Anti-emetics Flashcards

1
Q

Describe how chemotherapy can induce nausea and vomiting (CINV), giving a specific example as well of a chemotherapeutic agent

A
  • Chemotherapeutic agents are toxic to the lining of the stomach e.g. Cisplatin is toxic to enterochromaffin cells
  • Destruction of stomach cells leads to release of free radicals (which itself contributes to destruction of stomach cell) and XS 5-HT release from the stomach
  • 5-HT binds 5-HT3A receptors on:
  1. Nerve fibres to nucleus tractus solitarius which then send impulses via subtance P and neurokinin-1 receptors to the nerves to the vomiting centre
  2. Nerve fibres to vomiting centre
  3. Nerve fibres to chemoreceptor trigger zone (CTZ)
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2
Q

What is the name of the drug that is the main treatment for CINV (chemotherapy induced nausea and vomiting) and how does it work?

A
  • Ondansetron
  • 5-HT3A receptor antagonist so antagonises receptors on the nucleus tractus solitarius, vomiting centre and the chemoreceptor trigger zone
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3
Q

What other drugs are used to treat CINV apart from the main line treatment and how do they work to treat CINV?

A
  • Glucocorticoids - these reduce free radical production so there is less destruction of stomach cells
  • Aprepitant - this is a neurokinin-1 receptor antagonist - so it reduces the communication between the nucleus tractus solitarius and the vomiting centre
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4
Q

Summarise the treatments for CINV (chemotherapy induced nausea and vomiting)

A
  • Ondansetron - first line treatment
  • Glucocorticoids
  • Aprepitant
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5
Q

What occurs in motion sickness?

A
  • Neural mismatch between the labyrinth and central nervous system
  • Increased histamine release which activates the chemoreceptor trigger zone
  • Vestibular system and hypothalamus may also activate the vomiting centre through the cholinergic system
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6
Q

Outline the pathways involved in motion sickness

A
  • Labyrinth to the vestibular system via muscarinic receptors
  • Vestibular system either directly to the vomiting centre or feed to the hypothalamus and then to the vomiting centre both via muscarinic receptors, then from the hypothalamus also to the chemoreceptor trigger zone via histamine receptors
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7
Q

What are the 2 treatments for motion sickness?

A
  1. Promethazine
  2. Hyoscine
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8
Q

What is Promethazine used to treat and describe its mechanism of action?

A
  • Treats motion sickness
  • H1 receptor antagonist - it prevents hypothalamus to CTZ (chemoreceptor trigger zone) remember because it goes labyrinth to vestibular system to hypothalamus and one of the ones after is to the CTZ
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9
Q

What is Hyoscine used to treat and describe its mechanism of action?

A
  • Treats motion sickness
  • Non-selective muscarinic antagonist - therefore blocks muscarinic transmission from the labyrinth to the vestibular system and from the vestibular system to the vomiting centre or from the hypothalamus to the vomiting centre
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10
Q

Describe how GI problems may lead to nausea and vomiting

A
  • Gastroparesis (delayed stomach emptying) → ↓ stomach contraction → 5-HT release → activation of 5-HT receptors on:
    • Nerve fibres to the vomiting centres via 5-HT receptors then via D2 receptors
    • Nerve fibres to CTZ via 5-HT receptors directly
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11
Q

How might T2DM lead to nausea and vomiting?

A
  • T2DM → gastroparesis → nausea and vomiting (see another flashcard for more detailed breakdown of how gastroparesis leads to this)
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12
Q

Describe the treatment for nausea and vomiting in gastroparesis - the main treatment and then another treatment and then describe the mechanism of action of these drugs

A
  • Metoclopramide - D2 receptor antagonist
    • Prokinetic (stimulate gastric emptying) so therefore directly acts against the gastroparesis
    • Inhibits D2 receptors in the vomiting centre
    • Metoclopramide is also a 5-HT receptor antagonist → inhibits activation of CTZ
  • 5-HT receptor antagonists - inhibit activation of CTZ
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13
Q

List 3 areas of physiological control of nausea and vomiting

A
  1. Nucleus tractus solitarius - leading to the vomiting centre
  2. Vomiting centre
  3. Chemoreceptor trigger zone
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14
Q

Summarise the 3 main mechanistic triggers for nausea and vomiting

A
  1. Cytotoxic drugs = CINV - chemotherapy induced nausea and vomiting
  2. Motion sickness
  3. GI problems = gastroparesis
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15
Q

Outline the 5-HT3A side effect profile

A
  • Headaches and constipation
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16
Q

Outline the histamine receptor antagonist (promethazine) side effect profile

A
  • Drowsiness
17
Q

Outline the side effect profile of muscarinic receptor antagonists (Hyoscine)

A
  • Constipation
  • Drowsiness
  • Dry mouth
18
Q

Outline the side effect profile of D2 receptor antagonists

A
  • Extra-pyramidal side effects