Anti emitics

Question 1

name a drug induced cause of vomiting presentation

Answer 1

Chemotherapy (Cisplatin) for lung cancer

Chemotherapy induced nausea & vomiting (CINV)

Question 2

what cells does cisplatin damage in fundus

Answer 2

Cisplatin is toxic to enterochromaffin cells (ECs)

Question 3

what are the consequences of this damage that trigger vomiting

Answer 3

ECs apoptose and release free radicals

excessive 5-HT is released

5-HT – activates 5-HT3A receptors

Question 4

which locations are 5-HT3A receptors found

Answer 4

Nerve fibres to nucleus tractus solaris (NTS)

Nerves fibres to vomiting centre (VC) -DIRECT

Nerve fibres to chemoreceptor trigger zone (CTZ)

Question 5

what location of the brain do these receptors reside in

Answer 5

Medulla oblongata (brainstem)

Question 6

how exactly does the CTZ contribute

Answer 6

incomplete blood brain barrier (sense hormones etc.) - signals to VC (independent of VC)

Question 7

what is the treatment for Chemotherapy induced nausea & vomiting (CINV)

Answer 7

Ondansteron - 5-HT3A receptor antagonist

Question 8

what is it often coadmistered with (not essential)

Answer 8

Glucocorticoids - reduce free radical production

Arepepritant – neurokinin-1 receptor antagonist

Question 9

what are 5-HT rc otherwise known as

Answer 9

serotonin receptors

Question 10

simply what causes motion sickness

Answer 10

Auditory labyrinth - neural(sensory) mismatch

Question 11

describe what areas the labyrinth projects to after this sensory mismatch

Answer 11

Vestibular system (via muscarinic (M) receptors)

Increased hypothalamic histamine (H) release

Question 12

what do both these pathways affect which produces the effect of motion sickness

Answer 12

Vomiting centre

Question 13

what receptors does the hypothalmic histamine act on

Answer 13

activates H1 receptors in CTZ

Question 14

describe a separate pathway by which sensory mismatch in labyrinth travels

Answer 14

Vestibular system & hypothalamus may also activate the VC though cholinergic system (M1-5)

Question 15

the hypothalamus affects the VC in 2 ways. describe them

Answer 15

via the CTZ (histamine release) which then sends input to VC

Directly via cholinergic stimulation)

Question 16

is pharmacological therapy first line treatment for motion sickness

Answer 16

No

associated with drowsiness

Question 17

how do drugs lessening affects of motion system act

Answer 17

H1 rc antagonist

or

non selective muscarinic rc antagonist

Question 18

name these drugs and ther mechanisms

Answer 18

Promethazine - H1 receptor antagonist

Hyoscine (scopolomine) – non-selective muscarinic receptor antagonist

Question 19

what is a cause of bloating and vomiting in T2DM

Answer 19

Gastroparesis – delayed emptying of the stomach

Reduced stomach contraction

Question 20

besides the 5-HT rc pathway what other pathway is triggered in this condition

Answer 20

direct stimulation of the VC via dopamine D2 receptors

Question 21

name a drug treatment for gastroparesis

Answer 21

Metoclopramide

Dopamine D2 receptor antagonist

Question 22

state some additional MOAs that metoclopramide has

Answer 22

Prokinetic – stimulates gastric emptying
Inhibits D2 receptors in VC

5-HT3A receptor antagonist
Inhibits activation of CTZ

Question 23

summarise the physiological control of vomiting

Answer 23

Vomiting centre (area postrema): innervated by the nucleus of the tractus solitarius

CTZ: communicates with the vomiting centre

Question 24

summarise the Mechanistic triggers of vomiting

Answer 24

Cytotoxic drugs, motion sickness, gastrointestinal problems

Question 25

what is side effect profile of motion sickness drugs

Answer 25

drowsiness

Question 26

what is side effect profile of D2 rc antagonists

Answer 26

galactorrhea and extrapyramidal side effects

Question 27

5-HT3A receptor antagonists side effects

Answer 27

constipation and headaches