Antiemetics Flashcards
What are 7 drug classes used as anti-emetics?
1) Serotonin 5-HT3 receptor antagonists
2) Corticosteroids
3) Neurokinin receptor antagonists
4) Dopamine receptor antagonists
5) Muscarinic receptor antagonists
6) Histamine H1 receptor antihistamines
7) Benzodiazepines
What are 4 sites that can trigger the vomiting center?
1) Chemoreceptor trigger zone (postrema area of 4th ventricle floor)
2) GIT (mechano/chemoreceptors)
3) Vestibular system
4) Higher centers of CNS
What are 3 examples of 5-HT3 serotonin antagonists (-setron)?
In order of T1/2
Ondansetron (4-9hr) < Granisetron (9-12hr) < Palonosetron (40-50hr)
How and how often is Odansetron administered?
Once daily (Oral/IV)
What is the moa of 5-HT3 serotonin antagonists?
Blocks 5-HT receptors on afferent dorsal root nerve primarily in the GIT (CNS 5-HT receptors not impt for nausea/vomiting)
→ block transmission of signals of distension and noxious stimuli from GIT to CNS
When are 5-HT3 antagonists given for chemotherapy-induced vomiting?
IV 30mins before / Oral 1 hr before
(not effective >24 hours/delayed)
What are drug classes that are combined with 5-HT antagonists to increase its efficacy?
Corticosteroids
NK1-receptor antagonists
Which 5-HT3 antagonist is associated with a small risk of orofacial malformations in early pregnancy?
Odansetron
In which px should 5-HT3 antagonists be avoided/used in caution?
1) px with cardiac anomalies (prolong QT interval)
2) px on other drugs that prolong QT interval
3) early pregnancy (odansetron → orofacial malformation)
How are 5-HT3 antagonists metabolised?
CYP450
What are 3 common AEs of 5-HT3 antagonists?
1) Headaches
2) Dizziness
3) Drowsiness
4) Constipation or diarrhoea
5-HT3 antagonists have a small risk of inducing ____________ as a AE?
Cardiac arrythmias (prolong QT interval)
What are 2 examples of corticosteroids used as anti-emetics?
Dexamethasone
Methylprednisolone
What is the main concern of long term (> 2 wks) use of corticosteroids as anti-emetics?
Iatrogenic Cushing’s syndrome
What drugs are used with corticosteroids as anti-emetics?
5-HT3 antagonists for acute and delayed chemotherapy-induced vomiting
What is an example of a substituted benzamide used as a anti-emetic?
Metoclopramide
What is the moa of substituted benzamide?
1) Dopamine (esp D2) receptor antagonism @ chemoreceptor trigger zone (CTZ)
2) Prokinetic → stimulate GI motility (except in complete obstruction)
What are 2 AEs of substituted benzamines used as anti-emetics?
1) Extrapyramidal symptoms → parkinsonian symptoms (eg. bradykinesia, restlessness, tremor) + tardative dyskinesia (LT treatment)
- elderly esp susceptible
2) Elevated prolactin → galactorrhea, menstrual disorders, gynaecomastia, impotence
What are 2 examples of Neurokinin Receptor/Substance P Antagonists used as anti-emetics (-prepitant)?
1) Aprepitant (Oral)
2) Fosaprepitant (IV → converted to aprepitant in 30mins)
What is the moa of substance P/NK antagonists?
Antagonise Neurokinin 1 receptors in area postrema (CNS)
What drugs are used with NK/substance P antagonists as anti-emetics?
Corticosteroids
5-HT3 receptor antagonists
What are 6 AEs of NK antagonists?
Common:
1) Fatigue
2) Hiccups
3) Diarrhoea/constipation
Severe:
1) Peripheral neuropathy
2) blood dyscrasias
How are NK antagonists metabolised?
Hepatic CYP3A4
(DDI with chemotherapy, CYP3A4 inhibitors eg. ketoconazole, clarithromycin, ritonavir, verapamil)
What are 4 drug classes used for acute chemotherapy-induced nausea?
1) 5-HT3 antagonist (eg. Odansetron)
2) Corticosteroids (eg. dexamethasone)
3) NK1 antagonists (eg. aprepitant)
4) Olanzapine (Atypical antipsychotic)
5) Dopamine receptor antagonist (eg. metoclopramide)
What are 4 drug classes used for acute chemotherapy-induced nausea?
1) Corticosteroids (eg. dexamethasone)
2) Olanzapine (Atypical antipsychotic)
3) Metoclopramide
4) Aprepitant
What are 4 examples of antipsychotics used as anti-emetics?
Phenothiazines: Dopamine, muscarinic antagonist, antihistamine
1) Promethazine
2) Prochlorperazine
Butyrophenones: dopamine antagonism, weak antihistamine
3) Droperidol
Atypical antipsychotic:
4) Olanzapine
What are the moas for antipsychotics used as anti-emetics?
1) Dopamine receptor antagonism (CTZ)
2) Muscarinic antagonism (Vestibular system & vomiting center)
3) Antihistamine (Vestibular system & vomiting center)
What are 4 AEs of antipsychotics used as anti-emetics?
1) Sedative (antihistaminergic effects)
2) Extrapyramidal syndrome
3) Hypotension
4) Prolonged QT interval (Properidol)
Muscarinic receptor antagonism has additional ____________ effect when used as a anti-emetic?
Antispasmodic
Olanzapine controls CINV delayed-nausea with less ___________.
Extrapyramidal syndrome
Which anti-emetics are used for prevention of nausea by noxious GIT stimulation (eg. small-bowel obstruction)?
1) 5-HT3 Antagonist (-setron)
2) Promethazine
3) Prochlorperazine
Which anti-emetics are used to prevent anticipatory nausea and vomiting?
1) Benzodiazepines (-zepams)
2) Anticholinergic (eg. hyoscine)
3) Mixed H1 antihistamine and muscarinic receptor antagonists (eg. cinnarizine, diphenhydramine)
What are 2 examples of benzodiazepines used as anti-emetics?
1) Lorazepam
2) Diazepam
What is the moa of benzodiazepines used as anti-emetics?
1) Allosteric inhibition of GABA receptors → ↑Cl conductance
2) Anxiolytic
3) ↓ anticipatory/anxiety-induced vomiting
What are 2 AEs of benzodiazepines used as anti-emetics?
1) Sedative/hypnotics
2) Additive effects on CNS depressants (respi depression)
In which px should benzodiazepines be avoided?
Pregnant (esp 1st trimester)
- risk of cleft palate
What is an example of an anticholinergic used as an anti-emetic?
Hyoscine
What are 2 AEs of anticholinergics used as anti-emetics?
1) PNS-lytic (eg. xerostomia, vision blur)
2) CNS (eg. sedation, confusion)
Which anti-emetic can also be used as an antispasmodic for abdominal cramps?
Anticholinergic (hyoscine)
What are 2 examples of mixed H1 antihistamine and muscarinic receptor antagonists used as anti-emetics?
1) Cinnarizine
2) Diphenhydramine
Which anti-emetics are particularly useful in the treatment of motion sickness?
Diphenhydramine
Cinnarizine
The sedative effects of diphenhydramine is also useful in treating emesis due to ____________.
chemotherapy
What are 2 AEs of mixed H1 antihistamine and muscarinic receptor antagonists used as anti-emetics?
1) Sedative (H1 antagonism)
2) PNS-lytic (eg. xerostomia, blurring vision, constipation)
In which 2 demographics should anti-emetics generally be avoided?
Pregnant women
Infants/children
How is nausea and vomiting managed in pregnancy?
1) Dietary changes
- avoid empty/overly full
- Avoid coffee, odourus, high-fat, acidic, very sweet foods
- Choose high-protein, salty, low-fat, bland, dry foods
- Sip fluid/take fluids 30min before solid food
- Avoid noxious triggers
- Take ginger-containing foods
2) Pharmacotherapy
- Only if dietary dont work
- Pyridoxine (vit B6) supplements
- Doxylamine (if pyridoxine dont work coz 1st gen antihistamine → AE on pregnancy/fetal development
What are 3 pharmacotherapies used for persistent nausea and vomiting in children?
1) Gastroparesis
- prokinetic (eg. metoclopramide)
2) Post-op
- 5-HT3 antagonists
3) Chemo
- 5-HT3 antagonists
- NK1 antagonists
