S10 L2 Antiemetics Flashcards
What is vomiting?
Involuntary, forceful, expulsion of gastric contents through the mouth
What is the difference between vomiting and regurgitation?
Regurgitation- mechanical problem (almost always)
Food or liquid won’t go into the stomach
Brought up effortlessly
e.g. babies- when they have had enough milk it overflows- regurgitation
What actually happens when we vomit?
Vomiting centre in the medulla signals to vomit
- Nausea, salivation and sweating
- Retrograde peristalsis
- Deep inspiration
- Closure of glottis
- Abdominal muscle contract
- LOS relaxes
- Expulsion out of mouth
What triggers the vomiting centre?
Different things trigger the chemoreceptor trigger zone
- Direct triggers- chemicals
- Visceral afferents from the gut → detect stretch caused by overload in the small bowel, take some of the pressure off by vomiting
- Vestibular nuclei → motion sickness
- Sensory afferent via midbrain
Where is the chemoreceptor trigger zone located?
Floor of the 4th ventricle
Blood side of BBB
Blood not too thick here so some substances can pass through
How can we stop vomiting?
- Remove the triggers
- Inhibit the pathways via drugs
What drugs can be used?
Often antagonists- block the pathway
Different drugs work on the different triggering centres
Often work in multiple areas
- Vestibular nuclei → muscarinic receptor antagonist, H1 receptor antagonists
- Visceral afferent from gut → 5HT3 antagonists, D2 receptor antagonists
- Directly inhibit the trigger zone → D2 receptors, 5HT3 receptor antagonists, muscarinic receptor antagonists, H1 receptor antagonists, corticosteroids, cannabinoids and NK1 receptor antagonist
What drugs act on the vestibular nuclei?
Muscarinic receptor antagonists
H1 receptor antagonists
How do the muscarinic receptor antagonists work?
Competitive blockade of muscarinic acetylcholine receptors
→ receptor are found all over the parasympathetic NS
What is an example of a muscarinic receptor antagonist that work on the vestibular nuclei?
Hyoscine hydrobromide
- Patch
Ideal for people who can’t take tablets
What are the muscarinic receptor antagonists used for?
Motion sickness
Bowel obstruction
What are the side effects of muscarinic receptor antagonists?
- Sedation
- Memory problems
- Glaucoma
- Dry mouth
- Constipation
(block the parasympathetic functions)
What are H1 receptor antagonists?
Inhibits histaminergic signals from the vestibular system to the CTZ in medulla
What are the H1 receptor antagonists good for?
Motion sickness - long plane journeys
Morning sickness in pregnancy - promethazine
What are examples of the H1 receptor antagonists?
‘-zine’
- Cyclizine → not good for little elderly ladies or children - disorientated/confused
(-promethazine (morning sickness, cinnirazine, diphenhydramine)
What are the side effects of H1 receptor antagonists?
- Sedation
- Excitation
- Antimuscarinics → dry mouth, constipation, urinary retention
- Cardiac toxicity- long QT interval
What drugs act on the visceral afferents in the gut?
5HT(3) receptor antagonists → serotonin
D2 receptor antagonists
Where is serotonin produced?
95% produced in the gut
Produced by the enterochromaffin cells
Response to parasympathetic stimulation - excites enteric neurones
→ smooth muscles contraction increases motility (except in the stomach)
→ ↑gut secretions
Regulates appetite
How do the 5HT(3) receptor antagonists work?
Peripherally → Reduced GI motility, reduced GI secretion
Centrally → acts to inhibit the CTZ
Good for almost everyone
What is an examples of the 5HT(3) receptor antagonists?
‘-setron’
- Ondansetron
What are the side effects of 5HT(3) receptor antagonists?
Uncommon
- Constipation
- Headache
- Elevated liver enzymes
- Long QT syndrome
- Extra-pyramidal effects → dystonia, parkinsonism
How do the D2 receptor antagonists work?
↑ACh at muscarinic receptors in the gut
Promotes gastric emptying
- ↑tone at lower oesophageal sphincter so it closes
- ↑tone and amplitude of gastric contractions
- ↓tone of pylorus so it opens
↑peristalsis
What are examples of the D2 receptor antagonists?
Metoclopramide
Domperidone
What can D2 receptor antagonists be used to treat?
Metoclopramide: Vomiting caused by: - GORD - Ileus → inability of the intestines to contract normally leading to a build up of food material Domperidone - Lactation in breastfeeding mothers
What are the side effects of metoclopramide?
- Galactorrhoea via prolactin release
- Extra-pyramidal effects → Dystonia, parkinsonism
What are the side effect of domperidone?
- Sudden cardiac death (long QT and VT)
- Galactorrhoea