Motility Pharmacology Flashcards
(45 cards)
Describe the difference between intrinsic and extrinsic networks of enteric nervous system
Intrinsic network can operate autonomously (works in spinal cord injury pts) and NT is serotonin for iPANs
Extrinsic input from cholinergic, adrenergic and dopaminergic neurons to control motor/secretory activity
What are three serotonin receptor subtypes in enteric nervous system?
5HT3: on extrinsic afferent nerves to induce nausea and abdominal pain (some effect on colonic activity)
5HT1P: on iPANs which contain Ach and calcitonin gene related peptide and project to myenteric plexus interneurons
5TH4: on presynaptic terminals of iPANs to enhance release of Ach and CGRP to promote reflex activity (GI motility and peristalsis)
What is effect of other NTs?
Dopamine
Ach
Epinephrine
DA: binds D2 receptors and reduces cholinergic effects
Ach: Binds mAchRs to stimulate intestinal motility
Epinephrine: binds adrenergic receptors and has nominal effect on motility
Three phases of emesis
Pre-ejection: gastric relaxation and retro-peristalsis
Retching: rhythmic contraction of abdominal, intercostal and diaphragmatic muscle against a closed glottis
Ejection: intense contraction of abdominal muscles and relaxation of upper esophageal sphincter
Describe the central control in emesis: what is the vomiting center?
What are inputs to it? (4)
Vomiting center in medulla next to chemoreceptor trigger zone (CTZ)
Input: CTZ, vestibular apparatus, vagus nerve, cerebral cortex
What is the CTZ and why is called that?
The chemoreceptor trigger zone, area of medulla next to 4th ventricle.
It has high concentrations of receptors (i.e histamine, 5HT3, DA, Ach, neurokinin)
Describe therapeutic approach for controlling emesis?
Sine there are so many receptors, should know the cause of emesis first– this way you can block the appropriate receptor (cannot block them all)
Which histamine receptor is involved in emesis?
What drug do you use to block this receptor and in which situations?
H1 receptor (involved in rhinitis,
Use diphenhydramine as antihistamine– it is a reversible H1 antagonist in situations such as motion sickness and vertigo
What are significant effects that are observed with antihistamines as antiemetics? (2)
Muscarinic and sedative effects
What are some of the functions of serotonin as it relates to GI? (5)
Vasoconstrictor
Intestinal smooth muscle stimulant
Mediator of symptoms of carcinoid syndrome (ECL neoplasm)
Involved in vomiting
Which serotonin receptor is in GIT and vomiting center?
In which situations is it stimulated?
5HT3 is in both GIT and vomiting center as part of vomiting reflex.
Chemotherapy drugs cause an increase in ECL serotonin release– stimulates vagus nerve to induce nausea via 5HT3R in CTZ
What are the 5HT3 receptor antagonists? (2)
Are they effective?
Ondansetron and granisetron
Very effective in severe nausea/vomiting associated with chemo
How does DA affect GI motility? (2)
Decreases esophageal and gastric motility
Inhibits cholinergic SMC stimulation
What is MOA of drugs that target DA-mediated emesis?
How does this relate to adverse effects?
D2 receptor antagonists– but they are dirty and also antagonize histamine and 5HT3 receptors.
AE profile due to activity and DA and nonDA receptors in dose dependent manner
What are four D2 antagonists?
What are they used for? (2)
Chlorpromazine, promethazine, prochlorperazine, metoclopramide
Used in chemo, motion sickness
What are AE of D2 antagonists? (3)
Extrapyramidal effects, dystonia, hypotension
Describe metoclopramide: Activity on receptors, use, AE (3)
Has 5HT3 activity at higher doses. It is effective in treating chemo-induced nausea BUT it is passed into breast milk and is associated with restlessness, tremor, drowsiness
Describe antiemetic drugs that target acetylcholine. What is its use and AE
M1 receptor antagonists: scopolamine
Used as prophylaxis against motion sickness, only AE is dry mouth
Drug that targets Neurokinin?
NK1 antagonist– novel drug
What is dorabinol?
Describe MOA and its use (2)
A cannabinoid that activates CB1 receptor close to CTZ
Used in combination with other antiemetics and as an appetite stimulant
What is the toxicity for dorabinol? (3)
What are symptoms of withdrawal? (3)
Tachycardia, high, paranoia
Withdrawal==>irritability, insomnia, restlessness
Which receptors increase motility?
Which ones decrease?
D2 Receptors: Decrease motility
5HT Receptors: Increase motility
M3 Receptors: Increase motility
What is effect of metoclopramide?
Why is its use limited?
It is a D2 antagonist– diminished inhibitory impact increases gastric motility
Extrapyramidal AE: Use limited due to restlessness, tremor, drowsiness
What are indications for metoclopramide? (3)
Diabetic gastroparesis
Antiemetic agent for chemo pts
Third line for GERD
