Intestinal Motility Drugs Pharmacology Flashcards
Receptors on the myenteric plexus and their action (4)
- 5HTR4 (serotonin): facilitates enteric reflex + peristalsis
- Ach-MR: stimulates motility
- Enkphalin (opiate): stopes forward motility, stimulates symmetricl segmentation that allows for mixing but no moving forward
- Dopamine D2R: inhibits motility
5HT3R
serotonergic receptor type 3: located on sensory neurons. When open, they depolarize the nerve terminals, takes less stimulus to have them fire. THey decrease the threshold for pain and motility reflex.
two types of prokinetic agents
- over the counter laxatives
- drugs that stimulate fluid and eelctrolyte secretion
5 types of laxatives
*which are osmolar laxatives
- bulk forming (non-toxic, dont get absorbed or digested, just add bulk, also attract some water)
- emollients (keep water there, inswet themselves into contents and make them swell, allowing stretch of intestinal tract wall)
- hyperosmolar laxatives * (attract water from ISF, distal to stomach contents of GI tract need to be isoosmotic)
- Saline laxatives * (shouldn’t be used too often, because Mg and Na can be absorbed)
- Stimulant laxatives (act as emollients and osmolar laxatives, but also stimulate secretion of fluid and irriate the GI tract)
What is the caution with chronic use of stimulant laxatives?
Associated with permanent damage to the ENS
Agents that increase electrolyte and fluid secretion (2)
- prostaglandin analog (lubiproston/amitiza)
- Uroguanylin analog (linaclotide-approved for IBS for adults only)
MOA of lubiprostone (prostaglandin analog)
Lubiprostone increases fluid and electrolyte secretion from **crypt cells ** and stimulates motility.
When prostaglandin rececptor is activated, it directly stimulates/opens the CIC-2 channel –> chloride secretion into lumen –> Na and water follow
(note, CFTR is also present, and opens when high cAMP)
Uroguanlylin/linaclotide analog MOA
acts on both CFTR and CIC-2 channel in crypt cells. Theoretically would be more potent, but incidentally, there are natrual endogenous agonists that also open the CFTR channel (VIP and serotonin)
Anti-diarrheal agents can be assigned to these 3 cateogies
- stimulate fluid reabsorption and symmetric segmental contractions
- inhibit peristaltic reflex
- inhibit neuroendocrine stimulation of fluid and electrolyte secretion by tumors of the diffuse neuroendocrine system
When opiates are used for pain therapy, what are they usually supplemented with?
OTC laxative: opiates have a constipating action
MOA of opiates and opiate-like agents
- These drugs acts on the myenteric plexus, which in turn can affect the function of the submucosal plexus.
- these drugs alter the motility of the circular smooth muscle to promote symmetric segmental contractions (aka stop forward movement)
- also these drugs stimulate fluid reabsorption
Serotonin receptor (HTR) antagonist
actions (3)
- inhibits motility reflex and motility
- relaxes intestinal smooth muscle directly
- anti-emetic
What is the main Serotonin receptor antagonist (5HT3R) and what is its serious side effect
Alosetron (lotronex)
- serotonin is also necessary to keep blood vessels (splanchnic) in mucosa dilated, so antagonists can cause ischemic colitis = lethal
- a little less frequent in women than men, so only used for women with diarrhea dominant IBS
How does excess serotonin stimulate fluid secretion and peristalsis?
- we have mucosa with serotonin enteroendocrine cells, so if we have a tumor of these cells, way too much serotonin will be secreted
- serotonin stimulates cAMP and thus CFTR chloride channel
- serotonin also diffuses to the myenteric plexus and stimulates peristaltic reflex that way (recall peristaltic reflex is stimulated two ways-distension and effects directly from neuronal circuit in myenteric plexus)
Treatment of serotonin secreting tumor
Long acting somatostatin analogs (octreotide): these tumors have receptors for somatostatin
-decreases proliferation and secretory activity of 5HT-producing carcinoid tumors
