Nausea and vomitting Flashcards
What is vomiting?
The forceful evacuation of gastric content through the mouth
What is Emetic reflex?
Contraction of abdominal muscles and diaphragm increasing pressure in stomach
closure of glottis (prevents vomit entering lungs)
Nausea and vomiting are not a symptoms. TRUE OR FALSE?
FALSE - they are not a dignosis they are simply symptoms and the need to find a cause is important
Name the causes of emisis that may require treatment ?
-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 ther
What two brainstem areas control emesis?
- Chemo trigger zone (Fenestrated capillaries allow detection of circulating chemicals)
- Vomiting Centre (Nucleus of the Solitary Tract)
What occurs when chemical and neuronal inputs are intregrated?
- Signals from periphery sense “something wrong”
(Gut chemo-, mechano-sensation) - Signals from higher brain regions “contextualise” other inputs
(Sight & smell; balance; emotion)
What occurs during a vomiting reflex?
Co -ordinated motor-pattern
–Retroperistalsis, gastric contraction, abdominal wall contractio
1.Motion sicknes
2.Drug -induced nausea and vomiting
3.Post -operative vomiting
4.Migraine
5.Chemotherapy (CINV)
what are the treatment options for these 5 different causes of emesis?
1.Anti -histamines, anti-muscarinics
2.try minimize gastric irritation with equal spacing of drug; take with food–otherwise –Dopamine antagonists ,
antihistamine
3.Dopamine antagonists (phenothiazines)
– 5HT3 antagonists
4. Phenothiazines
helpful because also speeds gastric emptying and facilitates absorption of
analgesics
5.dexamethasone, 5HT3 antagonist, NK1 antagonists
Provide an example of anti-histamines (H1) drug?
Cinnarizine
Cyclizine
Promethazine
Promethazine may be used in pregnancy (severe morning sickness) TRUE OR FALSE?
TRUE
What do anti-histamines (H1) drugs act on?
they actt on vestibular apparatus, VC and CTZ
What are the indications for antihistamine drugs?
- Travel sickness,
- Vestibular disorders (vertigo)
- Space motion sickness (Promethazine - NASA)
what are the ADRs for anti-histamines?
- Sedation
- Anti-cholinergic effects (dry mouth, blurred vision, constipation, urinary retention)
- Blocks Ca2+ transport so also causes vasodilation
what are the cautions for anti-histamines?
- Significant antimuscarinic activity
- Use with caution in prostatic hypertrophy, urinary retention, susceptibility to angle-closure glaucoma, and
pyloroduodenal obstruction
Give an example of an anti-muscarinic drug/agent?
Hyoscine hydrobromide (previously known as scopolamine)
what are the indications for anti-muscarinic drug/agent?
OTC for motion sickness (both prophylaxis & treatment), GI disorders
What is the pharmacokinetics of anti-muscarinic drug/agent?
for motion sickness can use patch on skin behind ear
what are some ADRs for anti-muscarinic drugs/agents?
- causes less drowsiness than antihistamines but still caution when driving
- can cause typical anticholinergic ADR
What are the ADRs for anti-muscarinic drugs/agents?
- myasthenia gravis, paralytic ileus, pyloric stenosis, toxic megacolon and prostatic enlargement
Dopamine antagonists acts on CTZ so are useful for motion sickness/ vestibular disorders? TRUE OR FALSE?
FASLE
provide examples of Phenothiazines (dopamine antagonists)
Prochlorperazine
perphenazine
trifluoperazine
(less sedating than chlorpromazine)
what are the indications for dopamine antagonists?
N&V associated with diffuse neoplastic disease, radiation sickness, and emesis caused by drugs such as opioids, general anaesthetics, and cytotoxics
What are the ADRs for dopamine antagonists?
Resulting from DA antagonism (“extrapyramidal” motor effects), Sedative, dizziness
Prochlorperazine can cause anti-cholinergic effects. TRUE OR FALSE?
TRUE
what are the cautions of dopamine antagonists?
- Avoid prochlorperazine (also cholinergic antagonist) in patients with urinary retention or glaucoma
- Prochlorperazine prolongs QT and promotes hypotension
what are the contraindications of dopamine antagonists?
- Parkinson’s disease
- Phaeochromacytoma – can cause hypertensive crisis
What are the interactions of dopamine antagonists with other drugs?
- Prochlorperazine potentiates effects of other sedatives
- Increases effect of other drugs that lower bp or prolong QT
what is Domperidone?
A dopamine antagonist
Domperidone is also pro-kinetic – speed gastric emptying. TRUE OR FALSE?
TRUE
what are the indications of Domperidone?
N&V induced by chemotherapy, DA receptor agonists/
levoDOPA
What are the PK of Domperidone?
- dose adjustment usually not required with hepatic or renal insufficiency
- poor brain penetration:
- few extrapyramidal effects
- doesn’t antagonise anti-Parkinson’s effects of DA agonists (CTZ has poor BBB)
What do the MHRA/CHM advice for Domperidone: risk of cardiac side-effects?
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
What is Metoclopramide?
Dopamine antagonist
What are the indications of Metoclopramide?
N&V induced by drugs, post-operatively or migraine
metoclopramide is metabolized by
cyp enzymes - therefore reduce dose in hepatic insufficiency. TRUE OR FALSE?
TRUE
What are the ADRs of Metoclopramide?
Resulting from DA antagonism (“extrapyramidal” motor effects)
What are the cautions to take when administering Metoclopramide?
avoid metoclopramide in patients with GI obstructions or haemorrhage (prokinetic)
What are the contraindications of Metoclopramide?
– Parkinson’s disease
– Phaeochromacytoma can cause hypertensive crisis
what are the HRA/CHM advice on Metoclopramide:
risk of neurological adverse effects?
Metoclopramide should only be prescribed for short-term use (up to 5 days)
Provide an example of 5HT3 antagonist?
Ondansetron, Granisetron ,Palonosetron
How do Ondansetron, Granisetron ,Palonosetron work?
They decrease sensitivity of 5HT receptors:
•in the VC
•in vagal afferent nerve that detect cytotoxic damage to the gut
What are the indications for 5HT3 antagonist?
- chemotherapy induced nausea
- post operative nausea
What is the half life of 5HT3 antagonist drugs?
short t1/2 4hr
–schedule depends on indication
What are the ADRs of 5HT3 antagonist drugs?
- Headache and constipation are common (reduce peristalsis)
- Dizziness
Give three examples of Neurokinin Receptor Antagonists and provide their route of administration?
Aprepitant (p.o.)
Fosaprepitant (i.v.)
Rolapitant (p.o.)
Netupitant – should only be given in combination with Palonosetron. TRUE OR FALSE?
TRUE
What are the indications for Neurokinin Receptor Antagonists ?
Adjunct therapy to dexamethasone and 5HT3
antagonists for prevention of chemotherapy-induced N&V
What is the PK profile for Neurokinin Receptor Antagonists ?
- Fosaprepitant prodrug of aprepitant
- Allows single i.v. infusion to replace 3-day oral regime
- Aprepitant/fosaprepitant induce cyp3A4, rolaprepitant
does not
What are some of the ADRs of Neurokinin Receptor Antagonists ?
GI side effects (constipation, diarrhoea, dyspepsia) are common, as is dizziness and headache
Olanzapine is Off-label use for CINV. TRUE OR FALSE?
True
Olanzapine is 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. TRUE OR FALSE?
TRUE
Olanzapine is not used off-label for control of chemotherapy-induced N&V. TRUE OR FALSE?
FALSE
What are the side effects of Olanzapine?
Side effects include sedation at a higher level than with other agents
