Anti-Emetics Flashcards
State the 4 major classes of anti-emetic drugs.
- 5-HT3A receptor antagonists
- Histamine H1 receptor antagonists
- Muscarinic receptor antagonists
- Dopamine D2 receptor antagonists
Describe the process of vomiting.
- Stomach, oesophagus and associated sphincters are relaxed
- Contraction of upper small intestine, pyloric sphincter and pyloric region of stomach
- Contents of upper jejunum, duodenum and pyloric region of stomach move to the body and fundus of the stomach
- Lower and upper oesophageal sphincters and oesophagus relaxes
- Retching/vomiting may occur
What is special about the location of the CTZ and vomiting centre?
- The CTZ is located in a part of the brain that has a very porous blood brain barrier
- So the CTZ and vomiting centre act as an early warning system to protect the brain from toxin damage
What is meant by ‘prokinetic effects on the GI tract’?
- Increase smooth muscle motility
- Accelerate gastric emptying
- Accelerate the transit time of intestinal contents
What effect do chemotherpay drugs e.g. cisplatin have on the cells in the stomach?
Drugs are toxic to enertochromaffin cells in the fundus of the stomach Causes apoptosis of ECs Releases oxygen free radicals and 5-HT
What is the effect of 5-HT release in the stomach?
Binds to 5-HT3A receptors
3 nerve pathways:
- To nucleus tractus solaris and then to the vomiting centre (area pulstrama) in the medulla oblongata
- Directly to the vomiting centre
- To the chemo receptor trigger zone (CTZ)
What is the treatment for chemotherapy induced nausea?
- Ondansteron:
* 5-HT3A receptor antagonist - Glucocorticoids
* Reduce inflammation in the gut by reducing free radical production - Arepepritant
- Neurokinin-1 recetpor antagonsit
- NK-1 found concentrated in the fibres from the nucleus tractus solaris to the vomitimg centre
What is the significance of the location of the chemo receptor trigger zone?
- It is located at the level of the brain stem but outside the BBB
- This allows it to easily sample the systemic blood contents and signal to the vomiting centre if anything is wrong.
What is the main side effect of pharmacological treatment of motion sickness?
Drowziness
What the signalling pathway in motion sickness?
Labyrinth -> vestibular system
Vestibular system -> Hypothalamus & Vomiting centre
Hypothalamus -> Vomiting centre & CTZ
What receptors are important for the motion sickness pathway?
- Vestibular system = Muscarinic receptors (M1-5)
- Vomiting centre = Muscarinic receptors (M1-5)
- Chemoreceptor trigger zone = Histamine receptor (H1)
What is the pharmacological treatment of motion sickness?
- Promethazine - H1 receptor antagonist
- Hyoscine (scopolomine) – non-selective muscarinic receptor antagonist
What causes motion sickness?
- An auditory labyrinth to neural mismatch
- Increased histamine release from the hypothalamus
- Activate H1 receptors on the CTZ
- Vestibular system and hypothalamus also act directly on muscarinic receptors on the VC
What is gastroparesis?
- Delayed emptying of the stomach
- Due to reduced stomach contraction
How does Gastroparesis lead to vomiting?
- Release of 5-HT
- 5-HT3A receptors activated
- Nerve fibres to CTZ - release 5-HT
- Nerve fibres to VC - release dopamine onto D2 receptors
