Term
| what cells in the GI tract make acid? |
|
Definition
|
|
Term
| how do the parietal cells make acid? |
|
Definition
| H/K ATPase pumps H ions into the stomach lumen |
|
|
Term
| where do proton pump inhibitors work? |
|
Definition
| on the H/K ATPase of parietal cells |
|
|
Term
| what 3 things are parietal cells responsive to? |
|
Definition
1. Ach through muscarinic receptors
2. histamine through H2 receptors
3. gastrin through CCK receptors |
|
|
Term
| what cells make histamine? |
|
Definition
| enterochromaffin-like cells (ECL) |
|
|
Term
| what is the critical regulator of acid production in the stomach? |
|
Definition
|
|
Term
| how does histamine effect acid production? |
|
Definition
| stimulates the H/K ATPase through increased cAMP |
|
|
Term
|
Definition
|
|
Term
| what are the 3 inputs to the parietal cells? |
|
Definition
1. neural from vagus nerve - Ach
2. endocrine from antral cells - gastrin
3. paracrine from ECL cells - histamine |
|
|
Term
| how do gastrin and Ach increase the H/K ATPase? |
|
Definition
|
|
Term
| how does histamine increase the H/K ATPase? |
|
Definition
|
|
Term
| what is the critical regulator of acid production? |
|
Definition
|
|
Term
| where does histamine act to regulate acid production? |
|
Definition
| H2 receptors on parietal cells |
|
|
Term
| how does histamine cause acid production? |
|
Definition
| stimulates H/K ATPase through cAMP pathway |
|
|
Term
| how do Ach and gastrin cause acid production? |
|
Definition
| activate H/K ATPase through increase in Ca |
|
|
Term
| what makes up the gastric defense? |
|
Definition
1. tight junctions between epithelial cells - physical defense
2. mucin layer
3. secretion of bicarb into the mucin |
|
|
Term
| what stimulates secretion of bicarb into the mucin layer? |
|
Definition
|
|
Term
| what are the aggressive factors in the GI tract? |
|
Definition
1. acid
2. pepsin (a protease)
3. H. pylori |
|
|
Term
| H. pylori presence is associated with what? |
|
Definition
|
|
Term
| the balance between what 2 things is important in the GI tract? |
|
Definition
| the balance between gastric defense and aggressive factors |
|
|
Term
| drugs used to regulate acid secretion (7)? |
|
Definition
1. H2 receptor antagonists
2. proton pump inhibitors
3. prostaglandin derivatives
4. sucralfate
5. antacids
6. anti-cholinergic agents
7. antibiotics |
|
|
Term
| 4 histamine receptor antagonists? |
|
Definition
1. cimetidine
2. ranitidine
3. famotidine
4. nizatidine |
|
|
Term
| mechanism of action of histamine receptor antagonists? |
|
Definition
| inhibit H2 receptors on parietal cell --> inhibit basal and stimulated acid secretion |
|
|
Term
| histamine receptor antagonists are particularly effective for what? |
|
Definition
|
|
Term
| are histamine receptor antagonists absorbed orally? |
|
Definition
|
|
Term
| what histamine receptor antagonists has the shortest half life? |
|
Definition
|
|
Term
| which histamine receptor antagonists is the least potent? |
|
Definition
|
|
Term
| which histamine receptor antagonists is the most likely to cause side effects and why? |
|
Definition
cimetidine
because it inhibits cytochrome p450 systems |
|
|
Term
| side effects of cimetidine? |
|
Definition
may cause gynecomastia, reduction in sperm count, galactorrhea
blocks androgen receptors and estradiol metabolism |
|
|
Term
| cimetidine has drug interactions with 4 drugs? |
|
Definition
1. warfarin
2. phenytoin
3. quinidine
4. beta adrenergic antagonists - propanolol |
|
|
Term
| what histamine receptor antagonist has 1/10 the p450 effect of cimetidine? |
|
Definition
|
|
Term
| what histamine receptor antagonists are devoid of effects on p450? |
|
Definition
1. famotidine
2. nizatidine |
|
|
Term
| uses of histamine receptor antagonists? |
|
Definition
1. healing of gastric ulcers
2. suppress nocturnal acid production
3. treatment of uncomplicated GERD
4. prophylaxis of stress ulcers |
|
|
Term
| what is the histamine receptor antagonist? |
|
Definition
|
|
Term
| what is better about the newer histamine receptor antagonists? |
|
Definition
| they have less side effects because less effect of p450 systems |
|
|
Term
| 5 proton pump inhibitors? |
|
Definition
1. omeprazole
2. esomeprazole
3. pantoprazole
4. lansoprazole
5. dexlansoprazole |
|
|
Term
| mechanism of action of proton pump inhibitors? |
|
Definition
| covalently interact through a disulfide bridge with the H/K ATPase and inhibit the pump |
|
|
Term
| are proton pump inhibitors reversible? |
|
Definition
NO
form a covalent interaction |
|
|
Term
| are proton pump inhibitors orally active? |
|
Definition
|
|
Term
| how are proton pump inhibitors given? |
|
Definition
in a delayed release form
need to be protected from the acid of the stomach |
|
|
Term
| where are proton pump inhibitors absorbed? |
|
Definition
|
|
Term
| how do proton pump inhibitors get to parietal cells? |
|
Definition
| enter from the blood --> as weak bases they are trapped in the acidic canaliculi of the parietal cell --> interact with the pump to inhibit it |
|
|
Term
| how do proton pump inhibitors interact with H/K ATPase? |
|
Definition
through a disulfide bridge
irreversible covalent interaction |
|
|
Term
| incidence of adverse reactions with proton pump inhibitors? |
|
Definition
|
|
Term
| adverse reactions with proton pump inhibitors? |
|
Definition
1. can alter absorption of other drugs that require acid milieu of the stomach for activation or absorption
2. hypergastrinemia |
|
|
Term
what drugs' absorption can be altered by proton pump inhibitors?
why? |
|
Definition
ketoconazole or ampicillin esters
proton pump inhibitors alter the required acid milieu of the stomach for activation or absorption |
|
|
Term
| uses of proton pump inhibitors? |
|
Definition
1. healing of gastric and duodenal ulcers
2. treatment of GERD
3. Zollinger-Ellison syndrome
4. erosive esophagitis |
|
|
Term
| misoprostol is an analog of what? |
|
Definition
|
|
Term
| how does misoprostol work to regulate acid secretion? |
|
Definition
| acts on EP3 receptors on parietal cells --> decrease cAMP --> inhibit activity of H/K ATPase --> decrease acid secretion |
|
|
Term
| effect of misoprostol on acid secretion? |
|
Definition
|
|
Term
| besides secreting acid, what other effect does misoprostol have? |
|
Definition
| increases mucin and bicarb secretion - protective mechanisms |
|
|
Term
| is misoprostol orally active? |
|
Definition
|
|
Term
| absorption of misoprostol? |
|
Definition
|
|
Term
|
Definition
FDA approved for preventing mucosal injury caused by NSAIDs
also indicated in morning after pill |
|
|
Term
| adverse effects of misoprostol? |
|
Definition
| diarrhea - increases SM contractility in intestines |
|
|
Term
| when is misoprostol contraindicated? |
|
Definition
| pregnancy - will contract uterine SM |
|
|
Term
| sucralfate is a mixture of what 2 things? |
|
Definition
1. sucrose octasulfate
2. polyaluminum hydroxide |
|
|
Term
|
Definition
| prophylaxis of stress-induced ulcers |
|
|
Term
| mechanism of action of sucralfate? |
|
Definition
| at pH less than 4 --> undergoes cross-linking --> adheres to base of ulcer craters --> inhibits mucosal erosion |
|
|
Term
| is sucralfate orally active? |
|
Definition
|
|
Term
| how should sucralfate be taken? |
|
Definition
|
|
Term
| adverse effects of sucralfate? |
|
Definition
1. constipation - due to the aluminum
2. may inhibit absorption of other drugs |
|
|
Term
a general rule is that Mg causes?
Al causes? |
|
Definition
|
|
Term
| antacids are of what 2 types? |
|
Definition
1. hydroxides
2. carbonates |
|
|
Term
| how do hyroxides work as antacids? |
|
Definition
| bind to acid and form water |
|
|
Term
| how do carbonates work as antacids? |
|
Definition
| bind to protons to form water and carbon dioxide |
|
|
Term
|
Definition
1. aluminum and magnesium hydroxide - Maalox
2. magnesium hydroxide - milk of magnesia
3. calcium carbonate - tums |
|
|
Term
| mechanism of action of antacids? |
|
Definition
| weak bases --> neutralize acid |
|
|
Term
| which antacids are rapid acting? |
|
Definition
| Ca carbonate and Mg hydroxide |
|
|
Term
| which antacid neutralizes slowly? |
|
Definition
|
|
Term
| aluminum has what effect on the GI tract? |
|
Definition
|
|
Term
| aluminum in antacids can cause toxicity in people with what other condition? |
|
Definition
|
|
Term
| aluminum in antacids can cause toxicity leading to what? |
|
Definition
1. osteoporosis
2. encephalopathy
3. myopathy |
|
|
Term
| magnesium has what type of effect in the GI tract? |
|
Definition
|
|
Term
| what can happen if you take too much calcium carbonate? |
|
Definition
can cause hypercalcemia
about 15% gets absorbed |
|
|
Term
| what can a side effect of carbonate antacids be? |
|
Definition
| belching from the CO2 generation |
|
|
Term
| 2 anti-cholinergic agents used to regulate acid secretion? |
|
Definition
1. pirenzipine
2. telenzipine |
|
|
Term
| what type of drugs are pirenzipine and telenzipine? |
|
Definition
| muscarinic receptor antagonists |
|
|
Term
| pirenzipine and telenzipine use? |
|
Definition
| used in Europe for peptic ulcer disease |
|
|
Term
| mechanism of action of pirenzipine and telenzipine? |
|
Definition
| block Ach activity on enterochromaffin-like cells |
|
|
Term
| how are antibiotics used in the regulation of acid secretion? |
|
Definition
used in the treatment of H. pylori that causes ulcers
used in various combos of drugs |
|
|
Term
|
Definition
|
|
Term
| PGE receptor effect on H/K ATPase? |
|
Definition
|
|
Term
| how does sucralfrate work? |
|
Definition
forms a gel and adheres to craters of ulcers
cytoprotective |
|
|
Term
| production of mucus is mediated by? |
|
Definition
|
|
Term
| what is secreted into the mucus layer that is also protective? |
|
Definition
|
|
Term
| what are prokinetic drugs? |
|
Definition
| medications that increase GI motility and transit of material in gut |
|
|
Term
| effect of prokinetic drugs on the GI tract? |
|
Definition
| increase esophageal clearance, gastric emptying, intestinal transit |
|
|
Term
| mechanism of action of prokinetic drugs? |
|
Definition
work by multiple diverse mechanisms
final common mediator is Ach activation of M3 receptor to increase contractility of intestinal SM |
|
|
Term
| mechanism of prokinetic drugs? |
|
Definition
| anything that increases Ach half life or is a muscarinic agonist --> stimulate M3 receptor --> increase contractility of SM --> increase transit in the gut |
|
|
Term
|
Definition
stimulatory
anything that increases Ach or agonist will activate the receptor |
|
|
Term
| dopamine is what kind of NT? |
|
Definition
inhibitory
inhibits the release of Ach through D2 receptors |
|
|
Term
| how does DA affect Ach release? |
|
Definition
| inhibits release of Ach through D2 receptor |
|
|
Term
| how does DA affect gut motility? |
|
Definition
| anything that blocks DA effects --> increase Ach release --> increase SM activity in the gut |
|
|
Term
| how does serotonin affect gut motility? |
|
Definition
stimulatory - through 5HT4 and 5HT3 receptors
inhibitory - through 5HT1 receptors |
|
|
Term
| what serotonin receptors are most important in gut motility? |
|
Definition
5HT4 and 5HT3 receptors
serotonin is stimulatory through these receptors |
|
|
Term
| what is the effect of motilin in the gut? |
|
Definition
|
|
Term
|
Definition
| a naturally occurring peptide that stimulates the upper GI tract |
|
|
Term
| 5 categories of promotility drugs? |
|
Definition
1. muscarinic agonists
2. AchE inhibitors
3. DA inhibitors
4. 5HT4 agonists
5. motilin agonists |
|
|
Term
| prototype muscarinic agonist used as a promotility drug? |
|
Definition
|
|
Term
| mechanism of action of muscarinic agonists as promotility drugs? |
|
Definition
| increase contraction of GI SM |
|
|
Term
| prototype AchE inhibitor used as a promotility drug? |
|
Definition
|
|
Term
| mechanism of action of neostigmine as a promotility drug? |
|
Definition
|
|
Term
| what is the prototype DA inhibitor used as a promotility drug? |
|
Definition
|
|
Term
| mechanism of action of metoclopramide as a promotility drug? |
|
Definition
| block inhibitory pre-synaptic D2 receptors |
|
|
Term
| actions of metoclopramide? |
|
Definition
on the upper GI tract
increase gastric emptying and small bowel transit |
|
|
Term
|
Definition
|
|
Term
| adverse effects of metoclopramide? |
|
Definition
1. crosses BBB --> extra-pyramidal side effects
2. increases prolactin |
|
|
Term
| why does metoclopramide cause extra-pyramidal symptoms? |
|
Definition
cross BBB
leads to Parkinson's symptoms; tardive dyskinesia |
|
|
Term
| why does metoclopramide increase prolactin? |
|
Definition
|
|
Term
| what are 5HT agonists used as promotility drugs? |
|
Definition
1. cisapride
2. tegaserod
neither are availablel anymore |
|
|
Term
| mechanism of action of 5HT4 agonists as promotility drugs? |
|
Definition
| activate excitatory neuronal 5HT4 receptors |
|
|
Term
| actions of 5HT4 agonists as promotility drugs? |
|
Definition
| accelerate transit in esophagus, stomach, and small bowel |
|
|
Term
| adverse effects of 5HT4 agonists as promotility drugs? |
|
Definition
| myocardial and CNS ischemia |
|
|
Term
| what are motilin agonists used as promotility drugs? |
|
Definition
1. erythromycin
2. clarithromycin |
|
|
Term
| mechanism of action of motilin agonists as promotility drugs? |
|
Definition
| activate neural and SM motilin receptors |
|
|
Term
|
Definition
diabetic gastroparesis
stimulate upper GI tract |
|
|
