Antiemetics Lecture 16

Question 1

List causes of emesis (vomiting)

Answer 1

Disease associated- uraemia, gastroduodenal, hepatic, infection

Drug induced- cancer chemo and radiotherapy- cisplatin, dopamine agonists- L-Dopa, opiates, Ipecacuanha (Road side plant that makes you sick), alcohol

Anticipatory Post operative emesis (PONV)- due to general anaesthetic- location- abdominal and gynaecological Motion sickness

Pregnancy- 1st trimester due to increase hCG

Question 2

Describe the control for emesis

Answer 2

Higher centers- mood

Brain stem- floor of the fourth ventricle- the vomiting centre; lateral reticular formation- not a discrete nucleus, similar neurones for cardiovascular and respiration so no universal target for anti-emetics

Chemoreceptor outside the BBB

Question 3

List some antiemetics that are neuroleptics

Answer 3

Chlorpromazine

Haloperidol

Domperidone- does not cross BBB

Metoclopramide- high dose- extra efficacy with genuine antiemetic effects- decrease vomiting episodes- weak. High afffinity D2 receptor anatognist causes a block of vomiting

5-HT3 receptor antagonist- need high dose for effect

SE- have extrapyramidal side effects

True antiemetics- just sedation?

Question 4

List antiemetics that are selective 5-HT3 receptor antagonists

Answer 4

Highest level 5-HT3 receptor in whole body

1st gen setrons- ondansetron, granisetron, tropisetron

Attenuate cisplatin induced emesis with extra-pyramidal side effects

2nd gen- Palonosetron- long half life with 5-HT3 receptor internalisation. Effect in body is longer, internalises 5-HT3 receptor.

Question 5

How does cisplatin have it’s emetic effects?

Answer 5

Thins the GI mucous

Local inflammation activates enterchromaffin cells (mast cells) degranulates and releases 5-HT

Question 6

How does aprepitant have anti-emetic effect?

Answer 6

Substance P receptor antagonist

Vagal neurotransmitter

Used for ciplatin induced emesis and postoperative emesis, combined with a 5-HT3 receptor anatagonist

Question 7

List antiemetics that are steroids

Answer 7

Dexamethosone- reduce inflammation

Additive with 5-HT and substance P antagonists

Question 8

List antiemetics that are benzodiazepines

Answer 8

Diazepam- neuronal suppression - increase GABA receptors (inhibitory)

Metaclopramide + Dexamethosone + diazepam

Question 9

List antiemetics that are cannabinoids

Answer 9

Cannabis sativa- Nabilone

Euphoria and sedation

Question 10

How would you treat motion sickness?

Answer 10

Anti-muscarinics- Scopolamine (+/-hyoscine)- via the cholinergic labyrinthine-vestibular-cerebellar pathway (CTZ zone - sensitive to drugs)

Anti-histamines- Dimenhydinate- H1 antagonist on presynaptic membrane of neurones in the LVC pathway Cinnarizine, cycizine, promethazine

Pre synaptic receptors on cholernic nerurones. Histamine receptors will stimulae Ach releasse. Anti-histamine blocks H1 receptors, so no histamine is released and decreases Ach

Also useful in vertigo (spinning sensation) and tinnitus (hear sounds when there is no stimulus)