Antiemetics Flashcards
Are male or female more at risk for PONV?
female, especially with PDNV
Results of PONV
delayed discharge
increased cost and convenience
electrolyte imbalance
increased bleeding
Risk Factors for PONV in Adults
–Positive overall
Female sex (B1) History of PONV or motion sickness Nonsmoking (B1) Younger age (B1) General versus regional anesthesia Use of volatile anesthetics and nitrous Postoperative opioids Duration of anesthesia (B1) Type of surgery
what types of surgeries are at greater risk for PONV?
choley, laparoscopic, gynecologic
What 4 things are taken into account with the apfel risk score for PONV?
female gender
non-smoker
history of PONV
postoperative opioids
5 risk factors for PDNV in adults?
female sex hx PONV Age <50 use of opioids in pacu nausea in pacu
Risk factors peds?
increased incidence age 3 thru puberty, NOT gender specific
vomiting incidence is 2X adults at 40%
6 things to minimize PONV risk factors
- avoid GA
- use propofol
- avoid nitrous
- avoid volatiles
- minimize opioids
- hydrate
Pathophysiology of PONV
Brainstem vomiting center located in
the lateral medullary reticular
formation
7 receptors involved with patho of PONV?
Acetylcholine - Muscarinic Histamine H1 Serotonin 5-HT3 Dopamine Substance P GABA Neurokinin-1
Afferent Input to the Vomiting Center - Chemoreceptor trigger zone (4th ventricle) receptors activated
dopamine, serotonin 5-HT, opioid receptors
Afferent Input to the Vomiting Center -Vestibular system (motion sickness) receptors activated
muscarinic and H1 receptors
Irritation of the pharynx (vagus nerve) causes
gag and retch response
Vagal and enteric afferents (mucosa of the GI
tract)
5-HT33 receptors activated by serotonin released by the receptors activated by serotonin released by the
mucosa, then stimulate vagal input to CTZ and vomiting center
CNS afferent input to vomiting center?
stress and anticipatory vomiting
the vomiting center sends efferent signals via which cranial nerves
V, VII, IX, X, XII through pns fibers and alpha motor neurons
where does the efferent output from the emetic center travel through?
phrenic and spinal nerves of abd wall musculature
CTZ stand for?
chemoreceptive trigger zone
decreasing dopamine input at the chemoreceptor trigger zone as well as anxiolysis; it may also decrease adenosine reuptake leading to decreased synthesis, release, and postsynaptic action of dopamine at the CTZ
benzodiazepines
when should you give a benzo if using solely as antiemetic?
end of the case
MOA: Anticholinergic effect, histamine receptor
blockade
antihistamines
3 antihistamines you can give as antiemetic
diphenhydramine, meclizine, dimenhydrinate
What type of PONV do antihistamines work best for?
motion sickness, weak effect with other causes
limitations of antihistamines for PONV?
sedation, dizziness, confusion, dry mouth, urinary retention
MOA: Inhibition of dopamine and muscarinic
receptors
phenothiazines
2 examples of phenothiazines?
Prochlorperazine (Compazine 2.5-10mg IV),
promethazine (Phenergan 25mg IV)
Limitations phenothiazines
sedation extrapyramidal effects lowers seizure threshold hypotension (alpha blockade) pseudoparkinson's
MOA: Antimuscarinic (vestibular system), antagonizes histamine and serotonin
Blocks transmission to the medulla of impulses from overstimulation of vestibular apparatus
scopolamine
how should you apply scopolamine patch?
Apply patch 60 minutes prior to induction and it can provide adequate drug levels for 48-72 hours. (5 mcg/hr for 72 hours – total dose absorbed less than 0.5 mg)
Limitations scopolamine?
ocular effects (glaucoma), restlessness, delirium, sedation, dry mouth, tachycardia
MOA: Dopamine blockade (alpha blockade)
Extremely sedating, dissociative state
Butyrophenones (droperidol, Inapsine)
Dose of Butyrophenones (droperidol, Inapsine)
Dose: 0.625-1.25 mg IV (0.05 mg/kg)
MAX 2.5 mg
Limitations butyrophenones
prolonged QT interval (torsade de pointes), extrapyramidal effects (Parkinson’s, elderly avoid), hypotension, sedation
how to treat extrapyramidal effects of Butyrophenones (droperidol, Inapsine)
benadryl
MOA: Dopamine blockade in the CTZ and cholinergic stimulus to GI tract (increased gastric and small intestine motility)
Metoclopramide (Reglan)
increased incidence of extrapyramidal effects (restlessness, dystonias, parkinsonian) with reglan when given with
phenothiazines or droperidol
Avoid reglan with:
: intestinal obstruction, Parkinson’s
WHAT IS Serotonin (5-HT)
endogenous vasoactive substance and neurotransmitter (emesis and pain), cerebral stimulant stored in enterochromaffin cells of GI tract
4 types of 5 HT receptors
1F – cerebral vasoconstriction (agonist for migraines)
2 – coronary artery and pulmonary vessel vasoconstriction with stimulation
3 – PNS – visceral pain; CNS – emesis, appetite, addiction, pain, and anxiety (antagonism for antiemetic)
4 – gastrokinesis (agonist to treat constipation, IBS)
Serotonin 5-HT3 Receptor Antagonists are appropriate for what types of patients and not appropriate?
Chemotherapy induced NV, PONV (not effective in motion sickness)
MOA: Block peripheral receptors on the intestinal vagal afferents and central receptors in the vomiting center, CTZ (vagal stimulation)
Serotonin 5-HT3 Receptor Antagonists
what receptors do Serotonin 5-HT3 Receptor Antagonists NOT effect and why is this important?
NO effect on the dopamine, histamine, adrenergic, or muscarinic receptors (no Parkinsonian, restlessness, hypotension, or sedation)
MINIMAL SIDE EFFECTS
examples of Serotonin 5-HT3 Receptor Antagonists
Ondansetron (Zofran) 4-8 mg (0.15mg/kg) IV
Dolasetron (Anzemet) 12.5 mg IV
Granisetron (Kytril) 1 mg (0.01 mg/kg) IV
Palonosetron (Aloxi) 0.075 mg IV
Side effect Serotonin 5-HT3 Receptor Antagonists
: headache, constipation, theoretically cardiac arrhythmias (Anzemet)
Limitation Serotonin 5-HT3 Receptor Antagonists
cost, prolonged QT interval
MOA: Unknown mechanism – possibly inhibit prostaglandin synthesis centrally and control endorphin release
Corticosteroids
Enhances the effectiveness of 5-HT3 antagonists (6-10 mg)
Corticosteroids
Dexamethasone (Decadron) dose
0.15 mg/kg
Limitations corticosteroids?
: (chronic therapy) interference with healing, immune suppression, ? avascular necrosis, increased blood glucose in diabetic and obese patients
when should you give scopalamine patch?
prior to induction
when should you give dexamethasone?
at induction, every other drug given towards the end
Choice of antiemetic agent? 6 things
Risk factors
Patient factors – gender, age, medical status
Side effects
History – PONV, motion sickness
Cost – is cheaper really the most cost-effective choice?
Surgical procedure
Guidelines
Identify patients at high risk
Reduce baseline risks of PONV
Use prophylaxis with high risk and, maybe, moderate risk patients
Use appropriate rescue treatment
Use prophylaxis with high risk and, maybe, moderate risk patients by
Consider 5-HT3 antagonist + 2nd agent
when can you give 5HT3 dose?
If within 6 hours, don’t redose with 5-HT3 antagonist – no additional benefit
If after 6 hours, repeat dose of 5-HT3 antagonist and second agent from different class.
what is Neurokinin (NK1), Substance P
Substance P is the natural ligand of the neurokinin receptor found in the area postrema, nucleus of the solitary tract and afferent fibers of the vagus nerve
Antagonist of the NK1 receptor
Approved by FDA for PONV prophylaxis
40 mg po one hour preop
[subtance P]
aprepitant (emend)
Alternative Treatments
acupressure
hypnosis
propofol – 0.5 mg/kg or 10-15 mg (sub-induction dose)
Ephedrine – IM dose of 0.5 mg/kg = droperidol iv
