GI Pharmacology Flashcards
Acid Suppression is the goal of most GI therapy. Which cells produce the Hydrogen ions released in the stomach?
Parietal cells release H+ and IF and happen to be spaceship shaped.
Pathway for hydrogen accumulation in parietal cells.
CO2 + H2O with the help of Carbonic Anhydrase form H2CO3 aka Carbonic Acid. Hydrogen freely dissociates and gets pumped out by an ATP antiporter exchanging them for K+ in and H+ into the stomach.
Sidenote: K+ just migrates right back into lumen via passive transport. carte blanche for K+ in the gut, apparently.
When H+ dissociates from Carbonic acid, who is left behind?
Bicarb ion aka HCO3-. Then Bicarb via a passive antiporter exchanges for Cl- and moves through an apical channel right into the lumen of the stomach to meet its love match, Hydrogen.
This means you’re alkalinizing your blood and acidifying your gut lumen.
Gastric cells are the generals, who are the sargeants and what do they produce to increase acid production?
ECL cells are the sargeants and they produce Histamine to increase acid production which then act on H2 receptors on the Parietal cells.
Of the 3 methods of stimulating acid production, which is the main?
While Gastrin itself can slightly stimulate the Parietal release of acid, it is actually the Gastrin –> ECL Histamine –> H2 receptor on Parietal that is the main method.
What are the 3 main actors of acid stimulation?
Gastrin tells ECL to produce Histamine which acts on H2 receptors of Parietal cells. Gastrin also has mild action directly and weirdly on the CCKb receptor.
Vagus nerve which stimulates entire enteric system also has direct ACh mediated action on Parietal cell’s via mACh receptor to produce acid secretion. But Vagus also indirectly increases acid by stimulating the G spot…I mean G cells. Don’t forget that the CNX doesn’t use ACh on Gastrin - it uses a special gentle GRP.
Histamine acts on the H2 receptor which is coupled to which type of G protein?
Which molecules use the weaker Gq pathway?
Gs - cAMP and PKA - exocytosing vesicles via Proton Pumps. Gq is used by Gastrin and ACh. Gi is used to stop acid secretion by Somatostatin and PGs.
Which histamine receptor is used on parietal cells and which is used for most allergic rxns?
H1 is for allergic rxns. H2 is parietal cell acid producing.
What 2 sexy ass molecules act on the Gi pathway to reduce acid secretion?
Somatostatin from Delta cells and Prostaglandins which are so protective and sweet until NSAIDS harass them.
Sidenote if anyone cares: Somatostatin is from bloodstream while PGs are secreted locally and in addition to countering acid production, they stimulate mucus secretion for more protection.
Name H2 blockers and their simple MOA.
Adverse effects?
Cimetidine, Ranzatidine,
Name H2 blockers and their simple MOA.
Adverse effects?
Cimetidine, Ranitidine, Famotidine, Nizatidine.
Cimetidine is the oldest and only one with any actual side effects. P450 inhibitor and an anti-androgen. Crosses BBB and may cause dizziness esp in elderly so just don’t. Cim and Ranitidine may cause transient but benign increased Creatinine clearance, fyi.
Why are H2 blockers less effective than PPIs? Should be obvious if you know the biochemical physiology of acid into the lumen.
Blocking H2 receptor still allows for the weaker Gastrin and Vagal pathways to act on the Parietal cells. While, I would think a good balance like that is created, apparently not.
Whereas blocking at the Proton Pump just eliminates the final doorway for Hydrogen to enter the lumen of the gut.
Some Drugs Cause Awesome Knockers is a mnemonic for what?
Drugs that induce gynecomastia. Spironolactone. Digitalis. Cimetidine. Alcohol (chronic). Ketaconazole.
MAGIC KNOCKERS in GQ is a mnemonic for what.
CYP 450 Inhibitors.
What adverse effects do PPIs even have?
How do PPIs help with Zollinger Ellison syndrome?
Why must we wait for Parietal cell to slough off to lose the effect of PPI?
Decreased absorption of calcium and Mg. Like, so whatever.
If they block the proton pumps, what’s the gastrin gonna do? Cry?
They bind irreversibly - which actually helps for long lasting relief.
What are the 2 antacids we use and where do they work?
Bismuth and Sucralfate; these are topical in the lumen just like in that Peptobismol commercial with pink stuff coating your tummy.
They just bind to the Hydrogen ions to neutralize and form water. Simple si baat hai.
Why are antacids limited in helpfulness?
Body just generates more acid. So only helpful for intermittent dyspepsia. Long term use will cause Hypokalemia.
What are the most important associations to have regarding Bismuth and Sucralfate, respectively?
Bismuth is part of H. Pylori quadruple therapy.
Sucrose aluminum sulfate (the aluminum can lead to hypophosphatemia and then body leeches it from bones).
What are side effects of Bismuth and Sucralfate use?
Bismuth aka Peptobismol benignly turns poop black but be aware of this in the case of GI pts which may have blood in poop also. If pt has epigastric pain, one of the first things to ask in RoS is “do you have black, darkened, or bloody stools?” aka signs of GI bleed.
