GI Pharm

Question 1

4 signalling molecules that regulate GI motility

Answer 1

Contraction: ACh, Substance P
Relaxation: VIP, NO

Question 2

what do pro kinetic agents do?

Answer 2

MODULATE rather than mediate motility (regulate ACh activity - either release more or make it longer lived)

Question 3

4 classes of prokinetic agents

Answer 3

cholinergic agents
dopamine antagonists
serotonin agonists
macrolides

Question 4

neostigmine

Answer 4

not very useful now –activity is too diffuse

Mech: reversible inhibition of acetylcholinesterase

Question 5

domperidone

Answer 5

Dopamine D2 receptor antagonist - inhibits dopamine in myenteric plexus but does not penetrate the BBB/CNS
inhibits gastric motility –> reduces lower esophageal and intragastric pressure by reducing ACh release

Question 6

phenothiazine

Answer 6

classic dopamine antagonist. works for GI but produces extrapyramidal side effects

Question 7

metoclopramide

Answer 7

5HT4 receptor activation - on interneurons –> to stim ACh release
effects on GI tract –> increased gastric emptying and decreased transit time through duodenum, jejunum & ileum
secondary activity @ D2R

Question 8

which medication is acts at the motion receptor?

Answer 8

erythromycin

Question 9

erythromycin

Answer 9

macrolide antibiotic; motilin agonist –> enhances upper GI motility w/ little or no effect in the colon
useful for gastroparesis
utility limited by tolerance and antibiotic effects

Question 10

ghrelin

Answer 10

effect: increased gastric movement

possibility for future drug development

Question 11

chemoreceptor trigger zone

Answer 11

area of the brain that lacks BBB – can monitor blood and CSF for toxicants

Question 12

central pattern generator

Answer 12

neurons coordinating complx series of events that occur during emesis

Question 13

name 3 dopamine receptor agonists for antiemesis

Answer 13

phenothiazine, metoclopramide, domperidone

Question 14

which antiemetic is most effective for chemo-induced nausea?

Answer 14

high dose metaclopramide

ondansetron

Question 15

ondansetron

Answer 15

5HT3R antagonist for nausea (esp originating in the gut)
mech: binds to 5HT3R on vagal neurons lining GI tract –> block signal to vomiting center in the brain –> prevent nausea and vomiting

Question 16

dronabinol

Answer 16

cannabinoid useful prophylactically for cancer chemo-related nausea
sim appetite
potential for abuse

Question 17

diphenhydramine

Answer 17

histamine H1 antagonist, useful in mild-moderate motion sickness

Question 18

what is the most commonly used agent in combination anti-emetic therapy?

Answer 18

dexamethasone

Question 19

nature’s antiemetic

Answer 19

ginger!

definitely works for motion sickness, morning sickness, post-op, unclear about chemo-induced

Question 20

diarrhea tx

Answer 20

oral rehydration therapy

some pharmacotherapy options: bulk forming agents, clays, bismuth, opioids, alpha-2-adrenergic agonist

Question 21

metamucil

Answer 21

bulk forming agent, unknown MOA

Question 22

kaopectate

Answer 22

clay for diarrhea tx, binds water avidly

Question 23

loraperamide

Answer 23

antidiarrheal agent, opioid

limited ability to enter CNS, safe

Question 24

tx for mild constipation

Answer 24

fiber rich diet, increased fluid intake, increased physical activity, development of bowel habits

Question 25

antacids - MOA, types, side effects

Answer 25

neutralize secreted acid (from proton pump) –> raise pH –> inactivate pepsin
Aluminum or magnesium hydroxide
- aluminum –> can cause constipation
- Mg –> has laxative properties

Question 26

omeprazole

Answer 26

PPI for GERD
prodrug. covalent and irreversible binding to pump –> inhibits.
safe and well tolerated for short term use (though increased risk of pneumonia
risks of long term use: C. diff, fractures, acute interstitial nephritis

Question 27

alosetron

Answer 27

5HT3 receptor antagonist for IBS-D in women –> reduces motility and intestinal sensitivity to distension
withdrawn from market b/c severe GI side effect os ischemic colitis
now allowed again for refractory IBS-D pts

Question 28

lubiprostone

Answer 28

for IBS-C in adult women, chronic idiopathic constipation, opioid-induced constipation
MOA: mimicks prostaglandin, involves Cl- channels

Question 29

linaclotide

Answer 29

for IBS-C, CIC
MOA: guanylate cyclase-C –> increases [cGMP] –> increases [Cl-] in intestinal lumen –> increase in intestinal fluid and faster transit

Question 30

how do we currently approach medical tx for IBD?

Answer 30

anti-inflammatory, b/c we don’t understand the disease yet

try to tx the effected area w/out too much systemic effect

Question 31

sulfasalazine

Answer 31

for mild/moderate UC (less useful in Crohn’s)
MOA: anti-inflammatory
prodrug- prevents absorption in stomach or small intestine

Question 32

difference b/t sulfasalazine and mesalamine

Answer 32

mesalamine mostly absorbed in upper GI tract - doesn’t get as much to the colon where it is needed

Question 33

budesonide

Answer 33

locally active glucocorticoid for oral tx of mild-moderate Crohn’s involving ileum and/or ascending colon
high first-pass effect on liver

Question 34

integrins

Answer 34

possible target for future tx of IBD w/ antibodies

Question 35

infliximab

Answer 35

anti-TNFalpha mAB for tx of refractory CD and UC – formation of regulatory macrophages w/ immunosuppressive properties, including production of anti-inflammatory cytokines
possible induction of neutralizing antibodies (“anti-drug antibodies”/ANA) –> loss of response