Session 11: Anti-emetics Flashcards
What is vomiting?
Involuntary, forceful expulsion of gastric contents through the mouth.
What is the vomiting centre?
Chemoreceptor trigger zone (CTZ)
What activates the CTZ?
Sensory afferent via midbrain
Vestibular nuclei (inner ear)
Visceral afferents from gut via vagus nerve
Direct triggers like drugs
Drugs acting on vestibular nuclei
Muscarinic receptor antagonists
H1 receptor antagonists
Drugs acting on the visceral afferents from gut
5HT3 antagonists
D2 receptor antagonists
Drugs acting on CTZ
D2 receptor antagonist
5HT receptor antagonist
Muscarinic receptor antagonist
H1 receptor antagonist
Corticosteroid
Cannabinoid
NK1 receptor antagonist
Give an example of a muscarinic receptor antagonist acting on the vestibular nuclei.
Hyoscine hydrobromide
Explain the action of hyoscine hydrobromide.
Competitive blockade of muscarinic acetylcholine receptors.
It also acts on the CTZ.
What is hyoscine hydrobromide good for?
People who can’t take tablets
Motion sickness (first line for motion sickness)
Bowel obstruction
Side effects of hyoscine hydrobromide
Sedation
Memory problems
Glaucoma
Dry mouth and constipation
All due to the muscarinic receptor antagonist acting on the parasympathetic system all throughout the body.
Give examples of H1 receptor antagonists acting on the vestibular nuclei.
Cyclizine
Levomepromazine
Cinnirazine
Promethazine
Diphenhydramine
Explain the action of H1 receptor antagonists
Inhibits histaminergic signals from the vestibular system to the CTZ in the medulla.
What are H1 receptor antagonists good for?
Motion sickness (second line)
Morning sickness in pregnancy (especially promethazine)
What are H1 receptor antagonists especially not good for?
Young children and elderly
Give side effects of H1 receptor antagonists.
Sedation
Excitation
Antimuscarinic effects such as dry mouth, constipation and urinary retention.
Cardiac toxicity (long QT interval)
What is serotonin produced by in the gut?
Enterochromaffin cells.
Explain serotonins action in the gut.
95% of serotonin in the body is found in the gut.
In response to the parasympathetic system serotonin excites enteric neurones.
This leads to smooth muscle contraciton and increases motility.
It also increases gut secretions.
Also regulates appetite
Give examples of 5HT (serotonin) receptor antagonists.
Reduces GI motility
Reduces GI secretions
Also acts to inhibit the CTZ
What is 5HT receptor antagonists good for?
Almost everyone is often a 1st line treatment due to the very uncommon side effects.
Side effects of 5HT receptor antagonists.
Constipation
Headache
Elevated liver enzymes
Long QT syndromes
Extra-pyramidal effects such as dystonia and parkinsonism
They are uncommon as most of the serotonin is found in the gut.
Give examples of D2 receptor antagonists acting in the gut.
Metoclopramide
Domperidone
Explain the action of metoclopramide.
Increases ACh at the muscarinic receptors in the gut.
This promotes gastric emptying and leads to a higher tone of the lower oesophageal sphincter.
Increases tone and the amplitude of contractions.
Decreases tone of pylorus so it opens.
Increases peristalsis
What is metoclopramide good for?
GORD
Ileus
What is ileus?
When the gut goes to sleep
Side effects of metoclopramide.
Galactorrhoea via prolactin release
Extra-pyramidal effects such as dystonia and parkinsonism.
They are especially bad in children and old people.
Special side effects of domperidone.
Similar mechanism to metoclopramide.
However specific side effects sudden cardiac death (long QT and VT)
Galactorrhoea
What is domperidone especially good for?
Improving lactation in breastfeeding mothers.
Give examples of D2 receptor antagonists acting on the CTZ that are also antipsychotics.
Prochlorperazine
Chlorpromazine
Levomepromazine
Haloperidol
Explain the action of prochlorperazine, chlorpromazine, and levomepromazine.
They act on the CTZ to block the D2 receptor.
It can also block the H1 receptor and the muscarinic receptors.
What is prochlorperazine, chlorpromazine and levopromazine good for?
Motion sickness and vertigo
Prochlorperazine can be used in pregnancy.
Action of haloperidol.
Acts on the CTZ to block the D2 receptor.
It is especially good in chemotherapy and in palliation.
Side effects of the D2 receptor antagonists.
Extra-pyramidal effects such as dystonia and parkinsonism.
Sedation
Hypotension
Give examples of corticosteroids acting on the CTZ.
Dexamethasone
Methylprednisolone
What are corticosteroids good for related to anti-emesis?
Perioperative nausea and vomiting
Chemotherapy
Palliation
Side effects of corticosteroids.
Increased appetite
Increased blood sugar
Insomnia
Give an example of a cannabinoid.
Nabilone
What is nabilone used for?
Last line chemotherapy
Side effects of nabilone.
Drowsiness
Dizziness
Give examples of neurokinin 1 receptor antagonists.
Aprepitant
Fosaprepitant
Netupitant
Explain the action of neurokinin 1 receptor antagonists.
Prevents the action of substance P (which is usually excitatory) at the CTZ and also in peripheral nerves.
It also boosts the effects of 5HT3 receptor antagonists.
Also have anxiolytic properties as well as antidepressant.
What are neurokinin 1 receptors antagonists good for?
Chemotherapy and especially in delayed emesis.
Side effects of neurokinin 1 receptor antagonists.
Headache
Diarrhoea
Constipation
Steven-Johnson syndrome
1 st line for motion sickness
Hyoscine hydrobromide (muscarinic receptor antagonist)
Cinnirazine can also be used and typically has fewer side effects.
When should domperidone or metoclopramide be given? (D2 receptor antagonists)
GORD
Ileus
When should domperidone and metoclopramide not be given?
When there is a history or current bowel obstruction or perforation.
What is the medication pathway for almost any GI problem where anti-emetics are needed?
Ondansetron first line (5HT3 receptor antagonist)
+/- Cyclizine (H1 receptor antagonist)
after that
add Dexamethasone.
Give an example of a hormone related to pregnancy that is a direct trigger of the CTZ.
beta-hCG in hyperemesis gravidarum
Give examples of drugs that are direct triggers on the CTZ.
Chemotherapy
Anaesthetics
Opiates
Explain hyperemesis gravidarum.
A rapid rise in beta-hCG that stimulates the CTZ making the patient sick.
This is typically weeks 4-16 however it can persist.
There is a higher risk with multiple pregnancies and is not just morning sickness.
Give signs associated with hyperemesis gravidarum.
Dehydration
Weight loss
Electrolyte imbalance
Urinary ketones
Medication pathway of hyperemesis gravidarum.
Promethazine
or
Prochlorperazine
then add
Metoclopramide
then add ondansetron.
What is the risk of ondansetron in pregnancy?
Can lead to cleft lip and cleft palate
Medicaton pathway in low risk chemotherapy
Dexamethasone
Medication pathway in moderate risk chemo
Dexamethasone and ondansetron
Medication pathway in high risk chemo.
Dexamethasone, ondansetron and aprepitant.
Risk factors of post-operative nausea and vomiting.
Female
Young age
Non smoke
General anaesthetics
Nitrous oxide
PO opioids
Long duration of surgery
Laparoscopic surgery
How does medication regiment change with risk of emesis in of post-operative nausea and vomiting?
Low risk you just wait and see
Moderate risk you pick 1 or 2 anti-emetic agents
High risk pick more than 2 anti-emetic agents.
Give an example of medication used to treat diarrhoea.
Opioid receptor agonists
Give examples of opioid receptor agonists used to treat diarrhoea.
Loperamide
Codeine
Morphine
Explain the action of loperamide.
Specific action on u-receptors in the myenteric plexus leading to a decrease in tone of longitudinal and circular smooth muscle.
It also reduces peristalsis but increases segmental contraction.
This all leads to decreased colonic mass movement and suppression of gastrocolic reflex.
Explain the difference in action of codeine and morphine compared to loperamide.
Affects not only u receptors but also delta receptors.
When would codeine and morphine be used to treat diarrhoea?
When the patient is in pain as well
Side effects of opioid receptor agonists.
Paralytic ileus
Nausea and vomiting
Sedation and addiction.
Give examples of food that can cause constipation or treat diarrhoea.
Bananas
White rice (binds stool)
White bread and pasta (low in fibre)
Foods to avoid in diarrhoea.
Limit fruit to 3 portions a day
Avoid caffeine, sorbitol, fatty or spicy foods and fizzy drinks.
What dietary changes are done to avoid constipation?
Drink more water
Increase fibre intake by eating wholegrain foods, fruit, vegs, nuts and pulses.
Regular exercise
How can conspitation be treated medically?
Laxatives and enemas
Give examples of actions of laxatives.
Osmotics
Stimulants
Bulk forming
Stool softeners
Give examples of actions of enemas
Osmotics
Stimulants
Give examples of osmotic laxatives
Lactulose
Movicol
Cosmocol
Explain the action of osmotic laxatives.
Draws fluid in (lactulose)
or
Retain fluid that they came with like movicol
Give examples of stimulant laxatives.
Bisacodyl
Sodium picosulphate
Senna
Co-danthromer
Docusate sodium
Explain the action of stimulant laxatives.
Increases that intestinal motility and may be given orally or per rectum.
Give examples of bulk forming laxatives.
Also called medicinal fibres such as ispahgula husk or methylcellulose
Give examples of stool softeners.
Docusate sodium
Glycerin suppository
Arachis oil
Liquid paraffin
Explain the action of stool softeners
Decrease surface tension of stool
Increase penetration of fluid into stool
