GI - Nausea & Vomiting Flashcards
(30 cards)
What is emetic reflex
– contraction of abdominal muscles and diaphragm increasing pressure in stomach
– closure of glottis (prevents vomit entering lungs)
which drugs can cause vomiting
cancer drugs
Causes of emesis (that you might need to treat)
– motion sickness
– drug induced nausea and vomiting
– post-operative vomiting
– intracranial pathology (eg migraine, increased pressure due to inflammation or haemorrhage)
– emotional causes
– pain
– drugs and radiation eg during cancer therapy
The Brain and Vomiting – Control Centres
draw diagram
Vomiting reflex
draw diagram
Emesis controlled by
• Emesis controlled by two brainstem areas
– Chemo trigger zone (CTZ) – Area Postrema
• Fenestrated capillaries allow detection of circulating chemicals
– Vomiting Centre – Nucleus of the Solitary Tract
Emesis - Integrate chemical and neuronal inputs
– Signals from periphery sense “something wrong” • Gut chemo-, mechano-sensation
– Signals from higher brain regions “contextualise” other inputs • Sight and; smell; balance; emotion
Emesis - Vomiting reflex
– Co-ordinated motor-pattern
– Retroperistalsis, gastric contraction, abdominal wall contraction
What ascends from stomach to brain
Vagal afferents
What is very responsive to chemicals in the blood
Chemo Trigger Zone (Area Postrema) D2, 5-HT, NK1
Therapy listed by cause of emesis - motion sickness
Anti-histamines, anti-muscarinics
Therapy listed by cause of emesis - DI nausea + vomiting
– try minimize gastric irritation with equal spacing of drug; take with food
– otherwise –Dopamine antagonists , antihistamine
Therapy listed by cause of emesis - post op vomit
– Dopamine antagonists (phenothiazines)
– 5HT3 antagonist
Therapy listed by cause of emesis - migraine
Phenothiazines helpful because also speeds gastric emptying and facilitates absorption of analgesics
Therapy listed by cause of emesis - CINV (chemotherapy)
– dexamethasone, 5HT3 antagonist, NK1 antagonist
Anti-emetics: anti-histamines (H1)
indications, adr, cautions
– Cinnarizine, (cyclizine, promethazine)
– Promethazine may be used in pregnancy (severe morning sickness)
– act on vestibular apparatus,VC and CTZ
Indications
– travel sickness,
– Vestibular disorders (vertigo)
– Space motion sickness (Promethazine – NASA)
ADR
– Sedation
– anti-cholinergic effects – dry mouth, blurred vision, constipation, urinary retention
– blocks Ca2+ transport so also causes vasodilation Cautions:
– Significant antimuscarinic activity
– use with caution in prostatic hypertrophy, urinary retention, susceptibility to angle-closure glaucoma, and pyloroduodenal obstruction
Anti-emetics: anti-muscarinic agents
indications, PK, adr, cautions, contraindications
• Hyoscine hydrobromide (previously called scopolamine)
• Indications
– OTC for motion sickness (both prophylaxis & treatment), GI disorders
• PK
– for motion sickness can use patch on skin behind ear
• ADR/Cautions
– causes less drowsiness than antihistamines but still caution when driving
– can cause typical anticholinergic ADR
• Contraindications
– myasthenia gravis, paralytic ileus, pyloric stenosis, toxic megacolon and prostatic enlargement
Anti-emetics: dopamine antagonists (1)
indications, adr, cautions, contraindications
ACT ON CTZ SO NOT USEFUL FOR MOTION SICKNESS/VESTIBULAR DISORDERS
Phenothiazines
– Prochlorperazine, perphenazine, and trifluoperazine (less sedating than chlorpromazine)
• Indications
– N and V associated with diffuse neoplastic disease, radiation sickness, and emesis caused by drugs such as opioids, general anaesthetics, and cytotoxics
• ADR
– resulting from DA antagonism (“extrapyramidal” motor effects), Sedative, dizziness
– Prochlorperazine can cause anti-cholinergic effects
• Cautions
– avoid prochlorperazine (also cholinergic antagonist) in patients with urinary retention or glaucoma
– prochlorperazine prolongs QT and promotes hypotension
• Contraindications
– Parkinson’s disease
– Phaeochromacytoma – can cause hypertensive crisis
• Interactions
– prochlorperazine potentiates effects of other sedatives
– increases effect of other drugs that lower bp or prolong QT
MHRA/CHM advice - Domperidone:
risk of cardiac side- effects
– Domperidone should only be used for the relief of the symptoms of nausea and vomiting;
– Domperidone should be used at the lowest effective dose for the shortest possible duration (max. treatment duration should not normally exceed 1 week);
– Domperidone is contra-indicated for use in conditions where cardiac conduction is, or could be impaired, or where there is underlying cardiac disease, when administered concomitantly with drugs that prolong the QT interval or potent CYP3A4 inhibitors, and in severe hepatic impairment
HRA/CHM advice Metoclopramide:
risk of neurological adverse effects
– in adults over 18 years, metoclopramide should only be used for prevention of postoperative nausea and vomiting, radiotherapy-induced nausea and vomiting, delayed (but not acute) chemotherapy-induced nausea and vomiting, and symptomatic treatment of nausea and vomiting, including that associated with acute migraine (where it may also be used to improve absorption of oral analgesics)
– Metoclopramide should only be prescribed for short-term use (up to 5 days)
5HT3 antagonists
Indications, PK, ADR
• Ondansetron, Granisetron, Palonosetron
– decrease sensitivity of 5HT receptors: • inVC
• in vagal afferent nerve that detect cytotoxic damage to gut
• Indications
– chemotherapy induced nausea
– post operative nausea
• PK
– short t1/2 4hr
– schedule depends on indication
• ADR
– headache and constipation are common (reduce peristalsis) – dizziness
Neurokinin Receptor Antagonists
Indications, PK, ADR
• Aprepitant (p.o.), Fosaprepitant (i.v.), Rolapitant (p.o. – launched 2017)
– Netupitant – only in combination with Palonosetron
• Indications
– Adjunct therapy to dexamethasone and 5HT3 antagonists for prevention of chemotherapy-induced N and V
• PK
– Fosaprepitant prodrug of aprepitant
– Allows single i.v. infusion to replace 3-day oral regime
– Aprepitant/fosaprepitant induce cyp3A4, rolaprepitant does not
• ADR
– GI side effects (constipation, diarrhoea, dyspepsia) are common, as is dizziness and headache
Olanzapine – Off-label use for CINV
• Antagonist at multiple receptors
– D1, D2, D3 receptors, serotonin 5-HT2a, 5-HT2c, 5-HT3 and 5-HT6 receptors, α1 adrenergic receptors, muscarinic receptors and histamine H1 receptors
• Used off-label for control of chemotherapy-induced N and V
– Growing body of evidence
• Side effects include sedation at a higher level than with other agents
Why Does Chemotherapy Induce CINV?
• Chemotherapy administration -> free radical formation -> 5HT release from enterochromaffin cells in
small intestine
• 5HT
– acts directly on chemoreceptor trigger zone, and
– Stimulates sensory receptors on vagal afferents -> CTZ
• CTZ activates vomiting centre
• Dopamine/D2 and substance P/Neurokinin NK1 are also important signalling mechanisms in this pathway
