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
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)
3
Q
PK of PPIs
- Peak serum concentration coincides w/ what?
A
The maximal activity of proton pump secretion
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)
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
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
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
8
Q
- What is released by the D-cell, which then enters the G-cell in the antrum of the stomach?
A
Somatostatin
9
Q
What enters the parietal cell in the fundus of the stomach?
A
Gastrin
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
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
12
Q
3 SE of PPIs
A
- Diarrhea**
- HA
- Abdominal pain
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
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
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
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”
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”
18
Q
PPI Drug Interaction
Which drug may decrease the metabolism of Diazepam?
A
Esomeprazole
19
Q
PPI Drug Interactions
- Lansoprazole may enhance clearance of what drug?
A
Theophylline
20
Q
PPI Drug Interactions
- Which 2 PPIs have no significant drug interactions?
A
- Rabeprazole
- Pantoprazole
“A rabbi wearing pants is getting no action…”
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
22
Q
PPI Drug Interactions
- Which 2 PPIs are preferred bc/ of minimal CYP2C10 inhibition?
A
Rabeprazole & Pantoprazole
“Rabbi wearing Pants”
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
24
Q
What substance appears to be important in stimulating mucus and bicarbonate secretion and mucosal blood flow?
A
Mucosal prostaglandins
25
What are the 3 Mucosal Protective Agents?
* Sucralfate
* Prostaglandin analogs
* Bismuth
26
**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
27
**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
28
**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
29
**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
30
**Prostaglandin Analongs**
* Gastrointestinal mucosa synthesizes a number of prostaglandins
* What are the 2 primary prostaglandins?
E & F
31
What is the name of a prostaglandin analog? (Methyl Analog of PGE1)
Misoprostol
32
**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**
33
**T/F**
* Dose reduction of Misoprostol is NOT needed in pts w/ renal insufficiency
True
34
**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
1. Intestinal electrolyte & fluid secretion
2. Intestinal motility
3. Uterine contractions
35
**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)
36
**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)
37
What are the 2 bismuth compounds?
* bismuth subsalicylate
* bismuth subcitrate potassium
38
**Which bismuth compound?**
* nonprescription formulation containing bismuth and salicylate
Bismuth subsalicylate
39
**Which bismuth compound?**
* combination prescription product that also contains metronidazole and tetracycline for the treatment of H pylori.
bismuth subcitrate potassium
40
**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
41
**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
42
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
43
Which bismuth treats nonspecific tx of dyspepsia and acute diarrhea?
**Bismuth compounds** (Pepto-Bismol, Kaopectate)
44
Which bismuth is for prevention of traveler's diarrhea?
Bismuth subsalicylate
45
* 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**
46
**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
47
**ADEs of what drug?**
* Nausea, Vomiting, Diarrhea
* Flatulence
* hypomagnesemia, hypocalcemia
PPI
48
**Which med?**
* Well tolerated
* May be associated w/ increased risk of fractures, PNA, C. diff infections
PPI
49
**ADEs of what drug?**
* Dizziness
* Somnolence
* Gynecomastia
* Pancreatitis
Histamine 2 receptor antagonists
50
Sucralfate causes what ADE?
Constipation
51
**ADEs of what drug?**
* Abdominal pain
* Dysmenorrhea
* Hypophosphatemia
Misoprostol
52
**Which drugs require monitoring of:**
* Baseline and periodic CBC, serum electrolytes, renal/liver function
PPI & H2 blockers
53
**Which drug requires monitoring of:**
* Pregnancy test
* Serum phosphate
* Should avoid in pregnancy
Misoprostol
54
H. pylori can lead to what 2 cancers?
* Mucosa-associated lymphoid tissue (MALT) lymphoma
* Gastric cancer
55
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
56
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
57
What is the triple therapy to eradicate H. pylori?
* #1: PPI
* #2: Clarithroymycin
* #3: Amoxicillin or Metronidazole
(all twice daily)
58
What is the quadruple therapy to tx H. pylori?
* bismuth
* metronidazole
* tetracycline
* PPI
59
Eradication of H. pylori after abx tx may be confirmed how?
* urea breath test
* Stool antigen test
* upper endoscopy
(+ result = persistent infection)
P2 E2 Shea
flashcards
Decks in class (19)
# Cards
-
GI & Peptic 142
-
GI & Peptic 259
-
Antiemetics62
-
GI Motility 147
-
Gout57
-
GI Motility 245
-
GI Motility 349
-
Antidepressants 150
-
Antidepressants 247
-
Anxiolytic22
-
Pancreatitis & Celiac Disease47
-
Blocking Drugs - 153
-
Blocking Drugs - 233
-
Rheum- OA27
-
Rheum- RA61
-
Rheum- RA (Biologics)22
-
Antipsychotics/Lithium- 241
-
Antipsychotics&Lithium 130
-
Antiemetic popcorn33
