GI Pharmacology

Question 1

mylanta

Answer 1

class: neutralizing antacid
- fast acting, short t1/2
- immediate relief

use:
- GERD

mx:
- 2 strong bases:
- - Al(OH)3
- - Mg(OH)2
- +1 antiflatulant
- - simethicone

Question 2

reversible H2 inhibitors (inverse agonists)

Answer 2

use:

• GERD
• duodenal or gastric ulcer
• hypersecretion of gastric acid

mx:

• reversible competitive antagonist to H2 receptors
• H2 binds histamine, which increases acid production when bound to this receptor

pk:

• onset: 30-60 min
• duration: 6-12 h

AEs:

• diarrhea
• dizziness
• rash
• headache

e. g.:
- cimetidine
- famotidine (Pepcid)
- nizatidine

Question 3

nizatidine

Answer 3

reversible H2 antagonist

GERD

Question 4

cimetidine

Answer 4

reversible H2 antagonist
GERD

special note:

• CYP450 antagonist: 1A2, 2C9, 2D6, 3A4
• –> drug-drug interactions

Question 5

famotidine

Answer 5

reversible H2 antagonist

GERD

Question 6

proton pump inhibitors (PPIs)

Answer 6

use:
- GERD
- peptic ulcer disease and H. pylori
- Zollinger-Ellison syx (rare pancreatic tumor)
- idiopathic hyper-H+
- upper GI prophylaxis w/ LT NSAID use

mx:

• irreversible H+/K+-ATPase antagonist
• block H+ secretion

PK:

• prodrugs converted by acid
• ion trapping in canalicula on parietal cells
• local accumulation
• enteric-coated: don’t dissolve until SI
• t1/2 1-2 h
• duration: 36 ~ 72 h
• onset: 2-5 days for full effect
• CYP2C19 metabolism

AEs:

• few
• some concerns about unjustified long-term use

e. g.: -prazole
- omeprazole (Prilosec)
- esomeprazole (Nexium)

Question 7

-prazole

Answer 7

PPI

GERD - long term

Question 8

omeprazole

Answer 8

PPI
GERD
Prilosec

Question 9

esomeprazole

Answer 9

PPI
GERD
Nexium

Question 10

EC drugs

Answer 10

enteric-coated

bypasses stomach

Question 11

GI effects of NSAIDs

Answer 11

COX1 inhibitors
mucosal injury to upper GI
peptic ulcer disease
possible hemorrhage

worst: aspirin
best: celecoxib

Question 12

misoprostol

Answer 12

use:
- NSAID injury prophylaxis and tx

mx:

• prostaglandin E1 agonist
• stimulates mucus and bicarb secretion in GI
• weak antagonist of acid

AEs:

• often poorly tolerated
• diarrhea
• abdominal pain

Question 13

sucralfate

Answer 13

use:

• NSAID injury prophylaxis and tx
• anti-ulcer

mx:
- Al salt, basic
- preferentially neutralizes + proteins near ulcers
- stimulates mucosal repair via x-linking

Question 14

Scopalamine

Answer 14

Dramamine

Class: anti-cholinergic antiemetic

Mx:
- blocks M1 receptors in area postrema to prevent nausea

Uses:

• nausea
• motion sickness

Sfx/AEs

• drowsiness
• dizziness
• xerosterma (dry mouth)

Question 15

prochlorperazine

Answer 15

Class: D2 (dopamine) antagonist
- same class as many antipsychotics 

Mx:
- blocks dopamine 2 receptors in area postrema to prevent nausea

Uses:
- general antiemetic

Sfx/AEs:

• extrapyramidal effects (e.g. twitching)
• neuroleptic malignant syx (serious, treatable: high fever, muscle stiffness
• drowsiness

Question 16

diphenhydramine (as a GI drug)

Answer 16

class: antihistamine antiemetic

mx:
- blocks H1 receptors in area postrema to prevent nausea

uses

• general antiemetic
• non-GI

Sfx/AEs:

• drowsiness
• constipation
• xerostomia (dry mouth)
• urinary retention
• high risk in >65 y/o

Question 17

ondansetron

Answer 17

Zofran

class: 5HT3 antagonist antiemetic

mx:
- blocks 5HT3 receptors in area postrema to prevent nausea

uses:

• general antiemetic
• chemo
• pregnancy

Sfx/AEs:

• constipation
• QT prolongation
• headache

Question 18

metaclopramide

Answer 18

class: mixed 5HT3 ANTagonist/5HT4 AGonist, D2 antagonist

mx:

• see above
• CNS

uses:

• antiemetic
• reflux esophagitis
• promotility (for gastroparesis and pre-op)
• migraine

Sfx/AEs

• drowsiness
• dystonia (spasm)
• tardive dyskinesia (involuntary repetitive body movements)
• limited to ~3 mo use

Question 19

loperamide

Answer 19

class: opioid AGonist, non-absorbed

mx:

• slows intestinal motility
• decreases secretion
• via opioid receptor effects

uses:

• non-bloody diarrhea
• acute, nonspecific diarrhea
• IBD chronic diarrhea

Sfx/AEs

• minimal as not absorbed
• constipation
• c/i in bloody diarrhea

Question 20

eluxadoline

Answer 20

class: mixed opioid agonist/antagonist

mx:

• slow motility
• decrease pain
• via opioid receptor effects

uses:

• diarrhea
• abdominal pain
• IBS-D only

Sfx/AEs

• constipation
• nausea
• sphincter of Oddi spasm –> pancreatitis, hepatic enzyme elevation

Question 21

octreotide

Answer 21

class: somatostatin analog

mx:

• decreases endocrine and exocrine secretions
• decreases blood flow
• reduces GI motility
• inhibits secretion of many GI regulatory factors

uses:

• carcinoid secretory diarrhea
• gastrinoma secretory diarrhea
• VIPoma secretory diarrhea
• chemo-induced diarrhea
• sx of intestinal tumors
• sx of variceal bleeding

sfx:

• abdominal cramps
• nausea

Question 22

atropine (GI effects)

Answer 22

class: muscarinic antagonist

mx:

• decreased GI motility
• decreased salivation

uses:
- prevent respiratory secretions before anesthesia

Sfx/AEs:

• dry eye and mouh
• urinary retention
• tachycardia
• c/i glaucoma
• c/i prostatic hyperplasia

Question 23

antacids

Answer 23

class: acid-base neutralizers

e. g.
- Al(OH)3
- Mg(OH)2
- CaCO3
- NaHCO3

uses:
- mild intermittent GERD

Sfx/AEs

• Al: constipation
• Mg: diarrhea

Question 24

simethicone

Answer 24

class: antiflatulant

mx:

• surfactant
• decreases foaming of gas
• allows for non-flatus passing of gas

uses:

• flatulance
• belching

Question 25

aprepitant

Answer 25

class: NK-1 receptor ANTagonist antiemetic mx: - blocks substance P:NK-1 at chemotrigger zone (CTZ), which receives inputs from drugs and hormones uses: - chemo nausea and vomiting - postoperative nausea and vomiting Sfx/AEs: - asthenia (weakness, low energy) - diarrhea

Question 26

dexamethasone (GI effects)

Answer 26

class: glucocorticoid mx: - anti-inflammatory - multiple effects at area postrema - direct action at solitary tract nucleus uses: - chemo and radiation nausea and vomiting - postoperative nausea and vomiting Sfx/AEs: - minimal w/ single dose - irritability, insomnia, fluid retention, weakness, delayed wound healing, hyperglycemia

Question 27

olanzapine (GI effects)

Answer 27

class: atypical antipsychotic mx: - D2, 5-HT2A, H1, and muscarinic receptors at area postrema to reduce nausea uses: - off-label for chemo nausea and vomiting - psych SFx/AEs: - low bp - drowsiness - extrapyramidal sx - others

Question 28

neostigmine (GI effects)

Answer 28

class: carbamate-type peripheral ACh-ase inhibitor mx: - periphery only ACh-ase inhibitor uses: - increases gastric motility - non-GI SFx/AEs: - bowel cramps - diarrhea

Question 29

erythromycin

Answer 29

class: macrolide abx; also motilin AGonist mx: - motilin receptor AGonist - increases GI motility - direct and indirect neurotransmitter effects uses: - gastroparesis - abx: respiratory and soft-tissue AEs: - GI upset

Question 30

diphenoxylate

Answer 30

class: opioid antidiarrheal mx: - inhibits GI motility, slows propulsion - no other opiate effects uses: - acute, nonspecific diarrhea - IBD chronic diarrhea SFx/AEs - at high doses, antimuscarinic effects - atropine added to prevent drug misuse

Question 31

PAMORAs

Answer 31

class: peripherally acting mu-opioid receptor ANTagonists e. g.: - methylnaltrexone - naloxegol - naldemedine mx: - does not cross bbb - antagonizes mu receptors in periphery only uses: - opioid-induced constipation SFx/AEs - abdominal pain w/ methylnaltrexone and naloxegol - diarrhea w/ naldemedine

Question 32

methylnaltrexone

Answer 32

PAMORA | opioid-induced constiption

Question 33

naloxegol

Answer 33

PAMORA | opioid-induced constipation

Question 34

nalemedine

Answer 34

PAMORA | opioid-induced constipation

Question 35

linaclotide

Answer 35

class: guanylate cyclase-C AGonist mx: - secretory laxative - pro-motility - GCC activation --> cAMP --> CFTR --> Cl- and HCO3- & increased transit rates uses: - CIC and IBS-C SFx/AEs: - diarrhea

Question 36

lubiprostone

Answer 36

class: chloride channel activator mx: - secretory laxative - prostaglandin E1 derived bicyclic fatty acid - specifically activates chloride channel on GI epithelium uses: - CIC and IBS-C - opioid-induced constipation SFx/AEs: - nausea - headache - diarrhea

Question 37

plecatinide

Answer 37

Trulance class: guanylate cyclase-C AGonist mx: - secretory laxative - pro-motility - minimal absorption d/t pH dependent binding - GCC activation --> cAMP --> CFTR activation --> Cl- and HCO3- secretion uses: - CIC and IBS-C SFx/AEs - stomach bloating or tenderness - gas - diarrhea

Question 38

prucalopride

Answer 38

class: 5HT4 prokinetic AGonist mx: - increased gastric emptying - increased small bowel, colonic transit uses: - CIC SFx/AEs - headache - nausea - diarrhea

Question 39

cisplatin

Answer 39

platinum-based chemo | colon cancer among others

Question 40

pemetrexed

Answer 40

antimetabolite chemo

Question 41

docetaxel

Answer 41

taxane chemo

Question 42

bevacizumab

Answer 42

anti-VEGF | colon cancer among others

Question 43

osimertinib

Answer 43

EGFR inhibitor

Question 44

lorlatinib

Answer 44

ALK (tyrosine kinase) inhibitor

Question 45

capmatinib

Answer 45

MET (tyrosine kinase) inhibitor

Question 46

sotarasib

Answer 46

KRAS G12C (tyrosine kinase) inhibitor

Question 47

trastuzumab deruxtecan

Answer 47

not yet approved HER2 antagonist Ab-drug conjugate (ADC)

Question 48

pembrolizumab

Answer 48

PD-1 inhibitor

Question 49

atezolizumab

Answer 49

PD-L1 inhibitor

Question 50

durvalumab

Answer 50

PD-L1 inhibitor