Nausea and Vomiting

Question 1

Define vomiting [1]

What is vomiting physiologically caused by? [1]

Answer 1

Vomiting: forceful expulsion of gastric contents from the mouth.

This is caused directly by powerful contractions of the abdominal muscles, opening of the gastric cardia (connection between oesophagus and stomach) and contraction and descent of the diaphragm

Question 2

What is the vomiting centre in the brain called? [1]

Which part of the brain does is connect to? [2]

Answer 2

Vomiting centre: area posterma

Connexts to: nucleus of solitary tract; in the brainstem

Question 3

Name the sensory inputs that the area posterma recieves from the GI tract [5]

Answer 3

Motion/space (e.g. migraine) feed into the brainstem to initiate a response in the AP.

Compression: also, feeds into brainstem.

Pain: also, feeds into brainstem.

Vagus Nerve: links various inputs together: pregnancy, ischaemia, obstruction, poisons, cytotoxins - feeds into NTS.

Blood circulation: can directly activate AP

Question 4

The area postrema recieves input from:

• motion [1]
• blood circulation [1]
• steroids [2]
• Ischaemia & GI [1]

Name what each of the messager molecule that the following receive input from

Answer 4

Receptors: each of these inputs acts on variable receptors in the brainstem/NTS/AP

Motion: Acetylcholine (M1)

Blood circulation: Dopamine (D2)

Steroids: Histamine (H1), Cannabinoid (CB1)

Ischaemia, GI: 5-HT receptors, NK1.

Question 5

What does hyoscine (scopolamine) treat? [1]

Answer 5

Motion Sickness (Old drug used to prevent vomiting)

Question 6

MoA of hyoscine? [2]

Answer 6

Hyoscine: blocks the effects of Ach in brainstem and/or vestibular nuclei (and is therefore a muscarinic receptor antagonist)

Question 7

Diphenhydramine MoA? [2]
AE? [1]

Answer 7

H1 receptor antagonist
(pKi 7.9)1

M2 receptor antagonist (estimated Ki 0.08 µM)2

Crosses blood-brain barrier: cause somnolence (drowsiness)

Question 8

Cyclizine MoA? [2]

AE? [1]

Answer 8

Histamine H1 receptor antagonist at NTS / Brainstem: Ability to inhibit pre-ganglionic cholinergic and vagal nerve activity

Drowsiness

Question 9

Cyclizine used to treat? [2]

Answer 9

Nausea
Vomiting
Vertigo
Motion sickness
Labyrinthine disorders

Question 10

MoA of:
Phenothiazines
Metoclopramide
Domperidone
[1]

Answer 10

Dopamine D2 receptor antagonists

Worked to antagonise D2 receptors directly on the area posterma.

Question 11

What is MoA of Metoclopramide?

What is an alternative effect & therefore use?[1]

Answer 11

Metoclopramide: Dopamine D2 receptor antagonist

Also stimulates gastric emptying (5-HT4 receptor agonist): Widespread use as a stimulant of upper gut motility

Question 12

Domperidone MoA? [1]

Why is Domperidone free of extrapyramidal side effects?

Answer 12

Domperidone: Dopamine D2 receptor antagonist

No extrapyramidal because does not cross blood-brain barrier

Question 13

What is MoA of Delta-9terahydrocannabinoids? [1]

Answer 13

Cannabinoid (CB1) Receptor Agonists