Antiemetics Flashcards
Vomiting
Involuntary, forceful expulsion of gastric contents through the mouth
Regurgitation
Effortless, bring something back up that was sat in the oesophagus/stomach
Vomiting process
Vomiting centre in medulla signals to vomit
- Nausea, salivation, sweating
- Retrograde perstalsis- upper part of small bowel(duod and stomach)
- Deep inspiration
- Closure of glottis- present aspiration
- Abd muscles contract
- LOS relaxes- gastric contents out
Chemo receptor trigger zone - vomiting zone
Part of brain involved
Floor of 4th ventricle
Blood side of BBB
Things in b stream hit CTZ, cause vomiting
What activate CTZ
Sensory Afferent by midbrain: eww gross
Vestibular nuclei- inner ear (infection), motion sickness (car/sea sick/vertigo)
Visceral afferents from gut- vagus n. problem w gut
Direct triggers- drugs/hormone
Stop CTZ
Avoidance
Drugs- work in diff places/ways eg CTZ/PNS
Agents acting on vestibular nuclei
Muscarnic receptor antagonists
H1 receptor antagonists
Muscarnic receptor antagonist
Eg: Hyoscine hydrobromide
Competitive blockade of muscarnic ACHR- work by PNS, found:
Vestibular nuclei/CTZ/PNS
Good for:
- not take tablets/ motion sickness/ bowel obs
Side effects:
- sedation = good in cancers agitated
- memory problems
- dry mouth/constipation = if D with V
H1 receptor antagonist
Centrally:
- act on VN
- inhibits histaminergic signals from vestibular system to CTZ in medulla
Good for:
- motion sickness
- promethazine:morning sickness preg
Not good for:
Cyclizine- little old ladies/children
H1 receptor antagonists
Cyclizine Levomepomazine Cinniarizine Promethazine Diphenhydramine
Side effects:
- sedation/excitation
- antomuscarinic- dry mouth/constipation/ urinary retention
- cardiac toxicity (long QT interval)
Agents acting on visceral afferents in gut
5HT3 receptor antagonists
D2 receptor antagonists
Serotonin (5HT) in gut :)
Production: enterochromaffin cells
Act: respond to parasymp stimulation: excite enteric neurones
- smooth muscle contraction: increase motility (except stomach)
- increase gut secretions
Regulates appetite
5HT3 receptor antagonist
Peripherally
- reduce motility (stop retrograde peristalsis) and GI secretions
Centrally:
-inhibit CTZ
Good for:
- everyone: 1st line
5HT3 receptor antagonists
Ondansetron (most common)
Granesitron
Palonosetron
Side effects- uncommon:
- constipation
- headache
- elevated liver enzymes
- long QT syndrome
- extra-pyramidal: dystonia, Parkinsonism
D2 receptor antagonists- metoclopramide
- increase Ach at muscarnic receptor in gut
- promote gastric emptying:
increase tone at LOS so it closes
Increase tone and amplitude of gastric contractions
Reduce tone of pylorus, so it opens
-increase peristalsis
Good for: GORD/ileus (gut go to sleep, no peristalsis= eg after laparotomy/infectuon/illness)
D2 receptor antagonists- metoclopramide
Side effects:
- galactorrhoea: prolactin release
- extra pyramidal effects: dystopia, Parkinsonism
D2 receptor antagonist- domperidone
- mechanism similar to metoclopramide
- get increase risk cardiac side effects
Good for:
- improve lactation in breast feeding mothers
Side effects:
- sudden cardiac death (long QT and VT)
- galactorrhoea
Agents acting on the CTZ
5HT3 receptor antagonists H1 receptor antagonists Muscarnic receptor antagonist D2 receptor antagonists Corticosteroids Cannabinoids NK1 receptor antagonists
D2 receptor antagonists- Prochlorperazine Chlorpromazine Levomepromazine Haloperidol
Zines:
- act:CTZ
- also block h1 and muscarnic receptors
- Good for: motion sickness/vertigo/prochloperazine=pregnancy
Haloperidol:
- act at CTZ
- Good for: chemotheapy and palliation
D2 receptor antagonists- zines and haloperidol
Side effects:
- extra pyramidal effects- dystonia, Parkinsonism
- sedation
- hypotension
Corticosteroids
Dexamethasone
Methylprednisolone
- act at CTZ, May also have D2 receptor antagonist properties
Good for:
- perioperative N and V (anaesthesia related)
- chemotherapy
- palliation (increased appetite in palliation)
Corticosteroids-side effects
Insomnia
Increased appetite
Increased blood sugar
Cannaboids
Nabilone
Act at CTZ
Good for: chemo, used as last line
Side effects:
- drowsy, dizziness
Neurokinin 1 receptor antagonists
Aprepitant
Fosaprepitant
Netupitant
- prevent action of substance P at CTZ and in peripheral n.s
- boost effects of 5HT3 receptor antag
- anxiolytic and anti depressive properties
Good:
- chemo:esp in delayed eyes is
NK1 receptor antagonists
Side effects:
- headache
- diarrhoea/ constipation
- Stevens-Johnson syndrome
Random drugs used as antiemetics
Midazolam- benzodiazepine
- act at CTZ, bind to GABA receptor, reduce serotonin secretion
- used perioperatvely
Gabapentin:
- mitigation of effects of neurokinins and tachykinins
- used perioperatively and hyperemosis gravidarum
Cisapride:
- prokinetic
- chemo
Mirtazepine:
- tetracyclic antidepressant
- effect serotonin
