CA - Drugs for chemo-induced N&V & motion sickness

Question 1

What are serotonin 5HT-3 antagonists, corticosteroids & neurokinin receptor antagonists used tgt for?
Give one eg for each drug.

Answer 1

Acute & delayed N&V

5HT-3: Ondensetron
Corticosteroids: Dexamethasone
NK1-antagonist: Aprepitant (oral)

Question 2

Whats the MOA of serotonin antagonist, dopamine receptor antagonist & NK1 receptor antagonist?

Answer 2

Serotonin 5HT3 & Dopamine: CTZ
NK1: CTZ (chemoreceptor trigger zone) of the area postrema

Question 3

What are serotonin 5HT-3 antagonists used alone for?

Answer 3

ONLY acute N&V,
not that good with delayed N&V

Question 4

When is dopamine receptor antagonist used?

Give an example.

Answer 4

MOA: CTZ
- used tgt with dexamethasone - corticosteroid if Aprepitant - NK1 125mg for acute N&V

Metoclopramide

Question 5

When are antipsychotics / mixed dopamine/muscarinic receptor antagonists &/ antihistamines used?

Name.

Answer 5

• Olanzapine + Dexamethasone controls high risk non-ac delayed N&V

1. Dopamine & muscarinic antagonism & Antihistamine: Prochlorperazine
2. Atypical antipsychotic: Olanzapine

Question 6

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)?

Answer 6

1. Serotonin 5-HT3 antagonist - ondansetron AND
2. Corticosteroid - dexamethasone

Question 7

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?

Answer 7

1. Serotonin 5-HT3 antagonist - ondansetron AND
2. Corticosteroid - dexamethasone AND
3. Neurokinin NK1 antagonist - Aprepitant (oral)

Question 8

What are benzodiazepines used for?
Give an example.

Answer 8

Anticipatory N&V / Before Chemo
MOA: Higher centres

Lorezapam

Question 9

What are muscarinic receptor antagonists and mixed H1 antihistamine and muscarinic receptor antagonists used for?
What is another use of muscarinic receptor antagonists?

Name the drugs.

Answer 9

Motion sickness

• Antispasmodic for abdominal cramps

MRA: Hyoscine
Mixed: Cinnarizine

Question 10

What are the side effects of serotonin 5HT-3 antagonists?

Name.

Answer 10

• small risk of cardiac arrthymia -> caution for pts with cardiac problems & with drugs prolonging QT interval
• risk of orofacial malformations in early pregnancy -> dont eat in 1st trimester

Ondensatron

Question 11

What are the side effects of corticosteroids?
Name.

Answer 11

High doses OR Long-term use (>2 wks):
Cushing’s syndrome:
- Hyperglycaemia -> diabetes
- Hypertension, bradycardia
- Dyspepsia
- GERD
- Mood swings

• Redistribution of fat (rounded face)
• Muscle wasting
• Thinning of skin, easy bruising
• Osteoporosis
• Immunosuppression

Dexamethasone

Question 12

What are the side effects of dopamine receptor antagonists?
Name.

Answer 12

EPSE:
1. Restlessness, dystonia, and parkinsonian symptoms
- elderly very susceptible

Long-term:
2. Irreversible tardive dyskinesia can develop
Therefore, only used short-term

3. Elevated prolactin levels can cause:
   Galactorrhoea, gynaecomastia, impotence & menstrual disorders
   - reversible if drug is withdrawn

Metochlopramide

Question 13

What are the side effects of neurokinin receptor antagonist?
Name.

Answer 13

Common:
Fatigue, dizziness, diarrhoea

Severe:
- peripheral neuropathy, blood dyscrasia (imbalanced blood cell types)
- drug-drug interactions
- Drugs that inhibit CYP3A4 enzyme may influence plasma levels

Aprepitant (oral)

Question 14

What are the side effects of mixed dopamine, muscarinic and/or histamine receptor antagonists
Name.

Answer 14

1. Sedative (due to antihistamine effects)
2. Extrapyramidal side-effects [EPSE]
   - Parkinsonian motor adverse effects
3. Hypotension
4. Droperidol: prolongation of the QT interval
   - cardiac arrythmia

Question 15

What are the side effects of benzodiazepines
Name.

Answer 15

1. Sedative / hypnotic
2. Additive effects with other sedative drugs and CNS depressants
   - EG antidepressants, alcohol and opioids
3. Respiratory depression on overdose
4. Avoid during pregnancy, especially 1st trimester (risk of cleft palate)

LORAZEPAM

Question 16

What are the side effects of Muscarinic receptor antagonist?
Name.

Answer 16

Anticholinergic (parasympatholytic) adverse effects:
1. Dry mouth, blurry vision
2. Sedation, confusion

HYOSCINE

Question 17

What are the side effects of mixed h1 antihistamine & muscarinic receptor antagonist
Name.

Answer 17

1. Sedative due to antagonism of H1 receptors
2. Anticholinergic (parasympatholytic) adverse effects:
   - Dry mouth, blurry vision, constipation

Cinnarizine