Antiemetics Flashcards
What causes nausea
Physiologic, Metabolic, Treatment related, and Emotional.spiritual/psych all transmit signals to the Vomiting center of the brain AKA the lower medulla
What receptors are associated with nausea and vomiting
Cytotoxics, opiates: D2, 5HT3, NK1
Pain, anxiety, depression: H1, GABA in cortex and thalamus
Vertigo, motion: AChM, H1 in vestibular system
Cytotoxics, gastric irritants, ipecac: 5HT3 in GI
ALL those report to Emesis center receptors: AChM, H1, 5HT3, mu, and NK1
What is the “vomiting center”
Neuronal region in lateral medullary reticular formation
Coordinates vomiting thru CN VIII and X (control respiratory, salivatory, and vasomotor centers)
High concentrations in M1, H1, NK1, D2, GABA, and 5-HT receptors in the vomiting center
What are 4 important sources of afferent input to vomiting center
- Chemoreceptor trigger zone: emetogenic stimuli
- Vestibular system: motion sickness
- Vagal and spinal afferent nerves (from GI): chemo, radiation, distention, gastroenteritis
- CNS: psych d/p, stress, anticipatory vomiting before chemo
How does N/V present
Simple: self limiting, resolves spontaneously, requires Sx therapy. complain of “queasy” or discomfort
Complex: no relief after anti-emetic. Noxious agents or psych events. can cause weight loss, fever, abdominal pain
What lab tests can you get for n/v
simple: none
complex: Electrolytes, upper and lower GI eval
Both: fluid input/output, Med history, recent behavior or visual change, HA, pain, stress, or FHx of psychogenic vomiting
Treatment of choice for n/v involves
ID of neurotransmitters involved with emesis!
Can use combo meds that have different MOA, esp if vomiting 2/2 chemo
MC drugs used are
Antacids Antihistamine/anticholinergic Benzodiasepines Corticosteroids 5-HT receptor antagonists Phenothiazine Substance P/NK1 receptor antagonist
When should Antacids be used
Simple N/VUse sodium bicarbonate, calcium carbonate, magnesium hydroxide, or aluminum hydroxide
OTC liquid or oral
Slide 14 says ADE
Listen to recording
What are the serotonin antagonists (5HT3)
Ondansetron
Granisetron
Dolasetron
Palonosteron
What is the PK of 5-HT3 antagonists
Centrally block the 5HT3 receptors, which are in the vomiting center on extrinsic intestinal vagal and spinal afferent nerves
Antiemetic action of 5-HT3 antagonists is restricted to emesis attributable to
Vagal stimulation (post-op)
Chemotherapy
-NOT good for motion sickness
What is palonosetron
New IV agent with greater affinity for 5HT3 receptors
Has longer half life (40 hours)
-All others have a half life 4-9 hrs and PO or IV
What happens to 5HT3 antagonists in the body
Extensive hepatic metabolism
Renal and hepatic excretion
Do not inhibit dopamine or muscarinic receptors
No effect on esophageal or gastric motility
May slow colonic transit**
Do you need to adjust 5HT3 antagonists
NO dose reduction in elderly with renal excretion
Only reduce Zofran dose if w/ hepatic insufficiency
When should you take 5HT3 antagonists for chemo
IV, 30 minutes prior to getting chemo
PO 1 hr before chemo (but higher doses)
They are preventive, but have little efficacy in curing delayed n/v
Efficacy enhanced if combined w/ corticosteroid (DXM) or NK antagonist
5HT3 antagonists are also used for
post-op and post-radiation n/v, esp whole body radiation
What are ADE of 5HT3 antagonists
Headache*
Constipation*
Dizziness
QT prolongation (esp. dolasetron)
5HT3 antagonists interact with
Nothing significant!
Some CYP450 hepatic metabolism
But do not affect metabolism of other drugs
Slide 22, listen (red question marks)
What are NK1 antagonists
Aprepitant (emend), Fosaprepitant, Rolapitant (varubi); Netupitant + Palonosetron (Akynzeo) for acute and delayed prevention
They provide relief from delayed emesis associated with emetogenic meds
What are the ADE of NK1 antagonists
Constipation
diarrhea
HA
hiccups
What do you monitor when on NK1 antagonists
assess for efficacy as prophylaxis
episodes of n/v and hydration status
What antihistamines are used for nausea
Dimenhydrinate (Dramamine) OTC Diphenhydramine (Benadryl) Rx/OTC Hydroxizine (vistaril, atarax) Rx Meclizine (bonine, antivert) RX/OTC Scopolamine (transderm scop) Rx Trimethobenzamide (tigan) Rx
