pharm 24: anti emetics

Question 1

cis platinum as chemotherapy causes =

i.e SE of Cis platin

Answer 1

-induced nausea + vomiting

Question 2

How does Cis platin as chemotherapy drug cause nausea + vomiting ?

Answer 2

VERY MUCH REGULATED BY 5-HT3A RECEPTORS

Cisplatin= toxic to enterochromaffin cells (ECs) –> cause release of free radicals

Free radicals –> cause excessive 5-HT release

5-HT –> activates 5-HT3A receptors on:

a) Nerve fibres to nucleus tractus solaris (NTS)
b) Nerves fibres to vomiting centre (VC)
c) Nerve fibres to chemoreceptor trigger zone (CTZ)

–> signals up to vomiting centre –> causes contraction of stomach + expulsion of contents of stomach

Question 3

How would you treat nausea + vomiting due to cis platin?

Answer 3

MAIN = Ondansteron - 5-HT3A receptor antagonist

• Glucocorticoids - reduce free radical production
• Arepepritant – neurokinin-1 receptor antagonist

Question 4

How would you treat nausea + vomiting due to cis platin?

Answer 4

MAIN = Ondansteron - 5-HT3A receptor antagonist

• Glucocorticoids - reduce free radical production
• Arepepritant – neurokinin-1 receptor antagonist

–> give all three –> reduces vomiting + nausea in chemotherapy

Question 5

How does Cis platin as chemotherapy drug cause nausea + vomiting ?

Answer 5

VERY MUCH REGULATED BY 5-HT3A RECEPTORS

Cisplatin= toxic to enterochromaffin cells (ECs) in stomach –> cause release of free radicals

Free radicals –> cause excessive 5-HT release

5-HT –> activates 5-HT3A receptors on:

a) Nerve fibres to nucleus tractus solaris (NTS)
b) Nerves fibres to vomiting centre (VC)
c) Nerve fibres to chemoreceptor trigger zone (CTZ)

–> signals up to vomiting centre –> causes contraction of stomach + expulsion of contents of stomach

Question 6

How would you treat nausea + vomiting due to cis platin?

Answer 6

MAIN = Ondansteron - 5-HT3A receptor antagonist

others:
- Glucocorticoids - reduce free radical production

• Arepepritant – neurokinin-1 receptor antagonist

–> give all three –> reduces vomiting + nausea in chemotherapy

Question 7

Describe Motion sickness pathophysiology

Answer 7

• neural mismatch affects Auditory labyrinth –> causes Vestibular system (via muscarinic (M) receptors) –> to signal to vomiting centre

Increases hypothalamic histamine (H) release –> activates H1 receptors in CTZ

Vestibular system & hypothalamus may also activate the VC though cholinergic system

Question 8

How would you treat motion sickness?

Answer 8

• Promethazine = H1 receptor antagonist

- Hyoscine (scopolomine) = non-selective muscarinic receptor antagonist

Question 9

describe the pathophysiology of gastroparesis ?

Answer 9

it causes delayed emptying of the stomach

• reduces stomach contraction
  5-HT – activates 5-HT3A receptors on:
  a) Nerves fibres to vomiting centre (VC)
  b) Nerve fibres to chemoreceptor trigger zone (CTZ)

Question 10

How would you treat Nausea and vomiting caused by gastroparesis?

Answer 10

Metoclopramide

• Dopamine D2 receptor antagonist
• -> reduces signals to vomiting centres by Inhibits D2 receptors in VC
• -> it is Prokinetic (increases gastric emptying + contraction)
• 5-HT3A receptor antagonist
• -> Inhibits activation of CTZ

Question 11

Summarise the physiological control of nausea/vomiting and identify the main mechanistic triggers

a) Physiological control
b) Mechanistic triggers

Answer 11

Physiological control
Vomiting centre (area postrema): innervated by the nucleus of the tractus solitarius
Chemoreceptor Trigger Zone: communicates with the vomiting centre

Mechanistic triggers
Cytotoxic drugs, motion sickness, gastrointestinal problems

Question 12

Identify the main classes of anti-emetic drugs

Answer 12

5-HT3A receptor antagonists
Histamine H1 receptor antagonists
Muscarinic receptor antagonists
Dopamine D2 receptor antagonists

Question 13

Outline the principle clinical uses of anti emetic drugs and mechanism of action

Answer 13

5-HT3A receptor antagonists: chemotherapy induced N&V
Histamine H1 receptor antagonists: motion sickness
Muscarinic receptor antagonists: motion sickness
Dopamine D2 receptor antagonists: gastroparesis induced N&V

Question 14

Summarise the principle side effect profile of each class of anti-emetic drug

a) 5-HT3A receptor antagonists
b) Histamine H1 receptor antagonists
c) Muscarinic receptor antagonists
d) Dopamine D2 receptor antagonists

Answer 14

Summarise the principle side effect profile of each class of anti-emetic drug

a) 5-HT3A receptor antagonists
- constipation
- headaches

b) Histamine H1 receptor antagonists
- drowsiness

c) Muscarinic receptor antagonists
- dry mouth
- drowsiness

d) Dopamine D2 receptor antagonists
- galactorrhea
- extrapyramidal side effects