Anti-emetics

Question 1

What are the risk factors for PONV?

Answer 1

• Female gender
• History of PONV or motion sickness
• Non smoker
• General Anaesthesia (cf. regional anaesthesia)
• Use of volatile anaesthetics and nitrous oxide
• Perioperative use of opioids
• Certain types of surgery e.g. laparoscopic, gynaecological, otologic and squint surgery.
• Prolonged surgeries

Question 2

What are the strategies to reduce the incidence of PONV?

Answer 2

• Avoidance of general anaesthesia and use of regional anaesthesia if possible
• Use of propofol for induction and maintenance of anaesthesia
• Avoidance of nitrous oxide and volatile anaesthetics
• Minimise use of inerative and postoperative opioids
• Ensure adequate hydration

Question 3

What are the pharmacokinetics of 5HT3 Receptor Antagonists?

Answer 3

• Well absorbed from GIT and undergoes some first pass metabolism
• Metabolised by hepatic cytochrome P450 enzymes (CYP3A4, CYP2D6, CYP1A2)

Question 4

What are the dosing and timing of administration of 5HT3 Receptor Antagonists?

Answer 4

 Recommended dose for prophylaxis in adults is ondansetron 4 mg IV.
 Most effective in prophylaxis of PONV when given at end of surgery due to its short duration of action.
 Oral dose is administered 30 minutes before start of chemotherapy.

Question 5

What are the side effects of 5HT3 Receptor Antagonists?

Answer 5

 Has favourable side effect profile and generally considered safe.
 Side effects include: headache, diarrhoea, constipation, arrhythmia
 All 5HT3 receptor antagonists except palonosetron can prolong the QTc interval
 Higher doses of ondansetron may be used for chemotherapy induced nausea and vomiting (CINV), but should not exceed 16 mg in a single dose because of the risks of QT prolongation.

Question 6

What are the dosing and timing of administration of corticosteroids?

Answer 6

 IV 4 to 8 mg after anaesthesia induction
 For PONV prophylaxis, the efficacy is similar to ondansetron 4mg IV and droperidol 1.25 mg IV.
 Can be given IV, orally alone or in combination with other anti-emetics before chemotherapy and continued for 1-3 days after chemotherapy

Question 7

What are the side effects of corticosteroids?

Answer 7

 Dizziness, mood changes, nervousness
 Significant increases in blood glucose that occurs 6 to 12 hours postoperatively in normal subjects, those with impaired glucose tolerance, type 2 diabetics and obese patients who receive 8 mg. In view of this evidence, the use of dexamethasone in labile diabetic patients is relatively contraindicated.

Question 8

What is the mechanism of action of metoclopramide?

Answer 8

 It is a competitive antagonist at dopaminergic (D2) receptors.
 It is effective against acute vomiting when given IV at higher doses probably because it is a weak competitive antagonist (relative to other serotonin antagonists) at 5-HT3 receptors.
 Metoclopramide increases lower esophageal sphincter pressure and enhances the rate of gastric emptying, which may factor into its overall anti-emetic effects.

Question 9

what are the side effects of metoclorpamide?

Answer 9

 Extrapyramidal symptoms eg dystonic reactions (oculogyric crisis)
 Akathisia - the subjective sense of restlessness or inability to sit still
 May cause tardive dyskinesia (esp in elderly with prolonged use; often irreversible)

Question 10

What is the half life of aprepitant (NK1 receptor antagonist)?

Answer 10

40 hours

Question 11

What is the side effects of aprepitant (NK1 receptor antagonist)?

Answer 11

Dizziness, diarrhoea, headaches, weakness

Question 12

what is the dosing and timing of administration of butyrophenones (dropiderol)?

Answer 12

Dose and Timing of administration
 Dose is IV 0.625 – 1.25 mg
 Most effective when administered at the end of surgery.

Question 13

What is the side effects of butyrophenones (dropiderol)?

Answer 13

 Hypotension
 Extrapyramidal symptoms
 Prolonged QT interval

Question 14

What are the 3 distinct types of CINV?

Answer 14

 Acute emesis - which begins within1-2 hours of chemotherapy
 Delayed emesis - occurring more than 24 hours after chemotherapy
 Anticipatory emesis - a conditioned response that occurs in patients who experienced severe nausea and vomiting during previous chemotherapy cycles

Question 15

What are the 3 categories of drugs with highest therapeutic index for treatment of CINV?

Answer 15

 5HT3 receptor antagonists
 Neurokinin-1 (NK1) receptor antagonists and
 Glucocorticoids