Wk9 CTZ VOMITING and Anti emetics

What is the CTZ and where is it located?

Chemoreceptor Trigger Zone – located in the area postrema (medulla), adjacent to the 4th ventricle

Why can the CTZ "sample" blood directly?

It has fenestrated capillaries – NO blood-brain barrier

What does the CTZ detect?

Noxious chemicals in the blood: bacterial toxins, drugs, poisons

What receptors in the CTZ cause vomiting when activated?

D₂ receptors (dopamine)

What drug causes vomiting by stimulating D₂ receptors in the CTZ?

Apomorphine

What is the NTS?

Nucleus of the solitary tract – the "vomiting centre" in the medulla that coordinates vomiting

What are the 5 main inputs to the vomiting centre?

CTZ (blood toxins), GI tract (5-HT), vestibular apparatus (motion), gag reflex, emotional factors

How does the GI tract trigger vomiting?

Enterochromaffin cells release 5-HT → stimulates 5-HT₃ receptors on vagal afferents → signal to NTS

What are the 6 main neurotransmitters involved in vomiting?

ACh, histamine, 5-HT, dopamine, substance P, endocannabinoids

What is the mechanism of hyoscine (scopolamine)?

Muscarinic antagonist – blocks ACh receptors (motion sickness)

What is the mechanism of cyclizine/promethazine?

H₁ antihistamine – blocks histamine receptors (motion sickness)

What is the mechanism of ondansetron?

5-HT₃ antagonist – gold standard for chemotherapy-induced nausea

What is the mechanism of aprepitant?

NK₁ antagonist – blocks substance P (adjunct for chemotherapy)

What is the mechanism of nabilone?

CB₁ agonist (cannabinoid) – used for chemotherapy nausea when others fail

What are the two D₂ antagonists that are phenothiazines?

Prochlorperazine, chlorpromazine (block multiple receptors)

What is special about metoclopramide?

D₂ antagonist + direct prokinetic effects on GI tract

What is special about domperidone?

D₂ antagonist that DOES NOT CROSS THE BBB – blocks CTZ without brain side effects

What are the side effects of D₂ antagonists that cross the BBB?

Extrapyramidal symptoms (movement disorders) and hyperprolactinaemia

What is the mechanism of dexamethasone as an anti-emetic?

Not fully understood – effective for chemotherapy nausea

What happens during the autonomic responses before vomiting?

Salivation, sweating, pallor, increased HR, GI relaxation

What happens during the somatomotor responses of vomiting?

Diaphragm contraction, glottis closure, abdominal muscle contraction → expulsion of stomach contents