Nausea and vomiting

Four areas of origin - vomiting

1. CNS - cortex, thalamus, hypothalamus, and meninges

2. vestibular system - vestibular nuclei H1 or M1

3. vagal afferent system - gastrointestinal tract and cardiovascular system 5-HT3, H1 or M1

4. chemoreceptor trigger zone - medulla; outside BBB - 5-HT3, D2, Nk-1

list the 5 drug classes of anti-emetics

1. anti-histamines (H1 antagonists)

2. Anti-muscarinic (m1 antagonist)

3. DA antagonists (D2 antagonist)

4. 5-HT3 antagonist

5. substance P antagonist (NK-1 antagonist)

anti-histamine MOA - nausea nad vomiting

prefer to use sedating anti-histamines as it is sufficiently lipophilic to cross BBB

• inhibit H1 receptors

Drugs:

• promethazine - motion sickness and morning sickness

• cyclizine - motion sickness

• dimenhydrinate - motion sickness

• bethistine - meniere’s disease and vertigo

anti-histamine adverse effects

sedation most common

anti-cholinergic properties - dry mouth, blurred vision

• muse cautiously for elderly

anti-muscarinic MOA

• hyoscine hydrobromide - cross BBB and preferentially blocks the muscarinic receptors in the gut

anti-muscarinic adverse effects

• anti-cholinergic properties - dry mouth, blurred vision

• sedation - lesser than antihistamine

Dopamine antagonist (DA) MOA

Metoclopramide and domperidone - prokinetics

prochlorperazine - phenothiazine

inhibit D2 receptors in the CTZ

• stimulate activity of the 5-HT4 receptor in the intestine to promote gastrc movement, hence used in gastroparesis

Dopamine antagonist (DA) adverse effects of prokinetics

Metoclopramide is smaller than domperidone; crosses BBB

• extra pyramidal side effecrs: distonia, tardive, dyskinesia

Metoclopramide + DA agonist/DOPA precursors in patients with Parkinson’s disease

5-HT3 antagonists MOA

inhibit 5-HT3 receptors 

• pathways include intestine, CTA and VC

• e.g. ondansetron - available orally 

long duration of action and do not cross BBB - no sedation 

5-HT3 antagonists adverse effects

constipation

headache

minor QT prolongation

Substance P antagonist (NK-1 antagonist)

• inhibit NK-1 receptors in the CTZ

• e.g. aprepitant (PO) and fosaprepitant (IV)

anticipatory nausea and vomiting and treatment

exact stimulus and reflex are not directly understood - associated with chemotherapy but not the chemo itself

thought of living with cancer, sight and smell of the hospital, subsequent cycles can provoke nausea and vomiting

Lorazepam - benzodiazepine SL - we dk why tho

Migraine treatment options

• paracetamol or NSAID

• diclofenac potassium has prokinetic property to relieve nausea

• metoclopramide combined with paracetamol

• prochlorperazine

pregnancy 

common first trimester - avoid drugs

• ginger, vit b6, and sedating anti-histamine are safe

cyclic vomiting syndrome

repeated episodes of nausea and vomiting

• fluid loss and electrolyte disturbance