Anti-emetics Flashcards
Define nausea
subjective, unpleasant sensation in the throat and stomach; often precedes vomiting
Define vomiting
forceful propulsion of stomach contents out of the mouth.
What is the vomiting pathway
- deep breath, glottis closes and the larynx rises to open the upper oesophageal sphincter. Soft palate elevates
- diaphragm contracts sharply to create a negative intrathoriacic pressure to facillitate sphincter opening
- 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 consequences of acute nausea
Interferes with mental/physical activity
What are consequences of severe vomiting
Dehydration
Loss of gastric HCl -> hypochloraemic metabolic alkalosis
Reduction in renal HCO3- excretion/increased reabsorption -> increased sodium reabsorption and potassium excretion -> hypokalaemia
Where does the vomiting centre and chemoreceptor trigger zone sit
In a location of the brain with v porous BBB in the medulla
Where can drugs interefere with the vomiting and nausea pathway
Vestibular system
Chemoreceptor trigger zone
Cortex
Peripheral pathways eg 5HT3 receptors in GI and mechanoreceptors and chemoreceptors
What is an example of a mixed receptor antagonist
Promethazine
What cranial nerves mediate signals to stomach/heart to vomit
CN9 and 10
MoA of promethazine
Competitive antagonist at histaminergic, cholinergic and dopaminergic receptors (potency goes in this order too), acting centrally (vestibular nucleus, CTZ and vomiting centre) to block the activation of the VC
When is promethazine used
As an atni emetic: motion sickness disorders of the labyrinth (eg menieres disease) hyperemesis gravidarium (pregnancy complication) Pre and post op allergy relief anaphylaxis night sedation
Administration, onset of action and duration of action of promethazine
Administation oral
Onset of action 1-2 hr
Duration of action 24 hr
What are unwanted side effects of promethazine
Dizziness Tinnitus Fatigue Excitation in excess Sedation Convulsions Anti muscarinic effects
What are examples of d2 receptor antagonists
Metoclopramide,
Domperidone
What is the receptor antagonistic potency order for d2 receptor antagonists
D2»_space;> H1»_space;> muscarinic receptors
MoA of d2 receptor antagonists
Acts centrally, especially on the CTZ.
Why do d2 receptor antagonists not combat motion sickness
Since they block D2 receptors in the CTZ but they don’t block the rest of the signals going directly from the vestibular system
Effects of d2 receptor antagonists on GI
Prokinetic effects (effects of PNS) eg increase in SM motility, accelerate gastric emptying, accelerate transit through tract. Less to vomit
What are uses of d2 receptor antagonists
Uraemia
Cancer chemotherapy in high doses
Parkinsons disease treatment as they block large DA transmission induced by parkinsons drugs (only in CTZ)
Administration of metoclopramide and domperidone
Oral (extensive 1st pass metabolism) and IV
Do metoclopramide and domperidone cross the BBB or placenta
They cross both.
This causes CNS side effects and care must be taken about the bioavailability of the drugs
what happens if metoclopramide or domperidone are taken with digoxin
Absorption or effectiveness of digoxin can be reduced
What is important about metoclopramide and domperidone in diabetes mellitus patients
Nutrient supply might be compromised
What are unwanted side effects of metoclopramide and domperidone
In CNS (mainly metoclopramide): drowsiness, dizziness, anxiety, extrapyramidal reactions - parkinsons like symptoms In endocrine system: hyperprolactinaemia, galactorrhoea, disorders of menstruation
What is the receptor antagonistic potency order for muscarinic receptor antagonists
Muscarinic»_space;> D2/H1
What are examples of muscarinic receptor antagonists
Hyoscine
Where does hyoscine act, and how
Centrally, especially on vestibular nuclei, CTZ and vomiting centres to block activation and prevent motion sickness. However little effect once nausea establised
When is hyoscine used
In pre op medication
Adminstation of hyoscine
Oral (peak effect in 1-2 hrs)
IV
Transdermal
What are unwanted side effects of hyoscine
Anti muscarinic side effects - blocked PNS
Drowsiness, dry mouth, cycloplegia (paralysis of cililary muscles), mydriasis, constipation
What is an example of a serotonin (5-HT3) receptor antagonist
Ondansetron
What does ondansetron do
Blocks transmission in visceral afferents (vagus and splanchnic nerves) and CTZ. This CTZ block and from the peripheries makes it good at treating sickness from chemo and radio
What are uses of ondansetron?
- preventing anti cancer drug induced vomiting
- radiotherapy induced sickness
- post op nausea and vomiting
administration of ondansetron
Oral (well absorbed, excreted in urine - need good renal function)
What are unwanted side effects of ondansetron
Headache
Sensation of flushing and warmth
Constipation - increased large bowel transit time
What happens when ondansetron is used in combination with corticosteroids
5-HT3 receptor antagonist that can be used for low emetogenic chemotherapy. Corticosteroids may be used in combination for high or moderately high emetogenic chemotherapy and improved efficacy of combined therapy may be due to anti inflammatory properties of corticosteroids
What can cannabinoids treat in an anti emetic way
Treats emesis from anti cancer drugs when other anti emetics are not effective eg cisplatin
MoA of cannabinoids working as anti emetics
Acts via CB1 receptors located pre synaptically to decrease release of NTs associated with vomiting. Also inhibit prostaglandin synthesis which is implicated in emesis from anti cancer drugs
