PUD and GERD Med Chem (Dr. J)

Question 1

What are stimulatory signals for HCl secretion?

Answer 1

Histamine
Ach
Gastrin

Question 2

When histamine binds to the H2 receptor, what kind of GPCR is stimulating the proton pump?

Answer 2

Gs (adenylyl cyclase, cyclic AMP, PKA)

Question 3

When Ach binds to the M3 receptor, what kind of GPCR is stimulating the proton pump?

Answer 3

Gq (PLC, IP3, Ca2+)

Question 4

When gastrin binds to the CCK2 receptor, what kind of GPCR is stimulating the proton pump?

Answer 4

Gq (PLC, IP3, Ca2+)

Question 5

What is the core structure of PPIs?

Answer 5

pyridine and benzimidazole moiety liked by methylsulfinyl group

Question 6

Which PPIs are racemic mixtures?

Answer 6

Lansoprazole
Omeprazole
Pantoprazole
Rabeprazole

Question 7

PPIs are prodrugs activated by _______ ___________

Answer 7

acidic environment

Question 8

What happens when PPIs are in an acidic environment before reaching the site of action?

Answer 8

can bind to other proteins—> inactivated drug

Question 9

What is the target reaction when PPI reaches the site of action?

Answer 9

sulphenamide interacts covalently with the sulphydryl groups of cysteine residues in extracellular domain of the proton pump

Question 10

How long does it take for new proton pump molecules to be synthesized after taking PPI?

Answer 10

24-48 hours

Question 11

PPIs need enteric coating to reach site of action, what dosage forms can PPIs come in?

Answer 11

1. capsules
2. powder for suspension
3. tablets
4. IV
5. enteric coated granules

Question 12

How do we prevent degradation of PPIs by acid outside of the desired site of action?

Answer 12

eteric coating

Question 13

How are PPIs metabolized?

Answer 13

CYP2C19 and CYP 3A4 (1st pass metabolism)

Question 14

How many days does it take to achieve a 70 % inhibition of proton pumps?

Answer 14

2-5 days

Question 15

What type of environment do DR and enteric coated tablets dissolve in?

Answer 15

alkaline pH

Question 16

What is a bioisotere?

Answer 16

mimic natural ligand but inhibit its natural action

Question 17

What is the MOA of H2RAs?

Answer 17

inhibit acid production by reversibly competing with histamine for binding of H2 receptors on the basolateral membrane of parietal cells

Question 18

How much acid is suppressed by H2RAs in 24 hours?

Answer 18

70%

Question 19

Why is Ranitidine recalled?

Answer 19

NDMA (a carcinogen) increases over time under normal storage conditions

Question 20

What FG was added to ranitidine in order for NDMA not to form?

Answer 20

thiazole ring replaces furan

Question 21

What is absorption of H2RAs enhanced by?

Answer 21

food

Question 22

What is absorption of H2RAs decreased by?

Answer 22

antacids

Question 23

When do serum concentrations of H2RAs peak?

Answer 23

1-3 hours

Question 24

What neuro-endocrine cells are most prominent in acid-secreting regions of the stomach?

Answer 24

Enterochromaffin- like cells

Question 25

What are the cytoprotective effects of Prostaglandin E2?

Answer 25

1. Stimulation of mucin 2. Stimulation of bicarbonate secretion 3. increased mucosal blood flow

Question 26

What does Misoprostol (EP3 agonist) on parietal cells result in?

Answer 26

decreased acid secretion (Gi mediated)

Question 27

How can pepsin-mediated hydrolysis of mucosal proteins leading to mucosal erosion and ulcerations be inhibited?

Answer 27

sulfated polysaccharides (sucralfate)

Question 28

How does sucralfate produce a physical and chemical barrier?

Answer 28

cross-linking produces a sticky polymer that adheres to epithelial cells and ulcer craters

Question 29

Why does CaCO3 (antacid) produce more gas and pain as a side effect?

Answer 29

produces CO2 as a byproduct; can cause belching, distention, flatulence

Question 30

How does food effect antacids?

Answer 30

Food elevates gastric pH to ~5 for ~1hour and prolongs the effects of antacids for ~2-3 hours

Question 31

What properties of antacids can cause drug interactions?

Answer 31

Alter gastric and urinary pH

Question 32

Antacids can _________ other drugs due to Mg2+ and Al3+

Answer 32

Chelate

Question 33

Which type of ulcer is more dependent on intragastric pH?

Answer 33

H. Pylori

Question 34

H.pylori is significantly less common in places with _______ socioeconomic status

Answer 34

High

Question 35

When is H. Pylori usually contracted and how long does it last?

Answer 35

Early child hood; can be dormant for life

Question 36

How is H.pylori able to adhere to epithelial cells?

Answer 36

Uses flagella to swim through the mucus layer of the stomach/ intestines where pH is near neutral

Question 37

What mechanism does H.pylori use to protect itself from acidic environment?

Answer 37

Produces acid inhibitory protein that blocks acid secretion by parietal cells

Question 38

How does H. Pylori lead to excessive production of cytokines and inflammation?

Answer 38

Release toxins

Question 39

How does our immune system destroy the mucosa when trying to eradicate H. Pylori?

Answer 39

1. Neutrophils leave capillaries and accumulate in areas of infection 2. Release lysosomes for extracellular killing 3. Destroys bacteria and mucous membranes of stomach 4. Gastric acid causes ulcerations

Question 40

How does chronic gastritis due to H. Pylori affect other systems in the body?

Answer 40

Production of gastrointestinal hormones (somatostatin, gastrin, ghrelin) and neurotransmitters

Question 41

What other problems can chronic H. Pylori infection lead to?

Answer 41

MALT lymphoma Intestinal metaplasia Dysplasia Gastric cancer