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Clinical Pharmacology & Intro to Prescribing > Session 11: Anti-emetics > Flashcards

Session 11: Anti-emetics Flashcards

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1
Q

What is vomiting?

A

Involuntary, forceful expulsion of gastric contents through the mouth.

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2
Q

What is the vomiting centre?

A

Chemoreceptor trigger zone (CTZ)

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3
Q

What activates the CTZ?

A

Sensory afferent via midbrain

Vestibular nuclei (inner ear)

Visceral afferents from gut via vagus nerve

Direct triggers like drugs

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4
Q

Drugs acting on vestibular nuclei

A

Muscarinic receptor antagonists

H1 receptor antagonists

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5
Q

Drugs acting on the visceral afferents from gut

A

5HT3 antagonists

D2 receptor antagonists

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6
Q

Drugs acting on CTZ

A

D2 receptor antagonist

5HT receptor antagonist

Muscarinic receptor antagonist

H1 receptor antagonist

Corticosteroid

Cannabinoid

NK1 receptor antagonist

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7
Q

Give an example of a muscarinic receptor antagonist acting on the vestibular nuclei.

A

Hyoscine hydrobromide

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8
Q

Explain the action of hyoscine hydrobromide.

A

Competitive blockade of muscarinic acetylcholine receptors.

It also acts on the CTZ.

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9
Q

What is hyoscine hydrobromide good for?

A

People who can’t take tablets

Motion sickness (first line for motion sickness)

Bowel obstruction

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10
Q

Side effects of hyoscine hydrobromide

A

Sedation

Memory problems

Glaucoma

Dry mouth and constipation

All due to the muscarinic receptor antagonist acting on the parasympathetic system all throughout the body.

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11
Q

Give examples of H1 receptor antagonists acting on the vestibular nuclei.

A

Cyclizine

Levomepromazine

Cinnirazine

Promethazine

Diphenhydramine

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12
Q

Explain the action of H1 receptor antagonists

A

Inhibits histaminergic signals from the vestibular system to the CTZ in the medulla.

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13
Q

What are H1 receptor antagonists good for?

A

Motion sickness (second line)

Morning sickness in pregnancy (especially promethazine)

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14
Q

What are H1 receptor antagonists especially not good for?

A

Young children and elderly

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15
Q

Give side effects of H1 receptor antagonists.

A

Sedation

Excitation

Antimuscarinic effects such as dry mouth, constipation and urinary retention.

Cardiac toxicity (long QT interval)

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16
Q

What is serotonin produced by in the gut?

A

Enterochromaffin cells.

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17
Q

Explain serotonins action in the gut.

A

95% of serotonin in the body is found in the gut.

In response to the parasympathetic system serotonin excites enteric neurones.

This leads to smooth muscle contraciton and increases motility.

It also increases gut secretions.

Also regulates appetite

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18
Q

Give examples of 5HT (serotonin) receptor antagonists.

A

Reduces GI motility

Reduces GI secretions

Also acts to inhibit the CTZ

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19
Q

What is 5HT receptor antagonists good for?

A

Almost everyone is often a 1st line treatment due to the very uncommon side effects.

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20
Q

Side effects of 5HT receptor antagonists.

A

Constipation

Headache

Elevated liver enzymes

Long QT syndromes

Extra-pyramidal effects such as dystonia and parkinsonism

They are uncommon as most of the serotonin is found in the gut.

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21
Q

Give examples of D2 receptor antagonists acting in the gut.

A

Metoclopramide

Domperidone

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22
Q

Explain the action of metoclopramide.

A

Increases ACh at the muscarinic receptors in the gut.

This promotes gastric emptying and leads to a higher tone of the lower oesophageal sphincter.

Increases tone and the amplitude of contractions.

Decreases tone of pylorus so it opens.

Increases peristalsis

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23
Q

What is metoclopramide good for?

A

GORD

Ileus

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24
Q

What is ileus?

A

When the gut goes to sleep

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25
Side effects of metoclopramide.
Galactorrhoea via prolactin release Extra-pyramidal effects such as dystonia and parkinsonism. They are especially bad in children and old people.
26
Special side effects of domperidone.
Similar mechanism to metoclopramide. However specific side effects sudden cardiac death (long QT and VT) Galactorrhoea
27
What is domperidone especially good for?
Improving lactation in breastfeeding mothers.
28
Give examples of D2 receptor antagonists acting on the CTZ that are also antipsychotics.
Prochlorperazine Chlorpromazine Levomepromazine Haloperidol
29
Explain the action of prochlorperazine, chlorpromazine, and levomepromazine.
They act on the CTZ to block the D2 receptor. It can also block the H1 receptor and the muscarinic receptors.
30
What is prochlorperazine, chlorpromazine and levopromazine good for?
Motion sickness and vertigo Prochlorperazine can be used in pregnancy.
31
Action of haloperidol.
Acts on the CTZ to block the D2 receptor. It is especially good in chemotherapy and in palliation.
32
Side effects of the D2 receptor antagonists.
Extra-pyramidal effects such as dystonia and parkinsonism. Sedation Hypotension
33
Give examples of corticosteroids acting on the CTZ.
Dexamethasone Methylprednisolone
34
What are corticosteroids good for related to anti-emesis?
Perioperative nausea and vomiting Chemotherapy Palliation
35
Side effects of corticosteroids.
Increased appetite Increased blood sugar Insomnia
36
Give an example of a cannabinoid.
Nabilone
37
What is nabilone used for?
Last line chemotherapy
38
Side effects of nabilone.
Drowsiness Dizziness
39
Give examples of neurokinin 1 receptor antagonists.
Aprepitant Fosaprepitant Netupitant
40
Explain the action of neurokinin 1 receptor antagonists.
Prevents the action of substance P (which is usually excitatory) at the CTZ and also in peripheral nerves. It also boosts the effects of 5HT3 receptor antagonists. Also have anxiolytic properties as well as antidepressant.
41
What are neurokinin 1 receptors antagonists good for?
Chemotherapy and especially in delayed emesis.
42
Side effects of neurokinin 1 receptor antagonists.
Headache Diarrhoea Constipation Steven-Johnson syndrome
43
1 st line for motion sickness
Hyoscine hydrobromide (muscarinic receptor antagonist) Cinnirazine can also be used and typically has fewer side effects.
44
When should domperidone or metoclopramide be given? (D2 receptor antagonists)
GORD Ileus
45
When should domperidone and metoclopramide **not** be given?
When there is a history or current bowel obstruction or perforation.
46
What is the medication pathway for almost any GI problem where anti-emetics are needed?
Ondansetron first line (5HT3 receptor antagonist) +/- Cyclizine (H1 receptor antagonist) after that add Dexamethasone.
47
Give an example of a hormone related to pregnancy that is a direct trigger of the CTZ.
beta-hCG in hyperemesis gravidarum
48
Give examples of drugs that are direct triggers on the CTZ.
Chemotherapy Anaesthetics Opiates
49
Explain hyperemesis gravidarum.
A rapid rise in beta-hCG that stimulates the CTZ making the patient sick. This is typically weeks 4-16 however it can persist. There is a higher risk with multiple pregnancies and **is not just morning sickness**.
50
Give signs associated with hyperemesis gravidarum.
Dehydration Weight loss Electrolyte imbalance Urinary ketones
51
Medication pathway of hyperemesis gravidarum.
Promethazine or Prochlorperazine then add Metoclopramide then add ondansetron.
52
What is the risk of ondansetron in pregnancy?
Can lead to cleft lip and cleft palate
53
Medicaton pathway in low risk chemotherapy
Dexamethasone
54
Medication pathway in moderate risk chemo
Dexamethasone and ondansetron
55
Medication pathway in high risk chemo.
Dexamethasone, ondansetron and aprepitant.
56
Risk factors of post-operative nausea and vomiting.
Female Young age Non smoke General anaesthetics Nitrous oxide PO opioids Long duration of surgery Laparoscopic surgery
57
How does medication regiment change with risk of emesis in of post-operative nausea and vomiting?
Low risk you just wait and see Moderate risk you pick 1 or 2 anti-emetic agents High risk pick more than 2 anti-emetic agents.
58
Give an example of medication used to treat diarrhoea.
Opioid receptor agonists
59
Give examples of opioid receptor agonists used to treat diarrhoea.
Loperamide Codeine Morphine
60
Explain the action of loperamide.
Specific action on u-receptors in the **myenteric plexus** leading to a decrease in tone of longitudinal and circular smooth muscle. It also reduces peristalsis but increases segmental contraction. This all leads to decreased colonic mass movement and suppression of gastrocolic reflex.
61
Explain the difference in action of codeine and morphine compared to loperamide.
Affects not only u receptors but also delta receptors.
62
When would codeine and morphine be used to treat diarrhoea?
When the patient is in pain as well
63
Side effects of opioid receptor agonists.
Paralytic ileus Nausea and vomiting Sedation and addiction.
64
Give examples of food that can cause constipation or treat diarrhoea.
Bananas White rice (binds stool) White bread and pasta (low in fibre)
65
Foods to avoid in diarrhoea.
Limit fruit to 3 portions a day Avoid caffeine, sorbitol, fatty or spicy foods and fizzy drinks.
66
What dietary changes are done to avoid constipation?
Drink more water Increase fibre intake by eating wholegrain foods, fruit, vegs, nuts and pulses. **Regular exercise**
67
How can conspitation be treated medically?
Laxatives and enemas
68
Give examples of actions of laxatives.
Osmotics Stimulants Bulk forming Stool softeners
69
Give examples of actions of enemas
Osmotics Stimulants
70
Give examples of osmotic laxatives
Lactulose Movicol Cosmocol
71
Explain the action of osmotic laxatives.
Draws fluid in (lactulose) or Retain fluid that they came with like movicol
72
Give examples of stimulant laxatives.
Bisacodyl Sodium picosulphate Senna Co-danthromer Docusate sodium
73
Explain the action of stimulant laxatives.
Increases that intestinal motility and may be given orally or per rectum.
74
Give examples of bulk forming laxatives.
Also called medicinal fibres such as ispahgula husk or methylcellulose
75
Give examples of stool softeners.
Docusate sodium Glycerin suppository Arachis oil Liquid paraffin
76
Explain the action of stool softeners
Decrease surface tension of stool Increase penetration of fluid into stool
77

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