Anti-emetics Flashcards
(44 cards)
what is nausea?
subjective, unpleasant sensation in the throat and stomach; often precedes vomiting.
what is vomiting?
forceful propulsion of stomach contents out of the mouth.
what precedes nausea and vomiting?
salivation, sweating and increased heart rate.
describe the physiological vomiting pathway
o Deep breath, glottis closes and the larynx rises to open the upper oesophageal sphincter. Soft palate elevates.
o Diaphragm contracts sharply to create a negative intrathoracic pressure to facilitate sphincter opening.
o Whilst diaphragm contracts, abdominal walls contract to squeeze the stomach and raise intra-gastric pressure. With the pylorus closed and the upper sphincters open, pressure escapes proximally.
what are the consequences of acute and chronic nausea?
o Acute nausea – interferes with mental/physical activity.
o Chronic nausea – very debilitating.
what are the consequences of severe vomiting?
1) Dehydration.
2) Hypochloraemic metabolic alkalosis (Loss of gastric HCl)
3) hypokalaemia.
(Reduction in renal HCO3- excretion / increased reabsorption–> increased sodium reabsorption and potassium excretion)
where is the vomiting centre located?
the area postrema specifically is located in the medulla of the brainstem
where is the chemoreceptor trigger zone located?
in the medulla
what is significant about the location of the vomiting centre and the CTZ?
they have very porous BBBs
what cranial nerves are involved signalling vomiting?
CN IX and X
what system is involved in motion sickness (children particularly)?
vestibular system (labrinyth)
what are some causes of nausea and vomiting?
- chemotherapy e.g. cisplatin
- motion sickness
- gastroparesis
how does cisplatin induce nausea and vomiting?
- cisplatin is toxic to enterochromaffin cells that line the GIT
- damage leads to the release of free radicals
- there is excess 5HT release which activates the CTZ by binding to its 5HT3a receptors
what does 5HT bind to in the CTZ to induce nausea and vomiting?
5HT3a receptors (ligand gated ion channel)
what is the treatment option for chemotherapy induced vomiting?
Ondansetron (serotonin receptor antagonist)
given as triple therapy with cortiocosteroids e.g. glucocorticoids and aprepitant (neurokinin-1 receptor antagonist)
o Preventing anti-cancer drug-induced vomiting.
o Radiotherapy-induced sickness.
o Post-operative nausea and vomiting.
what is ondansetron? what does it do?
Serotonin (5-hydroxytryptophan) receptor antagonists
–> 5-HT3a
- Blocks transmission in visceral afferents (vagus and splanchnic nerves) that use serotonin receptors
- primary site: CTZ and GIT
why is ondansetron given with glucocorticoids at times?
serotonin receptor antagonist:
to have an anti-inflammatory effect
reduce the production of free radicals
use for anti-cancer drugs like cisplatin
why is ondansetron given as triple therapy?
anti-cancer treatment e.g. chemotherapy induced nausea and vomiting is biphasic
ondansetron is used to treat the first stage while the other 2 drugs are used to treat the second stage
describe ondansetron pharmacokinetics
Oral (well absorbed, excreted in urine)
– needs good renal function
what are some unwanted side effects of ondansetron?
o Headache.
o Sensation of flushing and warmth.
o Constipation – increased large bowel transit time.
how does motion sickness induce nausea and vomiting?
- there is a labyrinthine neuronal mismatch leading to the activation of H1 receptors
- these histamine receptors on the vestibular nuclei
- they have an afferent to the CTZ which bind to muscarinic receptors on the CTZ
- N&V induced
what is the treatment option for motion sickness induced nausea and vomiting?
promethazine and/or hyoscine
promethazine (H1 antagonist)used in: o Motion sickness – used prophylactically normally. o Disorders of the labyrinth – i.e. Meniere’s disease. o Hyperemesis gravidarium – a complication of pregnancy. o Pre- and post-operatively. o relief of allergy, combat anaphylaxis, night sedation.
hyoscine can be used in pre-operative medication.
what is promethazine?
- order of potency
Mixed receptor antagonist: phenothiazine derivative
Consider it as H1 antagonist
o Potency on receptors: H1>M>D2.
o other phenothiazines can have greater antagonistic effects on D2 to acts as neuroleptics.
describe the pharmacokinetics of promethazine
o Administration= Oral.
o Onset of action= 1-2 hours - Maximum effect at 4 hours.
o Duration of action= 24 hours.