Clinical Pharmacology of Anti Emetics

Question 1

Nausea due to vertigo

Answer 1

H1 receptor inverse agonist

• CYCLIZINE (no sedation)
• PROMETHAZINE (if sedation)

Question 2

Nausea due to pregnancy

Answer 2

H1 receptor inverse agonist: PROMETHAZINE

D2 antagonists: PROCHLORPERAZINE or METOCLOPRAMIDE

Question 3

Nausea due to motion sickness

Answer 3

Antimuscarinic: HYOSCINE HYDROBROMIDE

H1 receptor inverse agonist: CYCLIZINE or PROMETHAZINE

Question 4

Nausea due to post operative

Answer 4

5HT3 antagonists: DEXAMETHASONE PROCHLORPERAZINE CYCLIZINE

high risk -> combination of 2 with different MOAs

Question 5

Nausea due to migraine

Answer 5

D2 antagonist: PROCHLORPERAZINE or METOCLOPRAMIDE

Question 6

For nausea due to cancer chemotherapy

- LOW RISK pre treatment

Answer 6

DEXAMETHASONE or LORAZEPAM

Question 7

For nausea due to chemotherapy

- HIGH RISK

Answer 7

DEXAMETHASONE or APREPITANT

Question 8

For nausea due to cancer chemotherapy

- low - moderate emetogenic

Answer 8

D2 receptor antagonist- DOMPERIDONE HALOPERIDOL METOCLOPRAMIDE PROCHLOPERAZINE

Question 9

For nausea due to cancer treatment

- moderate - severe emetogenic

Answer 9

1) Before therapy - NK1 antagonist AMPREPITANT usually administered with 5HT3 receptor antagonist ONDANSTERON + DEXAMETHASONE
2) METOCLOPRAMIDE DEXAMETHASONE LORAZEPAM

Question 10

M1 receptor - nausea + vomiting

Answer 10

M1 - vestibular nuclei/nucleus of solitary tract/vomiting centre = triggers nausea + vomiting reflex
M1 + M3 in GI tract = increase secretions + motility

Question 11

HYOSCINE

Answer 11

blocks muscarinic cholinergic receptors M1
- in vestibular nuclei/nucleus of solitary tract + vomiting centre
MOTION SICKNESS + DRY SECRETIONS before surgery

Question 12

Antimuscarinic MAJOR SIDE EFFECTS

Answer 12

STRONG ANTICHOLINERGIC EFFECTS
most common = dry mouth&constipation
can cause= blurred vision + difficulty passing urine

Can’t see
Can’t pee
Can’t spit
Can’t shit

Question 13

Antimuscarinic: MAJOR PHARMACOKINETICS

Answer 13

HYOSCINE BUTYLBROMIDE - can’t cross BBB - reduce spasms of GI tract
HYOSCINE HYDROBROMIDE - can cross BBB - reduce nausea + vomiting

Question 14

D2 antagonists - clinical indications of use

Answer 14

DOMPERIDONE METOCLOPRAMIDE PROCHLORPERAZAINE

• increase GI motility throughout the entire GI tract = prokinetic
• enhanced gastric emptying
• reduction in volume of acid available to reflux
• increased lower oesophageal sphincter basal tone

Question 15

D2 receptor - mechanism of action

Answer 15

Gi GPCR

- function as cholinomimetics - inhibit dopamine inhibition of ACh-induced contraction

Question 16

D2 receptor antagonist - SIDE EFFECTS

Answer 16

• Parkinsonism + Tardive dyskinesia (shakes) + Dystonia
• drowsiness
• increased pituitary prolactin release

Question 17

D2 receptor antagonists - MAJOR PHARMACOKINETICS

Answer 17

• METACLOPRAMIDE crosses BBB - has CNS actions

- DOMPERIDONE does not cross BBB as easily - less CNS effects

Question 18

5HT3 antagonists - MECHANISM OF ACTION

Answer 18

GANISETRON ONDANSETRON

• primary agents for prevention + treatment of chemo induced nausea + vomiting
• most effective in preventing acute phase ( less than 24 hour after chemo) if given 30 minutes prior to antineoplastic drugs
• not particularly effective during delayed phase ( 2- 5 days) - used for postop and post radiation nausea + vomiting

selective blockade of peripheral 5HT3 receptors on intestinal vagaries afferents
CNS actions at both CTZ and vomiting centre

Question 19

5HT3 antagonists - SIDE EFFECTS

Answer 19

well tolerated - excellent safety profiles
Common side effects (transient) = mild headache/dizziness/constipation & can cause small prolongation of QT interval (avoid in cardiac pathology)

Question 20

5HT3 antagonists - pharmacokinetics

Answer 20

ADMINISTRATION = single dose prior to chemo
- slow IV administration

METABOLISM = longer duration of action - great for chemo induced emesis
- extensively metabolised by liver to an active metabolite

EXCRETION = urinary excretion via the kidney

Question 21

CYCLIZINE

Answer 21

MOTION SICKNESS
- control symptoms of nauseas + vomiting
Vestibular disturbances = labrinythitis + ménière’s disease

Question 22

H1 receptor inverse agonist - MECHANISM OF ACTION

Answer 22

Inverse agonist binds to inactive form of H1 receptor = reduce receptor activity

Question 23

H1 receptor inverse agonist - SIDE EFFECTS

Answer 23

drowsiness = most common - prominent CNS depressive effects

prolong QT interval

Question 24

H1 receptor inverse agonist: PHARMACOKINETICS

Answer 24

Well absorbed from GI tract - reach peak plasma concentration in 2-3 hrs
DISTRIBUTION
widely throughout the peripheral tissues + CNS
METABOLISM
metabolised by liver
- induce CYP450 enzymes = may affect the metabolism of other drugs
- dose adjustment required is severe liver disease

Question 25

APREPITANT

Answer 25

antagonist of NK1 receptor - substance P cannot bind
used in adults and children
- prevent nausea + vomiting caused by chemo - moderate/high emetogenic outcomes

PREVENTATIVE - will not treat nausea + vomiting that already have

Question 26

NK1 receptor antagonist - SIDE EFFECTS

Answer 26

fatigue + constipation

Question 27

NK1 receptor antagonists - PHARMACOKINETICS

Answer 27

ADMINISTRATION =
orally with addition of dexamethasone + a ‘setron’
METABOLISM =
CYP3A4 in liver - dose adjustments in hepatic insufficiency
- induces CYP3A4
= warfarin half-life shortened due to induction = increase dose

Question 28

DEXAMETHASONE

Answer 28

Corticosteroid 
Used for vertigo 
24-48 hours = short use 
- cautious in those with diabetes as can induce increased glucose in blood 
MOA = unknown