Gastrointestinal

Question 1

Amoxicillin

Answer 1

Antibiotic

Low resistance/toxicity

Question 2

Clarithromycin

Answer 2

Antibiotic

Has shown increasing resistance

Question 3

Metronidazole

Answer 3

Antibiotic
For patients who have penicillin allergies
Anaerobic-specific

Question 4

Tetracycline

Answer 4

Antibiotic
Used in bismuth-based quadruple therapy
(bismuth subsalicylate + metronidazole + tetracycline + PPI or H2RA)

Question 5

Bismuth subsalicylate

Answer 5

Antibiotic
Colloidal suspension in MgAl silicate clay
Salicylate is absorbed (anti-secretory, anti-inflammatory)
Bismuth is excreted in feces (antibacterial activity against HP, binds E. coli enterotoxins)
Use: PUD, diarrhea, nausea, cramping
Adverse: black discoloration of stool and tongue (bismuth sulfide), salicylism (tinnitus), Reye’s syndrome

Question 6

Aluminum hydroxide-magnesium hydroxide

Answer 6

Antacid
Alkaline compound that neutralizes gastric acid (raises stomach pH to ~5)
Acid-neutralizing capacity (ANC) unit
Rapid onset, short duration
Mg2+: diarrhea (stimulates peristalsis)
Al3+: smooth muscle relaxation (counters peristalsis)
Not well absorbed and don’t generate CO2
Use: relieve mild sx of dyspepsia and GERD
Interferes with absorption of other drugs

Question 7

Cimetidine

Answer 7

H2RA
Block acid secretin from parietal cells
Indirectly decreases gastrin and ACh-induced acid secretion
Competitive inhibitors of H2 receptors (highly selective)
Prophylaxis
Use: PUD (short term) , GERD (nocturnal), Aspiration pneumonitis
Adverse: very well tolerated, endocrine effects, CNS effects, pneumonia (bacterial colonization of stomach)
Inhibits multiple CYP isoforms

Question 8

Omeprazole

Answer 8

PPI
NOT ACTIVATED IN LUMEN
ABSORBED IN SI
Prodrug. Irreversibly inhibits H+/K+/ATPase.
Activated within parietal cells
Take 30 minutes before meals. (stimulate acid-formation within parietal cells)
Reduce acid secretions by 95% within 2 hours. Can persist for 2-3 days (irreversible)
Enteric coated formulation (bypass acidic environment), absorbed at alkaline pH.
CYP 2C19, 3A4
Asian variant of 2C19 –> slow metabolism, potential toxicity
Use: PUD, GERD, Zollinger-Ellison (gastrinoma), NSAID-assc ulcers in pts who continue NSAID use
Adverse: well tolerated, n, constipation/diarrhea, flatulence, pneumonia, decreased Ca absorption
Interacts with warfarin, diazepam, cyclosporine, clopidogrel
Rebound hypersecretion of stomach acid

Question 9

Sucralfate

Answer 9

Mucosal protectant
Sulfate sucrose and aluminum hydroxide
Forms gel at pH<4
Binds necrotic tissue (barrier to acid and pepsin)
Not absorbed, no acid-neutralizing activity, no acid-reduction
Take on empty stomach 1h before meals
Use: duodenal and stress ulcers
Lower risk of nosocomial pneumonia
Adverse: constipation, reduced absorption of other drugs

Question 10

Misoprestol

Answer 10

Prostaglandin (PGE1) analog
Substitues for PG when synthesis is inhibited by NSAIDs
Reduces acid secretion from parietal cells
Promotes bicarb and mucus secretion from epithelial cells
Use: prevent gastric ulcers in pts using NSAIDs for long-term therapy, in combo with mifepristone (RU-486) to induce abortion (uterine contraction)
Adverse: dose-dependent diarrhea
DO NOT USE DURING PREGNANCY

Question 11

Psyllium

Answer 11

Laxative (bulk-forming)
Group III (slow onset–1-3 days, soft stool)
MOA: non-digestible/non-absorbable, swell with water –> viscous solution –> stretches GI wall –> peristalsis
Use: temporary treatment of mild constipation
Adverse: administered with full glass of H2O to prevent impaction

Question 12

Bisacodyl

Answer 12

Laxative (stimulant (irritant))
Group II (intermediate latency–6-12 hours, semi-fluid stool)
MOA: stimulate (irritate) GI motility, increase H2O and electrolytes within lumen
Oral or rectal administration
Use: opioid-induced constipation, constipation from slow intestinal transit
Widely used and frequently misused/abused
Adverse: proctitis (long term)

Question 13

Methylnaltrexone

Answer 13

Laxative
Antagonist (mu)
Treat opioid-induced constipation
Quaternary derivative of naltrexone with reduced ability to cross BBB

Question 14

Docusate sodium

Answer 14

Laxative (surfactant–stool softener)
Group III (slow onset–1-3 days, soft stool)
MOA: lower surface tension –> water penetration
May decrease water absorption by intestinal wall
Use: mild constipation, take with full glass of water

Question 15

Magnesium hydroxide

Answer 15

Laxative (osmotic)
Group I (rapid action–2-6 hours, watery stool)
MOA: osmotic action drawing H2O into lumen –> stool swelling –> stretching
TAKE ON EMPTY STOMACH
Use: Low dose = group II effect, High dose = group I effect (colonoscopy), purge to remove ingested toxins/evacuate dead parasites
Adverse: substantial dehydration, electrolyte imbalance, Mg2+ can cause toxicity in patients with impaired renal function

Question 16

Lactulose

Answer 16

Laxative (osmotic)
Group I (rapid action–2-6 hours, watery stool )
MOA: osmotic action drawing H2O into lumen –> stool swelling –> stretching
TAKE ON EMPTY STOMACH
Use: Low dose = group II effect, High dose = group I effect (colonoscopy), purge to remove ingested toxins/evacuate dead parasites
Treat hepatic encephalopathy, reduce plasma ammonia levels (via acid trapping NH3 produced by bacteria in non–absorbable NH4+)
Titrate dose to achieve 2-3 soft stools/day
Adverse: substantial dehydration, electrolyte imbalance

Question 17

Loperamide

Answer 17

Antidiarrheal
Opioid
MOA: myenteric opiate receptors –> reduce secretory activity (delta) and GI motility (mu)
Loperamide: 40-50x more potent diarrheal than morphine
PK: well absorbed (oral), poor penetration of BBB
Adverse: constipation

Question 18

Diphenoxylate

Answer 18

Antidiarrheal
Opioid
MOA: myenteric opiate receptors –> reduce secretory activity (delta) and GI motility (mu)
PK: well absorbed (oral), high oral doses can cause morphine-like subjective responses (schedule V) (contain atropine [dysphoria] to discourage abuse)

Question 19

Bismuth subsalicylate

Answer 19

Antidiarrheal
Reduce stool frequency and liquidity
Salicylate inhibition of intestinal prostaglandin and chloride secretion

Question 20

Ondansetron

Answer 20

Antiemetic
5-HT3 receptor antagonist
MOA: most effective antiemetic agent, enhanced efficacy by corticosteroids
PK: IV administration, long duration, cleared by CYP3A4, 1A2, 2D6
Use: minimize/prevent emesis from CINV and radiation, hyperemesis of pregnancy, postoperative nausea (vagal stimulation)
NOT EFFECTIVE FOR MOTION SICKNESS OR DELAYED CINV NAUSEA
Adverse: well-tolerated

Question 21

Aprepitant

Answer 21

Antiemetic
Substance P receptor (NK1) antagonist
Blocks NK1 receptors in brain (STN and area pastrami) 
PK: 3A4, induces 2D6
Use: delayed nausea 
Adverse: well tolerated

Question 22

Metoclopramide

Answer 22

Prokinetic
MOA: dopamine D2 receptor antagonist
D2 receptor stimulation –> inhibits motility –> reduces ACh release (myenteric plexus)
Blockage of this = increased motility
Effects confined to upper GI trat, increases lower esophageal sphincter tone
Relieves n/v by antagonism of D2-R in CTZ
Use: n/v (GI dysmotility syndromes, migraines), GERD, gastroparesis
Adverse: extrapyramidal effects (parkonsonism), Tardive dyskinesia, hyperprolactinemia

Question 23

Alosetron

Answer 23

IBS
5-HT3 receptor antagonist
MOA: decrease GI motility, inhibits unpleasant visceral afferent sensations
Use: diarrhea-predominant IBS (FEMALE patients only)
Adverse: severe constipation (10%), life-threatening ischemic colitis (THIS SHIT IS DANGEROUS)
DO NOT USE IN CONSTIPATION-DEPENDENT IBS
LAST LINE AGENT

Question 24

Sulfasalazine

Answer 24

IBD
Mesalamine (5-ASA)-based therapy
Prodrug: azo (N=N) bond cleaved by intestinal flora –> 5-ASA
Topical (non-systemic) action on luminal surface of colon
MOA unclear: does not involve COX inhibition
Use: induce and maintain remission in UC
Adverse: due to sulfapyridine metabolite, GI problems, HA, arthralgia, myalgia, myelosuppression

Question 25

Infliximab

Answer 25

IBD Anti-TNF-based therapy MOA: chimeric monoclonal Ab against TNF-alpha (cytokine--> immune/inflammatory response) IV infusion slowly with antihistamines or anti-infl agents (prevent infusion reactions) Maintains remission in patients with Crohn's disease; closes fistulas Adverse (serious): neutropenia, INFECTION (TB), heart failure, MALIGNANCY (Lymphomas), pulmonary disease, demyelinating disease, cutaneous reactions, allergic reactions

Question 26

Psyllium

Answer 26

Laxative (Bulk forming) Creates a stretch to simulate peristalsis Group III: slow onset (1-3 days), soft-formed stool MOA: non-digestible/non-absorbale, swell with water --> viscous solution --> softer + increased volume --> stretch Use: mild constipation (temporary) Adverse: give with full glass of water (prevent impaction)

Question 27

Bisacodyl

Answer 27

Laxative (stimulant) Irritates colonic mucosa to stimulate peristalsis. Group II: intermediate latency (6-12h), semi-fluid stools MOA: stimulate (irritate) GI motility, increase water/electrolytes within lumen Oral or rectal suppository (rapid onset) Use: opioid-induced constipation, constipation from slow intestinal transit WIDELY USED AND MISUSED/ABUSED Adverse: proctitis (long-term use)

Question 28

Methylnaltrexone

Answer 28

``` Laxative Antagonist at mu receptor Treat opioid-induced constipation Quaternary derivative of naltrexone Reduced ability to cross BBB ```

Question 29

Docusate sodium

Answer 29

Laxative (surfactant) Stool softener. Pulls water into stool to create a stretch. Group III: slow onset (1-3 days), soft-formed stool MOA: lowers surface tension --> penetration of water May decrease water absorption by intestinal wall Use: mild constipation, take with full glass of water

Question 30

Magnesium hydroxide

Answer 30

Laxative (osmotic) Pulls water into colon. Group I: rapid action (2-6h), watery consistency MOA: poorly absorbed salts/sugars. Draw water into intestinal lumen--> stool swelling --> stretch TAKE ON EMPTY STOMACH Low dose: mild to mod constipation High dose: fluid evacuation of bowel (surgical prep) Adverse: dehydration, electrolyte imbalance, systemic absorption of Mg2+ --> toxicity (if impaired renal fxn)

Question 31

Lactulose

Answer 31

Laxative (osmotic) Group I: rapid action (2-6h), watery consistency Group I: rapid action (2-6h), watery consistency MOA: poorly absorbed salts/sugars. Draw water into intestinal lumen--> stool swelling --> stretch TAKE ON EMPTY STOMACH Low dose: mild to mod constipation High dose: fluid evacuation of bowel (surgical prep) Use: 1st line prevention/tx of HEPATIC ENCEPHALOPATHY (reduces plasma NH4 level via acid-trapping NH3. makes NH4+ which cannot be absorbed) Titrated to achieve 2-3 soft stools per day Adverse: dehydration, electrolyte imbalance

Question 32

Loperamide

Answer 32

Antidiarrheal OTC MOA: myenteric opiate receptor agonist (reduces secretory activity--delta; and GI motility--mu) 40-50x more potent antidiarrheal than morphine PK: well-absorbed (oral); poor penetration of BBB Adverse: constipation

Question 33

Diphenoxylate

Answer 33

Antidiarrheal Prescription MOA: myenteric opiate receptor agonist (reduces secretory activity--delta; and GI motility--mu) PK: well absorbed (oral); high doses --> morphine-lke response (schedule V); contains atropine (dysphoria) to discourage abuse Adverse: constipation

Question 34

Bismuth subsalicylate

Answer 34

Antidiarrheal Reduces stool frequency and liquidity Salicylate inhibition of intestinal prostaglandin and chloride secretion

Question 35

Ondansetron

Answer 35

Antiemetic (SETRON) 5-HT3 receptor antagonist MOA: most effective antiemetics, enhanced by corticosteroids PK: IV administration (prophylaxis), long duration, cleared by 3A4, 1A2, 2D6 Use: minimize/prevent emesis from CINV and radiation, hyperemesis of pregnancy, postoperative nausea (vagal stimulation) NOT EFFECTIVE AGAINST MOTION SICKNESS OF DELAYED CINV NAUSEA

Question 36

Aprepitant

Answer 36

Antiemetic Substance P receptor (NK1) antagonist Blocks NK1 receptors in brain (STN, area postrema) PK: 3A4 kinetics, 2D6 induction Use: delayed nausea, improves efficacy of other anti-emetics used for CINV

Question 37

Metoclopramide

Answer 37

Prokinetic Acts "upstream" of ACh. Coordinated GI motility/transit. MOA: dopamine D2 receptor antagonist D2 stimulation --> inhibits motility + reduces ACh release --> increased GI motility Effects confined to upper GI tract. Increases LES tone. Relieves n/v by antagonism of D2 receptors in CTZ Use: n/v (GI dismotility syndromes, migraine), GERD, gastroparesis Adverse: extrapyrimidal effects (parkinsonian), Tardive dyskinesia, hyperprolactinemia

Question 38

Alosetron

Answer 38

IBS (SETRON: don't confuse with antiemetic) MOA: antagonist 5-HT3 receptors Decrease GI motility --> inhibits unpleasant visceral afferent sensations Use: diarrhea-predominant IBS (female patients only) Adverse: severe constipation (10%), life-threatening ischemic colitis DO NOT USE IN CONSTIPATION-DEPENDENT IBS LAST LINE AGENT

Question 39

Sulfasalazine

Answer 39

IBD (UC) Mesalamine (5-ASA) based therapy Prodrug azo (N=N) bond cleaved by intestinal flora --> 5-ASA 5-ASA: topical (non-systemic), luminal surface of colon Does not involve COX inhibition Use: induce/maintain remission in mild to mod UC Also used in Crohn's (unclear efficacy) Adverse: systemic due to absorption of sulfapyridine metabolite, GI problems, HA, arthralgias, myalgia, myelosuppression

Question 40

Infliximab

Answer 40

IBD (Crohns) Anti-TNF-based therapy MOA: chimeric monoclonal Ab against cytokine TNF-alpha. (TNF-alpha promotes immune/infl responses) IV slow infusion with antihistamines/anti-infl agents Induces/maintains remission of Crohn's; closes fistulas Adverse (serious): neutropenia, INFECTION (TB), heart failure, MALIGNANCY (lymphomas), pulmonary disease, demyelinating disease, cutaneous reaction, allergic reactions