Nausea and Vomiting Pharmacology

Question 1

Vomiting is initiated by programming in vomiting center that involves activation of these 3 sites

Answer 1

1. ambiguus neurons
2. spinal cord neurons
3. vagal efferents from dorsal motor X nucleus

Question 2

Which 3 sites does the vomiting center receive its input?

Answer 2

1. laybrinth - where motion and sickness is detected (via cerebellum)
2. area pastrema: around 4th ventricle// chemical trigger zone
3. gastric and intestinal contents: various sensory neurons from these areas sending information via the **nucleus tractus solitarus **

*extra bonua: stretching and painful sensation in the GI tract pathway can reach NTS and vomiting center. So vomiting center can be triggered in response to pain

Question 3

4 receptors present in Nucleus Tractus Solitarius

Answer 3

1. H1
2. 5-HT3
3. Muscarinic (cholinergic)
4. D2

Question 4

While area postrema uses multiple neurotransmitters and receptors involved in forwarding information to the vomiting center, which receptor is NOT present?

Answer 4

histamine isn’t present

Question 5

2 improtant receptors present in labyrinth cerebellum

Answer 5

1. H1
2. Muscarinic cholinergic

Question 6

excessive amounts of this neurotransmitter in the GI tract also triggers a nausea and vomiting pathway

Answer 6

Serotonin!

Question 7

Why do Histamine receptor (H1) antagonists cause dry mouth as a side effect?

Answer 7

H1 also has muscarinic activity! So thus an antagonist also has muscarinic antagonist effect which is dry mouth. (recall Ach muscarinic agonists causes salivation, rest and digest)

Question 8

What are the two types of H1 receptor antagonists?

Answer 8

1. Ethanolamine Type (Diphenhydramine/Benadryl) - also used to treat allergic reactions
2. Piperazine type (Meclizine/Antivert) - excellent for post op nausea and vomiting

Question 9

Which type of vomiting would H1 receptor antagonists NOT be food for?

Answer 9

Nausea and vomiting originating from the chemotrigger zone (area postrema, because H1 receptors are not involved there)

Question 10

Two Muscarinig Acetylcholine Receptor antagonists

Answer 10

Scopolamine (travel sickness, chewable gum)

Benztropine

note**atropine would work but has too any unpleasant side effects

Question 11

what are the three pathways in which muscarinic receptor antagonists can be used for GI tract vomiting and nausea?

Answer 11

1. area postrema
2. labyrinth
3. GI tract induced

Question 12

What are the only two receptors present on the labyrinth pathway?

Answer 12

H1 and Muscarinic cholinergic

Question 13

Where is Dopamien Receptors found? Where is it not found?

Answer 13

Found on GI tract pathway, Area postrema, and NTS. Absent on labyrinth pathway , so they can’t be used for motion sickness.

Question 14

Complications with chronic use of Dopamine 2 receptor antagonists

Answer 14

1. basal ganglia function (important in their proper function)
   2) lactation (D2 receptors important in prlactin inhibition)

Question 15

Side effect of serotonin receptor antagonists (5HT3R)

Answer 15

constipation (serotonin stimulates motility, and we’re inhibiting this)

Question 16

Agent that stimulates gastric emptying

Answer 16

Motilin receptor agonist: erythromycin stimulates gastric emptyng

-decreases activity of gastric stretch receptors on vomiting center) via initiation the MMC

Question 17

D2 receptor antagonist agent with multiple targets: explain

Answer 17

Metoclopramide (Reglan)

• binds D2R antagonist
• binds 4HT3R agonist - promotes motility

net result: motility stimulation (serotoning receptor), prevents vomiting, and helps remove distention in the stomach and in the intestinal tract by stimulating motilitya nd moving intestinal contents towards the anus.

Question 18

What are the undesirable side effects of metaclopramide (a dopamine-2 receptor antagonist)

Answer 18

-prolongation of QT intervals

Question 19

Patient undergoing chemo for a maligancy is best treated with ___ to prevent nausea and vomiting and diarrhea

1. H1 antagonist
2. specific 5HTR antagonist
3. muscarinic receptor antagonist
4. Dopamine receptor antagonist
5. opiate agonist

Answer 19

answer: 2. specific 5HTR antagonist – reduces the afferent stimulus to the vomiting center from the GI tract and reduces synaptic activity in the vomiting center. Also, by interfereing with serotoninergic transmission in the ENS, it will reduce diarrhrea.

(the root cause of chemotherapy induced vomiting is excessive amount of serotonin release in the GI tract and activation of the serotonin receptors).