(17) Antacids, and H2 Antagonists

What makes make gastric acid?

Parietal cells

Parietal cells can be stimulated by:

• Acetylcholine

• Histamine

• Gastrin

3 drugs and what they do?

• Antacid are inorganic bases that neutralizes stomach acid

• H2 antagonist blocks H2 signaling

• PPI inhibits proton pumps

ANTACIDS

ANTACIDS

What are they?

• inorganic bases that neutralizes stomach acid

• main bases:

  • Carbonates

  • Hydroxides

• The metal portion can be:

  • Ca²⁺ / Mg²⁺ = divalent

  • Al³⁺ = trivalent

ANTACIDS

What they used for?

• mild dyspepsia/indigestion

• mild acid-related disorders

Carbonate antacids chemistry (draw too)

• Carbonate + H⁺
  → carbonic acid
  → carbonic acid is unstable
  → CO₂ + H₂O

• Therefore: CO₂
  → gas
  → bloating/belching

Hydroxide antacids - chemistry (draw too)

• OH⁻ + H⁺ → H₂O and metal salt

• No CO₂-producing reaction

antacids work speed?

• antacids work quickly because they directly neuatrailze acid that is already present.

• PPIs and H2 blockers take more time because they affect acid-production mechanisms instead.

Type of anatacid forms?

• liquid and tablet

  • Liquid antacids work a little faster because they do not have to dissolve first.

  • Tablets still work quickly;

H2 ANTAGONISTS

THE H2 PATHWAY

Histamine bonds to H2 → activates adenylate cyclase → produces cAMP → activates kinases → stimulates proton pump → ↑ gastric acid

What does an H2 antagonist do?

H2 antagonists work UPSTREAM from the proton pump.

H2 antagonists - activity type?

• inverse agonists

  • reduce H2 receptor activity below its basal level.

uses?

• Gastric ulcers

• GERD

• Upper GI bleeding

Where do H2 antagonists bind?

→ bind the H2 receptor active site
→ directly compete with histamine

H2 ANTAGONIST STRUCTURE

Professor said to treat these drugs as one class instead of memorizing each structure separately.

All have:

1. Heterocyclic structure with basic functionality

2. Thioether-containing 4-atom linker

3. Guanidine group

H2 ANTAGONIST STRUCTURE - draw

H2 ANTAGONIST STRUCTURE - drug names, idk if i need to know this??

• ranitidine

• cimetidine

• nizatidine

• famotidine

Why sulfur?

Sulfur increases potency compared with carbon or oxygen.

Guanidine - what does it need?

• EWG

  • EWG (CN, NO₂) → ↓ guanidine basicity → neutral guanidine → → active H₂ antagonist