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Pharmacology > Anti-Emetics > Flashcards

Anti-Emetics Flashcards

1
Q

What are some of the causes for nausea and vomiting?

A

Gastrointestinal irritation
Infections
Drugs
Radiotherapy / chemotherapy
Motion /travel sickness
Vertigo
Post operative
Psychological
Pregnancy
Intracranial pathology
Migraine

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2
Q

What are the consequences of nausea and vomiting?

A

Dehydration
Malnutrition
Alkalosis / electrolyte imbalance
Aspiration of gastric contents
Wound dehiscence
Reduced drug absorption
Mood changes

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3
Q

What treatments are used for severe and persistent vomiting?

A

Rectal suppositories
Buccal tablets

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4
Q

What systems are affected by vomiting?

A

Oesophagus
Stomach
Upper small intestine
Respiratory system
Diaphragm

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5
Q

What are the four basic steps of vomiting?

A

Relaxation
Contraction
Inspiration
Contraction

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6
Q

What has to relax in order for you to vomit?

A

Oesophagus
Oesophageal & cardiac sphincters
Fundus of stomach

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7
Q

What contracts during vomiting?

A

Duodenum
Pylorus of stomach
Diaphragm and abdominal muscles to compress the stomach
Push contents to exit via the mouth

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8
Q

What is the function of vomiting?

A

It is a defensive response to eliminate toxic irritating material
To empty the upper small intestine and stomach

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9
Q

How well understood is process vomiting?

A

Pathways are poorly defined
Multiple inputs and receptors involved
Key role for chemoreceptor trigger zone and vomiting centre in integration

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10
Q

Where is the chemoreceptor trigger zone found?

A

Located within the area postrema of the 4th ventricle

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11
Q

How can the chemoreceptor trigger zone detect emetic stimuli in the blood and CSF?

A

It lacks an effective blood brain barrier

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12
Q

Where does the chemoreceptor trigger zone receive info from?

A

Vagal afferent input from GI tract
Vomiting centre
Higher centres involved in visual, olfactory and emotional processing

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13
Q

What counts as emetic stimuli?

A

Bacterial toxins
Cytotoxic drugs
Mechanical distension

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14
Q

What is released due to activation by emetic stimuli?

A

Serotonin from enterochromaffin cells in the gut

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15
Q

What are enterochromaffin cells?

A

Neuroendocrine cells found in the gastric mucosa in the vicinity of parietal cells

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16
Q

What do enterochromaffin cells do?

A

Aid in the production of gastric acid via histamine release

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17
Q

What and where is the vomiting centre?

A

A collection of effector nuclei found in the medulla oblongata

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18
Q

Where does the vomiting centre receive inputs from?

A

Gut
Chemoreceptor trigger zone
Cardiovascular system
Limbic nuclei

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19
Q

What sort of information is passed on from the limbic nuclei?

A

Olfactory
Emotional
Hormonal
Stress
Pain
Anticipatory inputs

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20
Q

What does the vomiting centre do?

A

Coordinates visceral and somatic components of the emetic reflex

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21
Q

What are some of the treatments of nausea and vomiting?

A

Gastro-prokinetic agents
Sphincter modulators
5HT3 antagonists
Histamine antagonists
Muscarinic antagonists
Dopamine antagonists
Cannabinoids
Benzodiazepines

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22
Q

What treatments targets the higher centres pathway of vomiting?

A

Benzodiazepines

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23
Q

What pathway do 5HT3 antagonists target?

A

Stomach inputs to:
Chemoreceptor trigger zone
Vomiting centre

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24
Q

What treatments target the pathway from the chemoreceptor trigger zone to the vomiting centre?

A

Histamine, muscarinic, dopamine antagonists
Cannabinoids

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25
Q

What anti emetics are used for motion sickness and vertigo?

A

Muscarinic antagonists
Antihistamines

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26
Q

Give an example of a muscarinic antagonist used for vomiting

A

Hyoscine

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27
Q

What are the side effects of muscarinic antagonists?

A

Variable sedative and anti muscarinic side effects:
Dry mouth
Blurred vision

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28
Q

Give two examples of anti histamines used as ant emetics

A

Meclozine
Cinnarizine

29
Q

What is the side effect associated with anti histamines?

A

Sedation / sedative effects

30
Q

What is metocloperamide?

A

An anti emetic
Antagonist of D2 and 5HT3 receptors
Agonist of 5HT4 receptors

31
Q

When is metocloperamide used?

A

Emesis related to
hepatic/gastro-duodenal illness
Migraine
Chemo/ radio therapy
Initial emesis due to opioid analgesia in palliative care

32
Q

What does metacloperamide do?

A

Facilitates gastric emptying
Some effects on the chemoreceptor trigger zone

33
Q

What are the side effects associated with metocloperamide use?

A

Sedative
Prolactin release (menstrual disorders)
Extra pyramidal effects (D2)

34
Q

Describe the extra pyramidal side effects of metocloperamide

A

Dystonia - dragging leg / pulling of neck / difficulty speaking
Motor impairment
Muscle spasms
Rigidity

35
Q

What receptors does promethazine target?

A

Antagonism of:
M
H
D
5HT
Adrenoceptors
Chemoreceptor trigger zone

36
Q

What is promethazine useful?

A

Motion sickness
Pregnancy
Chemotherapy induced
Post operative vomiting

37
Q

What are the side effects of promethazine?

A

Sedative
Dystonic reactions

38
Q

What is olanzapine?

A

An atypical antipsychotic
Also useful as an anti emetic

39
Q

What receptors does olanzapine target?

A

Antagonism of
Dopamine
5HT
Histamine
Muscarinic
Adrenoceptors
Action on chemoreceptor trigger zone

40
Q

What is olanzapine mainly used to treat?

A

Breakthrough chemotherapy induced nausea and vomiting (CINV)

41
Q

What are side effects of using olanzapine?

A

Sedative
Dystonic reactions
Weight gain
Metabolic disturbances

42
Q

What receptors does doperidone interact with?

A

Chemoreceptor trigger zone D2/D3

43
Q

When is domperidone used?

A

To limit emesis associated with dopamine agonists in Parkinson’s disease
CINV?

44
Q

Why is domperidone less efficient than metocloperamide and promethazine?

A

It does not cross the blood brain barrier as readily as

45
Q

Is there a positive to taking domperidone?

A

Less sedative effects and less dystonia

46
Q

What drugs block the 5HT3 receptors in the GI tract?

A

Ondansetron
Granisetron
Ramosetron
Palonosetron

47
Q

When are serotonin antagonists used?

A

Acute chemo / radio therapy induced
Post operative emesis

48
Q

How is the desensitisation to 5HT3 antagonists overcome?

A

Adding corticosteroid (dexamethasone)
Mechanism unclear

49
Q

What are the side effects of ondansetron, granisetron and ramosetron?

A

Mild headaches
Constipation
Increased risk of QT wave prolongation
Cardiac dysrhythmias

50
Q

What is palonosetron?

A

2nd generation 5HT3 antagonist
Highly selective competitive antagonist with additional ‘allosteric’ antagonism

51
Q

What does palonosetron do?

A

Promotes receptor internalisation
Reduces receptor cross talk

52
Q

What are the benefits to using palonosetron?

A

Increased benefit in delayed benefit following CINV & PONV
Increased duration of action
Does not prolong QT interval

53
Q

What does dexamethasone do?

A

Anti inflammatory influence
Reduces pain
Reduces need for pro emetic opioids

54
Q

What does dexamethasone act on?

A

Direct action on Solitary tract nucleus
Interaction with Serotonin and tachykinin signalling pathways
Regulation of hypothalamic pituitary adrenal axis

55
Q

What are the two broad spectrum anti emetic drugs?

A

Aprepitant
Fosaprepitant (prodrug if Aprepitant)

56
Q

How do broad spectrum any emetics work?

A

Direct inhibition of substance P / neurokinin receptors in vomiting centre and terminal pathways

57
Q

What are broad spectrum anti emetic useful for?

A

Vomiting caused by
Peripheral / central emetic stimuli
Delayed emesis of chemo
Effective relief of nausea

58
Q

What are the side effects of aprepitant and fosaprepitant?

A

Flatulence
Hiccups
Fatigue
Drug interactions

59
Q

What is an example of a combination therapy used for vomiting?

A

5HT3 antagonist
NK1 antagonist
Dexamethsone
+ metocloperamide for breakthrough symptoms

60
Q

When are combination therapies used?

A

As prophylaxis in those at higher risk of CINV and PONV
Effective in 70-80% of acute and delayed phases

61
Q

What sort of sedatives and hypnotics are used for anticipatory anti emesis?

A

Barbiturates - phenobarbital
Benzodiazepines - midazolam

62
Q

What are risks associated with sedatives and hypnotics?

A

Increased risk of vomiting associated asphyxia due to a decreased level of consciousness

63
Q

What is nabilone?

A

A synthetic derivative of Cannabinoid found in marihuana

64
Q

When are Cannabinoids used?

A

An effective prophylaxis for CINV
Possible anxiolytic properties aswell

65
Q

What receptors do nabilone target?

A

CB1 in cerebral cortex
Area postrema (chemo trigger zone)
Solitary nucleus
CB2 in brainstem

66
Q

What are the side effects of using Cannabinoids?

A

Dysphoria
Hallucinations
Disorientation
Dizziness
Sedation
Dry mouth

67
Q

What are some of the non drug approaches that can be used in nausea and vomiting?

A

Ground ginger
Hypnosis
Fluid/ electrolyte replacement
Improving nutrition
Acupuncture

68
Q

How does acupuncture help?

A

Stimulation of P6 acupoint on the wrist
Useful in PONV
reduced need for rescue and breakthrough therapies

69
Q

Why is emesis discouraged in a patient who may have ingested a poison or corrosive?

A

There could be more damage done by the vomit and poison travelling back up the GI tract

Pharmacology (18 decks)

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