Nausea and vomiting

Question 1

Where is the vomiting centre located, and what receptors are responsible

Answer 1

Input: nucleus of tractus solitarius (H1, M1 receptors)
Output: medulla (M1 receptors)

Question 2

How do the GIT and heart activate the vomiting centre

Answer 2

Stimulation of mechano, chemoreceptors via glossopharyngeal, vagal afferents
Release of serotonin from enterochromaffin cells, to stimulate 5-HT3 receptors

Question 3

How do exogenous toxins in the blood (e.g chemo) activate the vomiting centre

Answer 3

Chemoreceptor trigger zone lacks BBB, toxins can freely enter
Stimulate D2, NK1, 5-HT3 receptors
Stimulate M1 receptors in vomiting centre

Question 4

What types of triggers stimulate the chemoreceptor trigger zone?

Answer 4

GIT stimuli, vestibular stimuli, endogenous toxins/drugs

Question 5

Combination treatment for low risk mimetics (e.g chemo)

Answer 5

Serotonin 5-HT3 antagonists, corticosteroids, NK1-receptor antagonist administered shortly before chemo

Question 6

Serotonin 5-HT3 antagonists: Class, names, moa, adr, contraindications

Answer 6

Chemo-induced acute vomiting
‘-setron’s
Act on 5-HT3 receptors that are primarily in GIT
Constipation, headache
Becareful in hepatic and renal insufficiency

Question 7

Corticosteroids: Class, names, moa, adr

Answer 7

Chemo-induced acute vomiting
Dexamethosone
Mimics cortisol, decrease blood flow to gut
Safe for short term use
Long term: iatrogenic Cushing’s (rounded face, muscle wasting, thinning of skin, immunosuppression)

Question 8

Neurokinin receptor antagonists: Class, names, moa, adr, contraindications

Answer 8

Chemo-induced acute vomiting
Aprepitant (oral)
Inhibit NK1 receptors in CTZ
Fatigue, dizziness, diarrhoea
CYP3A4 metabolised- hepatic insufficiency, DDI

Question 9

Antipsychotics: Class, names, moa, adr

Answer 9

Chemo-induced acute vomiting
Phenothiazines: D2, M1, H1
Butyrophenones: D2, M1
(atyipcal) Olanzapine: D2, 5HT2
D2 predominantly in CTZ, M1 in vestibular system and vomiting center
Sedative effect, extrapyramidal effects (not rly in olanzapine)

Question 10

Benzodiazepines: Class, names, moa, adr, contraindications

Answer 10

Anxiolytic, for anticipatory vomiting
Lorazepam, diazepam
Bind to GABA receptors
Sedative, do not use with other CNS depressants or else risk of respiratory depression
AVOID DURING PREGNANCY- risk of cleft palate

Question 11

Muscarinic antagonists: Class, names, administration, moa, adr

Answer 11

Motion sickness
Scopolamine- transdermal patch
M1 receptors in vestibular centre and vomiting centre
Anticholinergic side effects: dry mouth, blur vision, constipation

Question 12

Mixed H1, M1 antagonists: Class, names, moa, adr

Answer 12

Motion sickness
Diphenhydramine
Both receptors in vestibular center and vomiting center
Sedative effects (from H1 antagonism!)
Anticholinergic side effects: dry mouth, blur vision, constipation

Question 13

Dopamine antagonists: Class, names, moa, adr, contraindications

Answer 13

Nausea (more antipsychotic)
Metoclopramide
Block D2 receptors in CTZ
Elevated prolactin levels -> gynaecomastia, menstrual disorders
Extrapyramidal side effects- restlessness, parkinsonian symptoms (ESPECIALLY IN ELDERLY)
Not for long term use-> tardive dyskinesia