Pharmacology

Question 1

omeprazole

Answer 1

class: proton pump inhibitor
MoA: prodrug, weak base activated by acid, forms disulfide bond with cysteine residue on proton pump to irreversibly inhibit its action; ideally given 30 minutes before meals to coordinate with maximum pump expression/activity
uses: healing of peptic ulcers, GERD, erosive esophagitis, ulcers associated with H. pylori, Zollinger-Ellison syndrome
side effects: nausea, abdominal pain, constipation, flatulence, diarrhea
other: inhibits CYP2C19 (prevents activation of clopidogrel)

Question 2

esomeprazole

Answer 2

class: proton pump inhibitor
MoA: prodrug, weak base activated by acid, forms disulfide bond with cysteine residue on proton pump to irreversibly inhibit its action; ideally given 30 minutes before meals to coordinate with maximum pump expression/activity
uses: healing of peptic ulcers, GERD, erosive esophagitis, ulcers associated with H. pylori, Zollinger-Ellison syndrome
side effects: nausea, abdominal pain, constipation, flatulence, diarrhea
other:

Question 3

lansoprazole

Answer 3

class: proton pump inhibitor
MoA: prodrug, weak base activated by acid, forms disulfide bond with cysteine residue on proton pump to irreversibly inhibit its action; ideally given 30 minutes before meals to coordinate with maximum pump expression/activity
uses: healing of peptic ulcers, GERD, erosive esophagitis, ulcers associated with H. pylori, Zollinger-Ellison syndrome, recurrent NSAID-associated gastric ulcers
side effects: nausea, abdominal pain, constipation, flatulence, diarrhea
other:

Question 4

cimetidine

Answer 4

class: H2 receptor antagonist
MoA: reversibly and competitively inhibits H2 receptors; predominantly inhibits basal acid secretion
uses: healing of peptic ulcers, GERD, stress ulcer prevention
side effects: diarrhea, headache, drowsiness, CNS effects (rare)
other: less potent than PPIs, but good for nocturnal acid secretion; inhibits P450 metabolism (prolongs half-life of warfarin, gynecomastia in men)

Question 5

ranitidine

Answer 5

class: H2 receptor antagonist
MoA: reversibly and competitively inhibits H2 receptors; predominantly inhibits basal acid secretion
uses: healing of peptic ulcers, GERD, stress ulcer prevention
side effects: diarrhea, headache, drowsiness, CNS effects (rare)
other: less potent than PPIs, but good for nocturnal acid secretion

Question 6

aluminum hydroxide

Answer 6

class: antacid
MoA: weak base, reacts with gastric HCl to form salt and water and neutralize acid; stimulates protective functions of mucosa
uses: indigestion
side effects: constipation
other:

Question 7

calcium carbonate

Answer 7

class: antacid
MoA: weak base, reacts with gastric HCl to form salt and water and neutralize acid; stimulates protective functions of mucosa
uses: indigestion
side effects: gastric distention, belching, metabolic alkalosis
other:

Question 8

magnesium hydroxide

Answer 8

class: antacid
MoA: weak base, reacts with gastric HCl to form salt and water and neutralize acid; stimulates protective functions of mucosa
uses: indigestion
side effects: osmotic diarrhea
other:

Question 9

sucralfate

Answer 9

class: sucrose salt
MoA: unknown; forms paste-like substance in base of ulcers or erosion; stimulates mucosal prostaglandin and bicarbonate secretion
uses: short-term management of duodenal ulcers, NSAID mucosal damage, stress ulcer prevention
side effects: constipation (rare)
other: very small amount of drug is absorbed into systemic circulation

Question 10

misoprostol

Answer 10

class: prostaglandin analog
MoA: stimulates EP3 on parietal cells –> decrease cAMP –> decreased acid production; also EP3 –> promotes mucin and bicarbonate secretion
uses: replacement therapy for prevention of NSAID-associated ulcers
side effects: diarrhea, abortifacient
other:

Question 11

bismuth subsalicylate

Answer 11

class: bismuth salt
MoA: unknown; binds base of ulcer, promotes mucin and bicarbonate production, antibacterial effects, anti-inflammatory effects
uses: peptic ulcers, traveler’s diarrhea, episodic diarrhea, gastroenteritis
side effects: black stool, Reye’s syndrome
other: salicylate is absorbed but bismuth is not

Question 12

H. pylori treatment

Answer 12

initial treatment: PPI + amoxicillin + clarithromycin
penicillin allergy: PPI + metronidazole + clarithromycin
retreatment or clarithromycin resistance: omeprazole + bismuth subcitrate + metronidazole + tetracycline

Question 13

scopolamine

Answer 13

class: anticholinergic
MoA: competitively antagonizes ACh receptors
uses: motion sickness prophylactic, nausea prophylaxis during recovery from anesthesia
side effects: dry mouth, drowsiness, blurred vision
other: transdermal patch; most effective as prophylactic agent (4-6 hrs before exposure to stressor)

Question 14

dimenhydrinate

Answer 14

class: antihistamine
MoA: competitively inhibits H1 receptors, anticholinergic, blocks chemoreceptor trigger zone, diminishes vestibular stimulation
uses: motion sickness (off-label: nausea and vomiting during pregnancy)
side effects: sedation
other:

Question 15

ondansetron

Answer 15

class: 5-HT3 antagonist
MoA: blocks peripheral 5-HT3 receptors on extrinsic intestinal vagal and spinal afferent nerves
uses: anti-emetic (prevention), hyperemesis gravidarum
side effects: headache, dizziness, constipation, QT prolongation
other: oral; hepatic metabolism by conjugation and P450s (effect prolonged with liver disease)

Question 16

granisetron

Answer 16

class: 5-HT3 antagonist
MoA: blocks peripheral 5-HT3 receptors on extrinsic intestinal vagal and spinal afferent nerves
uses: anti-emetic (prevention), hyperemesis gravidarum
side effects: headache, dizziness, constipation, QT prolongation
other: transdermal patch (48 hrs to peak concentration)

Question 17

prochlorperazine

Answer 17

class: dopamine antagonist
MoA: blocks postsynaptic dopaminergic D2 receptors in chemoreceptor trigger zone; anticholinergic, antihistaminergic, and alpha-adrenergic antagonist
uses: management of surgical and non-surgical nausea and vomiting, opioid-induced PONV
side effects: sedation, dystonia, tradeoff dyskinesia, elderly pts with dementia-related psychosis at increased risk of death
other:

Question 18

dronabinol

Answer 18

class: cannabinoid
MoA: synthetic form of THC, acts on CB1 receptors in CNS, exact mechanism unknown
uses: nausea and vomiting in chemotherapy pts who are refractory to conventional antiemetic treatments
side effects: vertigo, dry mouth, hypotension, dysphoria (esp. in older pts)
other: CYP450 metabolism

Question 19

dexamethasone

Answer 19

class: corticosteroid
MoA: mechanism of antiemetic action is unknown
uses: adjunctive vomiting prophylaxis in chemotherapy, postoperative nausea/vomiting prophylaxis
side effects: insomnia, increased energy, mood changes
other:

Question 20

aprepitant

Answer 20

class: neurokinin receptor antagonist
MoA: crosses blood-brain barrier, antagonizes substance P at NK1 receptors in vomiting reflex center of brain
uses: prevention of nausea due to chemotherapy (in combination with 5-HT3 receptor antagonists and corticosteroids) or post-op
side effects: fatigue, dizziness, diarrhea
other: metabolized by CYP3A4 (inhibits metabolized by CYP3A4, i.e. warfarin)

Question 21

metoclopramide

Answer 21

class: prokinetic
MoA: 5-HT4 receptor antagonist, vagal and central 5-HT3 antagonist, sensitization of muscarinic receptors on smooth muscle; results in coordinated contractions that enhance transit (primarily effective in upper GI tract)
uses: GERD, diabetic gastroparesis, propylaxis for nausea and vomiting with chemotherapy, prophylaxis for post-op nausea and vomiting
side effects: extrapyramidal effects, tradeoff dyskinesia, galactorrhea
other: first-pass hepatic metabolism (at least in part by P450s)

Question 22

erythromycin

Answer 22

class: macrolide antibiotic
MoA: prokinetic, effects mimic motilin
uses: diabetic gastroparesis (off-label)

Question 23

loperamide

Answer 23

class: opioid
MoA: mu opioid receptor agonist; inhibits peristalsis, prolongs transit time, reduces fecal volume, increases stool viscosity
uses: traveler’s diarrhea, chronic diarrhea
side effects: dizziness, constipation, abdominal cramping, nausea
other:

Question 24

diphenoxylate

Answer 24

class: opioid
MoA: mu opioid receptor agonist; inhibits peristalsis, prolongs transit time, reduces fecal volume, increases stool viscosity
uses: traveler’s diarrhea, chronic diarrhea
side effects: penetrates CNS at high doses (abuse potential)
other: some preparations contain sub-therapeutic doses of atropine to discourage abuse

Question 25

octreotide

Answer 25

class: somatostatin analog MoA: inhibits secretion of 5-HT and other GI peptides uses: severe secretory diarrhea due to hormone-secreting tumors, chemotherapy, HIV, diabetes, gastric surgery side effects: nausea, bloating, injection site pain; long-term may cause gallstones or hypo-/hyperglycemia other:

Question 26

kaolin + pectin

Answer 26

class: aluminum silicate clay + plant polysaccharide MoA: binds water to increase stool bulk, alters stool viscosity uses: mild diarrhea, IBS side effects: other:

Question 27

magnesium hydroxide

Answer 27

class: saline laxative MoA: osmotic retention of water due to lack of absorption of magnesium; possibly induces production of inflammatory mediators uses: constipation side effects: other: use with caution in pts with renal insufficiency, cardiac disease, or preexisting electrolyte abnormalities

Question 28

lactulose

Answer 28

class: non-digestible sugar MoA: synthetic disaccharide of galactose and fructose, hydrolyzed to short-chain fatty acids in colon, stimulates propulsive motility, osmotically draws water into lumen, lowers lumenal pH, traps ammonia by conversion to ammonium ion uses: opioid-induced constipation, constipation in the elderly, chronic constipation side effects: gas, cramping, abdominal distention (first 24-48 hrs) other:

Question 29

polyethylene glycol

Answer 29

``` class: laxative MoA: poorly absorbed, osmotically retains water in intestinal lumen uses: colonic cleansing, constipation side effects: other: ```

Question 30

docusate salts

Answer 30

``` class: laxative MoA: anionic surfactant, lowers stool surface tension to permit easier defecation uses: constipation, colonic cleansing side effects: other: ```

Question 31

bisacodyl

Answer 31

class: stimulant/irritant laxative MoA: prodrug activated by endogenous esterases in bowel; has direct effects on enterocytes, enteric neurons, and GI smooth muscle; induces low-grade inflammation; produces giant migrating colonic contractions, induces water and electrolyte secretion uses: constipation

Question 32

senna

Answer 32

class: stimulant/irritant laxative MoA: has direct effects on enterocytes, enteric neurons, and GI smooth muscle; induces low-grade inflammation; produces giant migrating colonic contractions, induces water and electrolyte secretion uses: constipation

Question 33

lubiprostone

Answer 33

class: laxative MoA: poorly absorbed, activates chloride channels by activating EP4 receptors linked to adenylyl cyclase uses: chronic constipation, IBS side effects: nausea, headache, diarrhea, allergic reactions, dyspnea

Question 34

linaclotide

Answer 34

class: laxative MoA: synthetic peptide, poor absorption, activates guanylate cyclase C receptor on luminal surface of intestinal epithelium to stimulate cGMP production; leads to Cl- and bicarbonate secretion; may also reduce pain-sensing nerve activity uses: chronic idiopathic constipation, IBS side effects: diarrhea, abdominal pain other:

Question 35

methylnaltrexone

Answer 35

class: opioid antagonist MoA: acts peripherally to block mu opioid receptor uses: opioid-induced constipation in pts with advanced illness and inadequate response to conventional laxative regimens side effects: abdominal pain, gas, nausea other: limited ability to cross blood-brain barrier, orally active

Question 36

alvimopan

Answer 36

class: laxative uses: restricted - postoperatve ileus post-bowel resection

Question 37

dietary fiber

Answer 37

lignin (bran): unfermented, has laxative effect pectins, hemicelluloses (fruits and vegetables): fermented, less effective than lignin, can cause bloating and gas fiber also effective against diarrhea (mild diarrhea, IBS); binds water to add bulk to stool

Question 38

alosetron

Answer 38

class: serotonin antagonist MoA: antagonizes 5-HT3 receptor; decreases gut contractility, decreases colonic transit, increases fluid absorption; may also blunt visceral sensation uses: diarrhea-predominant IBS side effects: ischemic colitis

Question 39

prednisone

Answer 39

class: corticosteroid MoA: dampens inflammatory response uses: moderate to severe episodes of IBD side effects: increased hunger, weight gain, sleep disturbance, behavioral changes, irritability, increased BP other: pts may be responsive, dependent, or unresponsive; treatment aims to limit duration and dose of use

Question 40

budesonide

Answer 40

class: corticosteroid (enteric release synthetic) MoA: dampens inflammatory response uses: mild to moderate Crohn's disease side effects: minimal (less than prednisone) - increased hunger, weight gain, sleep disturbance, behavioral changes, irritability, increased BP other: enteric release delivers therapy to bowel while minimizing side effects

Question 41

mesalamine

Answer 41

class: 5-aminosalicylate MoA: inhibits IL-1 and TNF-a, lipoxygenase pathway, free radical and oxidant scavenging, possibly NF-kB (not related to COX inhibition) uses: mild to moderate ulcerative colitis (first-line) side effects: infrequent and minor - headache, dyspnea, skin rash other: contraindicated in pts allergic to salicylates; delayed-release (active throughout s. and l. bowel) and pH-sensitive (active in ileum and colon) formulations available

Question 42

olsalazine

Answer 42

class: 5-aminosalicylate MoA: inhibits IL-1 and TNF-a, lipoxygenase pathway, free radical and oxidant scavenging, possibly NF-kB (not related to COX inhibition) uses: mild to moderate ulcerative colitis (first-line) other: contraindicated in pts allergic to salicylates, active in colon

Question 43

sulfasalazine

Answer 43

class: 5-aminosalicylate MoA: prodrug, activated by colonic bacteria; inhibits IL-1 and TNF-a, lipoxygenase pathway, free radical and oxidant scavenging, possibly NF-kB (not related to COX inhibition) uses: mild to moderate ulcerative colitis (first-line) side effects: fever, malaise, vomiting, headache other: contraindicated in pts allergic to salicylates, active in colon

Question 44

6-mercaptopurine

Answer 44

class: immunosuppressant MoA: impairs purine biosynthesis, inhibits cell proliferation uses: maintenance of remission of IBD, Crohn's-related fistulas, prophylaxis against recurrence of Crohn's following surgical resection side effects: bone marrow suppression, vomiting, jaundice, pancreatitis other:

Question 45

azathioprine

Answer 45

class: immunosuppressant MoA: impairs purine biosynthesis, inhibits cell proliferation uses: maintenance of remission of IBD, Crohn's-related fistulas, prophylaxis against recurrence of Crohn's following surgical resection side effects: bone marrow suppression, vomiting, jaundice, pancreatitis other:

Question 46

methotrexate

Answer 46

class: immunosuppressant MoA: inhibits dihydrofolate reductase, thereby blocking DNA synthesis and causing cell death uses: steroid-resistance or steroid-dependent IBD side effects: bone marrow suppression, vomiting, jaundice, pancreatitis other:

Question 47

infliximab

Answer 47

class: biologic (antibody) MoA: neutralizes TNF-a uses: moderate to severe Crohn's disease, Crohn's-related fistulas, acute flares, maintains remission side effects: fever, chills, anaphylaxis, lupus-like symptoms, risk of respiratory infection, reactivation of TB, non-Hodgkin's lymphoma other: contraindicated in pts with severe congestive heart failure

Question 48

adalimumab

Answer 48

class: biologic (antibody) MoA: neutralizes TNF-a uses: induce remission in mild to moderate, severe, and fistulizing Crohn's disease side effects: fever, chills, anaphylaxis, lupus-like symptoms, risk of respiratory infection, reactivation of TB, non-Hodgkin's lymphoma other: contraindicated in pts with severe congestive heart failure

Question 49

certolizumab pegol

Answer 49

class: biologic (pegylated Fab fragment) MoA: neutralizes TNF-a uses: moderate to severe Crohn's disease side effects: hepatotoxicity, hypersensitivity reaction other: contraindicated with other immune-modulating drugs (risk of progressive multifocal leukoencephalopathy)

Question 50

natalizumab

Answer 50

class: biologic (antibody) MoA: neutralizes alpha4-integrin (VLA-4), reduces migration of leukocytes to sites of inflammation uses: moderate to severe Crohn's disease side effects: hepatotoxicity, hypersensitivity reaction other: contraindicated with other immune-modulating drugs (risk of progressive multifocal leukoencephalopathy)