Anti-emetics Flashcards
Summarise the physiological control of nausea/vomiting?
Vomiting centre (area postrema) innervated by nucleus of tractus solitarius Chemoreceptor trigger zone communicates with vomiting centre
What are the main mechanistic triggers of nausea/vomiting?
- Cytotoxic drugs 2. Motion sickness 3. GI problems
What are the main classes of anti-emetic drugs?
- 5-HT3A receptor antagonists 2. Histamine H1 receptor antagonists 3. Muscarinic receptor antagonists 4. Dopamine D2 receptor antagonists
What are 5-HT3A receptor antagonists principally used for clinically? How do they work?
- Chemotherapy-induced N&V - Block activation of nerve fibres to nucleus tractus solaris, vomiting centre and chemoreceptor trigger zone
What are histamine H1 receptor antagonists principally used for clinically? How do they work?
- Motion sickness - Block the action of hypothalamic histamine release on chemoreceptor trigger zone - Blocks activation of vomiting cenre
What are muscarinic receptor antagonists principally used for clinically? How do they work?
- Motion sickness - Has little effect once nausea/emesis is established - In operative pre-medication - Block activation of vomiting centre by vestibular system and hypothalamus
What are dopamine D2 receptor antagonists principally used for clinically? How do they work?
Main ** = gastroparesis induced N&V and N& V associated w/ cancer chemotherapy (high doses) e.g. Cisplatin (intractable vomiting) **Inhibit D2 receptor in VC - Prokinetic - stimulates gastric emptying
What are some possible side effects of anti-emetics?
- Headaches - Constipation - Dry mouth - Extrapyramidal side-effects
What are the side effects of H1 receptor antagonists?
** Sedation (‘do not drive or operate machinery’) - Dizziness - Tinnitus - Fatigue - Excitation in excess - Convulsions (children more susceptible) - Anti-muscarininc side-effects
What are the side effects of 5-HT3A receptor antagonists?
- headache - sensation of flushing and warmth - increased large bowel transit time (constipation)
What are the side effects of muscarinic receptor antagonists?
Typical anti-muscarinic side-effects: - drowsiness - dry mouth - cycloplegia mydriasis - constipation (not usually at anti-emetic doses)
What are the side effects of dopamine D2 receptor antagonists
In CNS: - drowsiness - dizziness - anxiety - extrapyramidal reactions; children more susceptible than adults (Parkinsonian-like syndrome: rigidity, tremor, motor restlessness) Endocrine: - hyperprolactinaemia - galactorrhoea - disorders of menstruation
How can chemotherapy cause nausea and vomiting?
- Cisplatin is toxic to enterochromaffin cells in stomach lining - causes destruction and release of free radicals and excessive 5-HT (serotonin) release - Free radicals cause further destruction of EC cells - 5-HT activates 5-HT3A receptors on: 1. Nerve fibres to nucleus tractus solaris (NTS) 2. Nerve fibres from NTS to vomiting centre 3. Nerve fibres to chemoreceptor trigger zone (CTZ) - communicates w/VC
How can motion sickness cause nausea and vomiting?
- Auditory labyrinth - nerual mismatch - vestibular system (via muscarinic receptors) - Increased hypothalamic histamine release(due to some kind of activation by the vestibular system ) -activates H1 receptors in CTZ .Vestibular system + hypothalamus may also activate VC thr cholinergic system
BAsically there is a senosory mismatch in the labryinth which results in the vestibular system signalling to thevomiting centre. The hypothalalmus and the chemorecepto trigger xzoine are thought to be involved and n obody is entirely sure how they are involved.
How can gastroparesis cause nausea and vomiting?
Gastroparesis = delayed emptying of stomach
Reduced stomach contraction leads activates neurones thaat innvervate the VC. These neurones release dopine , which acts on dopamine receptors on the VC. Also :5-HT activates 5-HT3A receptors on: 1. Nerve fibres to vomiting centre 2. Nerve fibres to chemoreceptor trigger zone
