Exam 3 Study Guide
Gastroenterology
● GERD.
○ H2 antagonists vs PPIs.
■ Answer: H2 blockers reversibly bind H2 receptors on the parietal cell, blocking
histamine from binding — since binding is reversible and not all receptors are blocked,
they are less potent than PPIs. Onset ~1 hour, duration ~4-10 hours. Tachyphylaxis (loss
of efficacy) can develop from beyond 2 weeks up to 2 months in some patients, due to H2
receptor upregulation. PPIs irreversibly inhibit ~94% of the H+/K+ ATPase pumps on the
parietal cell, making them far more potent — tachyphylaxis is NOT seen with PPIs, but
they cause a much more pronounced rebound hyperacidity when stopped. Potency
hierarchy: PPIs (highest) > H2 blockers (middle) > antacids/other agents (lowest,
symptomatic relief only).
○ Optimal duration of treatment for acute esophagitis.
■ Answer: 8 weeks (acute esophagitis heals within 6-8 weeks per the AAFP algorithm).
For a new GERD diagnosis or new heartburn, prescribe a PPI for no more than 8 weeks
— treating beyond that when only 8 weeks was needed unnecessarily increases risk of
rebound hyperacidity and adverse effects. Some cases become chronic and require
ongoing treatment, but that's the exception, not the default.
○ Long-term adverse effects.
■ Answer: H2 blockers: increased C. difficile risk (less acidic stomach), increased vitamin
B12 deficiency risk (B12 absorption requires an acidic environment). PPIs: increased C.
difficile risk; decreased B12 and iron absorption (can cause anemia); decreased calcium
absorption (can cause fractures); decreased magnesium (especially significant if also on a
diuretic — presents as tremors, seizures, weakness, QT prolongation); possible (mixed
evidence) increased pneumonia risk from a less acidic, more bacteria-friendly gastric
environment plus aspiration during recumbency. Rebound hyperacidity is the other major
long-term issue — a 2-month course of daily omeprazole can cause up to 11 months of
rebound hyperacidity after stopping; PPI rebound takes up to ~2 weeks to manifest after
discontinuation.
○ Monitoring parameters.
■ Answer: H2 blockers: check B12 levels at least every 6-12 months with long-term use.
PPIs: check B12, iron, calcium, and magnesium levels at least annually with chronic use
(e.g., unresolvable chronic GERD).
○ Administration instructions.
■ Answer: PPIs should be taken on an EMPTY stomach — parietal cell ATPase pump
density is highest when the stomach is empty (anticipating food), so this is when the drug
has the most targets to irreversibly bind. Most patients do well with once-daily dosing,
typically first thing in the morning; can increase to BID if needed, and if symptoms flare
specifically after dinner, BID can be structured as one dose before breakfast and one
before dinner. H2 blockers don't have a specific empty-stomach requirement noted. Note:
omeprazole should be avoided with clopidogrel (Plavix) due to a drug interaction —
pantoprazole is generally used instead in patients on Plavix.
○ Safe in pregnancy?
■ Answer: The notes don't explicitly give a pregnancy category for H2 blockers or PPIs as
a class. For reference, among the related acid-suppression/protective agents that ARE
specified: sucralfate is pregnancy category B and is a good option for breakthrough
symptoms while tapering off a chronic PPI; misoprostol is pregnancy category X and is
, contraindicated (it's also an abortifacient); bismuth subsalicylate should be avoided in
pregnancy due to its salicylate component.
○ I recommend printing the H2 antagonist chart and the PPI chart.
● Constipation (adult and child)
○ I recommend printing out the chart comparing the constipation medications.
○ First-line therapy?
■ Answer: Always start with a medication review, lifestyle changes, dietary evaluation,
and adequate fiber intake (25-30 g/day for adults and children ≥4; ~19 g/day for children
1-3). A thorough medication review often reveals the culprit — anticholinergics, calcium
channel blockers, antihistamines, iron supplements, and especially opioids are common
constipation-causing drug classes, and simply switching/adjusting these can resolve the
problem. If pharmacologic therapy is needed, MiraLAX (polyethylene glycol 3350) is
first-line for the vast majority of patients, including children (with psyllium or a short
stimulant course as alternatives if there's parental concern about MiraLAX) and pregnant
women. Expected response: good, formed stool within 1-2 days. If MiraLAX alone isn't
enough, keep the patient on it and add a stimulant laxative. Poor response after 3 different
agents warrants further workup (e.g., ruling out small bowel obstruction).
○ Categories of each and expected onset of action (remember, combining two medications from the
same category only increases the risk for side effects).
■ Bulk-forming (psyllium, polycarbophil, Benefiber): adds bulk/retains water in stool; very
gentle, OTC, pregnancy category B; requires adequate hydration to avoid bowel
obstruction risk.
■ Stool softeners (docusate calcium, docusate sodium): decrease stool surface tension to
increase water/lipid absorption into stool; OTC, pregnancy category B; multiple RCTs
have failed to show significant benefit over placebo despite common use.
■ Osmotic laxatives (lactulose, sorbitol, polyethylene glycol 3350/MiraLAX): draw water
into the bowel via osmosis. MiraLAX onset is about a day; lactulose/sorbitol also ferment
via gut bacteria causing flatulence. PEG has outperformed lactulose/sorbitol in
comparative evidence with fewer side effects.
■ Glycerol (enema/suppository): rapid onset, within about 1 hour.
■ Mineral oil: lubricant, fallen out of favor; cannot use in children, cannot use >7 days,
avoid in GERD (aspiration → lipid pneumonitis risk).
■ Stimulant laxatives (bisacodyl, senna): irritate bowel tissue to stimulate peristalsis; oral
onset 6-12 hours, rectal onset ~1 hour; limit to <7 days due to hypokalemia/electrolyte
risk.
■ Saline laxatives (magnesium-based): draw water into the lumen via osmosis and trigger
cholecystokinin release; limit to <7 days (theoretical hypermagnesemia risk); avoid if
GFR <30.
■ Enemas (sodium phosphate, soap suds, saline, Pink Lady): onset within 5-15 minutes;
sodium phosphate carries a dehydration risk not seen with the others.
■ General principle behind the study guide's note: combining two agents from the SAME
category (e.g., two stimulants) only stacks the shared side-effect risk without added
benefit — if escalation is needed, add an agent from a DIFFERENT category instead
(e.g., MiraLAX + a stimulant, not two stimulants).
○ Use of peripheral mu-opioid receptor antagonists.
■ Answer: Agents: methylnaltrexone (Relistor), naloxegol, and naldemedine (Symproic).
These are FDA-approved specifically for opioid-induced constipation — they antagonize
mu-opioid receptors located in the GI tract (which normally slow peristalsis when opioids
bind) without crossing the blood-brain barrier, so they don't block the opioid's analgesic
effect and are NOT controlled substances/addictive. None of these are first-line, even for
opioid-induced constipation — standard therapy (MiraLAX, lifestyle changes) should be
Gastroenterology
● GERD.
○ H2 antagonists vs PPIs.
■ Answer: H2 blockers reversibly bind H2 receptors on the parietal cell, blocking
histamine from binding — since binding is reversible and not all receptors are blocked,
they are less potent than PPIs. Onset ~1 hour, duration ~4-10 hours. Tachyphylaxis (loss
of efficacy) can develop from beyond 2 weeks up to 2 months in some patients, due to H2
receptor upregulation. PPIs irreversibly inhibit ~94% of the H+/K+ ATPase pumps on the
parietal cell, making them far more potent — tachyphylaxis is NOT seen with PPIs, but
they cause a much more pronounced rebound hyperacidity when stopped. Potency
hierarchy: PPIs (highest) > H2 blockers (middle) > antacids/other agents (lowest,
symptomatic relief only).
○ Optimal duration of treatment for acute esophagitis.
■ Answer: 8 weeks (acute esophagitis heals within 6-8 weeks per the AAFP algorithm).
For a new GERD diagnosis or new heartburn, prescribe a PPI for no more than 8 weeks
— treating beyond that when only 8 weeks was needed unnecessarily increases risk of
rebound hyperacidity and adverse effects. Some cases become chronic and require
ongoing treatment, but that's the exception, not the default.
○ Long-term adverse effects.
■ Answer: H2 blockers: increased C. difficile risk (less acidic stomach), increased vitamin
B12 deficiency risk (B12 absorption requires an acidic environment). PPIs: increased C.
difficile risk; decreased B12 and iron absorption (can cause anemia); decreased calcium
absorption (can cause fractures); decreased magnesium (especially significant if also on a
diuretic — presents as tremors, seizures, weakness, QT prolongation); possible (mixed
evidence) increased pneumonia risk from a less acidic, more bacteria-friendly gastric
environment plus aspiration during recumbency. Rebound hyperacidity is the other major
long-term issue — a 2-month course of daily omeprazole can cause up to 11 months of
rebound hyperacidity after stopping; PPI rebound takes up to ~2 weeks to manifest after
discontinuation.
○ Monitoring parameters.
■ Answer: H2 blockers: check B12 levels at least every 6-12 months with long-term use.
PPIs: check B12, iron, calcium, and magnesium levels at least annually with chronic use
(e.g., unresolvable chronic GERD).
○ Administration instructions.
■ Answer: PPIs should be taken on an EMPTY stomach — parietal cell ATPase pump
density is highest when the stomach is empty (anticipating food), so this is when the drug
has the most targets to irreversibly bind. Most patients do well with once-daily dosing,
typically first thing in the morning; can increase to BID if needed, and if symptoms flare
specifically after dinner, BID can be structured as one dose before breakfast and one
before dinner. H2 blockers don't have a specific empty-stomach requirement noted. Note:
omeprazole should be avoided with clopidogrel (Plavix) due to a drug interaction —
pantoprazole is generally used instead in patients on Plavix.
○ Safe in pregnancy?
■ Answer: The notes don't explicitly give a pregnancy category for H2 blockers or PPIs as
a class. For reference, among the related acid-suppression/protective agents that ARE
specified: sucralfate is pregnancy category B and is a good option for breakthrough
symptoms while tapering off a chronic PPI; misoprostol is pregnancy category X and is
, contraindicated (it's also an abortifacient); bismuth subsalicylate should be avoided in
pregnancy due to its salicylate component.
○ I recommend printing the H2 antagonist chart and the PPI chart.
● Constipation (adult and child)
○ I recommend printing out the chart comparing the constipation medications.
○ First-line therapy?
■ Answer: Always start with a medication review, lifestyle changes, dietary evaluation,
and adequate fiber intake (25-30 g/day for adults and children ≥4; ~19 g/day for children
1-3). A thorough medication review often reveals the culprit — anticholinergics, calcium
channel blockers, antihistamines, iron supplements, and especially opioids are common
constipation-causing drug classes, and simply switching/adjusting these can resolve the
problem. If pharmacologic therapy is needed, MiraLAX (polyethylene glycol 3350) is
first-line for the vast majority of patients, including children (with psyllium or a short
stimulant course as alternatives if there's parental concern about MiraLAX) and pregnant
women. Expected response: good, formed stool within 1-2 days. If MiraLAX alone isn't
enough, keep the patient on it and add a stimulant laxative. Poor response after 3 different
agents warrants further workup (e.g., ruling out small bowel obstruction).
○ Categories of each and expected onset of action (remember, combining two medications from the
same category only increases the risk for side effects).
■ Bulk-forming (psyllium, polycarbophil, Benefiber): adds bulk/retains water in stool; very
gentle, OTC, pregnancy category B; requires adequate hydration to avoid bowel
obstruction risk.
■ Stool softeners (docusate calcium, docusate sodium): decrease stool surface tension to
increase water/lipid absorption into stool; OTC, pregnancy category B; multiple RCTs
have failed to show significant benefit over placebo despite common use.
■ Osmotic laxatives (lactulose, sorbitol, polyethylene glycol 3350/MiraLAX): draw water
into the bowel via osmosis. MiraLAX onset is about a day; lactulose/sorbitol also ferment
via gut bacteria causing flatulence. PEG has outperformed lactulose/sorbitol in
comparative evidence with fewer side effects.
■ Glycerol (enema/suppository): rapid onset, within about 1 hour.
■ Mineral oil: lubricant, fallen out of favor; cannot use in children, cannot use >7 days,
avoid in GERD (aspiration → lipid pneumonitis risk).
■ Stimulant laxatives (bisacodyl, senna): irritate bowel tissue to stimulate peristalsis; oral
onset 6-12 hours, rectal onset ~1 hour; limit to <7 days due to hypokalemia/electrolyte
risk.
■ Saline laxatives (magnesium-based): draw water into the lumen via osmosis and trigger
cholecystokinin release; limit to <7 days (theoretical hypermagnesemia risk); avoid if
GFR <30.
■ Enemas (sodium phosphate, soap suds, saline, Pink Lady): onset within 5-15 minutes;
sodium phosphate carries a dehydration risk not seen with the others.
■ General principle behind the study guide's note: combining two agents from the SAME
category (e.g., two stimulants) only stacks the shared side-effect risk without added
benefit — if escalation is needed, add an agent from a DIFFERENT category instead
(e.g., MiraLAX + a stimulant, not two stimulants).
○ Use of peripheral mu-opioid receptor antagonists.
■ Answer: Agents: methylnaltrexone (Relistor), naloxegol, and naldemedine (Symproic).
These are FDA-approved specifically for opioid-induced constipation — they antagonize
mu-opioid receptors located in the GI tract (which normally slow peristalsis when opioids
bind) without crossing the blood-brain barrier, so they don't block the opioid's analgesic
effect and are NOT controlled substances/addictive. None of these are first-line, even for
opioid-induced constipation — standard therapy (MiraLAX, lifestyle changes) should be
