antimetics Flashcards
7 classes of antimetics
- serotonin 5-HT3 antagonists
- corticosteroids
- neurokinin receptor antagonists
- dopamine receptor antagonists
- muscarinic receptor antagonists
- H1 histamine receptor antagonists
- benzodiazepines
what is an example of serotonin 5 HT antagonist
ondansetron, granisetron
when and how is ondansetron administered
IV 30min or ORAL 1h before chemotherapy - prevent chemotherapy induced nausea & vomiting (CINV)
what combination enhances its efficacy
corticosteroid and nk1 receptor antagonist
MOA of serotonin 5-HT 3 antagonists
acts at the 5-HT3 receptor in the GIT
also prevents nausea caused by other forms of noxious GIT stimulation
adverse effects of serotonin 5 HT-3 antagonists
headache
dizziness
constipation, diarrhoea
small risk of cardiac arrhythmia
what is the risk of using ondansetron in early pregnancy
small risk of orofacial malformations
what are examples of corticosteroids used for CINV
dexamethasone, methylprednisolone
adverse effects of using corticosteroids
higher dose or longer use (> 2 weeks) may cause iatrogenic cushing syndrome:
hyperglycaemia
GERD
what is an example of dopamine receptor antagonists
metoclopramide
what is the MOA of metoclopramide
dopamine (esp D2) receptor antagonism @ chemoreceptor trigger zone
also used as pro kinetics to stimulate GI motility
what are the adverse effects associated with metoclopramide
EPSE!!!
- parkinsonism (tremor, bradykinesia, restlessness)
- elderly are more susceptible
- long term use can lead to tardive dyskinesia
what are the options for treatment of acute nausea and vomiting induced by a chemotherapy regimen expected to have low emetogenic risk?
5 HT-3 receptor antagonists OR dexamethasone OR dopamine receptor antagonists
What are the recommended options for the treatment of acute nausea and vomiting induced by a chemotherapy regimen expected to have moderate emetogenic risk (other than carboplatin)?
5-HT3 receptor antagonist AND dexamethasone
What are the recommended options for the treatment of acute nausea and vomiting induced by a chemotherapy regimen expected to have a high emetogenic risk or carboplatin?
5-HT3 receptor antagonist AND dexamethasone AND neurokinin NK1 receptor antagonist
what are examples of neurokinin receptor antagonists
aprepitant (oral)
fosaprepitant (IV)
what is the MOA of neurokinin receptor antagonists
acts at the neurokinin 1 receptor in area postrema (trigger zone for emesis)
what are the adverse effects associated with the use of neurokinin receptor antagonists
common s/s: fatigue, hiccups, diarrhoea, constipation
severe: peripheral neuropathy
concerning if metabolised by cyp3a4:
- interacts with other chemotherapeutic agents (eg docetaxel and etoposide)
- drugs that inhibit cyp3a4 may influence plasma levels - ketoconazole, clarithomycin
which class of drugs are not effective to prevent DELAYED nausea and vomiting
5 HT-3 receptor antagonists
classes of drugs that can be used to prevent delayed nausea and vomiting
dexamethasone
metoclopramide
aprepitant
olanzapine
Name THREE examples of mixed dopamine, muscarinic and/or histamine receptor antagonists
-
Phenothiazines: prochlorperazine, promethazine
Dopamine, muscarinic & histamine receptor antagonism -
Butyrophenones: droperidol
Dopamine receptor antagonism and weak histamine receptor antagonism -
Atypical antipsychotic: olanzapine
Dopamine, muscarinic & histamine receptor antagonism
Also 5-HT3 receptor antagonism
what are the adverse effects associated with mixed dopamine, muscarinic and/or histamine receptor antagonists
sedative
EPSE
hypotension
** for droperidol - prolonged QT interval
Name ONE example of a benzodiazepine used to manage anticipatory nausea and vomiting.
Lorazepam, diazepam
MOA of benzodiazepines
binds to allosteric site on GABA receptors
anxiolytic
reduces anticipatory vomitting
adverse effects associated with benzodiazepines
sedative
additive effects with CNS depressants eg antidepressants, alcohol and opoids - causing resp depression on overdose
who should avoid benzodiazepines and why?
pregnant women esp during first trimester, may cause risk of cleft palate
which drugs are effective in preventing motion sickness
Scopolamine (also known as hyoscine), diphenhydramine
hyoscine - muscarinic receptor antagonists
diphenhydramine - mixed h1 antihistamine and muscarinic receptor antagonists
adverse effects of using scopolamine
anticholinergic
dry mouth, blur vision
sedation & confusion
**High incidence of adverse effects when given orally therefore often administered by transdermal patch
what are examples of mixed h1 antihistamine and muscarinic receptor antagonists
cinnarazine and diphenhydramine
adverse effects of using diphenhydramine/cinnarizine
sedative
dry mouth, constipation and blur vision
pharmacotherapy for nausea and vomiting during pregnancy
pyridoxine (vit B6) supplements
doxylamine - if pyridoxine is not sufficient
