peptic ulcer drugs

what does food ingestion stimulate?

1. peptic cells → release pepsinogen

2. cholinergic neurons → release ACh

pepsinogen is produced by…

• peptic cells

ACh from the cholinergic neurons activate ______ receptors

• endocrine receptors

  • muscarinic stomach receptors

endocrine cells release….

a) pepsinogen

b) histamine

c) ACh

d) HCl

b) histamine

endocrine cells are stimulated by….

a) pepsinogen

b) histamine

c) ACh

d) HCl

c) ACh

where are H2 receptors located?

• surface of parietal cells

what manufactures protons/HCl?

• parietal cells

how are the synthesized protons (HCl) pumped out of the parietal cells into stomach lumen?

• K+/ H+ / ATPase pump

the biological system protects the stomach walls from being digested by pepsin or corroded by the concentrated HCl by lining the stomach walls with ______

• mucin

  • muco-polysaccharide polymer

mucin production and secretion are stimulated by _______

• prostaglandins

T/F: There is no treatment for the ulcer

• true

  • only help stop ulcer deterioration by HCl/pepsin

what helps convert pepsinogen → pepsin

• HCl (makes pH = 2) which activates pepsinogen → pepsin

antacids MOA

• neutralizing HCl in stomach activation of pepsinogen

what do you get when you combine HCL + NaHCO3

• NaCl + H2CO3

  • H2CO3 → CO2 + H2O

SATA: which of the following antacids causes acid rebound?

a) sodium bicarbonate

b) calcium carbonate

c) magnesium hydroxide

d) aluminum hydroxide

a) sodium bicarbonate

b) calcium carbonate

why do some antacids cause acid rebound?

• rapid effects of neutralizing HCl

  • release of CO2 → stomach wall → increases HCl release

how does sodium bicarbonate (or all antacids) affect basic/acidic drugs?

• basic = more unionized = more reabsorbed

• acidic = more ionized = more water-soluble = more excretion

which of the following antacids causes diarrhea?

a) sodium bicarbonate

b) calcium carbonate

c) magnesium hydroxide

d) aluminum hydroxide

c) magnesium hydroxide

which of the following antacids causes constipation?

a) sodium bicarbonate

b) calcium carbonate

c) magnesium hydroxide

d) aluminum hydroxide

d) aluminum hydroxide

what the benefit of mixing magnesium hydroxide and aluminum hydroxide together?

• reduced constipation or diarrhea (not 100%)

T/F: NaHCO3 (Sodium bicarbonate) is water soluble and gets into circulation faster than other

• true

antacids with Mg or Al ions may be detrimental for _______ function after absorption from the stomach into circulation

• kidney

which of the following antacids does NOT appear as a white suspension (insoluble)?

a) sodium bicarbonate

b) calcium carbonate

c) magnesium hydroxide

d) aluminum hydroxide

a) sodium bicarbonate

what is Mylanta or Maalox

• combination of AlOH and MgOH to offset each others effects

what do the anti-muscarinic agents target?

• muscarinic cholinergic receptors on the endocrine cells → inhibits histamine production

what type of agent is dicyclomine

• anti-muscarinic agent

T/F: Dicyclomine is used as monotherapy

• false

  • used as adjunct therapy

  • can NOT be used by itself

what is the major problem with dicyclomine

• needs high concentrations to be effective → causes major ADE

what is the target/MOA with H-2 antagonists

• block H-2 receptors on the parietal cells = decreases HCl production

what are the 3 major components linked together in all H2 blockers?

• 5-membered heterocyclic ring w/ basic nitrogen

• CH2-SH-CH2-CH2

• guanido or amidino group with electron withdrawing group

what are the 3 electron withdrawing groups attached to guanido or the amidino group in H2 blockers? rank them by strongest → weakest

1. sulfonamide (SO2NH2; strongest)

2. nitric oxide (NO2)

3. cyano (CN)

what is the purpose of the electron withdrawing groups attached to the guanido or amidino group in H2 blockers?

• decreases basicity

• stronger electron withdrawing group = higher potency

what type of drug is Cimetidine?

• H2 blocker

what type of drug is Famotidine?

• H2 blocker

what type of drug is Ranitidine?

• H2 blocker

what type of drug is Nizatidine?

• H2 blocker

which of the following H2 blockers requires the largest dose (Least potent)?

a) famotidine

b) ranitidine

c) cimetidine

d) nizatidine

c) cimetidine

why does cimetidine have a large dose?

• CN (Weak electron withdrawing group)

which of the following H2 blockers requires the smallest dose (most potent)?

a) famotidine

b) ranitidine

c) cimetidine

d) nizatidine

a) famotidine

which of the following H2 blockers is a very strong CYP inhibitor?

a) famotidine

b) ranitidine

c) cimetidine

d) nizatidine

a) famotidine

how are H2 blockers administered?

• orally or injection (HCl salt)

what type of drug is this?

• H2 blocker

  • cimetidine

what type of drug is this?

• H2 blocker

  • famotidine

what type of drug is this?

• H2 blocker

  • ranitidine

what type of drug is this?

• H2 blocker

  • nizatidine

which of the following H2 blockers has a CN group?

a) famotidine

b) ranitidine

c) cimetidine

d) nizatidine

c) cimetidine

which of the following H2 blockers has a sulfonamide group?

a) famotidine

b) ranitidine

c) cimetidine

d) nizatidine

a) famotidine

why is FDA recalling H2 blockers? which H2 blocker was recalled first?

• detection of unacceptable levels of NDMA

  • ranitidine = first

proton pump inhibitor target/MOA

• inhibitors for K+ / H+ / ATPase pump

  • (parietal cells = site of action)

what is the most powerful class in decreasing HCl in stomach?

• PPI (proton pump inhibitor)

PPI additional indication

• Allison Zollinger Syndrome

  • parietal cell cancer

ALL PPIs are _____

• prodrugs

  • naturally activated by low pH

what is the backbone for PPIs?

• benzimidazole ring

• sulfoxide at position 2

• methylene group

• pyridine at position 2

T/F: the PPIs have different potencies based on their substituents

• false

  • all PPIs have same potency

  • substituents do NOT affect potency

how are PPIs activated?

• become an intermediate with sulfhydryl//mercapto group (SH) → reacts covalently with an SH group on enzyme structure → S-S bond to inactivate enzyme

  • cyclization → decomposition

all PPI react ______ with the enzyme

• covalently

what type of drug is this?

• PPI

  • omeprazole

what type of drug is this?

• PPI

  • esomeprazole

what type of drug is this?

• PPI

  • lansoprazole

what type of drug is this?

• PPI

  • pantoprazole

what is the purpose of adding a methoxy to PPI?

• help w/ metabolism

  • O-demethylation

what is the purpose of cytoprotective agents?

• to protect the ulcerated area of stomach wall from the corrosive HCl and/or digestive effects of pepsin

Misoprostol MOA

• inducing mucin secretion + inhibits HCl secretion

  • PGE1 derivative

Sucralfate MOA

• forms protective gel on the ulcerated area

Misoprostol CI

• pregnancy

  • can cause uterine contraction / abortion

what type of drug is this?

• cytoprotective agent

  • misoprostol

what type of drug is this?

• cytoprotective agent

  • sucralfate

sucralfate administration

• oral tablets used one hour before meal

what are the dual properties of sucralfate

1. non-absorbable (works locally in stomach)

2. Al salt → forms gel

in sucralfate, all hydroxyl groups of the sugar are making ______ with one of the sulfuric acid protons

• esters