Anti Emetic & Motility Flashcards
Vomiting center location
Ill-defined
In the medulla oblongata, consists of tractus solitarius and parts of reticular formation
Neurotransmitters involved in NV
Substance P
Acetylcholine
Y-aminobutyric acid
Cannabinoids
Serotonin
Dopamine
Chemoreceptor trigger zone
Highly vascular
Lacks true blood brain barrier-direct stimulation of circulating toxins
Communicates with vomiting center via D2 and 5-HT3 receptors
PONV factors
Women/non-smokers/hx of motion sickness
Length of procedure/type of procedure
Inhaled anesthetics, nitrous, opioids, neostigmine
Serotonin receptor antagonists (5-HT3)
Competitive antagonism of 5-HT3 receptors- very specific and free of neurological effects
Not effective for Motion induced NV
CYP450 and renal elimination
Ex Ondansetron
Ondansetron
Therapeutic after 30-60 min-typically given on induction
Half-life 4 hours
Adult 4-8mg
QTc
Granisetron and Dolasetron
Similar to zofran
Double the half-life- typically used in chemo
Palonosetron
Most effective 5-HT3 antagonist
40hr half-life…
Not used in anesthesia!! But fda approved for chemo
Dopamine receptor antagonists
Dopamine receptor blocker in the CNS-blocks adenylate cyclase to reduce cAMP….
Avoid in Parkinson’s
Increase EPS
Serotonin cascade
Serotonin is released from enterochromaffin cells of small intestine
- vagal afferents stimulated via 5-HT3 receptors
-initiates vomiting reflex.
Dopamine antagonist ex
Droperidol- QTc… eeek
Haloperidol (butyrophenone)-
Metoclopramide (benzamide)- antiemetic and prokinetic via GI cholinergic mechanisms
Corticosteroids MOA
Synthetic glucocorticoid with anti inflammatory properties
Elusive
Decreases serotonin release
Acts on glucocorticoid receptors in vomiting center
Primarily dexamethasone is given 4-8mg
Dexamethasone considerations
Perineal itching in awake patients
2 hour onset
Combine with 5-ht3
Transient hyperglycemia-careful in diabetics
And avoid in acute leukemia due to tumor lysis syndrome
Neurokinin-1 receptor antagonists
Competitive antagonism with substance P at central GPCRs (NK receptors)
Aprepitant
Only NK-1 approved by FDA
50% reduction in NV
PO only 40mg preop
Well tolerated w/out QTc
Anticholinergics MOA anti emetics
Ach acts on the CTZ, vestibular system and cerebellum
Blocking cholinergic impulses to vomiting center
Scopolamine- single most effective for motion sickness
Scopolamine
Anticholinergic
PO/IV/TD
4 hour onset with peak at 8-12 hrs up to 72 hours
Can be applied night before surgery
Treatment of side effects with physostigmine…other anticholinesterases are ineffective
Histamine receptor antagonists
Potentially acts on receptors in vestibular system and vomiting center
Sedation!!
Benadryl and Dramine
Promethazine- do not give IV
GABA agonists MOA anti-emetic
Elusive lol
Propofol-Rescue dosing in PACU- as effective as zofran with faster onset… 20mg
Can also give benzos
Opioid antagonists in antiemetic
Naloxone… can give low dose infusion in attempt to nor reverse analgesia
Cannabionoids
Not recommended in prevention
Have not been shown effective in PONV but are useful in chemotherapy
Oral antacids
Raise pH and increase gastric volume (30ml administration)
Quick acting 15-20 min
Histamine receptor antagonists in GI motility
Reduce Gastric volume
Do not alter pH of current stomach contents but do decrease secretion of hydrogen ion
Attach the receptor and prevent response mediated by histamine…
H2!!! No H1
1-3 hour onset
Ex> famotidine-Pepcid
Cimetidine-impairs CYP system, AMS in elderly
Proton Pump inhibitor
Decrease pH, no impact on volume
Inhibit secretion from gastric parietal cells
Some interfere with CYP but to a lesser extent than H2
Can take several days to have desired effect, given IV they take about an hour….
Metoclopramide….
Prokinetic
Improve gastric emptying=reduce volume
Does not alter hydrogen ion
Give 15-30 min prior
Beneficial with: “full stomach”, obesity, diabetic gastroparesis, parturients
Dopamine antagonist… do not give in Parkinson’s!
Risk factors for PONV
Female
Non smoker
Opioids
Previous hx
Name first gen 5-HT3 antagonists and main complication
Ondansetron
Granisetron
Dolasetron
QTc prolongation
Name first gen 5-HT3 antagonists and main complication
Ondansetron
Granisetron
Dolasetron
QTc prolongation
Populations with special considerations for corticosteroid administration
Diabetic
Cancer- tumor lysis syndrome
Drug with CYP inhibition and numerous drug interactions
Cimeditine
Signal cascade for vomiting center diagram
