reversible competition at H2 receptors in gastric parietal cells
What are the 2 major pathways of metabolism/inactivation of histamine?
1. ring methylation by histamine N-methyl transferase
2. oxidative deamination by MAO
Where is histamine excreted?
in the urine
T/F: histamine is widely distributed (but unevenly) in all mammalian tissues.
Where can you find histamine, specifically?
What endogenous chemical in the body has 3 subtypes and is a member of the superfamily of G-protein coupled receptors?
CNS and peripheral
How do prostaglandins interact with histamine?
prostaglandins counter the histamine adenylate cyclase pathway
prostaglandins are cytoprotective (NSAIDs knock them out)
prostaglandins increase mucus and bicarbonate production
_____ is a hydrophillic molecule whose active form is the monocation and is synthesized from the amino acid histidine by L-histidine carboxylase? It also contains nitrogens...
Which one can a tolerance be developed to? H2 antagonists or PPIs?
Which H2 blocker does not undergo extensive first pass effect?
What are the biological functions of histamine?
gastric acid secretion (powerful)
neurotransmitter functions in the CNS
increased capillary permeability
constriction of large vessels and bronchial tissue
increases HR, but decreases BP due to baroreceptor responses
This chemical has no positive charge at physiological pH and has electron withdrawing groups on the guanidine or guanidine-like group which decreases the basicity of the nitrogens in the molecule. What chemical is it?
Name the 4 H2 blockers mentioned in class.
What is the ultimate mediator of acid secretion?
H+K+ATPase proton pump
Why are PPIs so much better at treating GERD?
because they inhibit the proton pump (H+K+ATPase) system which is far more superior than blocking H2 receptors
This H2 blocker is a CYP450 INHIBITOR therefore has many drug interactions and should be the last choice?
This H2 blocker can cause gynecomastia, drug fever, neutropenia, and depression? It also acidifies the urine...
What are the 2 OTC H2 blockers that are indicated for sour stomach, heartburn and acid indigestion?
Pepcid and Tagamet
(I thought Zantac was too...)
Which H2 blocker may cause an increase in transaminases?
T/F: Ranitidine, famotidine, and nizatidine all inhibit CYP450 enzymes.
false; only cimetidine does
Which H2 blocker is 90% bioavailable (the highest of all of em)?
Where are the H+K+ATPase proton pumps located?
exclusively in the apical membranes of the parietal cells
they are transmembrane proteins
These have little to no effect on gastric juice production, secretion of pepsin, Intrinsic Factor, and GI motility?
T/F: you do not need to stagger doses of antacids and H2 blockers.
false; you do to maximize bioavailability
Ibuprofen + Famotidine
T/F: all PPIs are acid unstable.
If you have renal failure, would you use digitoxin or digoxin?
If you have hepatic failure, would you use digitoxin or digoxin?
These should not be chewed and are in enteric coated tab form or capsule form?
Which one has a narrower therapeutic index and is more toxic? Digoxin or Digitoxin?
Digoxin, but it is the one that is still on the market
Which one is 100% renally excreted? Digoxin or Digitoxin?
What do you give in a digoxin OD?
What do you die from in an OD of digoxin?
What are the two most common side effects of PPIs?
headache and diarrhea
Which ones are more highly protein bound- PPIs or H2 blockers?
PPIs are highly protein bound (95-98%)
What is the consequence of PPIs being highly protein bound?
prolonged duration of action (24-72 hours)
How are PPIs metabolized?
What is the MOA of PPIs?
within the parietal cells (at an acidic pH) they undergo an intramolecular rearrangement which generates a sulfenamide that covalently reacts with thiol functional groups forming a disulfide on the extracellular luminal domain of the pump protein
T/F: PPIs are prodrugs.
In order to get full inhibition of the proton pump, how many molecules of the PPI do you need?
T/F: PPIs are permanent inhibitors of the proton pump system.
T/F: PPI action can be overridden after a few days.
How long does it take for the protein/membrane turnover to occur after a PPI has inhibited the system?
Where do PPIs act?
not in the stomach!!!
in the parietal cells
What is hypochlorhydria?
poor absorption of calcium salts which leads to malabsorption
What can cause hypochlorhydria?
taking a PPI without a meal
What do PPIs do to bone?
they decrease bone resorption of calcium by inhibiting osteoclastic vacuolar H+K+ATPase
High dose PPI use for ____ long can significantly increase your risk for _____?
T/F: women have a higher risk of hip fracture while taking a PPI than men
If you are taking a PPI, what should you supplement with?
if insoluble calcium salts, take with a meal
What enzyme metabolizes the R enantiomer of omeprazole?
What enzyme metabolizes the S enantiomer of omeprazole?
This drug is the S enantiomer of omeprazole? And what enzyme metabolizes it?
Which one would you recommend for an Asian? Prilosec or Nexium?
Nexium because it is metabolized by 3A4, not 2C19 (Asians have trouble with 2C19)
Asians show prolonged plasma levels of which drug?
T/F: if patient has hepatic disease, you should decrease the dose of omeprazole.
false; don't need to because it is urinally and fecally excreted
T/F: protonix can be taken with antacids, with food, or without food
This PPI is indicated for the maintenance of healing of GERD?
Kids aged 1-11 years old can take which PPI?
This drug is the pure enantiomeric form of Prevacid?
This PPI can decrease levels of the AIDS drug atazanvir by more than 70%?
This PPI is not a CYP inhibitor, but is metabolized by 3A4 and 2C19?
Consider dosage adjustment or use caution with which PPIs if hepatic impaired?
T/F: you can take PPIs if you are pregnant.
T/F: PPIs can cause hypomagnesemia.
What 2C19 metabolized cardiac drug displays significant interactions with omeprazole?
What are some important pearls to watch for if recommending an antacid?
be aware of sodium content in hypertensive patients
do not abuse antacids = rebound hyperacidity
use extreme caution with aluminum and magnesium products in renal failure patients
Amphojel, Alu-Cap, Dialume
Do not take antacids 30 minutes before or after which drug?
90% of this drug is excreted in the feces and most of it is not absorbed?
What is sucralfate indicated for?
active duodenal ulcer
What is the MOA of sucralfate?
under acidic pH, the aluminum is split off, which produces a sulfated sucrose which forms a complex with proteinaceous exudate protecting the ulcer against acid, pepsin, and bile salts
This drug is indicated for the prevention of ASA and NSAID induced gastric ulcers?
What is the MOA of cytotec?
it is a synthetic prostaglandin analog with anti-secretory and mucosal protective properties
increases bicarbonate and mucus production
it counters histamine and increases adenylate cyclase activity
this drug is absolutely contraindicated in pregnant women due to abortifacient properties?