Antiemetics Flashcards
Ways of triggering emetic reflex?
All goes through vomiting centre: Medulla oblongata - muscarinic receptor
- Outside BBB: CTZ - dopamine 2 and 5HT
- more permeable to circulating agents - Vestibular Nuclei in pons - Histamine1 and Muscarinic receptors –> CTZ –> medulla oblongata (morning and motion sickness)
- Higher cortical area –> stimulates medulla oblongata
- Enterochromaffin cells - serotonin release and 5HT3 on vagus nerve
Classes of antiemetics?
Histamine1 receptor antagonists - PROMETHAZINE, CYCLIZINE (motion and morning sickness)
5HT3 receptor antagonist (-setron eg ONDANSETRON) work at CTZ and GI tract
Dopamine receptor antagonists at CTZ (used for psychosis too):
- -azines, PROCHLOPERAZINE, chlorpromazine (phenothiazines)
- METOCLOPRAMIDE, inhibit dopamine2 receptor and stimulate GI motolity
- DROPERIDOL / HALOPERIDOL (butyrophenones)
- DOMPERIDONE
Muscarinic receptor antagonists (anticholinergic / antimuscarinic) eg HYOSCINE HYDROBROMIDE aka scopolamine, block receptors in the vomiting centre.
Indications and SE of each class of antiemetic?
Histamine1 receptors antagonist PROMETHAZINE, CYCLIZINE
- motion and morning sickness
- SE drowsiness, sedation
5HT3 receptor antagonist ONDANSETRON
- chemo, radiation and post surgery
- SE headache, GI upset
Dopamine2 receptor antagonists/ antipsychotics:
- PROCHLOPERAZINE / CHLOPROMAZINE
- chemo, radiotherapy
- also histamine and muscarinic receptors
- SE sedation (prochlor.. less so), hypotension and extrapyramidal - METOCLOPRAMIDE
- chemo, radiotherapy, reflux and hepatobiliary disorder
- SE fatigue, extrapyramidal - DROPERIDOL
- acute chemo vomiting and post op
- less likely to cross BBB
Anticholinergics / antimuscarinics HYOSCINE HYDROBROMIDE
- prophylaxis and motion sickness
- dry mouth, blurry vision and drowsiness (anticholinergic side effects)
What are extrapyramidal SE and which antiemetics cause them?
- akathesia (fidget)
- tardive dyskinesia (involuntary repetitive jerking, grimacing, tongue, lips)
- spasmodic torticollis (involuntary turning of the neck)
- oculogyric crisis (upward deviation of the eyes)
And pseudoparkinsonism: rigidity, tremor, pill roll, shuffle, stooped, bradykinesia
Prolactin release:
a. galactorrhoea
b. menstrual problems
c. lactation
Caused by dopamine2 receptor antagonists: prochlorperazine, metoclopramide, etc
What are 3 other types / classes / drugs for emesis?
- neurokinin 1-receptor antagonists eg APREPITANT / FOSAPREPITANT
- increase effectiveness of 5HT3 antagonists ie -setrons
- for chemo induced emesis - dexamethasone
- in chemo - nabilone, synthetic cannabinoid
- add on treatment in chemo emesis
Vomiting in pregnancy?
First trimester is generally mild and does not require drug therapy.
Rare severe vomiting, short term PROMETHAZINE (or prochlorperazine or metoclopramide). 48hrs then specialist opinion.
Hyperemesis gravidarum is more serious. Cyclizine?
Consider: IV fluid, electrolytes, nutritional support, thiamine
Post op vomiting?
Depends on anaesthetic and type and duration of surgery.
Risk: female, non-smokers, intra-op opioids, Hx of motion sickness
Assess risk and use prophylaxis.
Use:
- 5HT3-receptor antagonist ONDANSETRON
- Dexamethasone
- dopamine antagonists PROCHLOPERAZINE, DROPERIDOL
- antihistamines, CYCLIZINE
Drugs for motion sickness?
HYOSCINE HYDROBROMIDE is most effective
sedating antihistamines might be tolerated more eg PROMETHAZINE or CYCLIZINE (less sedating)
Nausea in other vestibular disorders?
Treat underlying cause.
Vertigo and nausea associated with Ménière’s disease and middle-ear surgery can be difficult to treat.
BETAHISTINE DIHYDROCHLORIDE is an analogue of histamine and is claimed to reduce endolymphatic pressure by improving the microcirculation.
Menieres: Diuretic and salt restriction, antihistamine (cinnarizine), phonethiazines (prochlorperazine) can also be used.
