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Pharmacology > Treatment of Nausea and Vomitting > Flashcards

Treatment of Nausea and Vomitting Flashcards

1
Q

Vomiting?

A

A physiological response that comes as a result of stimulation of the
chemoreceptor trigger zone (CTZ) and/or the vomiting centre in the
CNS.

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2
Q

Aetiology of N & V?

A
  1. GI mechanisms
  2. Cardiovascular disease
  3. Neurologic processes
  4. Metabolic Disorders
  5. Psychiatrist causes
  6. Therapy induced causes
  7. Drug withdrawl
  8. Other causes: pregnancy, noxious, poperative procedure
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3
Q

Chemical transmitters involved in N & V?

A

Dopamine-D2

Acetylcholine

Histamine

Serotonin

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4
Q

Antiemtics defintion?

A

Antiemetic drugs are medicines that ease nausea or vomiting

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5
Q

Antiemtics?

A

A. H 1Receptor Antagonists
B. Muscarinic Receptor Antagonists
C. D 2Receptor Antagonists
D. 5HT 3Receptor Antagonists
E. Substance P (NK1) Antagonists
F. Other

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6
Q

H 1Receptor Antagonists I?

A

*NV induced by any stimuli
*Vomiting produced by substances acting directly on
the CTZ
*Motion sickness, substances acting on the stomach

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7
Q

H 1Receptor Antagonists drugs?

A

Cyclizine
Cinnearizine
Buclizine
Doxylamine
Promethazine

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8
Q

H 1Receptor Antagonists MOA?

A

Mostly 1st generation anƟhistamines → enter
the CNS

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9
Q

Cyclizine MOA?

A

Inhibition H 1receptors in the VC (also has antimuscarinic action)

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10
Q

Cyclizine I?

A

Used for all types of vomiting including motion sickness

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11
Q

Cyclizine Kinetics?

A, D, M & E.

A

A=well orally
D=does not readily cross
BBB
M=extensively in liver, E=inactive
metabolites in urine, DOA=4‐6 hrs

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12
Q

Cyclizine AE?

A

Drowziness, xerostomia

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13
Q

Cyclizine CI?

A

closed‐angle glaucoma, urinary retention, prostatic hypertrophy, chronic pulmonary disease, acute asthma

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14
Q

Cyclizine DI?

A

CNS depressants,
anƟcholinergics➡️ ⬆️anƟcholinergic effects

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15
Q

Doxylamine MOA?

A

competes for H 1‐receptors sites on target
cells; has anƟcholinergic effects ➡️ depresses
labyrinthine function, blocks CTZ; diminishes
vestibular stimulation

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16
Q

Doxylamine I?

A

Used for all types of vomiting including motion sickness

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17
Q

Doxylamine Kinetics?

A

A=well absorbed orall, D=crosses BBB,
M=hepatic
E=urine
T 1/2=10‐12 hrs

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18
Q

Doxylamine AE?

A

tachycardia
urinary retention
constipation
drowsiness
blurred vision

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19
Q

Doxylamine CI?

A

children <12 yrs

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20
Q

Doxylamine DI?

A

CNS depressants,
anƟcholinergics➡️ ⬆️anƟcholinergic effects

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21
Q

Cinnarizine MOA?

A

Inhibition (‐) H 1receptors in the VC & vestibular
system (also has antimuscarinic action; CCB)

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22
Q

Cinnarizine I?

A

motion sickness, vestibular disorders
(Meniere’s)

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23
Q

Cinnarizine Kinetics?

A

A=fairly rapid
D=91% protein bound
M=extensively in liver
E=excreted unchanged in
faeces, metabolites in urine, t 1/23‐6 hrs ?

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24
Q

Cinnarizine AE?

A

extrapyramidal symptoms + depressive
feeling (with prolonged therapy), hypotension
(at high doses)

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25
Q

Cinnarizine CI?

A

hypersensitivity to the drug

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26
Q

Cinnarizine DI?

A

CNS depressants, anticholinergics,
antihistamines, MAOIs, tricyclic antidepressants

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27
Q

Buclizine (long‐acting)
MOA?

A

(‐) H 1receptors in the VC & vestibular system (also has anticholinergic properties)

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28
Q

Buclizine (long‐acting) I?

A

motion sickness, radio/chemo‐induced NV

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29
Q

Buclizine (long‐acting) A/E?

A

sedation
dizziness
headache
anxiety
hypotension
tight chest
dry mouth
urinary retention

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30
Q

Buclizine (long‐acting) CI?

A

asthma, pulmonary disease, bladder neck
obstruction, closed‐angle glaucoma

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31
Q

Buclizine (long‐acting) DI?

A

CNS depressants

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32
Q

Promethazine HCL
MOA?

A

(‐) D 2, muscarinic and H 1receptors,
crosses BBB

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33
Q

Promethazine HCL I?

A

all types of vomiting including severe morning
sickness in pregnancy (only if absolutely
essential), prevention of motion sickness

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34
Q

Promethazine Kinetics?

A

A=well orally
D=crosses BBB,
M=extensively in liver, E=inactive conjugates in
urine, T 1/2= 10‐14hrs

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35
Q

Promethazine Kinetics A/E?

A

strong sedative effect
dizziness
Fatigue,
incoordination
extrapyramidal symptoms

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36
Q

Promethazine CI?

A

children <2yrs

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37
Q

Promethazine DI?

A

CNS depressants, anticholinergic agents

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38
Q

Hyoscine MOA?

A

(‐) M receptors, blocks impulses from the
CTZ to the vomiting centre (act directly on the
VC)

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39
Q

Hyoscine I?

A

motion sickness, nausea as a result of labyrinth disturbances

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40
Q

Hyoscine Kinetics?

A, D, M & E?

A

A=poor orally
D=unclear
M=in liver,
E=in urine

41
Q

Hyoscine AE?

A

drowsiness
dry mouth
dry skin
blurred vision, urine retention (at high doses)
constipation
dementia

42
Q

Hyoscine CI?

A

glaucoma
GI obstruction
porphyria

43
Q

Hyoscine DI?

A

tricyclic antidepressants, antihistamines,
antipsychotics

44
Q

D2 Receptor Antagonists drugs?

A

Domperidone [(CTZ), peripheral actions]
Droperidol(butyrophenone, (‐) GIT)
Metoclopramide [(‐) CTZ & GIT]
Prochlorperazine (phenothiazine, (‐) CTZ)

44
Q

D2 Receptor Antagonists drugs?

A

Domperidone [(CTZ), peripheral actions]
Droperidol(butyrophenone, (‐) GIT)
Metoclopramide [(‐) CTZ & GIT]
Prochlorperazine (phenothiazine, (‐) CTZ)

45
Q

D2 Receptor Antagonists I?

A

NV caused by motion sickness or other labyrinth
disturbances
*Chemotherapy induced NV (CINV)
*Post Operative NV (PONV)
*Radiation Induced NV (RINV)

46
Q

D2 Receptor Antagonists A/E?

A

sedation
dizziness
dyskinesia
dystonias

47
Q

Domperidone MOA?

A

(‐) D 2receptors in the CTZ, to prevent the
action of circulation emetic agents

48
Q

Domperidone I?

A

post‐operative NV, NV of central/peripheral
origin

49
Q

Domperidone Kinetics?

A, D, M & E?

A

A=well absorbed orally, D=limited entry into the CNS (poor lipid‐solubility)
M=in liver by CYP3A4 enzymes, E=65% in faeces and 35% in urine (as metabolites), T 1/2=7‐8 hrs

50
Q

Domperidone A/E?

A

Extrapyramidal symptoms (⬇️), drowsiness,
headache, reversible galactorrhoea

51
Q

Domperidone CI?

A

hepatic impairement, GI obstruction or perforation, GI haemorrhage, cardiovascular
disease

52
Q

Domperidone DI?

A

CYP3A4 inhibitors
potassium depleting agents, macrolides
antacids
anticholinergics
protease inhibitors

53
Q

Droperidole ?

A

(‐) D 2receptors at the CTZ

54
Q

Droperidole I?

A

prevention of PONV where other treatments
are ineffective or inappropriate

55
Q

Droperidole Kinetics?

D & M

A

D=rapid crosses BBB
M=in liver, T 1/2=2‐3 hrs

56
Q

Droperidole A/E?

A

Extrapyramidal symptoms, drowsiness,
hypotension
blurred vision, anxiety

57
Q

Droperidole CI?

A

electrolyte imbalance, Parkinson’s, severe
depression, pregnancy

58
Q

Droperidole DI?

A

alcohol, K‐depleting diuretics,
glucocorticoids, CNS depressants, opioids,
Bromocriptine, levodopa, CYP3A4/1A2
inhibitors➡️⬆️ risk of QT prolongaƟon

59
Q

Metoclopramide MOA?

A

(‐) D 2receptors in the CTZ and VC, also has a
stimulant effect on the GIT (facilitates emptying of
the stomach, relaxes the pylorus and increases GI
motility)

60
Q

Metoclopramide I?

A

vomiting caused by uraemia, radiation
GIT disorders
drug related NV (cytotoxic drugs)
PONV

61
Q

Metoclopramide CI?

A

epilepsy
phaeochromocytoma, mechanical bowel
obstruction
intestine perforation

62
Q

Metoclopramide Kinetics?

A, D & M.

A

A=rapid oral absorption; bioavailability 30‐100% due to first‐pass metabolism

D=widely distributed and readily crosses BBB

M=in the liver, E=85% unchanged in urine, T 1/2=4‐6 hrs

63
Q

Metoclopramide A/E?

A

extrapyramidal symptoms, light sedation,
consƟpaƟon
⬆️ prolacƟn release➡️
galactorrhoea

64
Q

MetoIclopramide D

A

antipsychotic agents, CNS depressants,
digoxin, paracetamol, ampicillin, tetracyclines

65
Q

Prochlorperazine
MOA?

A

(‐) D 2receptors in the CTZ, also (‐) cholinergic and ∝‐adrenergic receptors➡️sedation, muscle relaxation, hypotension.

66
Q

Prochlorperazine I?

A

vomiting due to uraemia, radiation,
oncotherapy
viral gastroenteritis severe
morning sickness (if absolutely essential)

67
Q

Prochlorperazine CI?

A

CNS depression
coma bone‐marrow
suppression

68
Q

Prochlorperazine kinetics?

A ,D, M & E?

A

A=well absorbed orally
D=well distributed including CNS
M=extensively metabolised in liver
E=excreted in urine and
bile, DOA=3‐4 hrs

69
Q

Prochlorperazine A/E?

A

extrapyramidal
constipation, dry mouth,
drowsiness, blurred vision, hypotension, reflex
tachycardia

70
Q

Prochlorperazine DI?

A

CNS depressants
anti‐Parkinson’s agents,
metoclopramide(↑extrapyramidal SE)

71
Q

5HT 3Receptor Antagonists Drugs?

A

Granisetron
Ondansetron
Palonosetron

72
Q

5HT 3Receptor Antagonists I?

A

Vomiting caused by cytotoxic anti‐cancer drugs,
post‐operative NV
radiation‐induced NV
(oncotherapy)

73
Q

5HT 3Receptor Antagonists A/E?

A

headache
Dizziness
muscle pains
GIT upsets
constipation

74
Q

Granisetron MOA?

A

(‐) 5HT 3in vagal nerve terminals and
centrally in CTZ (selecƟve) → anƟemesis

75
Q

Granisetron I?

A

Post‐cytotoxic chemo‐/radiotherapy NV, PONV

76
Q

Granisetron CI?

A

hypersensitivity to any of the ingredients

77
Q

Granisetron Kinetics?

A

A=rapid and complete orally,
bioavailability 60% due to first‐pass effect

D=extensively; 65% plasma protein binding

M=in liver

E=predominantly by hepatic
metabolism, unchanged in urine, some in
faeces, T 1/2= 9 hrs

78
Q

Granisetron DI?

A

QT prolonging agents, serotonergic agents,
cardiotoxic drugs, phenobarbital

79
Q

Granisetron AE?

A

headache
dizziness
muscle pains
GIT upsets
constipation

80
Q

Ondansetron MOA?

A

(‐) 5HT 3in vagal nerve terminals and
centrally in CTZ (selecƟve) → anƟemesis

81
Q

Ondansetron Kinetics?

A, D, M & E.

A

A=well absorbed orally; bioavailability slightly enhanced by food

D=extensively
distributed; slowly crosses BBB

M&E=extensively metabolised and excreted in
the urine and faeces

82
Q

Ondansetron I?

A

Post‐cytotoxic chemo‐/radiotherapy NV, PONV

83
Q

Ondansetron AE?

A

headache
flushing
Constipation,
dry mouth
sedatio
hypersensitivity reactions,
seizures
CVS effects (arrhythmia, bradycardia, hypotension), fatique

84
Q

Ondansetron CI?

A

congenital long QT syndrome, concomitant use of apomorphine

85
Q

Ondansetron DI?

A

tramadol, rifampicin, carbamazepine,
phenytoin

86
Q

Palonosetron MOA?

A

selectively (‐) 5HT 3receptors both peripheral and CNS with primary effects in GIT

87
Q

Palonosetron Kinetics?

A, D, M & E

A

A=low oral bioavailability

D=widely distributed (62%
protein bound)

M=in liver (CYP2D6, CYP3A, CYP1A2)

E=urine (80‐93%),
faeces (5‐8%), T 1/2=40 hrs

88
Q

Palonosetron I?

A

Post‐cytotoxic chemo‐/radiotherapy NV, PONV

89
Q

Palonosetron A/E?

A

AE: anxiety, dizziness, headache, weakness,
consƟpaƟon, pruritus, hyperkalaemia, ↑LFTs

90
Q

Palonosetron CI?

A

CI: hypersensitivity to drug, coadministration
with apomorphine ➡️profound hypotension and loss of consciousness

91
Q

Palonosetron DI?

A

DI: serotonergic agents, SSRIs, SNRIs, anti‐
arrythmic agents, QT‐prolonging agents, agents
resulting in electrolyte abnormalities

92
Q

Aprepitant/fosaprepitant
MOA?

A

selecƟve ⬆️‐affinity (‐) of human
substance P/neurokinin 1 (NK1) receptors; little
or no affinity for 5HT 3, D 2, and corticosteroid
receptors

93
Q

Aprepitant/fosaprepitant
I?

A

adjunct to other antiemetics for prevention of
acute or delayed CINV, PONV

94
Q

Aprepitant/fosaprepitant
CI?

A

hypersensitivity
concomitant Pimozideor
Cisapride use

95
Q

Aprepitant/fosaprepitant
Kinetics?

A, D, M & E.

A

A=well absorbed orally bioavailability
60‐65%,
D=crosses BBB; 95% protein bound

M=hepatic CYP3A4 (major); CYP1A2, CYP2C19
(minor)Fosaprepitant (IV) rapidly converted
into Aprepitant in vivo

E=(IV admin): 57% urine;
45% faeces

96
Q

Aprepitant/fosaprepitant DI?

A

CYP3A4 substrates, ketoconazole, rifampicin,
corticosteroids, benzodiazepines, warfarin, oral
contraceptives

97
Q

N&V drugs to treat pregnancy?

A

*Sucrose/Phosphoric acid

*Dicyclomine/Doxylamine succinate/Pyridoxine

Pharmacology (44 decks)

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