Pharmacology of vomiting Flashcards
Where is vomiting coordinated?
The brain - the two areas are the chemo-receptor trigger zone (in the brain-stem - near the 3rd ventricle), and the vomtting centre in the medulla
N.B in cats, there is a distributed control system rather than a distinct vomiting centre.
What can trigger the vomiting centre?
Mechanoreceptors in the pharynx
Any abdominal disease which can irritate the GI tract (e.g. a pyo/ pancreatitis/ peritonitis etc.) (This occurs through visceral receptors and vagal afferents)
Central Nervous System
What can stimulate the CRTZ, and why is this?
It is located very near the third ventricle, meaning it is very close to the blood-brain barrier.
Drugs / Toxins/ Inflammatory Mediators/ Uraemia
How does the vestibular system trigger vomiting?
Either through the CRTZ or the vomiting centre
How does maropitant work?
Neurokinin 1 antagonist - inhibits substance P from binding to NK1 receptors
Acts as a central and peripheral antiemetic
Could potentially cause parkinson’s type disease with >5d usage - should either give body a break or drop to half the normal dosage once past 5d
Highly protein bound so should be used with caution in hypoproteinaemic patients or those with other highly protein bound drugs
What is substance P?
Substance produced by variety of cells; binds to NK1 receptors in the gut, vomiting centre and CRTZ and causes emesis
How does metoclopramide work?
Acts on both the CRTZ and vomiting centre
Prokinetic and anti-emetic
Antagonises dopamine D2 receptors
At high doses can antagonise 5HT3 receptors causing sedation and prolactin release
Possibly works better as a CRI but is light sensitive
Not massively useful in cats
Dose should be halved in renal failure
How is metoclopramide different in cats and dogs?
More prokinetic in the oesophageal area in cats
More antiemetic in dogs as cats don’t have many dopamine receptors
How does ondansetron work?
5HT3 receptor antagonist
Works at CRTZ, in a damaged GI tract, and at vagal nerve terminals
Unclear if it is causing its effect do to central or peripheral actions, seems to work best v peripheral emetogens
Outline the process of vomiting
- Inhibition of proximal GI tract motility/ +/- anti peristaltic activity
- Relaxation of the stomach and oesophagus, and closure of the pylorus
- Abdominal muscle contraction and closure of the glottis
- Dilation of cardia & opening of the upper esophageal sphincter
- Abdominal muscle contraction & explosion of abdominal contents
What other anti-emetic drugs are there?
ACP (D2 and H1 antagonist)
Butorphanol
What are the 3 types of chemotherapy induced emesis?
- Anticipated vomiting (common in humans, not demonstrated in animals)
- Acute vomiting. Within the firs 24 hours. Caused either by CRTZ stimulation or peripherally. Most common type
- Delayed. 1-5 days after treatment. Complex. May be due to reduction in intestinal motility, alteration of mucosa and release of hormones, reduction of urinaty cortisol excretion. Can also occur due to accumulation of metabolites of cyto-toxic agents.
How do a adrenergic receptors differ in cats and dogs?
More important in cats - this is why xylazine is a better emetic in cats than dogs
Where does apomorphine work?
At the CRTZ
Which antibiotics are associated with emesis?
Erythromycin and other macrolides
Metronidazole
Doxycycline
