GI Drugs

Question 1

Name an H2 receptor antagonists

Answer 1

ranitidine; famotidine

Question 2

Name a PPI

Answer 2

omeprazole

Question 3

List 3 antacids

Answer 3

Mg(OH)2; Al(OH)3; CaCO3

Question 4

List some mucosal protective agents

Answer 4

sucralfate; bismuth subsalicylate

Question 5

Anti-emetics

Answer 5

metoclopramide; ondansetron

Question 6

Stimulant laxative

Answer 6

lubiprostone

Question 7

What is a saline laxative

Answer 7

Mg(OH)2

Question 8

Antidiarrheal

Answer 8

loperamide, alosetron*

Question 9

What is a mesalamine?

Answer 9

sulfasalazine

Question 10

List a thiopurine anti-metabolite

Answer 10

azathioprine

Question 11

Name a TNF alpha inhibitor

Answer 11

infliximab

Question 12

What is the MOA of H2 blockers?

Answer 12

Directly block histamine-stimulated gastric acid
secretion – H2 receptor blockers
Blunt parietal cell responses to ACh and gastrin

Very low toxicity – but reduce dose in _renal dysfunction _

*CROSSES PLACENTA

Question 13

What are H2 blockers proven to prevent?

Answer 13

gastric and duodenal ulcers
GERD

*can use as prophylaxis for NSAID induced ulcers (better for duodenal)

Question 14

What is the MOA of PPIs?

Answer 14

Irreversible inhibition of parietal cell proton pump
(H+/K+-ATPase) results in prolonged (90-98%) inhibition
of gastric acid secretion

The weak base accumulates in parietal cell
canaliculus, then protonated form of drug binds
covalently to enzyme. PPIs are acid labile, so need
enteric coating to get past stomach

Only work with acid secretion

Question 15

True/false: PPIs are administered as prodrugs.

Answer 15

True

In order to get through stomach to be absorbed in the intestine. ITs a base, absorbed in the parietal cell; once it crosses over to canaliculi of parietal cell (acidic) becomes protonated and doesn’t come out

*Has a short 1/2 life but effects long term. *

Question 16

What is the effect of PPIs vs. H2 blockers on acid secretion during the day?

Answer 16

Note excellent control of nocturnal acid (less Ach/gastrin) for both H2 block and PPI, but PPI much better during the day

H2 is good nocturnally

Question 17

What are PPIs proven to have efficacy for, and what are they a DOC for?

Answer 17

Efficacy proven in ulcers and GERD

First choice in Zollinger-Ellison syndrome

Question 18

What is the MOA of antacids?

Answer 18

Weak bases that are poorly absorbed (so stay in GI lumen) and directly neutralize stomach acid

Good for occasional heartburn –
but for long term use compliance is not
as good as for H2 blockers or
omeprazole

Question 19

What are some DIs to be concerned about for antacids?

Answer 19

Antacids can increase or decrease the
absorption of many classes of drugs

Al(OH)3 or CaCO3: Decreased absorption
of tetracycline, isoniazid, ketoconazole, etc

Increase in urinary pH alters
elimination of *acidic (e.g., salicylates)
and basic (e.g., quinidine) drugs *

Question 20

How do you treat H. Pylori infection?

Answer 20

Treatment: usually a PPI plus several antibiotics

Question 21

True/false: you can administer sucralfate with other antacids.

Answer 21

FALSE

Question 22

How does sucralfate work?

Answer 22

Forms paste-like gel at low pH that adheres
to positively charged proteins of epithelial cells as well as ulcer craters.

PROBLEM: Can adsorb other drugs – e.g.,
tetracycline, phenytoin, digoxin – _wait 2 hrs
before admin of sucralfate_

Question 23

How does Pepto bismol work?

Answer 23

Binds selectively to ulcers to protect against acid and pepsin

CAUTION: Blackens stool/tongue

Question 24

How does metoclopramide work as an antiemetic?

Answer 24

Central CNS: 5-HT4 receptor agonist; 5-HT3 receptor antagonist (vagal/CNS), also D2

Blocking stimulus to the brain, tries to keep things going in one direction . . .
Enhances ACh release in myenteric plexus and
improved tone in esophageal sphincter

Used for chemotherapy-induced nausea and
vomiting

Question 25

What is an adverse effect of metoclopramide?

Answer 25

Adverse: **Dopamine D2 receptor antagonist activity** *that can cause extrapyramidal (Parkinsonism-like) symptoms and tardive dyskinesia* _** 2009 FDA black box warning: long term use can result in irreversible muscle spasms (dyskinesia)**_

Question 26

How does odansetron work?

Answer 26

***_Selective_*** **5-HT3 receptor antagonist**- effective when administered prior to chemotherapy or surgery. \*\*_**has little or no effects on muscarinic or dopaminergic receptors. **_

Question 27

True/false: lubiprostone is approved for chronic constipation use.

Answer 27

TRUE

Question 28

What is the MOA of luboprostone?

Answer 28

**Cl channel activator: **increases *intestinal fluid secretion,* results in increased number of bowel movements Recall that Cl moves out into GI lumen and takes water with it. TYPE C for PREGNANCY

Question 29

What is an example of a saline laxative?

Answer 29

** Mg(OH)2** **hypertonic solution,** osmotic pressure leads to accumulation of fluids in GI tract and stimulation of peristalsis **_Cathartic dose_** leads to complete evacuation in **less than 3 hour**s (e.g., for colonoscopy prep)

Question 30

What is the prototype anti-diarrheal agent?

Answer 30

Loperamide **Opioids with low abuse potential** because they are very poorly absorbed from the GI ***Slows intestinal transit time due to stimulation of mu opioid receptors in intestinal smooth muscle*** Adverse: _toxic megacolon, CNS tox (less with lop)_ Avoid in patients with *ulcerative colitis or acute bacillary or amoebic dysentery*

Question 31

What do you treat IBS-**_D_** with?

Answer 31

**• Loperamide** • Restricted Use Drug: If standard therapies fail, the **5-HT3 receptor antagonist alosetron** is FDA approved for *_women_* with diarrhea-predominant IBS Mech: _**decreased colonic motility via enteric and CNS blockade of 5-HT3 receptors.**_ _**\*\*AR: ischemic colitis**_

Question 32

What do you use to treat IBS-C?

Answer 32

Mg(OH)2

Question 33

How do you treat active IBD?

Answer 33

Both ulcerative colitis and Crohn’s disease: • Glucocorticoids (prednisone) t_o rapidly reduce ulceration and cause initial remission _ • **Long term therapy**: immunosuppressives including purine anti-metabolites **_azathioprine_** or 6-mercaptopurine, **takes several months for full effect** Adverse: bone marrow suppression, rashes, fever, nausea

Question 34

What is a first line tx for ulcerative colitis?

Answer 34

**sulfasalazine** • Mech: interferes with *_intermediates in inflammatory pathways_* – **_topical_ 5-ASA (onto intestinal wall) is effective**, _not systemic_5-ASA Adverse: up to 40% of pts cannot tolerate.

Question 35

What is infliximab used for?

Answer 35

**Crohn's disease** _*Immunosuppresant: antibody to TNF-alpha. Binds to TNF-alpha to block its inflammatory effects at TNF receptors.*_ **Also approved for ulcerative colitis** – Adverse: increased infections

Question 36

What are the stimuli for acid secretion?

Answer 36

Stimulus: food (esp peptides), vagus (stretch receptor, release ACh to stimulate gastrin release), direct stimulation of G cells stimulate gastrin release . . . gastrin stimulates histamine and parietal cells \>\> HCl

Question 37

Pathways for acid secretion

Answer 37

Gastrin and ACH work through a **calcium** dependent pathway (could use a muscarinic antagonist, but not preferable) Histamine works through H2 receptors (**cyclic AMP** pathway) H/K ATP ase \>\> HCL

Question 38

Antacids causing diarrhea/constipation

Answer 38

MgOH diarrhea producing Al- constipation