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How many subunits does the H+, K+ - ATPase have and what are they?
2, catalytic alpha (larger) and glycosylated regulatory beta
Which residue is responsible for H+, K+ ATPase loss of the enzyme bound H+ into the extracytoplasmic space?
Is the potassium binding region of H+, K+ - ATPase affected by LYS791?
Extracystolic K+ binds to what residues on the H+, K+ - ATPase before being transferred into the parietal cell? GLU795 and GLU820
Dephosphorylation of the H+, K+ - ATPase occurs at what point in its operation?
Right before K+ release in the cytoplasm
Phosphorylation of the H+, K+ - ATPase occurs at what point in its operations?
Right before the H+ is expelled into the cytoplasm
H+, K+ - ATPase has how many transmembrane segments?
The H+, K+ - ATPase has how many CYS residues?
What H+, K+ - ATPase residue is most critical to binding PPIs?
Which residue of H+, K+ - ATPase is the inner CYS?
What type of PPIs can interact with CYS882 (inner)?
Those that are activated more slowly
What type of bonding interaction do PPIs have with the H+, K+ - ATPase?
Irreversible Covalent Disulfide (between sulfurs on CYS and PPI)
(True/False) PPIs have very potent long lasting effects.
Are the disulfide bonds formed between the H+, K+ -ATPase and the PPI readily reversible?
What is capable of regenerating the PPI inhibited pump?
What limits GSH reactivation of the PPI inhibited pump?
Limited stores and PPIs that bind CYS822 (as CYS822 is deep and hidden from GSH)
What races are the Poor CYP2C19-metabolizing phenotypes are
- Chinese (14.3%),
- Korean (14.0%)
- Japanese (21.3%)
- 3-5% of Caucasians and African Americans
The greatest risk of PPI toxicity due to CYP2C19 inhibition occurs with what drugs?
omeprazole and esomeprazole
What PPI would you use in a CYP2C19 poor metabolizer to prevent toxic effects?
Doses of PPIs should be decreased in what groups?
Severe Hepatic impairment and febrile elderly
What is achlorhydria?
Lack of gastric acid
Some PPIs have DDIs that cause decreased absorption of the other drugs, what are these drugs?
- cephalosporin antibiotics (decreased
- ketoconazole (decreased tablet dissolution,leading to decreased absorption)
- indinavir (decreased tablet dissolution,leading to decreased absorption)
Some PPIs have DDIs that cause increased absorption of the other drugs, what are these drugs?
- clarithromycin (increased absorption)
- digoxin (increased absorption)
- salicylates (increased enteric-coated tabletdissolution, leading to an increase in gastric side effects)
- theophylline (increased absorption fromsustained release formulations)
- vitamin B12 (decreased absorption)