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Clinical Pharmacology > 10.2 Antiemetics > Flashcards

10.2 Antiemetics Flashcards

1
Q

what is vomiting?

A

involuntary forceful expulsion of gastric contents through the mouth

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2
Q

what is the difference between vomiting and regurgitation?

A

vomiting is a forceful expulsion through the mouth and is a protective mechanism to remove any toxins and avoid unpleasant situations.
Regurgitation is a mechanical problem usually due to overflow. food or liquid has not yet got to the stomach

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3
Q

describe the mechanism of vomiting? (7)

A
  1. vomiting centre in the medulla signals for us to vomit
  2. nausea, salivation and sweating occur
  3. retrograde peristalsis
  4. deep inspiration
  5. closure of glottis
  6. abdominal muscles contract
  7. lower oesophageal sphincter relaxes
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4
Q

how is the vomiting centre in the medulla stimulated?

A 
the vomiting centre is triggered by the chemoreceptor trigger zone. The chemoreceptor trigger zone can be stimulated by:
sensory afferents via the midbrain 
vestibular nuclei 
visceral afferents from the gut 
direct triggers
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5
Q

what is the chemoreceptor trigger zone?

A

The chemoreceptor trigger zone (CTZ) is an area of the medulla oblongata that receives inputs from blood-borne drugs or hormones, and communicates with other structures in the vomiting center to initiate vomiting. It is located in the floor of the fourth ventricle

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6
Q

what agents act of the vestibular nuclei?

A

muscarinic receptor antagonists

H1 receptor antagonists

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7
Q

give an example of a muscarinic receptor antagonist

A

hyoscine bromide

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8
Q

describe the mechanism of action of hyoscine bromide

A

competitive blockade of the muscarinic acetylcholine receptors. Act as an antiemetic by blocking these receptors in the vestibular nucleus.

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9
Q

what are the indications for hyoscine bromide?

A

antiemetic

  • good for people who cant take tablets as can be given as a patch
  • motion sickness
  • bowel obstruction
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10
Q

what are the side effects of hyoscine bromide?

A

sedation
memory problems
glaucoma
dry mouth and constipation as blockage of the parasympathetic nervous system means sympathetic like effects.

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11
Q

give an example of H1 receptor antagonists

A 
cyclizine 
levomepromazine
cinnirazine 
promethazine
diphenhydramine
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12
Q

what is the mechanism of action of H1 receptor antagonists

A

acts centrally on the vestibular nuclei to inhibit the histaminergic signals from the vestibular system to the chemo receptor trigger zone in the medulla.

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13
Q

what are the indications of H1 receptor antagonists?

A

motion sickness - long plane journeys

promethazine - morning sickness in pregnancy

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14
Q

why might cyclizine be contraindicated?

A

contraindicated in little old ladies and children as causes confusion
should be avoided in patients susceptible to anticholinergic effects such as those with prostatic hypertrophy ( who may develop urine retention )

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15
Q

what are the main side effects for H1 receptor antagonists?

A

sedation
excitation
antimuscarinic - dry mouth, constipation, urinary retention
cardiac toxicity

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16
Q

what agents act on the visceral afferents of the gut?

A

5HT3 receptor antagonists

D2 receptor antagonists

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17
Q

describe the role of serotonin in the gut

A

95% of serotonin is located in the gut. It is produced by enterochromaffin cells in response to parasympathetic stimulation as serotonin excites the enteric neurones and therefore causes increased smooth muscle contraction in the gut but not in the stomach to increase motility and increase gut secretions. Its main role is to regulate appetite

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18
Q

give some examples of 5HT3 receptor antagonists?

A

ondansetron
granisetron
palonosetron

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19
Q

describe the mechanism of action of ondansetron

A

ondansetron is a 5HT3 receptor antagonist (serotonin receptor)
it acts peripherally to reduce GI motility and secretions
it acts centrally to inhibit the chemoreceptor trigger zone

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20
Q

what are the indications for ondansetron?

A

vomiting and nausea - often the first line treatment

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21
Q

what are the common side effects for ondansetron?

A 
constipation
headache
elevated liver enzymes
long QT interval 
extra-pyramidal effects - dystonia, parkinsonism
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22
Q

what antiemetics should not be given to a patient with parkinsons disease?

A

5HT3 receptor antagonist

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23
Q

give some examples of D2 receptor antagonists that act on the visceral afferents of the gut

A

metoclopramide

domperidone

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24
Q

what is the mechanism of action of metoclopramide?

A

increases Ach in muscarinic receptors in the gut
promotes gastric emptying by increasing tone at the LOS (making it close), increasing tone and amplitude of gastric contractions and decreasing tone of pylorus so it opens. It acts to increase peristalsis

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25
Q

what are the common indications for metoclopramide?

A

GORD

Ileus

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26
Q

what is ileus?

A

when bowels are inflamed, often after being handled during surgery, peristalsis can stop. This results in the patient presenting a bit like there is an obstruction even through there is no mechanical blockage.

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27
Q

what are the main side effects of metoclopramide

A

galactorrohoea via prolactin release

extra-pyramidal effects - dystonia and parkinsonism

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28
Q

why is metoclopramide used preferentially to domperidone?

A

as domperidone has shown increased risk of cardiac side effects than metoclopramide

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29
Q

what are the common indications for domperidone?

A

imporving lactation in breastfeeding mothers

- rarely used as antiemetic - metoclopramide used preferentially

30
Q

what are the side effects of domperidone?

A

sudden cardiac death (QT prolonged and VT)

galactorrhoea

31
Q

what agents act on the CTZ?

A 
5HT3 receptor antagonists 
H1 receptor antagonists 
Muscarinic receptor antagonists 
D2 receptor antagonists 
Corticosteroids 
Cannabinoids 
nk1 receptor antagonists
32
Q

give some examples of D2 receptor antagonists that act on the CTZ?

A

prochlorperazines
chlorpromazine
levomepromazine
haloperidol

33
Q

what are the indications for procholrperazine?

A

motion sickness
vertigo
pregnancy sickness

34
Q

what are the indications for haloperidol?

A

good as an antiemetic during chemotherapy and palliation

35
Q

what are the side effects of D2 receptor antagonists that act on the CTZ?

A

extra-pyrimidal effects - dystonia and parkinsonism
sedation
hypotension

36
Q

what are the indications of corticosteroids as antiemetics?

A

perioperative nausea and vomiting
chemotherapy
palliation

37
Q

what are the side effects of corticosteroids

A

insomnia
increased appetite
increase blood sugar

38
Q

give some examples of corticosteroids prescribed as antiemetics?

A

dexamethasone

methylprednisolone

39
Q

what is nabilone?

A

nabilone is a cannabinoid that is used last line as an antiemetic in for chemotherapy. its side effects include dizziness and drowsiness

40
Q

give some examples of neurokinin 1 receptor antagonists

A

aprepitant
fosaprepitant
netupitant

41
Q

what is the action of neurokinin 1 receptor antagonists?

A

prevent the action of substance P at CTZ and in peripheral nerves
anxiolytic and antidepressant properties

42
Q

what are the common indications for aprepitant?

A

delayed emesis after chemotherapy

43
Q

what are the common side effects of neurokinin 1 receptor antagonists?

A

headache
diarrhoea/constipation
stevens-johnson syndrome

44
Q

what is stevens-johnsons syndrome?

A

A severe inflammatory eruption of the skin and mucous membranes, usually occurring after an infection, with malignancy, or as an allergic reaction to drugs or other substances.

45
Q

what antiemetics are used in motion sickness?

A

hyoscine hydrobromide

cinnirazine if driving as less sedatory side effects

46
Q

what are the indications for inserting a nasogastric tube?

A

when gut problems are causing repeated emesis
- relieves the pressure off the gut and eases the process of vomiting making patient more comfortable and allowing tracking of fluid balance. Practical for bowel obstruction and ileus

47
Q

what are prokinetics and how are they used?

A

prokinetics are drugs that increase peristalsis and gut secretions. These include drugs such as domperidone and metoclopramide (D2 receptor antagonists that act on the visceral afferents of the gut). Used in GORD and ileus treatment. Not used for obstruction or when there is risk of perforation

48
Q

what antiemetics are used in the treatment of emesis due to gut problems?

A

ondansetron and/or cyclizine

then add some dexamethosone

49
Q

what are some examples of direct triggers of the CTZ?

A

hormones - Bhcg

drugs - chemotherapy, anaesthetics, opiates

50
Q

what is hyperemesis gravidarum?

A

Hyperemesis gravidarum (HG) is a pregnancy complication that is characterized by severe nausea, vomiting, weight loss, dehydration, urinary ketones. Feeling faint may also occur. Caused by rapic rise in Bhcg that stimulates the CTZ directly. Typically occurs in weeks 4 to 16 but may continue beyond. There is a higher risk with mutliple pregnancies (twins)

51
Q

what is used to treat hyperemesis gravidarum?

A

promethazine or prochlorperazine
then add metoclopramide
then add ondansteron

52
Q

why is ondansetron only used as a very last resort in hyperemesis gravidarum?

A

as there is evidence that it increases the occurrence of cleft lip and palate. only used if the hyperemesis gravidum is severe and benefits outweigh the risks

53
Q

what is used in the treatment of chemotherapy emesis?

A

dexamethosone
then add ondansetron
then add aprepitant
use metoclopramide as a rescue

54
Q

what are risk factors of post-operative nausea and vomiting?

A

patient - female, history of PONV or motion sickness, younger age, non smoker
anaethetic - general, volatile anaesthetic gases or nitrous oxide, post-operative opioids
surgery - duration of operation, laparoscopic surgery

55
Q

what is used for treatment of post-operative nausea and vomiting?

A

ondansetron and/or cyclizine

and then add dexomathasone

56
Q

what is diarrohoea?

A

change in consistency - more fluid
increased frequency of stools
different in comparison to individuals normal bowel habit

57
Q

what are some of the causes of diarrhoea?

A

infective gastroenteritis - viral, bacterial, protozoal
toxin mediated - lactose intolerance, drugs, alcohol,
systemic issues - thyrotoxicosis, IBS, anxiety, overflow incontinence, inflammatory bowel disease, malabsorption, CF, bowel cancer

58
Q

give some examples of opioid receptor agonists?

A

loperamide
codeine
morphine

59
Q

describe the mechanism of action of loperamide

A

a opioid receptor agonist that is specific to mu receptors in the myenteric plexus. Transit of bowel contents is slowed as the tone of the longitudinal and circular smooth muscle in decreased, reducing peristalsis. Sphincter tone is increased. decreases colonic mass movement by suppressing gastrocolic reflex. This allows more time for water absorption.

60
Q

how do codeine and morphine differ from loperamide?

A

loperamide only acts on mu receptors in the gut and therefore does not act on the CNS
morphine and codeine act on mu and delta receptors and therefore have central and peripheral effects. more commonly used when patients also have pain due to analgesic effects

61
Q

what are the side effects of opioid receptor agonists?

A

paralytic ileus
nausea and vomiting
sedation and addiction (codeine and morphine)

62
Q

what is the constipating diet?

A

a diet for those with long term loose stools - IBS, IBD, short bowel, hypermotility and drug side effects

63
Q

what foods slow down the bowel and are in the constipating diet?

A

bananas
white rice
white bread
pasta

64
Q

what foods should be avoided in the constipating diet?

A

only 3 pieces of fruit

avoid caffeine, sorbitol, fatty or spicy food and fizzy drinks

65
Q

what is the purpose of probiotics?

A

re-instate a balanced intestinal flora

66
Q

what diet and lifestyle changes are advised to patients with chronic idiopathic constipation?

A

drink more water
increase fibre intake
regular exercise
toilet routine and positioning

67
Q

what medications are used to treat constipation?

A

laxatives - osmotic, stimulants, bulk forming

enemas - osmotic, stimulants

68
Q

what are the 2 different types of osmotic laxatives ?

A

draw fluids in - lactulose

retain the fluid they came in/ prevent reabsorption - macrogols (movicol and cosmocol)

69
Q

give 2 examples of stimulant laxatives?

A

both increase intestinal motility

  • docusate sodium acts as stimulant and stool softener
  • glycerin suppositories cause rectal irritation and lubrication
70
Q

what are bulk forming laxatives?

A

medicinal fibre to soften stool and bulk up. Examples are ispaghula husk
methylcellulose

71
Q

what are stool softeners?

A

stool softeners act to decrease the surface tension of stool and increase the penetration of fluid into the stool. examples are docusate sodium and glycerin suppository

Clinical Pharmacology (26 decks)

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