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MJ- P2 E2 > GI & Peptic 2 > Flashcards

GI & Peptic 2 Flashcards

1
Q

PK of Proton Pump Inhibitors

Which drug?

–Oral products are formulated for delayed release as acid-resistant, enteric-coated capsules or tablets to avoid rapid destruction within the gastric lumen

–prodrug rapidly becomes protonated within the canaliculus

A

Inactive Acid Labile Prodrugs

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2
Q

PPI

  • Bioavailability of all agents is decreased by 50% by what?***
  • How is this fixed?****
A
  • Food***
  • Administer approximately 30 - 60 mins BEFORE a meal (usually breakfast)***

(Know this)

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3
Q

PK of PPIs

  • Peak serum concentration coincides w/ what?
A

The maximal activity of proton pump secretion

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4
Q
  • PPIs inactivate acid pumps that are doing what?
  • PPIs have NO EFFECT on pumps in what?
A
  • Actively secreting
  • Quiescent (in a state or period of inactivity or dormancy)
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5
Q

PK of PPIs

  • Acid inhibition lasts up to __ hours owing to the irreversible inactivation of the proton pump
  • How many hours are required for synthesis of new H+/K+-ATPase pump molecules
  • Undergo which rapid 1st pass systemic effect?
  • Which type of clearance neglible?
A
  • 24 hours
  • 18 hours
  • 1st pass hepatic
  • neglible: renal clearance
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6
Q

PK of PPIs

  • Dose reduction in pts w/ what condition?
  • •H+/K+-ATPase appears to exist only in what cells?
A
  • Severe liver impairment
  • Parietal cells
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7
Q

PPI Pharmacodynamics

  • Blocks what?
  • Inhibits 90-98% of 24 hour acid secretion
  • Acid suppression is more dependent upon what than the PK of different agents?
A
  • Final common pathway of acid secretion (the proton pump)
  • Dependent upon: irreversible inactivation of the proton pump
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8
Q
  • What is released by the D-cell, which then enters the G-cell in the antrum of the stomach?
A

Somatostatin

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9
Q

What enters the parietal cell in the fundus of the stomach?

A

Gastrin

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10
Q

5 uses of PPIs

A

•GERD

•PUD

•Nonulcer dyspepsia

•Prevention of Stress-Related Mucosal Bleeding

•Gastrinoma and other Hypersecretory Conditions

–isolated gastrinomas–surgical resection

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11
Q

Which nerve stimulates postganglionic neurons of the enteric nervous system to release acetylcholine (ACh), which binds to M3 receptors on parietal cells and ECL cell?

A

Vagus

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12
Q

3 SE of PPIs

A
  • Diarrhea**
  • HA
  • Abdominal pain
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13
Q

PPI adverse effects

  • Acid is important in releasing what from food?
  • Acid also promotes absorption of what 3 food bound minerals?***
    • What should you monitor?
    • What could you supplement with?
A
  • Releasing B12 from food
  • 3 food-bound minerals: iron, Ca, Mg*** (know this)
  • Monitor: bone density
  • Ca supplements
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14
Q

Adverse effects of which agent?

  • Community-acquired respiratory infections and nosocomial pneumonia
  • 2- to 3-fold increased risk for hospital- and community-acquired Clostridium difficile infection
  • small increase risk of other enteric infections
    • Salmonella, Shigella, E coli, Campylobacter
A

PPI

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15
Q

PPI adverse effects

  • Gastrin levels rise 1.5 - 2 fold may stimulate hyperplasia of what 2 cells?
    • Transient rebound acid hypersecretion increase in what 2 sxs?
    • Abates/subsides in how many weeks?
A
  • ECL & parietal cells
  • Sxs: dyspepsia or heartburn
  • 2 - 4 weeks
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16
Q

PPI Drug Interactions

  • Decreased gastric acidity may alter absorption of what 4 drugs? Which drug especially?**
A
  • Ketoconazole
  • Itraconazole
  • Digoxin***
  • Atazanavir

“A KID”

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17
Q

PPI Drug Interactions

  • Omeprazole may inhibit the metabolism of what 3 drugs? Especially which drug?
A
  • Warfarin***
  • Diazepam
  • Phenytoin

“Omeprazole went to War w/ P. diddy”

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18
Q

PPI Drug Interaction

Which drug may decrease the metabolism of Diazepam?

A

Esomeprazole

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19
Q

PPI Drug Interactions

  • Lansoprazole may enhance clearance of what drug?
A

Theophylline

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20
Q

PPI Drug Interactions

  • Which 2 PPIs have no significant drug interactions?
A
  • Rabeprazole
  • Pantoprazole

“A rabbi wearing pants is getting no action…”

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21
Q

PPI Drug Interactions

  • Metabolized by P450 cytochromes, including CYP2C19 and CYP3A4
  • What is the “prodrug” which requires activation by the hepatic P450 CYP2C19?
  • PPIs could reduce activation of what drug?
A
  • Clopidogrel
  • Clopidogrel
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22
Q

PPI Drug Interactions

  • Which 2 PPIs are preferred bc/ of minimal CYP2C10 inhibition?
A

Rabeprazole & Pantoprazole

“Rabbi wearing Pants”

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23
Q

Mucosal Protective Agents

  • Gastroduodenal mucosa evolved a number of defense mechanisms to protect itself against the noxious effects of what 2 substances?
  • Mucus and epithelial cell-cell tight junctions restrict what?
  • Blood flow carries what 2 substances to surface cells?
A
  • acid & pepsin
  • back diffusion of acid & pepsin
  • bicarbonate & vital nutrients
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24
Q

What substance appears to be important in stimulating mucus and bicarbonate secretion and mucosal blood flow?

A

Mucosal prostaglandins

25
Q

What are the 3 Mucosal Protective Agents?

A
  • Sucralfate
  • Prostaglandin analogs
  • Bismuth
26
Q

Which Mucosal Protective Agent?

  • Salt of sucrose complexed to sulfated aluminum hydroxide
  • In water or acidic solutions it forms a viscous, tenacious paste that binds selectively to ulcers or erosions for up to 6 hours
A

Sucralfate

27
Q

Which Mucosal Protective Agent?

  • Negatively charged sucrose sulfate binds to positively charged proteins in the base of ulcers or erosion
  • Forms a physical barrier that restricts caustic damage
  • Stimulates mucosal prostaglandin and bicarbonate secretion
A

Sucralfate

28
Q

Which Mucosal Protective Agent?

  • Used to prevent stress-related bleeding
    • •concerns that acid inhibitory therapies (antacids, H2 antagonists, and proton pump inhibitors) may increase the risk of nosocomial pneumonia
A

Sucralfate

29
Q

Adverse effects of which Mucosal Protective Agent?

  • Constipation occurs in 2% of patients due to the aluminum salt
  • Small amount of aluminum is absorbed
  • Do not be used for prolonged periods in patients with renal insufficiency
A

Sucralfate

30
Q

Prostaglandin Analongs

  • Gastrointestinal mucosa synthesizes a number of prostaglandins
  • What are the 2 primary prostaglandins?
A

E & F

31
Q

What is the name of a prostaglandin analog? (Methyl Analog of PGE1)

A

Misoprostol

32
Q

Misoprostol (prostaglandin analog)

  • Approved for GI conditions
  • Rapidly absorbed
  • Metabolized to what?
  • Serum half life is how long?
  • Must be administered 3 - 4 x daily
  • Excreted how?
A
  • Metabolized to a metabolically active free acid
  • Half life: less than 30 mins
  • Excreted in the urine
33
Q

T/F

  • Dose reduction of Misoprostol is NOT needed in pts w/ renal insufficiency
A

True

34
Q

Prostaglandin Analogs: Misoprostol

Pharmacodynamics

  • Has what 2 properties?
  • Stimulates mucus and bicarb secretion and enhance mucosal blood flow
  • Binds to prostaglandin receptor on parietal cells, reducing histamine stimulated _____ production and causing modest acid inhibition
  • Prostaglandins stimulate what 3 things?
A
  • Acid inhibitory & Mucosal protective properties
  • cAMP
  1. Intestinal electrolyte & fluid secretion
  2. Intestinal motility
  3. Uterine contractions
35
Q

Which medication?

  • Peptic ulcers develop in approximately 10–20% of patients who receive long-term NSAID therapy
  • Reduces the incidence of NSAID-induced ulcers to less than 3% and the incidence of ulcer complications by 50%
  • Approved for prevention of NSAID-induced ulcers in high-risk patients
  • Cyclooxygenase-2-selective NSAIDs offer another option for patients at high risk for NSAID-induced complications.
A

Misoprostal

(Prostaglandin Analog)

36
Q

Adverse reactions of which medication?

  • Diarrhea and cramping abdominal pain occur in 10–20% of patients
  • stimulates uterine contractions
  • should not be used during pregnancy or in women of childbearing potential unless they have a negative serum pregnancy test and are compliant with effective contraceptive measures
  • No significant drug interactions are reported
A

Misoprostol

(Prostaglandin Analog)

37
Q

What are the 2 bismuth compounds?

A
  • bismuth subsalicylate
  • bismuth subcitrate potassium
38
Q

Which bismuth compound?

  • nonprescription formulation containing bismuth and salicylate
A

Bismuth subsalicylate

39
Q

Which bismuth compound?

  • combination prescription product that also contains metronidazole and tetracycline for the treatment of H pylori.
A

bismuth subcitrate potassium

40
Q

Bismuth

  • Bismuth subsalicylate undergoes rapid dissociation within the stomach allowing absorption of what?
  • Over 99% of bismuth appears where?
  • What % of bismuth is absorbed?
  • What substance is (like ASA), readily absorbed and excreted in the urine
A
  • salicylate
  • in the stool
  • minimal <1% of bismuth is absorbed (stored in many tissues and has slow renal excretion)
  • Salicylate
41
Q

Bismuth Compounds

  • Precise mechanics unknown
  • Coats ulcers & erosions, creating protective layer against acid & pepsin
  • May stimulate what 3 things?
  • Which bismuth reduces stool frequency and liquidity in acute infectious diarrhea?
A
  • secretion of: prostaglandin, mucus, bicarbonate
  • Bismuth subsalicylate
42
Q

Bismuth has direct ____ effects against what and binds enterotoxins, accounting for its benefits in preventing and treating what?

A
  • antimicrobial effects against H. pylori
  • traveler’s diarrhea
43
Q

Which bismuth treats nonspecific tx of dyspepsia and acute diarrhea?

A

Bismuth compounds (Pepto-Bismol, Kaopectate)

44
Q

Which bismuth is for prevention of traveler’s diarrhea?

A

Bismuth subsalicylate

45
Q
  • Which bismuth therapy is first line due to “superior compliance?”
  • Which is 2nd line?
A

1st: “Triple Therapy”

  • Proton Pump Inhibitor
  • Clarithromycin
  • Amoxicillin or Metronidazole

(twice daily)

2nd: Bismuth based quadruples

46
Q

ADEs of Bismuth Compounds

  • Excellent safety profiles
  • What are 2 harmless effects?
  • Avoided in pts w/ _____ insufficiency
  • Bismuth toxicity results in what?
  • Bismuth toxicity is NOT reported in which 2 forms of bismuth?
  • High dosages of bismuth subsalicylate can lead to what?
A
  • 2 harmless: blackening of stool & darkening of tongue
  • Avoided in renal insufficiency
  • Bismuth toxicity -> encephalopathy (ataxia, HAs, confusion, seizures)
  • 2 forms: bismuth subsalicylate & bismuth citrate
  • salicylate toxicity
47
Q

ADEs of what drug?

  • Nausea, Vomiting, Diarrhea
  • Flatulence
  • hypomagnesemia, hypocalcemia
A

PPI

48
Q

Which med?

  • Well tolerated
  • May be associated w/ increased risk of fractures, PNA, C. diff infections
A

PPI

49
Q

ADEs of what drug?

  • Dizziness
  • Somnolence
  • Gynecomastia
  • Pancreatitis
A

Histamine 2 receptor antagonists

50
Q

Sucralfate causes what ADE?

A

Constipation

51
Q

ADEs of what drug?

  • Abdominal pain
  • Dysmenorrhea
  • Hypophosphatemia
A

Misoprostol

52
Q

Which drugs require monitoring of:

  • Baseline and periodic CBC, serum electrolytes, renal/liver function
A

PPI & H2 blockers

53
Q

Which drug requires monitoring of:

  • Pregnancy test
  • Serum phosphate
  • Should avoid in pregnancy
A

Misoprostol

54
Q

H. pylori can lead to what 2 cancers?

A
  • Mucosa-associated lymphoid tissue (MALT) lymphoma
  • Gastric cancer
55
Q

What are the 4 “established indications” to treat an H. pylori infection?

A
  • Gastric or duodenal ulcer
  • MALT lymphoma
  • After endoscopic resection of gastric cancer
  • Uninvestigated dyspepsia
56
Q

What are the 5 “controversial indications” to treat an H. pylori infection?

A
  • Nonulcer dyspepsia
  • Gastroesophageal reflux disease
  • Individuals taking NSAIDs
  • Individuals at high risk for gastric cancer
  • Unexplained iron deficiency anemia
57
Q

What is the triple therapy to eradicate H. pylori?

A
  • # 1: PPI
  • # 2: Clarithroymycin
  • # 3: Amoxicillin or Metronidazole

(all twice daily)

58
Q

What is the quadruple therapy to tx H. pylori?

A
  • bismuth
  • metronidazole
  • tetracycline
  • PPI
59
Q

Eradication of H. pylori after abx tx may be confirmed how?

A
  • urea breath test
  • Stool antigen test
  • upper endoscopy

(+ result = persistent infection)

MJ- P2 E2 (19 decks)

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