GI & Peptic 2 Flashcards
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
Inactive Acid Labile Prodrugs
PPI
- Bioavailability of all agents is decreased by 50% by what?***
- How is this fixed?****
- Food***
- Administer approximately 30 - 60 mins BEFORE a meal (usually breakfast)***
(Know this)
PK of PPIs
- Peak serum concentration coincides w/ what?
The maximal activity of proton pump secretion
- PPIs inactivate acid pumps that are doing what?
- PPIs have NO EFFECT on pumps in what?
- Actively secreting
- Quiescent (in a state or period of inactivity or dormancy)
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?
- 24 hours
- 18 hours
- 1st pass hepatic
- neglible: renal clearance
PK of PPIs
- Dose reduction in pts w/ what condition?
- •H+/K+-ATPase appears to exist only in what cells?
- Severe liver impairment
- Parietal cells
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?
- Final common pathway of acid secretion (the proton pump)
- Dependent upon: irreversible inactivation of the proton pump
- What is released by the D-cell, which then enters the G-cell in the antrum of the stomach?
Somatostatin
What enters the parietal cell in the fundus of the stomach?
Gastrin
5 uses of PPIs
•GERD
•PUD
•Nonulcer dyspepsia
•Prevention of Stress-Related Mucosal Bleeding
•Gastrinoma and other Hypersecretory Conditions
–isolated gastrinomas–surgical resection
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?
Vagus
3 SE of PPIs
- Diarrhea**
- HA
- Abdominal pain
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?
- Releasing B12 from food
- 3 food-bound minerals: iron, Ca, Mg*** (know this)
- Monitor: bone density
- Ca supplements
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
PPI
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?
- ECL & parietal cells
- Sxs: dyspepsia or heartburn
- 2 - 4 weeks
PPI Drug Interactions
- Decreased gastric acidity may alter absorption of what 4 drugs? Which drug especially?**
- Ketoconazole
- Itraconazole
- Digoxin***
- Atazanavir
“A KID”
PPI Drug Interactions
- Omeprazole may inhibit the metabolism of what 3 drugs? Especially which drug?
- Warfarin***
- Diazepam
- Phenytoin
“Omeprazole went to War w/ P. diddy”
PPI Drug Interaction
Which drug may decrease the metabolism of Diazepam?
Esomeprazole
PPI Drug Interactions
- Lansoprazole may enhance clearance of what drug?
Theophylline
PPI Drug Interactions
- Which 2 PPIs have no significant drug interactions?
- Rabeprazole
- Pantoprazole
“A rabbi wearing pants is getting no action…”
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?
- Clopidogrel
- Clopidogrel
PPI Drug Interactions
- Which 2 PPIs are preferred bc/ of minimal CYP2C10 inhibition?
Rabeprazole & Pantoprazole
“Rabbi wearing Pants”
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?
- acid & pepsin
- back diffusion of acid & pepsin
- bicarbonate & vital nutrients
What substance appears to be important in stimulating mucus and bicarbonate secretion and mucosal blood flow?
Mucosal prostaglandins
What are the 3 Mucosal Protective Agents?
- Sucralfate
- Prostaglandin analogs
- Bismuth
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
Sucralfate
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
Sucralfate
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
Sucralfate
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
Sucralfate
Prostaglandin Analongs
- Gastrointestinal mucosa synthesizes a number of prostaglandins
- What are the 2 primary prostaglandins?
E & F
What is the name of a prostaglandin analog? (Methyl Analog of PGE1)
Misoprostol
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?
- Metabolized to a metabolically active free acid
- Half life: less than 30 mins
- Excreted in the urine
T/F
- Dose reduction of Misoprostol is NOT needed in pts w/ renal insufficiency
True
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?
- Acid inhibitory & Mucosal protective properties
- cAMP
- Intestinal electrolyte & fluid secretion
- Intestinal motility
- Uterine contractions
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.
Misoprostal
(Prostaglandin Analog)
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
Misoprostol
(Prostaglandin Analog)
What are the 2 bismuth compounds?
- bismuth subsalicylate
- bismuth subcitrate potassium
Which bismuth compound?
- nonprescription formulation containing bismuth and salicylate
Bismuth subsalicylate
Which bismuth compound?
- combination prescription product that also contains metronidazole and tetracycline for the treatment of H pylori.
bismuth subcitrate potassium
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
- salicylate
- in the stool
- minimal <1% of bismuth is absorbed (stored in many tissues and has slow renal excretion)
- Salicylate
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?
- secretion of: prostaglandin, mucus, bicarbonate
- Bismuth subsalicylate
Bismuth has direct ____ effects against what and binds enterotoxins, accounting for its benefits in preventing and treating what?
- antimicrobial effects against H. pylori
- traveler’s diarrhea
Which bismuth treats nonspecific tx of dyspepsia and acute diarrhea?
Bismuth compounds (Pepto-Bismol, Kaopectate)
Which bismuth is for prevention of traveler’s diarrhea?
Bismuth subsalicylate
- Which bismuth therapy is first line due to “superior compliance?”
- Which is 2nd line?
1st: “Triple Therapy”
- Proton Pump Inhibitor
- Clarithromycin
- Amoxicillin or Metronidazole
(twice daily)
2nd: Bismuth based quadruples
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?
- 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
ADEs of what drug?
- Nausea, Vomiting, Diarrhea
- Flatulence
- hypomagnesemia, hypocalcemia
PPI
Which med?
- Well tolerated
- May be associated w/ increased risk of fractures, PNA, C. diff infections
PPI
ADEs of what drug?
- Dizziness
- Somnolence
- Gynecomastia
- Pancreatitis
Histamine 2 receptor antagonists
Sucralfate causes what ADE?
Constipation
ADEs of what drug?
- Abdominal pain
- Dysmenorrhea
- Hypophosphatemia
Misoprostol
Which drugs require monitoring of:
- Baseline and periodic CBC, serum electrolytes, renal/liver function
PPI & H2 blockers
Which drug requires monitoring of:
- Pregnancy test
- Serum phosphate
- Should avoid in pregnancy
Misoprostol
H. pylori can lead to what 2 cancers?
- Mucosa-associated lymphoid tissue (MALT) lymphoma
- Gastric cancer
What are the 4 “established indications” to treat an H. pylori infection?
- Gastric or duodenal ulcer
- MALT lymphoma
- After endoscopic resection of gastric cancer
- Uninvestigated dyspepsia
What are the 5 “controversial indications” to treat an H. pylori infection?
- Nonulcer dyspepsia
- Gastroesophageal reflux disease
- Individuals taking NSAIDs
- Individuals at high risk for gastric cancer
- Unexplained iron deficiency anemia
What is the triple therapy to eradicate H. pylori?
- # 1: PPI
- # 2: Clarithroymycin
- # 3: Amoxicillin or Metronidazole
(all twice daily)
What is the quadruple therapy to tx H. pylori?
- bismuth
- metronidazole
- tetracycline
- PPI
Eradication of H. pylori after abx tx may be confirmed how?
- urea breath test
- Stool antigen test
- upper endoscopy
(+ result = persistent infection)
