ICL 4.2: Disorders of Acid Production, GI Pharmacology & Acid Suppression Flashcards
1
Q
why are antacids used clinically?
A
- cheap and easily obtainable
- provide quick relief
- first-line treatment for mild intermittent (less than twice weekly) or breakthrough symptoms for patients receiving H2RA or PPI therapy
- not appropriate for chronic symptoms or for healing esophageal erosions
2
Q
which medications are antacids?
A
- calcium carbonate
- aluminum carbonate
- magnesium oxide
- alginic acid
3
Q
what is the MOA of antacids?
A
they neutralize gastric acidity, increase pH of the stomach and duodenal bulb
additionally, increasing the gastric pH above 4, inhibits the proteolytic activity of pepsin
alginic acid forms a viscous layer that floats on the surface of gastric contents as a protective barrier
4
Q
what is the dosing of antacids?
A
short duration of action requires several administrations throughout the day
in a fasting state, antacids reduce acidity for approximately 20 to 40 minutes because of rapid gastric emptying
if ingested 1 hour after meals, they reduce gastric acidity for at least 3 hours so it’s better to take an antacid after eating
5
Q
what are the side effects of antacids?
A
usually well tolerated with minimal adverse effects when used appropriately
- constipation (aluminum)
- diarrhea (magnesium)
- chalky taste
- abdominal cramps
- potential to cause acid rebound
- don’t use with renal dysfunction due to accumulation/electrolyte disturbances
- hypophosphatemia (aluminum)
6
Q
what are the interactions associated with antacids?
A
take 1–3 hours after other medications to avoid potential drug interactions (gut binding, increased/decreased absorption)
7
Q
why are histamine 2 receptor antagonists used clinically?
A
- cheap and easily obtainable
- empiric therapy for mild GERD symptoms
- maintenance therapy for those without erosive disease with intermittent symptoms (less effective than PPIs in healing)
- add-on therapy to PPI; can use on-demand for intermittent symptoms caused by food, exercise and/or at bedtime (quicker onset; peak in 1–2 hours)
8
Q
which medications are histamine 2 receptor antagonists?
A
- cimetidine
- famotidine
- ranitidine
- nizatidine
“tidine”
9
Q
what is the MOA of H2RAs?
A
competitive inhibition of histamine at H2 receptors of the gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen ion concentration
10
Q
what is the dosing of H2RAs?
A
OTC dose is usually one-half the entire prescription dose
dosing varies based on condition, refer to product labelling for specific dosing
11
Q
what are the side effects of H2RAs?
A
- headache
- dizziness
- fatigue
- confusion
- constipation
- diarrhea
caution with patients with hepatic and renal impairment
12
Q
what are the drug interactions associated with H2RAs?
A
- medications with pH-dependent absorption may be altered
ex. ketoconazole, itraconazole, protease inhibitors (HIV) - cimetidine inhibits the cytochrome P450 (CYP) enzyme system—specifically 1A2, 2C9, 2C19, 2D6, 2E1, and 3A4
ranitidine is a less potent inhibitor than cimetidine and famotidine; therefore, clinically significant interactions are less
13
Q
what are proton pump inhibitors used for clinically?
A
empiric therapy for individuals with frequent, continual symptoms: Standard once-daily dosing for 8 weeks
maintenance therapy: administer for persistent symptoms and in patients with complications (erosive esophagitis, Barrett esophagus)
chronic therapy should be administered at the lowest effective dose, including on-demand and intermittent strategies
14
Q
which medications are proton pump inhibitors?
A
- omeprazole (Prilosec)
- esomeprazole
- lansoprazole
- dexlansoprazole
- pantoprazole
- rabeprazole
15
Q
what is the MOA of proton pump inhibitors?
A
decrease acid secretion in gastric parietal cells through inhibition of the H-K-ATPase enzyme system reducing gastric acidity
16
Q
what is the dosing of proton pump inhibitors?
A
should be taken 30-60 minutes before meal, preferably breakfast or first meal of day as H-K-ATPase pump availability is greatest after a fast
dexlansoprazole can be administered without regard to meals
17
Q
what are the side effects of proton pump inhibitors?
A
- headache
- dizziness
- somnolence
- diarrhea/constipation
- nausea
- rebound hyper secretion after discontinuation; tape dose to ween off
- vitamin B12 deficiency
- osteoporosis and hip fractures due to decreased calcium absorption
- hypomagnesemia
- community acquired infections like C. diff and pneumonia
avoid long term use
18
Q
what are the drug interactions associated with proton pump inhibitors?
A
- medications with pH-dependent absorption may be altered
ex. ketoconazole, itraconazole, protease inhibitors (HIV) - medications metabolized by CYP 2C19 or 3A4 substrates (PPIs inhibit these to varying degrees
- clopidogrel
19
Q
what is sucralfate used for?
A
duodenal ulcers
forms a complex by binding with positively charged proteins in exudates, forming a viscous paste-like, adhesive substance that protects the gastric lining
20
Q
what is misoprostol used for?
A
- NSAID induced gastric ulcer prevention (200 mcg 4 times daily)
- termination of intrauterine pregnancy
it’s a synthetic prostaglandin E1 analog that replaces the protective prostaglandins consumed with prostaglandin-inhibiting therapies (ie, NSAIDs)
21
Q
which antibiotics are used for H. pylori infections?
A
- amoxicillin
- clarithromycin
- levofloxacin
- tetracycline
- metronidazole
22
Q
which NSAIDs are primarily COX-1 selective?
A
- aspirin
- ketoprofen
- indomethacin
4 .piroxicam
- sulindac
23
Q
which NSAIDs are slightly COX-1 selective?
A
- ibuprofen
- naproxen
- diclofenac
24
Q
which NSAIDs are slightly COX-2 selective?
A
- etdolac
- nabumetone
- meloxicam
25
which NSAIDs are primarily COX-2 selective?
celecoxib
26
what is the MOA of NSAIDs?
o Inhibit cyclooxygenase (COX), the enzyme that catalyzes the synthesis of cyclic endoperoxides from arachidonic acid to form prostaglandins
in the gastric mucosa, prostaglandins decrease gastric acid synthesis, stimulate the production of glutathione that scavenges superoxides, promote the generation of a protective barrier of mucus and bicarbonate, and promote adequate blood flow to the gastric mucosal cells
prostaglandin in the kidneys modulates intrarenal plasma flow and electrolyte balance.
COX-1 is constantly produced and important for homeostatic maintenance, such as platelet aggregation, the regulation of blood flow in the kidney and stomach, and the regulation of gastric acid secretion
COX-2 is induced during pain and inflammatory stimuli
27
what are the side effects of NSAIDs?
1. tinnitus
2. comprise renal fnction
3. serious GI bleeding, ulcerations, perforations
4. cardiovascular thrombotic events
5. increased bP, edema, water retention
6. rash
28
which medication is a Proton Pump Inhibitor (PPI)?
a. Ranitidine
b. Omeprazole
c. Sucralfate
d. Misoprostol
b. Omeprazole
29
which medication is a Histamine 2 Receptor Antagonist (H2RA)?
a. Esomeprazole
b. Bismuth
c. Famotidine
d. Calcium carbonate
c. Famotidine
30
which class of medication inhibits the H-K-ATPase enzyme system in gastric parietal cells to increase gastric pH?
a. H2RA
b. PPI
c. Antacids
d. Selective 5-HT3 Receptor Antagonist
b. PPI
31
which class of medications has a quicker onset of action?
a. H2RA
b. PPI
a. H2RA
32
which medication forms a viscous paste-like, adhesive substance that protects the gastric lining?
a. Aluminum hydroxide
b. Bismuth
c. Cimetidine
d. Sucralfate
d. Sucralfate
33
which medication has a boxed warning for birth defects and premature birth?
a. Misoprostol
b. Omeprazole
c. Aluminum hydroxide
d. Bismuth
a. Misoprostol
34
which medication would be most likely to cause dark stools?
a. Bismuth
b. Aspirin
c. Misoprostol
d. Calcium carbonate
a. Bismuth
35
which medication is most effective at decreasing gastric acidity when taken 30 minutes before first meal?
a. Cimetidine
b. Calcium carbonate
c. Sucralfate
d. Lansoprazole
d. Lansoprazole
36
which class of medication is most effective at promoting ulcer healing?
a. Antacid
b. H2RA
c. PPI
d. Bismuth
c. PPI
37
which class of medication is most likely to affect the absorption of other medications due to binding in the gut if taken together?
a. Antacid
b. H2RA
c. PPI
d. Misoprostol
a. Antacid
38
which medication inhibits CYP enzymes to a greater extent?
a. Ranitidine
b. Esomeprazole
c. Cimetidine
d. Sucralfate
c. Cimetidine
39
which medication would be best to use for gastric ulcer prevention in a patient at risk?
a. Misoprostol
b. Famotidine
c. Sucralfate
d. Alginic acid
a. Misoprostol
40
which medication requires several doses throughout the day due to a short duration of action?
a. Omeprazole
b. Ranitidine
c. Magnesium oxide
d. Famotidine
c. Magnesium oxide
41
which class may increase risk of osteoporosis & community acquired infections?
a. NSAID
b. PPI
c. H2RA
d. Antacids
b. PPI
42
which NSAID would be less likely to cause GI irritation?
a. primarily COX-1 Selective
b. slightly COX-1 Selective
c. slightly COX-2 Selective
d. primarily COX-2 Selective
d. primarily COX-2 Selective
43
wow COX-1/COX-2 selective are ibuprofen and naproxen?
a. Primarily COX-1 Selective
b. Slightly COX-1 Selective
c. Slightly COX-2 Selective
d. Primarily COX-2 Selective
b. slightly COX-1 selective
44
what are the symptoms of GERD?
1. heart burn
2. regurgitation
3. acid taste
4. extraesophageal symptoms = asthma, laryngitis, chronic cough
5. chest pain; rule out cardiac causes
atypical symptoms
1. dyspepsia
2. epigastric pain
3. nausea
4. bloating
5. belching
45
what are the alarm symptoms of GERD?
1. anemia
2. chest pain
3. choking
4. epigastric mass
5. GI bleeding
6. vomiting
7. unintentional weight loss
8. unimproved dysphagia
46
what are the non-pharmacologic treatments for GERD?
1. dietary changes
2. smoking cessation
3. tight clothing
4. weight loss
5. elevate HOB
6. avoid meals before bed
7. avoid chocolate, caffeine, alcohol, acidic/spicy foods
8. medications: anticholinergics, barbiturates, dihydropyridine calcium channel blockers, dopamine, estrogen, GABA agonists, NO inhibitors, progesterone, serotonin, antagonists, tetracycline, theophylline
47
how would you pharmacologically treat GERD?
PPI for 4-8 weeks taking 30 minutes before the first meal of the day
then maintenance with H2RAs; do not use PPIs for a prolonged time due to all the side effects
48
what are the symptoms of dyspepsia?
1. epigastric pain lasting at least 1 month
2. epigastric fullness
3. nausea/vomiting
4. heartburn
49
what are the alarm symptoms associated with dyspepsia?
1. weight loss
2. anemia
3. dysphagia
4. persistent vomiting
50
how do you treat dyspepsia?
if they're H. pylori positive, treat with antibiotics
if they're H. pylori negative or if there's still symptoms after giving antibiotics, give PPIs
51
what is Barrett's esophagus?
change of the normal squamous epithelium of the distal esophagus to a columnar-lined intestinal metaplasia
52
what are the risk factors for Barret's esophagus?
1. 50+ years old
2. male
3. smokers
4. obese
5. caucasian
6. family history
53
how do you treat Barrett's esophagus?
once daily PPI; 2x daily isn't recommended unless poor control of reflux symptoms or esophagitis
avoid aspirin or NSAIDs
54
what are the locations of more peptic ulcers?
1. duodenal
| 2. gastric
55
what are the common causes of peptic ulcers?
1. H. pylori
2. empiric PPIs
3. critical illness/stress
56
what are the high risk vs moderate vs low risk factors of peptic ulcers?
HIGH RISK
1. history of complicated ulcers
2. more than 2 risk factors
MODERATE RISK
1. 65+ years old
2. high dose NSAID use
3. previous peptic ulcer
4. aspirin use, corticosteroid use or anticoagulant use
LOW RISK = no risk factors present
H. pylori infection is an independent and additive risk factor which should be addressed separately
57
how do you treat peptic ulcers?
1. risk factor modification
2. reduce or eliminate NSAID use if possible
3. PPIs are first line therapy for ulcer healing!!
58
how do you prevent peptic ulcers?
LOW CV RISK
low GI risk = NSAIDs alone
moderate GI risk = NSAID + PPI/misoprostol
high GI risk = alternative therapy or COX2 inhibitors + PPI/misoprostol
HIGH CV RISK
low GI risk = naproxen + PPI/misoprostol
moderate GI risk = naproxen + PPI/misoprostol
high GI risk = avoid NSAIDs or COX2 inhibitors
59
how do you treat peptic ulcers?
1. risk factor modification
2. reduce or eliminate NSAID use
3. test and treat H. pylori
PPIs are FIRST LINE for ulcer healing and secondary prevention!!!!
other options include misoprostol and H2RAS
60
what are the symptoms of an upper GI bleed?
1. hematemesis
2. coffee ground emesis
3. melena (black tarry stools)
4. hematochezia
61
how o you treat upper GI bleeds?
hemodynamic stabilization if needed
pre-endoscopy: IV erythromycin and IV PPI
post-endoscopy: IV PPI for active bleeds or standard PPI for ulcers with clean bases/flat pigmented spots
62
what are the indications to test for an H. pylori infection?
1. active peptic ulcer disease
2. low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma, or a history of endoscopic resection of early gastric cancer (EGC)
3. uninvestigated dyspepsia who are under the age of 60 years and without alarm features, non-endoscopic testing
4. can consider in patients initiating low-dose ASA or chronic NSAID therapy
dont test people who just have symptoms of GERD without a history of PUD
63
how do you treat an H. pylori infection?
1. clarithromycin triple therapy = PPI, clarithromycin and amoxicillin or metronidazole for 14 days
2. bismuth quadruple therapy = PPI, bismuth, tetracycline and metronidazole for 10-14 days if they have a penicillin allergy or previous macrolide exposure
64
what are the tests to detect for H. pylori infection?
1. urea breath test (expensive and inconvenient)
2. stool monoclonal antibody test (cheaper but only detects active infections)
3. serologic tests( good for mass population surveys in patients who can't stop taking PPIs)
65
which of following should be considered an alarm symptoms in a patient with GERD?
a. Acid taste/regurgitation
b. Chronic cough/nausea
c. Choking/vomiting
d. Epigastric pain/bloating
c. Choking/vomiting
66
which of the following is not an appropriate non-pharmacologic intervention to treat GERD?
a. Elevate foot of bed
b. Smoking cessation
c. Avoid alcohol
d. Lose weight
a. Elevate foot of bed
67
how long should a patient with GERD be prescribed a PPI?
a. 2-4 weeks
b. 4-8 weeks
c. No more than 4 weeks
d. As long as needed
b. 4-8 weeks
68
which condition would be most appropriate to treat with long-term (>8 weeks) PPI therapy?
a. GERD
b. Heartburn
c. H. pylori
d. Berrett’s esophagus
d. Berrett’s esophagus
69
which symptom(s) is/are used to distinguish dyspepsia?
a. Epigastric pain >1 month
b. Heartburn and regurgitation
c. Dark stools
d. Acid taste in mouth
a. Epigastric pain >1 month
70
how long is a typical H. pylori eradication regimen?
a. 5-7 days
b. 7-10 days
c. 10-14 days
d. 14-21 days
c. 10-14 days
71
which H. pylori regimen would be the best choice for a patient allergic to PCN?
a. PMC
b. PAC
c. PAMC
d. Levofloxacin triple therapy
a. PMC
PPI, metronidazole and clarithromycin
72
which H. pylori regimen would be the best choice for a patient who previously received a macrolide?
a. PMC
b. PBMT
c. PAMC
d. Hybrid therapy
b. PBMT
PPI, bismuth, metronidazole, tetracycline
73
which of the following is NOT a risk factor for Barrett’s esophagus?
a. Age <50 years old
b. Central obesity
c. Smoking
d. Caucasian race
a. age <50 years old
74
screening for Barrett’s Esophagus should be considered in which of the following patients?
a. 40 yo white male with weekly GERD symptoms for the last 6 months and positive FH for BE
b. 60 yo black male with weekly GERD symptoms for the last 2 years and current smoker
c. 50 yo white male with weekly GERD symptoms for the last 5 years and central obesity
d. 55 yo white female with weekly GERD symptoms for the last 5 years
c. 50 yo white male with weekly GERD symptoms for the last 5 years and central obesity
75
which of the following patients has a moderate risk for developing a PUD?
a. 45 yo black male with a previous uncomplicated peptic ulcer
b. 50 yo white female with a recent complicated ulcer
c. 67 yo white male who received a ketorolac injection, is taking ibuprofen as needed, and takes a daily 81mg aspirin
d. 60 yo black female with symptoms of heartburn
a. 45 yo black male with a previous uncomplicated peptic ulcer
76
you would like to start a 50 yo white male with a history of peptic ulcer on an OTC NSAID. Which of the following regimens would be appropriate to minimize his risk of ulceration?
a. NSAID alone
b. Celecoxib
c. NSAID plus PPI
d. NSAID plus misoprostol
c. NSAID plus PPI
NSAID alone isn't appropriate; celecoxib and misoprostol are prescription only
