/cytotoxic drugs
    • N/V assoc. w/opioid use
  • SE:
    • HA, constipation, drowsy
    • QT prolongation

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Dopamine Receptor Antagonists: : MOA, use, SE

  • MOA:  Blockade of dopamine receptors in CTZ
  • Clinical use:
    • prochlorperazine ==> motion sickness
    • metoclipramide ==> N/V w/chemo
  • Side effects:  
    • extrapyramidal symptoms (movement disorders)
    • restlessness, fatigue, drowsiness
    • diarrhea

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Dopamine Receptor Antagonists: examples

  • Metoclopramide [Reglan]
  •  Phenothiazines: 
    • Prochlorperazine [Compazine]

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Metoclopramide [Reglan]: drug category/MOA

  • anti-emetic
  • MOA: block D receptors @ CTZ

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Prochlorperazine: drug category/MOA

  • anti-emetic
  • MOA: block D receptors @ CTZ

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Antihistamines: MOA, clinical use, examples

  • examples: meclizine [Bonine}, diphenhydramine [Dramamine]
  • First generation agents with good CNS penetration and additional muscarinic receptor blocking actions

  • Primary use for motion sickness and postoperative emesis

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Anticholinergics: MOA, clinical use, examples

  • example: scopolamine [Transderm = transdermal patch]
  • Primary use is prevention and treatment of motion sickness; some efficacy in post-operative nausea and vomiting

  • Most commonly administered transdermally with duration of action of 72 hours

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