Antiemetics And Antidiarrhoeals Flashcards
What is the vomiting centre in the brain and what is it called?
- is in medulla
- Chemoreceptor Trigger Zone
What triggers the Chemoreceptor Trigger Zone?
- sensory afferents via midbrain
- vestibular nuclei
- vesicular afferents from gut
- direct triggers
What classes of drugs target the vestibular nuclei?
- muscarinic receptor antagonist
- H1 receptor antagonist
What classes of drugs affect the visceral afferents from the gut?
- 5HT3 antagonist
- D2 receptor antagonist
What classes of drugs affect the CTZ?
- D2 receptor antagonist
- 5HT3 receptor antagonist
- Muscarinic receptor antagonist
- H1 receptor antagonists
- corticosteroids
- cannabinoids
- NK1 receptor antagonists
Hyoscine hydrobromide (muscarinic receptor antagonist)
- acts on vestibular nuclei and sometimes CTZ
- competitive blockade of ACTH receptor
- ACTH part of parasympathetic system so some effects and side effects mimic parasympathetics
- first line for motion sickness, useful for long journey
Good for:
- people who can’t take tablets (patch version)
- motion sickness
- bowel obstruction
Side effects
- sedation
- memory problems
- glaucoma
- dry mouth and constipation
H1 receptor antagonists (cyclizine, levomepromazine, cinnirazine, promethazine, diphenhydramine)
- centrally acts on vestibular nuclei
- inhibits histaminergic signals from the vestibular system to the CTZ in medulla
Good for
- motion sickness (long plane journeys)
- promethazine for morning sickness in pregnancy
Not good for
- cyclizine on little old ladies and children (causes excitation)
- if you’re car driving because you nee to concentrate
Side effects
- sedation
- excitation
- antimuscarinic: dry mouth, constipation, urinary retention
- cardiac toxicity: long QT interval
5HT3 receptor antagonist (Ondansetron, granesitron, palonosetron)
- acts on visceral afferent in the gut
- peripherally: reduces GI motility and GI secretions
- centrally: acts to inhibit the CTZ
- Good for almost everyone: often first line treatment
Side effects
- constipation
- headache
- elevated liver enzymes
- long QT syndrome
- extra-pyramidal effects: dystocia, Parkinsonism
Metoclopramide
- D2 receptor antagonist
- acts on visceral afferents in gut
- increases ACh at muscarinic receptors in the gut
- promotes gastric emptying
- increases tone at LOS so it closes
- increases tone and amplitude of gastric contractions
- decreases tone of pylorus so it opens
- increases peristalsis
- good for: GORD and ileum
Side effects
- galactorrhoea via prolactin release
- extra pyramidal effects: dystonia, Parkinsonism
Domperidone
- D2 receptor antagonist
- acts on visceral afferents in the gut
- similar MOA as metoclopramide
- used frequently BEFORE but new evidence showed increased risk of CVS side effects
- good for: improving lactation in breastfeeding mothers
Side effects
- sudden cardiac death
- galactorrhoea
Anti-psychotics (prochlorperazine, haloperidol)
- D2 receptor antagonists
- the “zines”
- act on CTZ
- may also block H2 and muscarinic receptors
- good for: motion sickness, vertigo
- prochlorperazine good in pregnancy
- haloperidol: acts on CTZ and good in chemo and palliation
Side effects
- extra pyramidal effects: dystonia, Parkinsonism
- sedation
- hypotension
Corticosteroids (dexamethasone, methyprednisolone)
- acts on CTZ
- may also have D2 receptor antagonist properties
Good for
- perioperative nausea and vomiting
- chemo
- palliation: helps with eating
Side effects
- insomnia
- increase in appetite and blood sugar
Cannabinoids (nabilone)
- acts on CTZ
- good for chemo
- used as LAST LINE
Side effects
- dizziness
- drowsiness
Neurokinin 1 receptor antagonist (aprepitant, fosaprepitant, netupitant)
- prevents action of substance P at CTZ and in peripheral nerves
- boosts effects of 5HT3 receptor antagonist
- anxiolytics and antidepressant properties
- good for chemo especially delayed emesis
Side effects
- headache
- diarrhoea
- Stevens-Johnson syndrome
What is the first line treatment in general for emesis?
- ondansetron and/or cyclizine
- then add dexamethasone if needed