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(UNI) Neuropharmacology (3rd Year) > Nausea and Vomiting > Flashcards

Nausea and Vomiting Flashcards

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1
Q

Define nausea.

A

(Prodromal) conscious recognition that the vomiting centre has been stimulated.

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2
Q

Define vomiting.

A

the forcible ejection of the stomach contents through the mouth.

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3
Q

For what reasons may one be stimulated to vomit?

A
  • Defence, upon injection of toxic substances.
  • Bacterial and viral infection.
  • Vestibular disorders (motion sickness and Meniere’s disease).
  • Pregnancy (usually 1st trimester, can be hyperemesis gravidarum [must be resolved]).
  • Iatrogenic (drug induced) – chemo, Parkinson’s medication.
  • Migraine.
  • Deranged biochemistry (hypercalcaemia, uraemia).
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4
Q

What is the chemoreceptor trigger zone?

A

The chemoreceptor trigger zone (CTZ) consists of twin areas in the floor of the 4th ventricle, partially outside of the BBB. It detects noxious ingested chemical stimuli and can be stimulated centrally by parenteral drugs. The CTZ stimulates the vomiting centre.

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5
Q

Where is the vomiting reflex controlled centrally?

A

The vomiting reflex is regulated centrally by a ‘central pattern generator for vomiting’ (location in the brain unknown) and the chemoreceptor trigger zone (CTZ) [D2 and 5HT3].

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6
Q

Which parts of the brain are involved in the vomiting reflex?

A

• CTZ (area postrema) sensitive to circulating chemical stimuli (humoral factors).
• The area postrema neurones projects into the nucleus tractus solitarius, which receives input from:
o The vagus nerve.
o Enterochromaffin.
o Vestibular system.
o Limbic system.

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7
Q

Give some central triggers for nausea and vomiting.

A
  • Raised intracranial pressure.
  • Dilation of arteries (migraines).
  • Sight, smell, and taste.
  • Stimulation of labyrinthine mechanisms.
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8
Q

Give some peripheral triggers from nausea and vomiting.

A 
•	Gastric dysrhythmias.
•	Motion sickness.
•	Delayed gastric emptying.
•	Gastric mucosal irritation (NSAIDS).
o	Via all vagal afferents.
•	Dilation and obstruction of GIT.
o	Via sympathetic and vagal afferents.
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9
Q

Which receptors are involved in nausea and vomiting?

A

• Acetycholine (muscarinic) [mACh].
• Histamine [H1].
• 5-Hydroxytryptramine [5-HT3, 5-HT2, 5-HT4].
• Dopamine [D2].
• Substance P (Neurokinin-1 receptors in CTZ).
Also:
• Enkephalins (CTZ, µ and δ opioid receptors).
• Cannabinoids.

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10
Q

What classes of drugs are used to treat nausea and vomiting?

A

Histamine antagonists, muscarinic acetylcholine receptor antagonists, phenothiazine related drugs, benzamides, selective 5HT3 antagonists, cannabinoids, corticosteroids, neurokinin 1 receptor antagonists.

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11
Q

Give some examples of hustamine antagonists that are used to treat nausea and vomiting.

A
  • Cyclizine (H1, mACh).
  • Cinnarizine (H1, mACh).
  • Promethazine (D2, H1, mACh).
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12
Q

What receptors does cyclizine act upon?

A

H1, mAch.

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13
Q

What receptors does cinnarizine act upon?

A

H1, mACh.

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14
Q

What receptors does promethazine act upon?

A

D2, H1, mACh.

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15
Q

What causes of nausea and vomiting are histamine antagonists used to treat?

A

These are often used in nausea and vomiting of pregnancy, having general anti-emetic activity but little activity at the CTZ. They are also used in motion sickness and vestibular disorders.

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16
Q

Where do histamine antagonist antiemetics act in the body?

A

They act at the vestibular nuclei and have some action at the central pattern generator for vomiting.

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17
Q

What side effects can histamine antagonist antiemetic drugs have?

A

These anti-emetic drugs cause drowsiness and sedation.

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18
Q

Give an example of drugs in the class muscarinic acetylcholine receptor antagonists used as antiemetics.

A

Hyoscine hydrobromide.

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19
Q

What causes of nausea and vomiting are muscarinic acetylcholine receptors used to treat?

A

Motion sickness.

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20
Q

Where in the body do muscarinic acetylcholine receptor antagonists work?

A

They work on the muscarinic receptors in the vestibular nuclei and the central pattern generator for vomiting.

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21
Q

In what forms can muscarinic acetylcholine receptor antagonists be found?

A
  • Transdermal patches - apply several hours before traveling as they have slow absorption.
  • Chewable tablets.
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22
Q

Why should transdermal patches for travel sickness be administered several hours before travel?

A

To allow for absorption and action as they have slow absorption.

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23
Q

What side effects do muscarinic acetylcholine receptor antagonists have?

A
  • Dry mouth.
  • Dizziness.
  • Blurred vision.
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24
Q

Why should one be careful when giving muscarinic acetylcholine receptor antagonists to the elderly?

A

One should be careful when giving these drugs to the elderly as the dizziness they can cause may lead to falls and these are more serious in the elderly population.

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25
What drugs in the class of phenothiazine related drugs are used to treat nausea and vomiting?
* Prochlorperazine. * Chlorpromazine. * Trifluoperazine. * Perphenazine. * Haloperidol. * Levomepromazine (5HT2 antagonism). * Olanzapine (5HT2 receptor antagonism).
26
Where do phenothiazine related drugs act in the body?
These drugs are mainly D2 antagonists with central action at the CTZ and may also block H1 and mACh receptors.
27
In what forms can phenothiazine related drugs come in?
* Suppositories. | * Buccal tablets (prochlorperazine).
28
What side effects can phenothiazine related drugs have?
The side effects of this class of drugs include dystonic reactions such as hypotension. These can be painful and potentially upsetting to the patient.
29
What class does metoclopramide fall under?
Benzamides.
30
Describe metoclopramide.
This drug is a D2 antagonist and a 5HT4 agonist, similar to the phenothiazines.
31
Where does metoclopramide at in the body?
• CTZ (central). • GIT (peripheral). o Slowing the GIT.
32
What side effects can be seen with the use of metoclopramide?
• Prolactin release (galactorrhoea). • Movement disorders. o Fatigue. o Motor restlessness. o Spasmodic torticollis (sharp neck muscle movements). o Oculogyric crisis (deviation of the eyes up for a prolonged period). o Treat with procyclidine (anti-muscarinic).
33
Describe domperidone.
Domperidone is a D2 antagonist, related to the phenothiazines.
34
What class of antiemetic agents does domperidone fall under?
Benzamides.
35
Where does domperidone act in the body?
* CTZ (central action). | * GIT (peripheral action).
36
Does domperidone cross the BBB?
No.
37
What is the half-life of domperidone?
4-5 hours.
38
What is one of the main side effects of domperidone?
One of the main side effects of domperidone is QT interval elongation, leading to Torsades des Pointes.
39
Give some drugs that fall under the class selective 5HT3 antagonists.
* Ondansetron. * Granisetron. * Tropisetron. * Dolasetron.
40
Where in the body do selective 5HT3 antagonists act?
These drugs are effective at the CTZ and at vagal afferents in the GI tract. They also act on 5HT3 receptors in the central pattern generator for vomiting.
41
What causes of nausea and vomiting are selective 5HT3 antagonists used to treat?
* Chemotherapy/radiation induced nausea and vomiting. | * Post-operative nausea and vomiting.
42
What are the side effects of selective 5HT3 antagonists?
* Headaches. * Constipation. * Reduced analgesic effect of tramadol.
43
Why arent selective 5HT3 antagonists used much in the clinic?
They are expensive.
44
Give an example of a cannabinoid used to treat nausea and vomiting.
Nabilone.
45
Where in the body does nabilone act?
The CTZ.
46
What can be used to antagonise the activity of nabilone?
Naloxone.
47
What cause of nausea and vomiting is treated by nabilone?
Occasionally for chemotherapy induced nausea and vomiting.
48
What are the side effects of nabilone?
* Drowsiness. * Dysphoria. * Dry mouth. * Visual disturbances.
49
Describe dexamethasone's use in the treatment of nausea and vomiting.
This drug is used usually for chemotherapy induced nausea and vomiting in combination with 5HT3 antagonists (domperidone). It is given in the short term when a course of chemotherapy is administered.
50
The precise mode of action for dexamethasone in nausea and vomiting is unclear, however what may it be mediated by?
Endorphins.
51
Give some examples of naurokinin 1 receptor antagonists used for the treatment of nausea and vomiting.
* Aprepitant. | * Fosaprepitant.
52
How are neurokinin 1 receptor antagonists used in the treatment of nausea and vomiting?
These anti-emetic drugs are licensed for the prevention of acute and delayed nausea and vomiting associated with cisplatin based regimens. They are given with 5HT3 antagonists and dexamethasone.
53
What is the main drawback of neurokinin 1 receptor antagonists as antiemetic agents?
Their cost.
54
How do NK1 antagonists work in nausea and vomiting?
NK1 antagonists work by competing with substance P, an endogenous ligand. This occurs in the area postrema and the nucleus tractus solitarus (NTS); tis interferes with the terminal emetic pathways.
55
What drugs can cause nausea and vomiting through gastric irritation?
Antibiotics, iron, NSAIDS.
56
What drugs can cause nausea and vomiting through causing gastric stasis?
Antimuscarinics, opioids, phenothiazines, tricyclic antidepressants.
57
What drugs cause nausea and vomiting through stimulation of the CTZ?
Antibiotics, cytotoxics, digoxin, opioids, imidazoles.
58
What drugs cause nausea and vomiting through stimulation of 5HT3 receptors?
Antibiotics, cytotoxics, SSRIs.
59
What percentage of patients experience nausea and vomiting as a complication of surgery and anaesthesia?
20-30%.
60
The likelihood of post-operative nausea and vomiting is based upon what risk factors?
* Female. * History of PONV. * Peri-operative (during) opioids. * Type of surgery. * Anaesthetic. * Delayed gastric emptying.
61
Explain how post-operative nausea and vomiting is treated.
Treatment is often done in the form of prophylaxis, given before treatment. Prochlorperazine or cyclizine are commonly used, with 5HT3 antagonists used in high risk patients. Treatment may require a combination of agents.
62
It metoclopramide an affective antiemetic for use in PONV?
No.
63
If a person as two factors from the APFEL score, what is their chance of experiencing PONV?
40%.
64
If a person has more than 2 factors from the APFEL score, what is their chance of experiencing PONV?
60-90%.
65
If antiemetics dont work to treat PONV, what should be done?
Specialist advice should be sought to ascertain the underlying cause.
66
Should the same antiemetic used for prophylaxis of PONV be used to treat PONV?
No.
67
What subtypes of CINV are there?
Anticipatory, acute emesis, delayed emesis, refractory.
68
Define anticipatory emesis with regards to CINV.
a conditioned response that is learnt from the previous chemotherapy cycle.
69
Define acute emesis with regards to CINV.
Occurring up to 24 hours post treatment.
70
Define delayed emesis with regards to CINV.
Up to 120 hours post treatment and subsides gradually.
71
Define refractory emesis with regards to CINV.
No response to treatment, common or acute.
72
What do highly emetogenic chemotherapy regimens often include?
* Cisplatin. * Carmustine. * Dacarbazine.
73
What do moderately emetogenic chemotherapy regimens often include?
* Cyclophosphamide. * Carboplatin. * Doxorubicin.
74
What is CINV treatment based upon?
Local guidelines.
75
How are 5HT3 antagonists used to treat CINV in highly emetogenic regimens of chemotherapy?
Parenterally.
76
How are 5HT3 antagonists used to treat CINV in mildly emetogenic regimens of chemotherapy?
Orally.
77
How can the effect of 5HT3 antagonists be enhanced when treating CINV?
The effect of these drugs can be enhanced with dexamethasone pre chemotherapy, together with lorazepam.
78
How are moderately to highly emetogenic regimens of chemotherapy, resistent to other anti-emetic combinations treated?
A combination of NK1 receptor antagonists (e.g. aprepitant) together with dexamethasone is used to treat moderate to highly emetogenic regimens resistant to other anti-emetic combinations.
79
Explain the cause of motion sickness.
This is caused by the stimulation of the nausea and vomiting pathways via afferent pathways to vestibular nuclei, activating brainstem nuclei. This uses histaminergic and muscarinic pathways. There is often a mismatch between the signals being received from the vestibular centre and visual stimuli in the higher centres.
80
What classes of antiemetic agents are ineffective in the treatment of motion sickness.
D2 and 5HT3 antagonists.
81
When is pregnancy associated nausea and vomiting most common?
Pregnancy associated nausea and vomiting is most common from 4 weeks after last menses to 12 weeks into the pregnancy.
82
What percentage of mothers experience nausea in the first trimester?
More than 80%.
83
What percentage of pregnant mothers experience vomiting in the first trimester?
50%.
84
What percentage of pregnancy associated nausea and vomiting resolve by week 16?
90%.
85
What condition much pregnancy induced nausea and vomiting be distinguished from?
Hyperemesis gravidarum.
86
Define hyperemesis gravidarum.
intractable vomiting 0.5-2% in of pregnancies.
87
What is the cause of pregnancy associated nausea and vomiting?
The cause of pregnancy associated nausea and vomiting is unclear and may be from the placenta (correlating with high levels of HCG).
88
What is the first line for treating pregnancy associated nausea and vomiting?
Not to treat pharmacologically, eat small frequent meals.
89
What drug treatment can be used for pregnancy associated nausea and vomiting?
* Antihistamines – oral promethazine/cyclizine – 24/48 hours. * Metoclopramide/oral prochlorperazine – 24/48 hours.
90
When treating vestibular disorders, as well as treating the nausea and vomiting, what also needs treating?
The underlying cause.
91
In addition to specific treatments, what classes of antiemetics can be used to treat nausea and vomiting in vestibular disorders?
IN addition to specific treatments, antihistamines such as cinnarizine or phenothiazines such as prochlorperazine, may help.
92
In palliative care, what is the first line treatment for biochemical causes of nausea and vomiting and CINV?
Haloperidol (2.5-10mg/24 hour) is used for biochemical causes and opioid induced nausea and vomiting.
93
In palliative care, what treatment is used for non-specific nausea and vomiting?
For non-specific causes, cyclizine (100-150mg/24 hours) can be used.
94
If there is gastric stasis associated with palliative nausea and vomiting, what treatment can be used?
Or one can use metoclopramide (30-100/24 hours) if gastric stasis.
95
What is the second line treatment for palliative nausea and vomiting?
A combination of the first line treatments.
96
What is the third line treatment for palliative nausea and vomiting?
Levomepromazine (5HT2) at a low dose (5-20mg/24 hurs) may be used. This may be infused sc over 24 hours via a syringe driver (or given as STAT SC levomepromazine which has a long half life and may be given OD).

(UNI) Neuropharmacology (3rd Year) (20 decks)

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