gastric pharmacology Flashcards
what are the 4 types of medications used in the treatment of gastric ulcers and gastroesophageal reflux disease
- chemical diffusion barriers
- histamine receptor antagonists
- H+, K+ ATPase antagonists (proton pump inhibitors)
- promotility drugs
what is an example of a chemical diffusion barrier drug
sucralfate (sucramal)
what does sucralfate dissociate into
sucrose octasulfate and aluminum hydroxide in acid of the sotmach
what does sucrose octasulfate do
polymerizes forming a paste that binds to damaged gastric epithelium
what is the mechanism of action of sucralfate
forms a physical barrier against stomach acid
what is an example of a histamine receptor antagonist
famotidine
what happens when histamine is released from ECL cells
stimulates H2 receptors on the parietal cell
what is an H2 receptor
histamine receptor
located on parietal cells and regulates histamine-mediated gastric acid secretion
what is famotidine (pepcid)
- 3rd generation H2-selective antagonist
- has poor bioavailability
what are examples of H+, K+ ATPase antagonists
omeprazole, pantoprazole
what does H+, K+ ATPase (proton pump) secrete
H+ into lumen of the stomach
how is omeprazole (prilosec) supplied as
enteric-coated capsule/tablet to survive the stomach
where is omeprazole (prilosec) absorbed
in alkaline pH of duodenum
how does omeprazole (prilosec) inactivate the pump
protonated form of the drug “covalently” and “irreversibly” binds to and inactivates the pump
why is it ok that omeprazole has a short half life
efficacy last longer than predicted from the plasma drug concentration (activoty despite no plasma conc)
b/c its irreversible
what is pantoprazole
- compound is a weak base like omeprazole
- supplied as a delayed-release tablet and delayed-release granules to survive the stomach
also covalent inhibitor
what are examples of promotility drugs
- cisapride
- metoclopramide
- erythromycin
- nizatidine
what does a promotility/prokinetic drug do
- helps control acid reflux by strengthening the lower esophageal sphincter
- decreases stomach emptying time allowing less time for reflux to occur
- stimulates smooth muscle contraction of stomach to speed emptying allowing less time for reflux to occur
what is cisapride (propulsid)
- 5HT4 receptor agonist that directly stimulates gastric motility
- increases the release of ACh at nerve endings in the myenteric plexus controlling gut motility in the ENS
what is metaclopromide (reglan)
- D2 antagonist activity
- results in increased LES and stomach tone
- results in increased nerve terminal ACh release and therefore increased ACh-mediated gastric motility
what do erythromycin and azithromycin do
- antibiotics are weak agonists for motilin receptor (GPCR) (serendipity)
- motilin binding to the motilin receptor on enteric neurons stimulates gastric motility
what do ranitidine and nizatidine do
- H2 antagonists that inhibit histamine-mediated gastric acid secretion
- weak inhibitors of the enzyme acetylcholinesterase
- blockade of acetylcholinesterase (ACh’ase) results in increased ACh at synapses increasing gastric motility
where is emesis coordinated
in the “emetic center” in the lateral reticular formation in the medulla oblongata
what are the 4 control centers of emesis
- chemotrigger zone (CRTZ)
- vestibular system (ear)
- peripheral sensory/irritant receptors (stomach, intestine)
- higher CNS centers
what are the 4 types of drugs that control emesis
- alpha-2 adrenergic antagonists
- dopamine antagonists
- 5-HT3 serotonin antagonists
- neurokinin-1 antagonists
what is an example of an alpha-2 adrenergic antagonists drug
chlorpromazine
what is chlorpromazine and what does it do
- alpha-2 adrenergic antagonism
- blocks vomiting reflex at emetic center and CRTZ
what is an example of a dopamine antagonist drug
metaclopramide
what is metoclopramide
anti-emetic action due to blockade of D2 dopamine receptors in the CRTZ
what is an example of a 5-HT3 serotonin antagonist drug
ondansteron
what is ondansteron
anti-emetic action dur to blockade of 5-HT3 serotonin receptors in the CRTZ and in the GI tract
does not relieve nausea
what is an example of a neurokinin-1 antagonists
maropitant
what happens when NK-1 receptor by substance-P in the CRTZ gets activated
induces vomiting
what does maropitant (cerenia) do
- blocks NK-1 receptor activation in CRTZ reduces vomiting
- blocks NK-1 receptors in the emetic center
