Gastrointestinal Drugs

Question 1

Three main types of GI drugs altering secretion

Answer 1

Antacids, H2 antagonists, proton pump inhibitors

Question 2

What is Barrett’s Esophagus

Answer 2

Transition from stratified squamous epi to simple columnar

Question 3

How do dietary peptides trigger acid release?

Answer 3

1. Activation of G cell to release gastrin into antrum BV
2. Gastrin hits ECL cell in fundus, triggers Histamine release
3. Histamine triggers H+ release from parietal cells

Question 4

Why doesn’t acid always cause ulcers?

Answer 4

Barrier or mucosa + bicarb

Question 5

Which prostaglandins work with NO to maintain mucosal defenses of the stomach

Answer 5

PGE2, PGI2

Question 6

Why do NSAIDS cause ulcers?

Answer 6

Inhibition on the PGE/I 2 that acts on EP3 to promote mucus and HCO3- release

Question 7

Name the four more common antacids and their most important adverse effects

Answer 7

NaHCO3 – Alkalosis, Fluid Retention
CaCO3 – Milk Alkali syndrome
Al(OH)3 – Constipation
Mg(OH)2 – Diarrhea

Question 8

What is Tums?

Answer 8

CaCO3

Question 9

What is Maalox, Mylanta?

Answer 9

Al(OH)3 + Mg(OH)2

Question 10

What is Gaviscon?

Answer 10

Sodium Alginate + Antacids

Prevents Reflux/GERD

Question 11

What is Simethicone (Mylicon, Phazyme)

Answer 11

Mild Surfactant to help with gas release

Question 12

What chemical component of drugs is common amongst H2 receptor antagonists

Answer 12

Amidazole Mimics

Question 13

Important 1st generation H2 blocker

Answer 13

Cimetidine (Tagamet)

A competitive antagonist of the H2 receptor

Question 14

Cimetidine may inhibit the activity of Cyp ___

Answer 14

2C6 + 2D9

Watch out for warfarin, phenytoin, benzos, sulfas

Question 15

Side effects of Cimetidine

Answer 15

CNS effects
Anti-androgen
Inhibition of estradiol metab (galactorrhea)
Thrombocytopenia

Question 16

Name the second generation H2 blockers

Answer 16

Ranitidine (Zantac)
Nizatidine (Axid)
Famotidine (Pepcid)

Question 17

Effect of 2nd gen H2 blockers on OH

Answer 17

Increase bioavailability by reducing first pass balance

Question 18

What makes a 2nd gen H2 blocker bettwe than Cimetidine?

Answer 18

Less CYP influence, Greater Potency

Once daily

Question 19

What are proton pump inhibitors (concept)

Answer 19

Prodrugs that become irreversible inhibitors of H/K ATPase

Question 20

Describe the mechanism of omeprazole fxn

Answer 20

1. Add an H+ to form Sulfenic Acid
2. Dehydration to Cyclinc Sulfenamide
3. Irreversible binding to HK ATPase

Question 21

Adverse effects of proton pump inhibitors

Answer 21

Nausea
B12 Deficiency
Osteoporotic Fracture if frequently used

Question 22

Relationship of proton pump inhibitors and the CYPs

Answer 22

Inhibitors of CYP2C19
Builds up Diazepam, Warfarin , Phenytoin
Decreased Plavix activity

Question 23

Risk of discontinuing treatment with H2 blocker or PP inhib.?

Answer 23

Acid rebound

No residual somatostatin inhib of gastrin secretion

Question 24

Two mucosal protective agents he mentioned

Answer 24

Sucralfate (Carafate)

Misoprostol (Cytotec)

Question 25

Why would you use a mucosal protective agent instead of an H2Block or PPI?

Answer 25

Severely ill patients at a high risk of nosocomial infection

Question 26

How does sucralfate (carafate) work?

Answer 26

After acid activation, Polymerizes and forms protective barrier at ulcer site

Question 27

Sucralfate (carafate) decreases absorption of...

Answer 27

tetracycline digoxin phenytoin

Question 28

How does misoprostol work?

Answer 28

It is a Prost. E1 derivative that reduces acid secretion and enhances mucus and bicarb secretion

Question 29

How is misoprostol used?

Answer 29

w/ chronic NSAIDS

Question 30

Adverse effects of Misoprostol?

Answer 30

Diarrhea | Abortions

Question 31

Combination therapy for H Pylori includes...

Answer 31

Bismuth salt Antibiotic H2 block or PPI (to heal the ulcer)

Question 32

Antibiotics typically used for H pylori

Answer 32

Metronidazole Tetracycline Amoxicilin Clarithromycin

Question 33

What does bismuth subsalicylicylate do?

Answer 33

Antibacterial, Antiviral, and anti-secretory | Treatment for mild diarrhea, h pylori eradication

Question 34

On a cholinergic motor neuron in the gut, what receptors are activated when getting the go signal from ENS? What drugs target this?

Answer 34

5-HT4 -- 5-HT | Motilin -- Erythromycin

Question 35

Role of dopamine 2 receptor on the enteric cholinergic motor neuron

Answer 35

Dopamine inhibits signalling | Metoclopramide inhibits dopamine activity (increasing signalling and also anti-emetic effects)

Question 36

How does atropine influence GI motor activity? Neotigmine?

Answer 36

Atropine inhibits M3 receptor | Neostigmine is an acetylcholinesterase

Question 37

Clinically, why gice metoclopramide (reglan)?

Answer 37

Small bowel intubation Post-Op+Diabetic Gastroparesis GERD Anti-emetic

Question 38

Side effects of Metoclopramide?

Answer 38

Sedation Parkinson's-like syndrome Hyperprolactinemia

Question 39

5-HT4 agonists used as prokinetics?

Answer 39

Cisapride (propulsid) * Tegaserod - withdrawn from CV tox * Prucalopride - unavailable in US

Question 40

Motilin agonist used as pro kinetic?

Answer 40

Erythromycin | rapid tolerance = limited usefulness

Question 41

What is Linaclotide?

Answer 41

Peptide activators of guanylate cyclase 2

Question 42

What is linaclotide used to treat?

Answer 42

IBS+Constipation | Idiopathic Constipation

Question 43

Main adverse effect of linaclotide?

Answer 43

Diarrhea

Question 44

Why does linaclotide turning on guanylate cyclase 2 matter?

Answer 44

1. Conversion of GTP to cGMP triggers CFTR receptor activity. This will increase H2O and electrolyte loss --> laxative effect. 2. cGMP will also move extracellularly to decrease activity of pain sensing fibers

Question 45

Important Secretory/Stimulant Laxatives

Answer 45

``` Bisacodyl (Dulcolax) Cascara Senna Aloes Lubiprostone ```

Question 46

What is Lubiprostone all about?

Answer 46

ClC2 activator for chronic idiopathic constipation | Used in IBS w/ chronic constipation

Question 47

Important Bulk laxatives

Answer 47

Psyllium, Methylcellulose, Bran, Milk of Magnesia | Lactulose

Question 48

lactulose is also used in patients with...

Answer 48

hepatic encephalopathy

Question 49

Isoosmotic electrolyte solutions with _______ produce similar effects to bulk laxatives

Answer 49

Polyethelene Glycol

Question 50

Important listed stool softeners

Answer 50

Docusate sodium (Colace) Mineral Oil Glycerin

Question 51

What are stool softeners?

Answer 51

Surfactants and lubricants that incorporate into stool to make passage easier

Question 52

How do anti-diarrheals work (broadly)

Answer 52

1. Slow peristalsis to increase water + electro. absorp. | 2. Absorp potential intestinal toxins + Water

Question 53

Anticholinergic used as an antidiarrheal?

Answer 53

Dicyclomine (Bentyl)

Question 54

Opiate use as an antidiarrheal?

Answer 54

Diphenoxylate (w/Atropine = Lomotil) | Loperamide (Imodium)

Question 55

Who should not get an optiate anti-diarrheal?

Answer 55

Patients with severe ulcerative colitis and bacterially induced diarrhea

Question 56

Name two kinds of antidiarrheals that stick around and grab stuff up to help out the diarrh.

Answer 56

Kaolin (attapulgite) and pectin | Low dose fiber

Question 57

What should you use to treat abdominal pain and distension + altered bowel habits in a woman w/ IBS

Answer 57

Alosetron (lotronex), a 5HT3 antagonist | This will lower the ACh release from the motor neurons, blocking visceral afferent pain and decreasing motility)