H2 receptor antagonists and PPI

Question 1

How is H+ released by the parietal cells in the stomach?

Answer 1

1. Histamine attaches onto the H2 cell surface receptor
2. Transforms into intracellular signal that releases H+
3. Leads to decrease in pKa

Question 2

What is the crucial ring thats found in H2 receptor antagonist drugs that makes it bind to the receptor?

Answer 2

Imidazole ring: HN-N

Question 3

What are the major H2 antagonist drugs that are currently on the market?

Answer 3

1. Cimetidine
2. Metiamide
3. Ranitidine
4. Famotidine

Question 4

What is the main criteria for the synthesis of Cimetidine via industrial route?

Answer 4

1. Short
2. High yielding (Cost effective)
3. Atom efficient (reduced waste)

Question 5

What are the problems that are associated with Cimetidine?

Answer 5

1. Interacts with cytochrome P450 to inhibit it and cause many drug interactions
2. E.g. Antiandrogen properties at high doses
3. Antagonises the binding of testosterone and DHT to androgen receptor
4. Interferes with metabolism of estrogen

Question 6

What are the problems associated with ranitidine?

Answer 6

1. Rare CNS problems such as general malaise, dizziness

2. Other rare effects on GI, cardiovascular, hepatic, respiratory and haematological system

Question 7

What makes famotidine better than cimetidine?

Answer 7

No effect on cytochrome p450

Question 8

How does omeprazole and other PPIs generally work?

Answer 8

Blocking the H+/K+ ATPase mechanism that’s found in gastric parietal cells

Question 9

What is the S enantiomer of omeprazole called?

Answer 9

Esomeprazole