Pharm of Emesis and GI Motility Disorders Flashcards
What is the enteric nervous system and what is its function?
Highly regulated neuronal network located in Auerbach’s myenteric plexus and submucosal plexus
Controls motor and secretory activity of the GI
What are neurons in the intrinsic network called? What is the main neurotransmitter?
Neurons called iPANS (intrinsic primary afferent nerves)
Main neurotransmitter is serotonin
Where are 5HT3 receptors located? What do they induce?
On extrinsic afferent nerves to induce nausea and abdominal pain
Where are 5HT1P receptors located? What do they induce?
On iPANS; release Ach and calcitonin gene related peptide (CGRP) into the myenteric plexus interneurons to increase motility and regulate peristalsis
Where are 5HT4 receptors located? What do they induce?
On presynaptic terminals of iPANS; enhance release of ACh and CGRP to increase motility and regulate peristalsis
What does dopamine do in GI?
Binds to D2 receptors to reduce cholinergic effects (inhibitory) and decreases esophageal and gastric motility
What does Ach do in GI?
Binds to muscarinic receptors to stimulate intestinal motility
What does epinephrine do in GI?
Binds to adrenergic receptors to stimulate motility (only nominally effect though)
What are the three phases of emesis?
Pre-ejection (gastric relaxation and retro-peristalsis)
Retching (rhythmic contraction of muscles)
Ejection (intense contraction of muscles and relaxation of UES)
Where is the vomiting center located?
Reticular formation of the medulla next to the chemo receptor trigger zone (CTZ) at the base of 4th ventricle
What receptors does CTZ have a high concentration of?
Histamine, 5Ht3, dopamine, neurokinin
What are the pharmacological approaches to emesis
Antihistamines (H1 receptor antagonist)
5HT3 receptor antagonism
D2 antagonism
M1 antagonism
CB1 agonism
Neurokin antagonism
What does histamine do in GI?
Mediates nausea, allergy and inflammatory response
How do antihistamines work as antiemetics?
Reversible H1 antagonists with no effects on other H receptors
Are antihistamines “dirty” or “clean”
Dirty. Have significant antimuscarinic and sedative effects
What is the first line treatment for motion sickness and vertigo?
H1 receptor blockers with antimuscarinic effects
What does serotonin do in the GI tract?
Vasoconstrictor and intestinal smooth muscle
Are 5HT3 Receptor Antagonists “dirty” or “clean”
Clean! No antagonism of other receptors or extra-pyramidal side effects
What is the first line/prophylactic treatment for chemo induced nausea/vomiting?
5HT3 Receptor antagonists
Ondansetron and Granisetron
Are D2 Receptor Antagonists “dirty” or “clean”
Very dirty. Frequently antagonize other receptor types including 5HT3 and histamine receptors
Have a lot of side effects
What is the most common use of muscarinic receptor antagonists?
transdermal patch attached to behind the ear for motion sickness (Scopolamine)
How do NK1 receptor antagonists work against emesis ?
Central blockade of chemoreceptor trigger zone (CTZ)
Are NK1 Receptor Antagonists “dirty” or “clean”
Clean
How do CB1 agonists work against emesis?
Activate cannabinoid receptors close to CTZ
Used in combination with other anti-emetics and as an appetite stimulant
