Vomiting (Emesis) + Anti-Emetics

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NK1 receptor antagonist drug?

aprepitant

how does aprepitant work?

blocks substance P (NK1) receptors in the CTZ and vomiting center

what can drug induce vomiting

cancer therapy opiates ipecacuanha (ipecac) alcohol post op

Dopamine antagonist drugs?

chlorpromazine (also an antipsychotic)

Histamine-1 antagonist drugs

cyclizine and promethazine

how is dolasetron used?

in preventing and treating vomiting and nausea (to a lesser extent) post-op or by radiation therapy or chemotherapy drugs like cisplatin

how is promethazine used by NASA?

in space motion sickness

what and where is the vomiting centre?

in the medulla's lateral reticular formation

what is the function of the vomiting centre

initiates and control the act of emesis (vomiting). Also integrates the visceral (GI s.muscle) and somatic (diaphragm skeletal muscle) functions in vomiting

nausea neurobiology is..

not as well understood. nausea may occur with vomiting or without therefore there might be different physiological funcitons

where does the vomiting centre get it's inputs from?

nucleus tractus solitaris chemoreceptor trigger zone higher centres

how is aprepitant administered?

oral or IV

what is the administration for scopolamine?

oral or trasdermal patch

how is chlorpromazine administered?

orally IV suppository

how is dolasetron administered?

orally or injected (esp if nausea is already present)

what stimulates the higher centres? via what?

pain repulsive sights repulsive smells emotional factors -via. sensory afferents and CNS pathways

what is scopolamine mainly used for?

prophylaxis - treatment given to prevent disease motion sickness

Muscarinic receptor antagonist drugs?

scopolamine

what are the unwanted effects of chlorpromazine?

sedation, hypotension, extrapyramidal symptoms

what is chlorpromazine common used for?

severe nausea vomiting associated with cancer, radiation therapy, opiods

what stimulates the nucleus of the solitary tract? via what?

stimuli from the pharynx and stomach via visceral afferents

substance P + vomiting...

substance P causes vomiting when injected I.V. and is released by GI vagal afferent nerves and in the vomiting centre itself

What is nabilone?

synthetic cannabinoid that decreases vomiting caused by agents that stimulates the CTZ

what does H1 antagonist do?

they are most commonly used and effective for nausea/vomiting arising from many causes incld. motion sickness and stomach irritants -not very effective for substances acting directly on CTZ

what are the unwanted effects of dolasetron?

uncommon. headaches and GI upsets

What is nausea and vomitting

unwanted side effect of many clinically used drugs, notably those used for chemo. and opioids and general anaesthetics also occurs in motion sickeness, early pregnancy and many disease states and infections.

what is the reflex mechanism of vomiting regulated by?

vomiting center and chemoreceptor trigger zone

what are the 4 mechanisms involved in vomiting?

- reverse peristalsis - relaxation of the lower esophageal sphincter - inhibition of the respiratory center - contraction of diaphragm and abdominal muscles

what is naloxone?

-antagonises the antiemetic effect (causes vomiting!) -is an opioid antagonist -because its an opioid antagonist it implies that opioid receptors may be important in the mechanism of action

Anti-emetic drugs are:

-mostly receptor antagonists -important as a supplement to chemotherapy as nausea/vomiting from cytotxic drugs are unbearable. -also important in morning sickness though must be wary of potential fetal damage therefore avoidance for 1st trimester recommended.

what are the main neurotransmitters involved with vomiting?

ACh histamine 5HT DA substance P

where is the main site of action for any emetic/antiemetic drugs?

CTZ

where is the primary site of dolasetron action?

CTZ

how does chlorpromazine and other antipsychotics act mainly as?

D2 antagonist at the CTZ also blocks histamine and musarinic receptors too

what cannabinoid can be used as an antiemetic?

nabilone

5HT3 receptor antagonist drugs?

dolasetron

what are the unwanted effects of naloxone?

drowsiness dizziness dry mouth mood changes postural hypotention

what are the side effects of H1 antagonists?

drowsiness and sedation

what are the unwanted side effects of scopolamine?

dry mouth blurred vision drowsiness - but less than antihistamines because of poor CNS prenetration

what is aprepitant used for?

effective at controlling late phase of emesis from cytotoxic drugs with few unwanted effects

what has been implicated in vomiting mediation?

enkephalins acting at the delta receptors in the CTZ and at the mu receptors at the vomiting centre. substance P acting at the neurokinin-1 receptors in the CTZ and endocannabinoids may also be involved

what is the chemoreceptor trigger zone (CTZ)?

located in the area postrema on the floor of the 4th ventricle in the medulla that receives input from bloodborne toxins, drugs, hormones, and local disease to communicate with the vomiting centre to initiate vomiting


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