GIT - vomitting and nausea

Question 1

Drugs for nausea and vomitting (7 groups)

Answer 1

CNS - H(F)MD -B
Serotonin 5-HT3 (vomitting centre) antagonists
Corticosteroids
Neurokinin receptor antagonists
Dopamine receptor antagonists
Muscarinic receptor (output) antagonists
H1 histamine receptor antagonists
Benzodiazepines

Question 2

Serotonin 5-HT3 (vomitting centre) antagonists drugs (2)

Answer 2

Ondansetron (1st generation)
Palonosetron (2nd generation)
once daily, oral/IV

1st line for acute chemotherapy nausea, but not good for delayed so need to use combination therapy

Question 3

Serotonin 5-HT3 (vomitting centre) antagonists MOA

• combination therapy
• clinical use

Answer 3

Act at 5-HT3 receptors primarily in the GIT
Efficacy enhanced by combination with a corticosteroid and NK1-receptor antagonist
IV 30 min before or orally 1 hour before chemotherapy: prevents acute chemotherapy-induced nausea and vomiting
(CNIV)
not effective for delayed (long run) nausea and vomiting (>24 hr after chemotherapy)

Question 4

Serotonin 5-HT3 (vomitting centre) antagonists ADR

Answer 4

May cause headache, dizziness and
constipation
Small risk of cardiac arrhythmia (prolongation of the QT interval) with first generation

Eliminated by hepatic metabolism and renal and hepatic excretion, no need for dose reduction
(exc ondansteron may be required for patients with hepatic insufficiency)

Undergo P450 metabolism,
does not interfere with metabolism of other drugs, but other drugs can reduce hepatic clearance of the 5-HT3 antagonists

Question 5

Corticosteroids drugs (2)

Answer 5

Dexamethasone

methylprednisolone

Question 6

Corticosteroids MOA

Answer 6

used in combination with 5-HT3 antagonists to prevent acute and delayed vomiting (and to some extent nausea) in patients on moderately to highly emetogenic chemotherapy regimens

Question 7

Corticosteroids ADR

Answer 7

Higher doses or longer-term use (> 2 weeks) may cause iatrogenic Cushing’s syndrome

Question 8

Neurokinin Receptor Antagonists

Substance P Antagonists) (2

Answer 8

Aprepitant (oral)

Fosaprepitant (IV) : will be converted to aprepitant

Question 9

Neurokinin Receptor Antagonists
(Substance P Antagonists)
- combination therapy
- clinical use

Answer 9

used in combination with corticosteroid and 5-HT3 receptor antagonists to prevent acute and delayed vomiting (and to some extent nausea) caused by highly emitogenic chemotherapy

Question 10

Neurokinin Receptor Antagonists

(Substance P Antagonists) ADR

Answer 10

Fatigue, dizziness, diarrhoea

Metabolism by CYP3A4: influence plasma levels

Question 11

Dopamine Receptor Antagonist drug

Answer 11

Metoclopramide

Question 12

Dopamine Receptor Antagonist MOA

Answer 12

D2 receptor antagonist

Question 13

Dopamine Receptor Antagonist ADR

Answer 13

Extrapyramidal side effects:
• Restlessness, dystonias and parkinsonian (tremors) symptoms
• Elderly are especially susceptible
• long-term: irreversible tardive dyskinesia
also increase prolactin levels:
• Galactorrhea, gynaecomastia, impotence and menstrual disorders

Question 14

Muscarinic Receptor Antagonist Drug

Answer 14

Hyoscine (Scopolamine): transdermal patch

Question 15

Muscarinic Receptor Antagonists MOA

Answer 15

Muscarinic receptor antagonist (action in vestibular
system and vomiting centre) - most efficient cause it blocks the output
Used for prevention of motion sickness

Question 16

Muscarinic Receptor Antagonists ADR

Answer 16

Anticholinergic effects: Dry mouth, blurring of vision, constipation

Question 17

Mixed H1 histamine receptor & muscarinic receptor antagonist drug

Answer 17

Diphenhydramine

Question 18

Mixed H1 histamine receptor & muscarinic receptor antagonist MOA
- clinical use

Answer 18

MOA of both: affecting vomiting centre and vestibular system
– Particularly useful for the treatment of motion sickness
– Sedative effects of diphenhydramine may also be useful in treatment of emesis due to chemotherapy

Question 19

Mixed H1 histamine receptor & muscarinic receptor antagonist ADR

Answer 19

ADR of both:
– Sedative due to antagonism of H1 receptors
– Anticholinergic (parasympatholytic) adverse effects:
• Dry mouth, blurring of vision, constipation

Question 20

Mixed dopamine, muscarinic and/or histamine receptor antagonists group name + drugs

Answer 20

antiphsychotics:
prochlorperazine
promethazine

Question 21

Antipsychotics MOA

Answer 21

mixed antagonist
– Dopamine receptor antagonism (chemoreceptor trigger zone)
– Muscarinic antagonism (vestibular system & vomiting center)
– Histamine receptor antagonism (vomiting centre & vestibular system)

Question 22

Antipsychotics ADR

Answer 22

– Sedative (due to antihistaminergic effects)
– Extrapyramidal side-effects [EPS] (e.g. Parkinsonian motor adverse effects)
– Hypotension
– prolongation of the QT interval

Question 23

Benzodiazepines drugs (2)

Answer 23

Lorazepam

diazepam

Question 24

Benzodiazepines MOA

Answer 24

– Binding to allosteric site on GABA receptors increases chloride conductance
– Anxiolytic (anxiety)
– Reduce anticipatory vomiting or vomiting caused by anxiety

Question 25

Benzodiazepines ADR

Answer 25

– Sedative / hypnotic
– Additive effects with other sedative drugs and CNS depressants e.g. antidepressants, alcohol and opioids -> Respiratory depression on overdose
– Avoid during pregnancy, especially first trimester (risk of cleft palate)

Question 26

combination therapy for nausea and vomitting

Answer 26

CNS (corticosteroid, neurokinin antagonist, serotonin antagonist)
dexamethasone, aprepitant, ondansetron (DAO)