Pharmacology-GI Drugs Flashcards
What stimulates mucous cells to secrete the glycoprotein and bicarb coat for the GI tract?
ACh, PGE2 and PGI2
What stimulates chief cell secretion of pepsinogen?
ACh, CCK and gastrin
What stimulates parietal cell secretion of HCl?
Neuroendocrine (ACh from vagus), endocrine (gastrin from G cells), paracrine (histamine from ECL cells). Note that the major source of regulation is from histamine secretion by ECL cells.
What causes histamine to be released by enterochromaffin-like (ECL) cells?
Gastrin stimulation from G-cell secretion
What cells are located in the fundus?
ECL, G and parietal cells.
What cells are located in the antrum?
G cells.
A 40 year old man presents with heartburn that typically happens after meals and just started a few weeks ago. He also has a long history of being bloated and having lots of gas. Why did his doctor say Mylanta instead of Tums?
Mylanta neutralizes HCl with H2O as a byproduct. Tums neutralizes HCl with CO2 as a byproduct and would make him more gassy.
Why do you mix aluminum hydroxide with magnesium hydroxide in Mylanta?
Aluminum hydroxide decreases gastric motility and magnesium hydroxide increases gastric motility. You mix these to optimal conditions.
Why wouldn’t you want to prescribe a patient sucraflate or bismuth-subsalicylate who has peptic ulcers from an H. pylori infection?
H. pylori is treated with tetracycline that must be absorbed by the stomach. Sucraflate coats the stomach in a water insoluble layer as if forms protein cross-links at the ulcer site. Tetracycline will not be absorbed if the patient is on sucraflate.
In a patient with gastric ulcers, how could you decrease acid secretion stimulation by ECL cells?
H2-receptor antagonists: cimetidine, ranitidine, famotidine and nizatidine. These block the histamine release by the ECL cell after gastrin stimulation. This reduces acid secretion by 90%.
A patient presents with history of heartburn and a new gastric ulcer. You prescribe him an H2 receptor antagonist, cimetidine. What is the relative dosage you will use in this drug?
Very high. H2 receptor antagonists have very short half lives of 1-2 hours, so you give high doses of them 1-2x per day. This is possible because they have very few side effects.
A patient presents with history of heartburn and a new gastric ulcer. You prescribe him an H2 receptor antagonist, cimetidine. What rare side effects should you be aware of with this drug?
Cimetidine is the only H2 antagonist that can cause gynecomastia, galactorrhea and impotence. All H2 antagonists can have rare side effects of confusion, somnolence and headaches.
What drugs can’t you take with cimetidine?
It inhibits multiple P450 enzymes and prolongs the half-life of phenobarbital, theophylline and diazepam.
What drugs work on the site shown below?
Omeprazole, esomeprazole, lansoprazole and pantoprazole IRREVERSIBLY inhibit the K+/H+ ATPase in the caniculi of parietal cells.
Why does the action of PPIs last longer than H2 antagonists?
PPIs irreversibly inhibit the K/H ATPase in the stomach.
Why shouldn’t you chew your PPIs when taking them?
They need to be absorbed in the duodenum so they can get into the general circulation, return to the parietal cell, get taken up by the parietal cell, get pumped into the acidic canaliculi and finally irreversibly inhibit the K/H ATPase. If the prodrug is vulnerable to stomach acid it is degraded and inactivated.
Why should you take your PPI 30-60 minutes before breakfast?
They only work when the pump is turned on. Anticipation of food turns pumps on and allows them to become vulnerable to the PPIs.
Conditions that you would treat with PPIs
Duodenal ulcers, gastric ulcers, NSAID GI symptoms, ZE syndrome and GERD (more effective than H2 antagonists).
Adverse reactions of PPIs
Not many because they solely target the parietal cell K/H ATPase. C. difficile associated diarrhea, respiratory infections, pneumonia (decreased killing of pathogens in stomach), osteoporosis (decreased Ca2+ absorption) and hypomagnesemia.
Drugs contraindicated in people on PPIs
Those that need an acidic gastric pH like iron, ketoconazole and ampicillin
A 47 year old woman presents with constipation. She also has a 5 year history of GERD. What drug could you prescribe her that would take care of both of these symptoms?
Metoclopramide, it is a 5-HT3 antagonist, 5-HT4 agonist and D2 antagonist. Action at these sites results in raising of the LES pressure to decrease GERD and increased ACh release from myenteric neurons that increase the rate of gastric emptying and decrease small bowel transit time.
What is a drug you could use to prophylax for vasovagal induced vomiting or chemotherapy induced vomiting?
Metoclopramide. It is a central D2 antagonist, 5-HT3 antagonist and 5-HT4 agonist.
What drugs are a step up from metoclopramide for anti-emetic treatment in chemotherapy-induced nausea and vomiting (CINV)?
Ondansetron, granisetron. It is a central and peripheral 5-HT3 antagonist that only acts on these receptors.
What drugs can be combined with ondansetron in patients who are not getting sufficient relief from CINV?
NK1 inhibitor, aprepitant
What drugs shouldn’t be used to treat a patient with mild inflammatory bowel disease if they are allergic to aspirin?
Any drug that can be converted to mesalamine (sulfasalazine, olsalazine, basalazide). Mesalamine is similar to aspirin as it inhibits production of AA metabolites in the colon.
A 40 year old woman has been on medication of constipation-predominant IBS for the past 3 weeks. What drugs might have been prescribed if they alter chloride secretion into the gut?
Linaclotide (increase cGMP levels and activates CFTR channel) and lubiprostone (PGE1 metabolite that opens CIC-2 Cl- channel). Both of these allow for increased Cl- transport into the lumen and consequently increased water transport into the lumen to get stools moving.
