3. Treating Emesis Flashcards
Vomiting is not just controlled by the gut; it is more than just gut motility
Emesis is under control of the CNS (Medulla Oblongata)
- Chemoreceptor trigger zone (CTZ)
- Vomiting centre
- Nuclei (group of neuron cell bodies) recieve input from several sources
+ The Cortex- eg. exam stress, or if you see or smell someone else vomiting
+The vestibular nuclei - when there is a mismatch between proprioception and visual information- eg: motion sickness
+ the nucleus iof the solitary tract (NTS) the gag reflex- eg. blood borne toxins, drugs, etc, which may cross the blood brain barrier or directly stimulate the GIT
How is vomiting stimuli transmitted?
Vomiting stimuli are transmitted from the brain to the smooth muscle of the GIT and abdominal muscles via the VAGUS and SOMATIC MOTOR NERVES (part of the peripheral nervous system associated with voluntary control).
Explain Vomiting reflex unfer control of the CNS
Vomiting is regulated centrally by the vomiting centre and the chemoreceptor trigger zone (CTZ), both of which lie in the medulla. The CTZ is sensitive to chemical stimuli, and is the main site of action of many emetic and anti emetic drugs. The BBB in the neighbourhood of the CTZ is relatively permeable, allowing circulation mediators to act directly on this centre. The CTZ also regulates motion sickness. Impulses from the CTZ pass to those areas of the brainstem collectively known as the vomitting centre. The final common pathway involves impulses from the vomiting center to the skeletal and visceral smooth muscles. The vomiting centre recieves impulses from the CTZ and the nucleus of the solitary tract, as well as from higher centres (the cortex)
Vomiting is best stopped by targeting the cause
We control vomiting by blocking the receptor types in these nuclei.
What are the FOUR CELL TYPES we block!
Nucleus of vestibular nuclei, solitary tract & vomiting centre = muscarinic & hisamine receptors
Chemoreceptor Trigger Zone = Dopamine and Serotonin receptors.
The best drugs control the CTZ- metaclopromide (dopamine antagonists)- which then controls the activity of the vomiting centre.
Brain Centre: Chemoreceptor Trigger Zone - what is the receptor?
Dopamine (D2) and Serotonin (5-HT3)
Brain Centre: Vomiting Centre- what is the receptor?
Cholinergic: Muscarinic and Histamine (H1)
Brain Centre: Nucleus of the Solitary Tract - what is the receptor?
Cholinergic: Muscarinic and Histamine (H1)
Brain Centre: Vestibular Nuclei: what is the receptor?
Cholindergic: Muscarinic and Histamine (H1)
OUTSIDE THE CNS: visceral afferent receptors within the GIT- what is the receptor?
Serotonin (5-HT3)
Name some Dopaminergic Antagonists
Metoclopramide (Maxolon) - Most commonly used
Prochlorperazine (Stemetil)
Domperidone
Theithylperazine
What are the pharmacodynamics of Metoclopramide?
First drug of choice for treating excessive vomitting due to a range of causes including:
- Alcohol abuse- can actually be used with alcohol poisoning
- Uraemia, radiation
- GI disorders and Cytotoxic drugs
What are the pharmacokinetics ? Ie. Cellular effects of of Metoclopramide?
Antagonists- therefore inhibits gastric smooth muscle relaxation due to dopamine, and increases gut motility- this assists and increases gut motility
Assists stomach emptying
Decreases vomiting reflex
What are the side effects of Metoclopramide?
Due to blockage of CNS dopamine receptors:
- Parkinsonian-like symptoms : eg tremors. This occurs especially in children and young adults or with an overdose situation. Tremors are short lived, and wear off as the drug does. BBB penetration is higher in children/young adults.- because BBB is much less developed
Drowsiness and fatigue are common
Motor restlessness, spasmodic torticollis (involuntary movement of neck) & oculogyric crises (eyes roll back into head) can also occur
Can stimulate the release of prolactin from the anterior pituitary - galactorrhoea (breast milk production) and menstrual disturbances may occur.
Increase gut motility and therefore may result in diarrhea
Pharmacodynamics of Prochlorperazine (Stemetil)
Useful in treating migraines, vestibular disorders eg. vertigo as seen in Meniere’s disease and motion sickness
Typically used as an antisphycotic agent; however, the anti-emetic dose of anti-psychotic drugs are generally less than one third of those used to treat psychoses.