Disorders of the Upper GI Tract Flashcards
Goals of treatment of upper GI
Raise the pH of stomach fluid.
Get the stomach contents out quicker (preferably downward)
Eliminate any mysterious (or known) force(s) that may be increasing stomach irritation.
How are intermittent dyspeptic symptoms treated?
antacids
OTC H2 antagonists
intermittent dyspeptic symptoms
occasional bloating
fullness
abdominal pain
heartburn
What are intermittent dyspeptic symptoms associated with?
overeating or drinking or consumption of certain foods
abdominal pain similar to gastritis, gastric ulcers or duodenal ulcers without demonstrable ulceration
non-ulcer dyspepsia
What is non-ulcer dyspepsia associated with?
GI motility abnormalities
How is non-ulcer dyspepsia treated?
antacids
OTC H2 antagonists
Rx H2 antagonists
epigastric pain that can be accompanied by nausea/vomiting resulting from diffuse inflammation of the stomach
gastritis
What is gastritis usually caused by?
H pylori
How is gastritis treated?
discontinue NSAIDs
Antacids
OTC/Rx H2 antagonists
Antibacterial regimen
diffuse gastric pain typically 1-3 hours after eating distinct ulcerations in stomach
gastric ulcers
symptoms of gastric ulcers
ulcerations in stomach
nausea/vomiting
belching
anorexia
How are gastric ulcers treated?
Discontinue NSAIDs Rx H2 antagonists Proton Pump Inhibitor Antibacterial regimen Misoprostol
diffuse epigastric pain typically with empty stomach
duodenal ulcers
What relieves duodenal ulcers?
eating
treatment of duodenal ulcers
discontinue NSAIDs Rx H2 antagonists proton pump inhibitors antibacterial regimen succralfate
symptoms of GERD
range from occasional heartburn to persistant burning substernal pain
treatment of GERD
antacids
OTC/Rx H2 antagonists
proton pump inhibitors
prokinetic agents
GERD alarm symptoms
dysphagia
odynophagia
anemia
weight loss
classic symptoms of GERD
heartburn
regurgitation
water brash
What is the treatment if a patient complains of alarm symptoms of GERD?
immediate upper endoscopy
What if a patient only complains of classic symptoms of GERD?
Begin conservative antireflux measures.
Discuss use of OTC preparations
Provide pt education
If a patient attempts conservative management of GERD and patietnts still persist, what is the next level of treatment?
begin empirical trial of proton pump inhibitor
If a patient attempts conservative symptoms, attempts an empirical proton pump inhibitor, but symptoms still persist, what is the next step?
Perform upper endoscopy.
GERD treatment - Ulceration
consider causes of ulceration; e.g. acid
Peptic disease
viral or fungal infection
neoplasia
GERD treatment - erosive esophagitis
Intensify proton pump inhibitor therapy
GERD treatment - Barrett’s esophagus
If dysphagia at initial endoscopy without inflammation, discuss utility of enrollment in endoscopic surveillance program.
GERD treatment - cancer
Referral to appropriate oncological service
GERD treatment - normal
Consider 24-hour pH probe to identify nonerosive reflux.
Consider other causes of symptoms.
Sporadic uncomplicated heartburn, often in setting of known precipitating factor. Often not chief complaint. No additional symptoms
Stage I GERD
How many episodes per week are seen with Stage I GERD?
Less than 2-3.
Medical Management of Stage I GERD
Lifestyle modification, including diet, positional changes, weight loss, etc.
Antacids and/or histamine H2 receptor antagonists as needed.
Frequent symptoms with or without esophagitis.
Stage II GERD
How many episodes per week are seen in Stage II GERD?
More than 2-3.
Treatment of Stage II GERD
Proton pump inhibitors more effective than histamine H2 receptor antagonists
Chronic, unrelenting symptoms; immediate relapse off therapy. Esophageal complications (e.g., stricture, Barrett’s metaplasia)
Stage III GERD
Treatment of Stage III GERD
Proton pump inhibitor either once or twice daily
Proton Pump Inhibitors
Omeprazole (Prilosec) Esomeprazole (Nexium) Lonsoprazole (Prevacid) Pantoprazole (Protonix) Rabeprazole (Aciphex) Dexlansoprazole (Dexilant)
What do PPIs act on?
Parietal Cell - decreases production of acid.
Increasing acetylcholine in the stomach…
… increases the action of the parietal cells which increases acid production causing nausea.
What creates a mucous layer around the cells allowing them to have a pH of 7?
Prostogandins
Number 1 best selling drug in the US?
Esomeprazole - Nexium
Tmax of Prilosec
1-3 hours
Tmax of Prevacid
1.7 hours
Tmax of Aciphex
3.1 hours
Tmax of Nexium
1.6 hours
Tmax of Protonix
2-4 hours
Half-life of Prilosec
0.5-3 hours
Half-life of Prevacid
1-2 hours
Half-life of Aciphex
1-2 hours
Where do PPIs work?
Hydrogen - Potassium - ATPase pump
Half-life of Nexium
1.4 hours
Half-life of Protonix
1-1.9 hours
Binding of Prilosec
95%
Binding of Prevacid
99%
Binding of Aciphex
96%
Binding of Nexium
97%
Binding of Protonix
98%
Clearance of the PPIs is completed by
the Liver
Bioavailability of Prilosec
40-60%
Bioavailability of Prevacid
85%
The PPIs are pro-drugs which means…
they are not activated until they reach the stomach. DO NOT open up/crush capsule/pill.
Bioavailability of Aciphex
52%
Bioavailability of Nexium
90%
Bioavailability of Protonix
77%
Dosage form(s) of Prilosec
Capsule
Dosage form(s) of Prevacid
Capsule/Tab
Dosage form(s) of Aciphex
Tablet
Dosage form(s) of Nexium
Capsule / IV
Dosage form(s) of Protonix
Tablet / IV
Indications for Prilosec
Short-term duodenal ulcer H.Pylori eradication Maintenance - duodenal ulcer Short-term active benign gastric ulcer Short-term-symptomatic GERD Short-term erosive esophagitis Maintenance-erosive esophagitis Pathological hypersecretory disorders
Indications for Prevacid
Short-term duodenal ulcer H.Pylori eradication Maintenance - duodenal ulcer Short-term active benign gastric ulcer Short-term-symptomatic GERD Short-term erosive esophagitis Maintenance-erosive esophagitis Pathological hypersecretory disorders
Indications for Aciphex
Short-term duodenal ulcer
Short-term erosive esophagitis
Maitenance-erosive esophagitis
Pathological hypersecretory disorders
Indications for Nexium
H.Pylori eradication
Short-term-symptomatic GERD
Short-term erosive esophagitis
Manitenance-erosive esophagitis
How long does it take for PPIs to work?
3-4 days
Indications for Protonix
Short-term erosive esophagitis
Maintenance-erosive esophagitis
Pathological hypersecretory disorders
Acid levels peak…
at meal times and during the night
Where to H2 blockers work well for acid inhibition?
Overnight acid production. Less successful for acid suppression around mealtimes.
Which drugs work best for acid suppression?
PPIs
True or False: PPIs are effected by first-pass metabolism
True
True or False: PPIs are renally excreted and must be adjusted.
False
What is the relationship between PPIs and fracture risk?
fracture risk in increased
What is the relationship between PPIs and clopidogrel?
PPIs interfere with a necessary metabolic step for clopidogrel. Effects 2C19. Increases clotting risk.
What is the relationship between PPIs and C.Diff?
May be associated with an increased risk of clostridium difficile - associated diarrhea.
What are PPIs not approved for?
use of treatment of upper GI bleeding
What PPI IV forms are available for quicker onset?
Protonix IV
Nexium IV
Physiologic activity at pH >3.5
decreased incidence of stress-induced bleeding
Physiologic activity at pH >4
Target pH- prevention of stress-related mucosal bleeding.
Physiologic activity at pH >4.5
Pepsin inactivation
Physiologic activity at pH 5
99.9% acid neutralization
Where do you want the pH of the stomach for a GI bleed?
between 5.1 and 7
Physiologic activity at pH 5.1 to 7
Alterations in caogulation and platelet aggregation
Physiologic activity at pH >6
Target pH - prevention of peptic ulcer reoccurrence
Physiologic activity at pH >7
Potential decrease in incidence of rebleeding.
Physiologic activity at pH >8
Pepsin destruction
Which PPIs have less drug interactions?
Prevacid & Protonix
ADRs of PPIs
Diarrhea
Abdominal pain
Headache
Dizziness
Possible long-term effects of PPIs
Inhibition of calcium absorption
Rise in gastrin levels
Omeprazole
Omeprazole
20 mg
One capsule one daily
Proton Pump Inhibitor Rx to know
Omeprazole
H2 Receptor Antagonists
Cimetidine - Tagamet
Ranitidine - Zantac
Famotidine - Pepcid
Nizatidine - Axid
Bioavailability of Cimetidine
~60%
Bioavailability of Ranitidine
50%
Bioavailability of Famotidine
40-45%
Bioavailability of Nizatidine
> 70%
Tmax of Cimetidine
0.75 to 1.5
Tmax Rantidine
2-3
Tmax of Famotidine
1-3
Tmax of Nizatidine
0.5 - 3
Instead of dosing a PPI twice a day…
… do a PPI in the morning and an H2 inhibitor at night.
Cmax of Cimetidine
2-3
Cmax of Ranitidine
0.44 - 0.55
Cmax of Nizatidine
0.7 - 1.8
Half-life of Cimetidine
~2
Half-life of Ranitidine
2.5-3
Half-life of Famotidine
2.5 - 3.5
Half-life of Nizatidine
1-2
Indications for Cimetidine
Short-term treatment of active duodenal ulcers and benign gastric ulcers.
Maintenance therapy of duodenal ulcer.
Treatment of gastric hypersecretory states.
Treatment of GERD.
Indications for Rantidine
Short-term and maintenance therapy of duodenal ulcer, gastriculcer, GERD, active benign ulcer, erosive esophagitis, and pathological hypersecretory conditions.
*As part of a multidrug regimen for H.pylori eradication to reduce the risk of duodenal ulcer recurrence.
Indications for Famotidine
Maitenance therapy and treatment of duodenal ulcer.
Treatment of GERD.
Treatment of active benign gastric ulcer.
Treatment of pathological hypersecretory conditions.
Indications for Nizatidine
Treatment of maintenance of duodenal ulcer.
Treatment of benign gastric ulcer.
Treatment of GERD.
Do H2-receptor antagonists require renal dosing adjustment?
Yes (look up thresholds in book)
What are the differences between the Rx and OTC H2-blockers?
10 hours of 50% acid inhibition at Rx dosing.
Less than 6 hours of 50% acid inhibition at OTC dosing.
MOA of H2 receptor antagonists
he H2 antagonists are competitive antagonists of histamine at the parietal cell H2 receptor. They suppress the normal secretion of acid by parietal cells and the meal-stimulated secretion of acid. They accomplish this by two mechanisms: Histamine released by ECL cells in the stomach is blocked from binding on parietal cell H2 receptors, which stimulate acid secretion; therefore, other substances that promote acid secretion (such as gastrin and acetylcholine) have a reduced effect on parietal cells when the H2 receptors are blocked.
H2 receptor antagonists are usually dosed twice per day. In what instance would they be dosed once per day?
If given in the evening in combination with a PPI. Double the dose of the H2 receptor antagonist.
ADRs of H2 receptor antagonists
Mental status changes - cimetidine; critical care; intravenous.
Thrombocytopenia.
Endocrine issues - cimetidine.
What is a common drug interaction with H2 receptor antagonists?
Cimetidine
Hw receptor antagonist to know
Famotidine
Famotidine
Famotidine
20 mg
one tablet twice a day
MOA of gastric protectant
complexes with protein-like exudate located at ulcerations.
Covers ulcer area.
ADRs of gastric protectant
Constipation major (2%) with all others at less than 0.5% incidence rate including rash, vertigo, headache, insomnia.
gastric protectant class drug
sucralfate - Carafate
Sucralfate
Sucrafate
1 g
Take 4 times a day on an empty stomach for 4-8 weeks.
MOA of antacids
neutralize or reduce gastric acidity
protects gastric mucosa
increases gastric pH, inactivates pepsin
stimulates production of prostaglandins
ADRs of antacids
GI - diarrhea, constipation, nausea/vomiting
antacids class drug
aluminum/magnesium hydroxide (Maalox)
Is sucralfate absorbed systemically?
No - goes in the mouth and out of the body.
What does sodium bicarbonate do?
provides a bicarbonate ion which in turn neutralizes hydrogen ion concentrations.
What does calcium carbonate do?
neutralizes gastric acid like aluminum and/or magnesium.
What does a gastric protectant need to work?
An acidic environment - do not give with antacids
What makes up sodium bicarbonate?
Formation of carbon dioxide and sodium chloride.
What can sodium bicarbonate potentially effect?
It is well absorbed and has potential to affect blood pH and sodium levels.
Compare calcium carbonate to sodium bicarbonate.
Calcium carbonate is less soluble and slower reacting than sodium bicarbonate.
Aluminum/magnesium Hydroxide suspension
Aluminum/magnesium Hydroxide suspension
30 ml every 4 hours as needed for epigastric pain relief.
MOA of prostaglandins
Synthetic prostaglandin E1 analog that replaces gastric prostaglandin.
Decreases gastric acid secretion.
ADRs of prostaglandins
diarrhea
abdominal pain
*avoid use during pregnancy - miscarriage/spontaneous abortion
prostaglandins class drug
misoprostol - Cytotec
Cytotec
Cytotec
200 mcg
one tablet 4 times a day with food
MOA of prokinetics
stimulation of release of acetylcholine at nerve ending to increase LES tone
improve esophageal peristalsis
ADRs of prokinetics
CNS effects including restlessness, fatigue, drowsiness, mental depression at higher doses.
Neuroleptic malignant syndrome very rare.
prokinetics class drug
metoclopramide - Reglan
Metoclopramide
Metoclopramide
10 mg
one tablet 4 times a day 30 minutes before meals and at bedtime.
How do antispasmodics work?
anticholinergic activity
ADRs of antispasmodics
may cause drowsiness and/or blurred vision.
impair physical or mental abilities - patients must be cautioned about performing tasks which require mental alertness like operating machinery or driving.
Antispasmodic products
Clidinium chlordiazepoxide - Librad Hyoscyamine atropine scopolamine phenobarbitol - Donnatal
Regional bacterium (5 main genetic groups) that likely migrated from mice and sheep (European strains) and cats, pigs, and gerbils (Asian strains)
Helicobacter pylori
How long does a h.pylori infection last?
Lifelong infection unless eradicated through drugs.
80% infected are asymptomatic
20% infected develop gastrointestinal disease
Nearly 100% of duodenal ulcers, unless NSAID-induced or gastromas are associatd with…
H.pylori infection.
If H.pylori is eradicated, duodenal ulcer rate recurrence…
… drops from 67% to 6%.
How many approved H.pylori regimens exist?
multiple
length of h.pylori eradication regimens
range from 10-14 days
Most complicated h.pylori eradication regimen
PeptoBismol, metronidazole, and tetracycline all 4 times a day for 2 weeks and an H2 blocker for 4 weeks.
Least complicated h.pylori eradication regimen
Prevacid, Biaxin, and amoxicillin twice a day for 10 days
downside to h.pylori eradication
People carrying H.pylori have a higher risk of developing peptic ulcers and stomach cancer (and Barrett’s esophagus)
People carrying H.pylori have a higher risk of developing peptic ulcers and stomach cancer (and Barrett’s esophagus) but…
They may also have a lower risk of acquiring diseases of the esophagus including esophageal adenocarcinoma which has been growing at a rate of 7-9% every year. Once diagnosed, 5 year survival is 10%.
