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47 Cards in this Set
- Front
- Back
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what is the normal pH of the stomach?
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2 or less
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where are parietal cells found in the stomach?
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in the body and the fundus
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5 specific pathways that stim acid production in parietal cells
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1. ACh binding to muscarinic receptor on parietal cell
2. gastrin --> CCK2 on ECL --> histamine --> H2 on parietal cell 3. gastrin binds to CCK2 on parietal cell 4. Ach binds to M receptor on ECL cell -->histamine release --> binds to H2 on parietal cell 5. plain old histamine release from ECL cell binds H2 on parietal cell |
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describe ECL cells and function
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enterochromaffin-like cell.
found in close proximity to parietal cell. kind of tells the parietal cell what to do wrt acid production. has CCK2 and M receptors (gastrin binds CCK2, Ach binds M. both cause histamine release) |
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what's the gradient between the mucosal cells in the stomach and the lumen of the stomach?
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mucosa = pH of 7
lumen = pH of less than 2 |
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function of PGE or PGE analogue
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binds to EP3, slows acid production somewhat in parietal cell.
main function, though is to reinforce mucosal lining. |
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when is pH at its lowest point during the day?
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in-between meals when we haven't eaten.
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when is the pH highest?
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right after eating (because of the buffer).
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when is pH production the highest?
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right after we eat.
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post-prandial pH?
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4-5 (X1 hr)
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4 elements of gastric defense
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1. Tight junctions
-Between gastric epithelial cells 2 .Mucin layer -Overlying cells 3. Bicarbonate ion -Secreted into mucin layer 4. Prostaglandins*** -Stimulate mucus production, bicarb, mucosal blood flow (prostaglandin E is most important) |
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4 categories of medicines to control gastric acidity
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Antacids (tums, maalox, mylanta)
Cytoprotectants H-2 receptor antagonists Proton pump inhibitors (types of all of these are available OTC - means they're safe and popular) |
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mechanism for antacids
how long do they take to work? |
local neutralization of H+.
works within 30 min. nothing works as fast. |
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common components of antacids
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Aluminum hydroxides; Al(OH)3
Magnesium hydroxides; Mg(OH)2 Calcium carbonate; CaCO3 Sodium bicarbonate; NaHCO3 |
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some side effects that can be associated with antacids?
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systemic effects (have to take a lot) Al and Mg – muscle toxicity, neurotoxicity.
local effects: Diarrhea - Mg2+ Constipation - Al3+ Abdominal distension, cramping, reflux - CaCO3 |
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2 cautions to consider with antacids
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Renal insufficiency
Drug interactions |
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what are drugs that might be problematic to give with antacids?
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chelation problems
tetracyclines fluoroquinalones |
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what is simethicone added to some antacids for?
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gas. doesn't work very well, though.
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how do sucralfate and bismuth cytoprotectant drugs work?
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they form a physical barrier on the stomach and intestines and give the tissue a chance to repair itself
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most common side effect for sucralfate?
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it's an aluminium salt, so constipation is a side effect.
also have to think about chelation. |
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why would sucralfate be especially good for stress ulcer prophylaxis?
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because it doesn't change the pH of the stomach and thus doesn't invite unfamiliar organism colonization that can lead to aspiration infections.
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adverse effects of sucralfate
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Constipation
Most common Accumulation of Al3+ Caution if renal insufficiency Drug interactions Separate administration times |
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strange normal side effect of bismuth?
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black tongue. bismuth binds with sulfates that are normally in mouth.
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describe bismuth compounds
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Bind to base of ulcers
Also promote mucin & bicarb production Have antibacterial effects also good for travelers diarrhea |
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describe misoprostol (cytoprotectant)
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Prostaglandin E1 analog
-Stimulates secretion of mucin & bicarb -Increases mucosal blood flow -Suppresses acid production in parietal cell by binding to EP3 receptor this is what is suppressed with NSAIDs, and is responsible for GI side effects. |
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misoprostol side effects
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Diarrhea - up to 30%
With or without abdominal pain/cramps Increased uterine contractility Contraindicated in pregnancy Used in combination with mifepristone or methotrexate for medical termination of pregnancy |
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examples of H2 receptor antagonists
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Cimetidine (Tagamet)
Ranitidine (Zantac) *just one pill once or twice a day. raise pH to 3 or 4. Famotidine (Pepcid) Nizatidine (Axid) |
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mechanism of H2 blockers?
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Compete with histamine for binding to H2 receptors on parietal cells
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which histamine receptors are responsible for drowsiness when they're blocked?
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H1
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H2 antagonists should be dose adjusted for renal insufficiency because...
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sedation can result otherwise.
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what bad thing can happen with cimetidine?
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cytochrome p-450 inhibitor
so watch with warfarin, phenytoin, theophylline |
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adverse effects of H2 antagonists
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General: Diarrhea, headache, drowsiness, fatigue, constipation
Bone marrow suppression (usu. of platelet counts) CNS - seen more w/IV use Confusion, delirium, hallucinations, slurred speech Cimetidine: Gynecomastia in men; galactorrhea in women, reduced libido in both sexes. (promotes prolactin) |
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2 PPIs to know
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Omeprazole (Prilosec, Zegerid)*
Esomeprazole (Nexium) |
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which drugs raise pH more than any other drugs?
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PPIs. can raise pH to 4,5, or even 7
omeprazol (prilosec), esomeprazol (nexium) |
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MOA of PPIs
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systemic! covalent binding to proton pump lasts for life of pump.
Prodrugs that require activation (protonation) in acidic environment BUT parent compound unstable in acid Enteric coated formulations usually required takes maybe 1 day or more of PPI use to get a full acid suppressive response (to block a critical mass of PPs. |
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where are proton pumps found?
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these H+ K+ pumps are found on the surface of parietal cells.
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duration of effect of PPIs?
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usu up to 48 hours (life of the pump)
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prilosec and plavix problem?
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PPI inhibits cytochrome 2C19, so less of plavix would be converted to the active metabolite.
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long periods of time adverse effects for PPIs?
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Nausea, diarrhea, abdominal pain, constipation
Myopathy, arthralgia, headache Skin rashes -**Reduced vitamin & mineral absorption (B12 needs acid for absorption) Infections? C. diff!, CAP. ECL cell hyperplasia in effort to produce more gastrin (& gastric tumors? In mice) Hypergastrinemic state |
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new recommendation for new PPIs for long-term use?
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Mg level check at baseline and periodically after.
because Mg levels seem to be chronically low. supplementation doesn't work so well. |
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what drugs were rebound hyperacidity associated with?
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PPIs.
so you have to taper them or overlap with antacids or H2 blockers. |
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what are 2 ways to promote smooth muscle motility (increase Ach?)
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dopamine antagonists
5HT4 -agonists |
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what's the promotility agent we need to know?
how does it work? |
metaclopromide
works as 5HT4 agonist and dopamine antagonist! |
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what is the black box side effect we're worried about with metaclopromide?
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movement disorders.
e.g.,acute dystonia. |
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how do you treat H.pylori with ulcers?
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PPIs high doses (promote healing)
combinations of antibiotics (e.g. amoxicillin and flagyl) |
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give an example of sequential therapy
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amoxilicillin (cell wall synth inhibitor). eases entry of.....
then flagyl (works inside cell) |
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what's an easy way to test for H. pylori?
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breath test.
radiolabeled carbon, tests if there's urease produced by H. pylori in stomach. if there's radiolabeled carbon in breath, there's H. pylori. |
