Antiemetics Flashcards
Difference between vomiting & regurgitation
Vomiting - involuntary forceful expulsion of gastric contents through mouth
Regurgitation - effortless bringing up of things that have not yet reached stomach or passive overflow stomach contents
What’s the sequence of steps that triggers vomiting?
Vomiting centre in medulla signals to vomit -> Nausea, salivation, sweating -> Retrograde peristalsis -> deep inspiration -> closure of glottis (if not choke)-> Abdo muscles contract -> LOS relaxes
What triggers the vomiting centre/ chemoreceptor trigger zone? Where is it?
- sensory afferents via midbrain
- vestibular nuclei (motion sickness, vertigo)
- visceral afferents from gut (mainly through vagus N)
- direct triggers (drugs/ hormones/ toxins in blood as blood side of BBB)
In medulla on floor of 4th ventricle, blood side of BBB
How do muscarinic receptor antagonists work? Give an example. Side effects
Competitive blockade of muscarinic Ach receptors in vestibular nuclei + chemoreceptor trigger zone
E.g. Hyoscine hydrobromide
Uses: can’t take tablets - patch, motion sickness, bowel obstruction, good for agitation (sedation), good for diarrhoea (constipation)
Side effects (receptors all over body, part of parasympathetic NS): sedation, memory Problems, glaucoma, dry mouth & constipation
How do H1 receptor antagonists (anti-histamines) work? Give examples. Uses and side effects.
Centrally - acts on vestibular nuclei, inhibits histaminergic signals from vestibular system to CTZ in medulla
E.g. cyclizine, levomepromazine, diphenhydramide
Uses: motion sickness - long plane journeys, promethazine - morning sickness
Cyclizine - not suitable for little old ladies or children <6yrs
Side effects: sedation, excitation, antimuscarinic - dry mouth, constipation, urinary retention, cardiac toxicity (long QT interval)
How is serotonin used in the gut?
95% serotonin in the body is located in the gut produced by enterochromaffin cells
PS stimulation -> serotonin excites enteric neurones -> Sm contraction increases motility (except in stomach), increases gut secretions, regulates appetite
How do 5HT3 receptor antagonists work? Give examples. Uses and side effects.
5HT = serotonin
Peripherally - reduces GI motility/ secretions
Centrally - inhibits CTZ
E.g. Ondansetron - common.
granesitron/ palonosetron - niche/ palliative/ oncology
Uses: good for almost everyone (often 1st line)
Side effects (uncommon): constipation, headache, elevated liver enzymes, long QT syndrome, extra pyramidal effects (dystopia, Parkinsonism)
How does metoclopramide work? Uses and side effects.
D2 receptor anatagonist
Metoclopramide increases Ach at muscarinic receptors in gut -> promotes gastric emptying, increases tone LOS closes, increases tone/ amplitude gastric contractions, decreases tone pylorus opens, increases peristalsis
Uses: GORD, Ileus (normal gut movement lost e.g. post op, infection)
Side effects: galactorrhoea via prolactin release, extra pyramidal effects (dystopia, Parkinsonism)
How does domperidone work? Uses and side effects
D2 receptor antagonist
Similar mechanism to metoclopramide, not used much anymore due to cardiac side effects
Uses: improving lactation breastfeeding mothers
Side effects: sudden cardiac death (long QT and VT), galactorrhoea (increases prolactin)
D2 (dopamine) receptors antagonists acting on the CTZ, how do they work? Give examples, uses and Side effects
The ‘zines’ act on CTZ, May also block H1 muscarinic receptors
E.g. prochlorperazine, chlorpromazine, haloperidol
Uses: motion sickness, vertigo,
Prochlorperazine in pregnancy, haloperidol (CTZ) chemotherapy & palliation
Side effects: extra pyramidal effects (dystonia, parkinsonism), sedation, hypotension
How do corticosteroids work to prevent vomiting? Give examples, uses and side effects
Act on CTZ
E.g. dexamethosone, methylprednisolone
Assumed act on CTZ, May also properties D2 receptor antagonists
Uses: perioperative nausea & vomiting, chemotherapy and palliation
Side effects: insomnia, increased appetite, increased blood sugar
How do cannabinoids work? Give an example, uses and side effects
Synthetic compounds assumed to act on the CTZ
E.g. Nabilone
Good for chemotherapy as last line
Side effects: dizziness, drowsiness
How do neurokinin 1 receptor antagonists work, give examples, uses and side effects?
Act on CTZ
Prevent action of substance P at CTZ and in peripheral nerves (painkillers), boosts effects of 5HT3 receptor antagonists, anxiolytic (reduces anxiety) + antidepressant properties
E.g. aprepitant, fosaprepitant, netupitant
Good for chemotherapy particularly delayed emesis
Side effects: headache, diarrhoea/ constipation, stevens- Johnson syndrome (rare, serious disorder of skin)
Best methods to treat motion sickness?
Prevention is better than cure - take before journey
1st line: Hyoscine hydrobromide - sedating
If driving/ need to concentrate: connirazine - fewer side effects
Trial & error
What are prokinetics useful for? Give examples. When should you use them?
Increase gut motility
E.g. Domperidone, metoclopramide
Uses: GORD, ileus (gum may help first)
Don’t use: obstruction, risk of perforation
What should you consider trying before medication for a lot of gut pathology if they are being sick?
A nasogastric tube - mechanical decompression of the stomach
What antiemetics are used normally for gut pathology bar prokinetics?
1st ondansetron (5HT3 receptor antagonist)
&/ or cyclizine (H1 R antagonist - not old ladies/ children)
Then add: dexamethasone if needed (corticosteroid)
Different classes
What is hyperemesis gravidarum?
V severe morning sickness
Rapid rise beta- hcg-> stimulates CTZ
Typically weeks 4-16
Higher risk with multiple pregnancies
Dehydration, weight loss, electrolyte imbalance, urinary ketones
Treatment of hyperemesis gravidarum
Promethazine (H1 R antagonist) Or prochlorperazine (D2 R antagonist)
Then add: metoclopramide (D2 R antagonist)
Then add: ondansetron (5HT3 R antagonist - 1st trimester risk cleft lip/ palate)
Treatment of emesis in chemotherapy
Low risk chemo: dexamethasone (if needed + metoclopramide)
Moderate: dexamethasone & ondasetron (+ metoclopramide)
High risk: dexamethasone & ondansetron & aprepitant (+ metoclopramide)
Dexamethasone - corticosteroid
Ondansetron - 5HT3 R antagonist
Aprepitant - NK1 antagonist
Metoclopramide - D2 R antagonist
Risk factors for post- operative nausea & vomiting
Female
History of PONV/ motion sickness
Younger
Non smoker
Genera anaesthetic
Volatile anaesthetic gases/ NO
PO opioids
Longer op
Laparoscopic surgery
Post- op N&V treatment
Low risk: wait and see
Moderate: pick 1/ 2 antiemetic agents
High: 3+ agents
If prophylaxis fails use antiemetic of different class
What do you use to treat infective gastritis?
Osmotic or secretory agents
Give examples of opioid receptor agonists, how do they work
Loperamide - specific to mu receptors in myenteric plexus
Decreases tone longitudinal/ circular SM, reduces peristalsis but increases segmental contractions, decreases colonic mass movement by suppressing gastrocolic reflex
Works just in the gut
Max effects in 24hrs
Also: codeine, morphine - mu and delta receptors - similar effects, more often used wine patients also have pain
Works all over body
Side effects of opioid receptor agonists
Paralytic ileus
N&V
Sedation
Addiction (codeine & morphine)
For those with long term loose stools what should they consider adding and limiting from their diet?
E.g. IBS, IBD, short bowel, hypermotility, drug side effects
The constipating diet:
Bananas, white rice, white bread/ pasta
Limit fruit 3per day
Avoid: caffeine, sorbitol, fatty/ spicy foods, fizzy drinks
Consider probiotics
Lifestyle/ diet changes for those with chronic idiopathic constipation?
More water
Increase fibre: whole grain foods, f&v, nuts, pulses
Regular exercise
Toilet routine and positioning
Consider probiotics
Categorise the medications for constipation
Laxatives - orally - osmotic, stimulants, bulk forming, stool softeners
Enemas - rectally - osmotic, stimulants
Give examples of osmotic laxatives, how do they work?
Lactulose (draws H2O in, mild constipation),
1st line: movicol (retains H2O, up to 12 sachets a day, bad constipation),
cosmocol (retains H2O)
Increases water in large bowel
Give examples of stimulant laxatives, how do they work?
Bisacodyl
Dosimeter picosulphate
Senna
Docusate sodium - stimulant & stool softener
Glycerine - rectal irritation & lubrication & stool softener
If need more help, increase intestinal motility, orally or rectally
Give examples of bulk forming laxatives, how do they work?
Ispaghula husk
Methylcellulose
Medicinal fibre - sometimes also helpful for diarrhoea
Ideally just get from diet or increase H2O
Give examples of stool softeners, how do they work?
Docusate sodium - stimulant
Glycerine - rectal irrational, lubrication, stimulant
Liquid paraffin
Decrease surface tension of stool
Increase penetration of fluid into stool
