Antiemetics

Question 1

name 2 dopamine D2 receptor antaagonists

Answer 1

domperidone

metoclopramide

Question 2

how do dopamine D2 receptor antagonists work?

Answer 2

domperidone = D2 receptor antagonist
Meoclopramide = D2 antagonist with antagonist activity at 5-HT3 and agonist activity at 5-HT4 receptors
Promotility agents

Question 3

what is the main difference between metocloparamide and domperidone?

Answer 3

domperidone doesn’t cross the blood brain barrier

Question 4

where are D2 receptors located and what do they do?

Answer 4

expressed in chemoreceptor trigger zone (CTZ) just outside of blood brain barrier
Important in detection of emetogenic substances in blood (e.g opiates)
Dopamine relaxes stomach and lower oesophageal sphincterand disrupts gastroduodenal coordination

Question 5

indications for dopamine D2 receptor antagonists?

Answer 5

variety of nausea + vomiting (particularly where reduced gut motility)
Domperidone used in drug/chemo induced vomiting
GORD add on if no response to PPI +/- H2 receptor antagonists

Question 6

side effects of dopamine D2 receptor antagonists?

Answer 6

diarrhoea

metoclopramide = rarely extrapyramidal syndromes/disorders of movement

Question 7

cautions for dopamine D2 receptor antagonists?

Answer 7

avoid is GI obstruction and perforation

metoclopramide best avoied in children/teens with common extrapyramidal effects

Question 8

name 3 histamine H1 receptor antagonists

Answer 8

cyclizine
cinnarazine
promethazine

Question 9

how do H1 receptor antagonists work?

Answer 9

competitive antagonism of H1 receptors in the vomiting centre and elsewhere in the CNS (causes sedation)
Blocks M1 Ach receptors in the vestibular apparatus (contributes to effectiveness)

Question 10

indications for H1 receptor antagonists?

Answer 10

nausea + vomiting due to motion sickness and vertigo and post operative

Question 11

side effects of H1 receptor antagonists?

Answer 11

drowsiness and sedation (avoid skilled tasks eg. driving)
reduced saliva/dry mouth (anti cholinergic action)
transient tachycardia if IV

Question 12

cautions for H1 receptor antagonists?

Answer 12

avoid in prostatic hyperplasia

avoid if at risk of hepatic encephalopathy

Question 13

name 2 phenothiazines

Answer 13

procloperazine

cholorpromazine

Question 14

how to phenothiazines work?

Answer 14

competitive antagonism of dopamine D2, histamine H1 and muscarinic M1 receptors in vomiting centre, vestibular centre and peripherally in gut

Question 15

indications for phenothiazines?

Answer 15

nausea + vomiting due to vertigo and sometimes chemo but not preferred
psychiatric disorders

Question 16

side effects of phenothiazines?

Answer 16

drowsiness and postural hypotension
extrapyramidal symptoms (same as D2)
QT interval prolongation

Question 17

cautions for phenothiazines?

Answer 17

avoid in severe liver disease and prostatic hyperplasia

reduce dose in elderly

Question 18

name a 5-HT3 receptor antagonist

Answer 18

ondansetron

Question 19

how do 5-HT receptor antagonists work?

Answer 19

competitive antagonist of inotropic 5-HT receptors located in CTZ, NTS and peripherally on terminals of vagal afferents innervating GI tract.
CTZ senses emetogenic stimuli in blood, 5-HT released from enterochromaffin cells n the gut stimulates vagal afferents that via the NTS activate vomiting centre

Question 20

indications for 5-HT3 receptor antagonists>

Answer 20

nausea + vomiting due to chemo and radiotherapy

post operative nausea and vomiting

Question 21

side effects of 5-HT3 receptor antagonists?

Answer 21

usually constipation

diarrhoea and headaches can occur

Question 22

cautions for 5-HT3 receptor antagonists?

Answer 22

severe or prolonged constipation
intestinal obstruction
stricture
toxic megacolon
ischaemic colitis
crohns
UC
diverticulitis
prolonged QT interval