Antiemetics Flashcards
Where does the signal to vomit come from?
What events happen in order to vomit?
Vomiting centre in medulla
- Nausea, Salivation, Sweating
- Retrograde peristalsis
- Deep inspiration
- Closure of glottis
- Ab muscles contract
- Lower oesophageal sphincter relaxes
List 4 things that can trigger the Chemoreceptor Trigger Zone (CTZ) and lead to vomiting?
- Sensory afferents via midbrain
- Vestibular nuclei
- Visceral afferents from gut
- Direct triggers
Where is the CTZ?
In the Area Postrema, on the floor of the 4th ventricle
List 2 types of Antiemetic agent acting on the Vestibular Nuclei
What are they usually used for?
- Muscarinic receptor antagonists
- H1 receptor antagonists
- Treating motion sickness
What kind of drug is Hyoscine hydrobromide?
This drug’s targets are where?
A muscarinic receptor antagonist
(mAChRs are the targets)
- Vestibular nuclei
- CTZ
- All over body as part of ParaS system
List 5 ADRs of Muscarinic receptor antagonists
- Sedation
- Memory problems
- Glaucoma
- Dry mouth
- Constipation
List 3 people who Hyoscine hydrobromide would be good for?
- Bowel obstruction
- Motion sickness
- People who can’t take tablets
The following drugs are what kind of drug?
- Cyclizine
- Levomepromazine
- Cinnirazine
- Promethazine
- Dipenhydramine
H1 receptor antagonists
Where do H1 receptor antagonists work?
- Vestibular nuclei
- CTZ (inhibition of histaminergic signals from vestibular system)
Lit 4 ADRs of H1 receptor antagonists
- Sedation
- Excitation
- Cardiac toxicity
- Antimuscarinic (Dry mouth, constipation, urinary retention)
For what patient groups are H1 receptor antagonists good and not good?
Give examples
Good for;
- Motion sickness
- Promethazine (Morning sickness in pregnancy)
Not good for;
- Cyclizine: Elderly women and children (makes them disoriented and confused)
List 2 types of Antiemetic agent acting on the Visceral afferents from the gut
- 5HT3 (Serotonin) antagonists
- SOME D2 receptor antagonists
Where is most of the body’s Serotonin found and what cells is it made by?
What does Serotonin do here?
- 95% found in gut, made by ECL cells
- Regulates appetite
- In response to ParaS stimulation, excites Enteric neurones-> Increased gut secretions and motility (except stomach motility)
What do 5HT3 Receptor Antagonists do Peripherally and Centrally?
Who are these drugs good for?
Peripherally;
- Reduced GI motility and secretions
Centrally;
- Inhibits CTZ
Almost everyone, often 1st line treatment
What kind of drugs are Ondansetron, Granisetron and Palonosetron?
List 5 ADRs of these drugs
5HT3 receptor antagonists
Uncommon;
- Constipation
- Headache
- Elevated liver enzymes
- Long QT Syndrome
- Extra-pyramidal effects (Dystonia, Parkinsonism)
What kind of drugs are Metoclopramide and Domperidone?
What are 2 ADRs of this class of drugs?
D2 Receptor Antagonists
- Galactorrhea (via PRL release)
- Extra-pyramidal effects (Parkinsonism, Dystonia)
How does Metoclopramide work?
- Increases ACh at mAChRs in gut-> Increased gastric emptying via;
- Increased tone at LOS so it closes
- Increased tone & amplitude of gastric contractions
- Decreased tone of Pylorus so it opens
- Increases GI peristalsis
Suggest 2 patient groups who Metoclopramide is good for?
- GORD
- Ileus (Peristalsis stops, similar presentation to bowel obstruction)
How does Domperidone work?
List 1 patent group who its for
List 2 ADRs
- Similar mechanism to Metoclopramide
- Good for improving lactation in breastfeeding mothers (due to its ADR)
- Galactorrhea
- Sudden cardiac death (Long QT, VTach)
List all 7 of the Antiemetic agents that act on the CTZ
- Muscarinic receptor antagonists
- H1 receptor antagonists
- 5HT3 receptor antagonists
- D2 receptor antagonists (not all)
- Corticosteoids
- Cannabinoids
- NK1 receptor antagonists
What kind of drugs are;
- Prochlorperazine (safe in pregnancy)
- Chlorpromazine
- Levomepromazine
- Halopiderol
Antipsychotics: D2 receptor antagonists that work centrally, not peripherally
(Not Metoclopramide or Dompiderone)
How do the ‘zine’ Antipsychotics work?
Suggest 2 patient groups that they are good for?
- Act o CTZ
- May block H1 and Muscarinic receptors
- Motion sickness
- Vertigo
What does Halopiderol work on?
Suggest 2 patient groups it’s good for
- Acts on CTZ
- Chemotherapy
- Palliation
List 3 ADRs of the Antipsychotics
- Sedation (especially Halopiderol)
- Hypotension
- Extra-pyramidal effects (Dystonia, Parkinsonism)
What kind of drugs are Dexamethasone and Methylprednisolone?
What are 3 things they’re good for?
- Corticosteroids (assumed to act on CTZ, possible D2 receptor antagonist properties)
- Perioperative nausea and vomiting
- Chemotherapy
- Palliation
What are 3 ADRs of Corticostetoroids?
- Insomnia
- Increased blood sugar
- Increased appetite
Are synthetic Cannabinoids cannabis?
Which one is used as an Antiemetic?
No
Nabilone
Nabilone is assumed to act on the CTZ
What is it good for?
What are 2 ADRs
- Chemotherapy but used as last line therapy
- Dizziness
- Drowsiness
What kind of drugs are Aprepitant, Netupitant and Fosaprepitant?
How do they work?
- NK1 Receptor Antagonists (Neurokenin 1)
- Prevent action of Substance P at CTZ & Peripheral nerves
- Boost effects of 5HT3 Receptor Antagonists
- Anxiolytic and antidepressant properties
What are NK1 Receptor Antagonists good for?
List 3 ADRs
- Chemotherapy, especially for delayed emesis
- Headache
- Diarrhoea/ Constipation
- Stevens-Johnson Syndrome
Compare the use of Hyoscine hydrobromide and Cinnirazine in treating motion/ travel sickness
Hyoscine hydrobromide (Muscarinic Receptor Antagonist);
- 1st line
- Stronger sedative effects so good for kids/ passengers
Cinnirazine (H1 Receptor Antagonist);
- Fewer side effects so good for driver
Prokinetics such as Metoclopramide and Domperidone are good to use for GORD and Ileus.
Suggest 2 occasions they’re bad to use?
- Obstruction
- Risk of perforation
What’s the usual combination of drugs used for vomiting due to bowel obstruction?
- Ondansetron and/ or Cyclizine
- Then add Dexamethasone (if not working)
Describe Hyperemesis Gravidarum
Higher risk with multiple pregnancies
- Rapid rise in Beta-HCG stimulates CTZ-> Vomiting
- Typically weeks 4-16, may continue beyond
(Dehydration, 5% weight loss, Urinary ketones, Electrolyte imbalance)
What’s the routine treatment for Hyperemesis Gravidarum
- Promethazine/ Prochlorperazine
- Then add Metoclopramide
- Then add Ondansetron
(Ondansetron has some evidence of Cleft lip/ palate if used in Trimester 1, so only if necessary)
List 4 patient risk factors for PONV (Post-Op Nausea and Vomiting)
- Female
- Young
- Non smoker
- History of PONV/ motion sickness
List 2 surgical risk factors for PONV
- Longer surgery
- Laparoscopic surgery
What’s the usual routine of treatment for PONV?
- Ondansetron and/ or Cyclizine
- Then add Dexamethasone
What kind of drugs are Codeine, Morphine and Loperamide?
What are they used for?
- Opioid receptor agonists
- Treating diarrhoea
Loperamide is specific to MOP receptors in the Myenteric Plexus.
List 3 ways it helps reduce diarrhoea
(Normally 1st line, takes 48 hours for maximal effect)
- Reduces tone of Longitudinal and Circular smooth muscle
- Reduces Peristalsis but increases segmental contractions
- Decreases colonic mass movement by suppressing Gastrocolic reflex
List ADRs of using Codeine and Morphine to treat diarrhoea
- Paralytic ileus
- Sedation
- Addiction
- Nausea and vomiting
Describe the Constipating Diet, used for those with long-term diarrhoea
- Bananas (high k+ and fibre)
- White rice (binds stool)
- Limit fruit to 3 portions per day
- Avoid caffeine, sorbitol, spicy foods, fizzy drinks
List diet and lifestyle changes to help constipation
- More water
- Increase fibre intake (Whole wheat, fruit + veg, nuts)
- Regular exercise
What drugs can be used to help constipation
Enemas;
- Osmotic
- Stimulants
Laxatives;
- Osmotic (Lactulose, Macrogol)
- Stimulant (Senna, Bisacodyl)
- Bulk forming (Methylcellulose, Ispaghula husk)
- Stool softeners (Docusate, Arachis oil)
Lactulose, Movicol and Cosmocol are what kind of drugs?
How do they differ in their mechanism
Osmotic laxatives
- Lactulose draws fluid into bowel
- Macrogols retain the fluid they came with (Movicol & Cosmocol)
Describe how Docusate Sodium works?
What are 2 effects of Glycerin suppositories
Docusate Sodium: Acts as a stimulant and stool softener
Glycerin Suppositories: Cause rectal irritation and lubrication
What kind of drugs are Ispaghula husk and Methylcellulose?
Bulk forming laxatives
Soften the stool while bulking it up, basically extra fibre
What class of drug contains;
- Docusate Sodium
- Glycerin Suppositories
- Arachis oil
- Liquid paraffin
How do they work?
- Stool softeners
- Decrease stool surface tension
- Increase penetration of fluid into stool
