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pharmacology 2 > pharmacology of nausea and vomiting > Flashcards

pharmacology of nausea and vomiting Flashcards

1
Q

vomiting centre

A

multiple distributed nuclei in the brainstem
located within the lateral medullary reticular formation
coordinates complex act of vomiting

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2
Q

four sources of afferent input into the vomiting centre

A
  • chemoreceptor trigger zone
  • vestibular system
  • vagal and spinal afferent nerves from GI tract
  • CNS
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3
Q

chemoreceptor trigger zone

A

caudal end of the forth ventricle within the area postrema, outside the blood brain barrier
responds to etoogenic stimuli from blood or CSF (drugs/toxins)

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4
Q

vestibular system

A

semicircular canals
motion sickness via CN 8
muscarinic and histamine receptors

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5
Q

vagal and spinal afferent nerves from GI tract

A

rich in 5-HT3 receptors
irritation to the mucosal results in release of mucosal serotonsis by enterochroomaffin (EC) cells
afferents to vomiting centre as well as CTZ

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6
Q

CNS inputs to vomiting centre

A

raised intracranial pressure

anxiety/stress

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7
Q

nausea

A

conscious recognition of the excitation of an area closely related to the vomiting centre
often prodrome of vomitting - not always

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8
Q

vomiting is created by

A

motor impulses that originate in the vomiting centre
peristalsis in the upper GI tract is reversed and halted in the lower GI tract
cranial nerves close epiglottis
diaphragm and abdominal muscles also required

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9
Q

non-pharmacological considerations of avoiding nausea and vomiting

A

avoiding strong odours
open area with air movement
diet - small amount to prevent distention,
- avoid spicy, rich, fatty and very sweet foods
- ginger thought to prevent vomiting

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10
Q

metoclopramide

A

metoclopramide

  • multiple mechanisms of action
  • enhances response to acetylcholine in the upper GI tract which slows peristalsis
  • blocks dopamine receptors in the CTZ
  • at higher doses also blocks CTZ serotonin receptors
  • multiple routes of administration PO/SV/IV/IM
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11
Q

adverse effects of metoclopramide

A

extrapyramidal symptoms - more common in younger patients and female patients
rarely causes tardive dyskinesia, higher risk with longer treatment

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12
Q

tardive dyskinesia

A

repetitive jerking movements that occur in the face neck and tongue

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13
Q

metoclopramide should not be used in patients with

A

Parkinson’s disease

suspected complete mechanical bowel obstruction duet to pro kinetic effects

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14
Q

prochlorperazine

A

a piperazine phenothiazine antipsychotic
antiemetic effects via dopamine and muscarinic receptor antagonism
subcutaneous administration not recommended due to irritation
risk of extrapyramidal side effects and it should not be used in Parkinson’s disease

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15
Q

what are extrapyramidal symptoms

A

involuntary movements, tremors or muscle contractions

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16
Q

prochlorperazine side effects

A

extrapyramidal side effects

should not bemused in Parkinson’s

17
Q

domperidone

A

dopamine antagonist

  • active peripherally
  • still effective at the CTZ because it lies outside the blood brain barrier
  • blocks dopamine receptos in the upper GI tract resulting in increased motility
  • oral
  • generally well tolerated
18
Q

domperidone side effects

A
  • increased prolactin levels

- may be confused for a cancer

19
Q

blood brain barrier

A

a monolayer of endothelial cells that are joined by tight junctions with a thick basement membrane and astrocytic end feet
multiple control mechanisms

20
Q

control mechanisms in the BBB

A
  • transmembrane diffusion - lower molecular weight, lipid soluble, no charge
    transport systems - both influx and efflux pumps, receptor mediated transcytosis, carrier mediated
    transcellular pathway
21
Q

5HT3 antagonists

A

ondansetron, granisetron, palonosetron
peripheral and central mechanism of action
- major effect is to block released serotonin in the upper GI tract
- micro effect is at the vomiting centre and CTZ
- mainly work on causes that relate too irriatation of the upper GI tract eg. post-operative, radiotherapy, and chemotherapy

22
Q

5HT3 antagonists side effects

A

constipation, headache, fatigue

23
Q

glucocorticoids

A

eg. dexamethasone
most commonly used in chemotherapy and peri-operative setting, usually in combination with other drugs
- exact method of anti-emetic effect unknown
- reduced peri-tumoural oedema in cases of raised intracranial pressure secondary to brain tumour
- oral and IV doses are equivalent

24
Q

side effects of glucocorticoids

A

short term - increased blood sugar levels, hunger, increased blood pressure
neuropsychiatric irritability and psychosis
long term - osteoporosis, steroid induced diabetes mellitus, proximal myopathy, thin skin

25
Q

aprepitant

A

highly selective neurokinin receptor NK-1 antagonist which readily crosses the BBB

  • blocks the effects of substance P which normally binds this receptor
  • oral- used in combination with 5HT3 antagonists and dexamethosome in the prevention of nausea and vomiting from mod-highly emetogenic chemotherapy
  • three day regimen
26
Q

side effects of aprepitant

A

associated with fatigue, dizziness and diarrhoea

27
Q

fosaprepitant

A
  • IV formulation is a prodrug

- rapidly metabolised to aprepitant by many tissue types in vitro

28
Q

hyoscine

A

anticholinergic at muscarinic receptor

  • minor histamine and serotonin antagonism
  • PO/IV/transdermal formulations
  • can be used as a patch for the prevention of motion sickness - less side effects
29
Q

side effects of hyoscine

A

anticholinergic side effects

- dry mouth, blurred vision, tachycardia, urinary retention, confusion

30
Q

hyoscine butyl bromide (buscopan) vs hyoscine hydrobromide (kwellen)

A

hyoscine hydrobromide is derived from plant sources, not charged and therefore able to cross the BB, where is has effect

hyoscine butyl bromide is not an effective antiemetic

31
Q

cyclizine

A

primarily a histamine antagonist

  • main action is at the CTZ
  • some central anticholinergic (muscarinic) effects have been noted
  • available in PO, SC, IV
  • useful when histamine pathway is involved eg. motion sickness or brain metastasis
32
Q

cyclizine side effects

A

tremulousness, hallucinations and drowsiness
dry mouth and other anticholinergic S+E are less common
- generally well tolerated

33
Q

Lorazepam

A

high potency, intermediate acting benzodiazepine used as an anxiolytic
- binds to benzodiazepine receptor at multiple sites within the CNS
PO or sublingual formulations
used for anticipatory nausea and vomiting associated with chemotherapy

34
Q

Lorazepam side effects

A

sedation, dizziness, unsteadiness

35
Q

hyperemesis gravidarum

A

morning sickness

36
Q

drugs from morning sickness

A

metoclopramide, pyridoxine - Cat A
ondansetron - Cat B1
prochloperazine - cat C(still commonly used)

37
Q

drugs for children

A

common presentation is acute gastroenteritis
main focus is oral rehydration therapy with avoidance of medications
high rate of extrapyramidal side effects from dopamine antagonists
if required ondansetron is safer and more effective

pharmacology 2 (19 decks)

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