Antiemetics Flashcards
How many patients experience PONV?
20-30%
Increased in pediatrics (children >3yo)
Patients w/ risk factors increases to 70-80%
PONV associated with
Delayed recovery
Patient dissatisfaction
Most common complication observed in PACU
Reason for hospitalization following ambulatory surgery
50% patients w/ emesis in PACU will continue to experience PONV when d/c home
How to prevent and treat PONV
Target various pathways associated w/ N/V (different receptors)
Peripherally & centrally acting
Combination therapies
Patient Risk Factors
Female (unknown genetic cause)
History PONV or motion sickness
Non-smoker
Age (risk decreases by 10% per decade in adults >50yo)
Pediatrics 3-12yo highest age risk
Apprehension = swallowing air → abdominal distension & ↑ catecholamines
Gastroparesis & recent food ingestion r/t stomach contents
Surgical Risk Factors
Increased anesthetic or surgery duration
Each 30min increases PONV risk by 60% from initial score
Surgery type - laparoscopic, ophthalmic, ENT, T&A, breast, GU, & GYN
Anesthesia Risk Factors
Pre-op opioid analgesics administration - receptor site stimulation & serotonin release
Inhalational induction - PPV causes gastric distension
Volatile anesthetic agents (dose dependent & exposure time w/ surgery duration)
Nitrous oxide causes ↑ middle ear pressure, GI distension, & sympathetic nerve activation
*Maintenance - longer anesthesia time, general, opioid admin → highest risk
Consider Propofol as maintenance anesthetic rather than volatile gas for high risk patients
Propofol found to result in less PONV than other hypnotic agents
Post-op Risk Factors
Ambulation
Postural hypotension
Uncontrolled pain ↑ catecholamines & endogenous nociceptor activators such as serotonin
Post-op opioid administration (regardless if opioid-free anesthesia)
Early PO intake
Lower FiO2 concentration
Reversal agents such as Neostigmine >2.5mg
How to treat at-risk patients?
MULTI-MODAL APPROACH
Benefit from one or more prophylactic measures
Target different receptors & pathways
SAMBA
Society of Ambulatory Anesthesia
Identify at-risk patients for PONV
Employ management strategies to reduce risk
1-2 prophylactic measures in moderate risk adults
Multiple interventions in patients at high risk
Failed prophylaxis treatment
Try another antiemetic to target different receptor
Different pharmacological class
Apfel Score
Female gender
Nonsmoker
PONV history
Post-op opioids
Combination Therapy
Targets multiple receptors
Rapid onset & longer duration to cover post-op period
High risk patients will benefit from combo therapy
Utilize for certain surgical procedures including gastric, esophageal, plastics, ↑ ICP, mandibular jaw wiring, & eye
Direct Triggers
Noxious stimuli, toxins, drugs, or irritants
Indirect Triggers
Vomiting center in medulla oblongata stimulation
- Cerebral cortex/thalamus
- Vestibular apparatus
- Vagal afferent GI tracts
- Chemoreceptor trigger zone (CTZ)
Pathway
Efferent motor nerves travel through cranial nerves V, VII, IX, X, XII, sympathetic, & spinal nerves to stimulate various areas
Receptors
5-hydroxytryptamine (serotonin) - Ondansetron, Palonosetron, Dolasetron Dopamine (D2) - Droperidol, Prochlorperazine, Metoclopramide Histamine - Dimenhydrinate, Promethazine Muscarinic - Promethazine, Scopolamine Opioid
Serotonin Receptor Antagonists
Most common in practice
5-HT3 receptor subtype mediates vomiting
Ion channel found in the GI tract (abdominal vagal afferents) & brain (CTZ area postrema & NTS)
- Outside the blood-brain barrier
- Trigger zone activated by anesthetics & opioids
- Signals nucleus tractus solitarius resulting in PONV
- GI emetogenic stimuli
Antagonists inhibit central & peripheral stimulation
Effective, well-tolerated, & no sedation
Administer near end surgery
Ondansetron (Zofran)
Selective serotonin type 3 receptor antagonist
Most common antiemetic
Effective prophylactic & post-op antiemetic to prevent & treat PONV
Most effective when administered toward end surgical procedure
Ondansetron PK
Onset 30min
Peak plasma almost immediate
60% bioavailability
70% protein binding
Metabolism: CYP450 (liver) hydroxylation & conjugation
Decrease dose in liver failure patients - severe hepatic impairment will decrease clearance d/t ↑ plasma half-life (do not exceed 8mg/day)
No renal dose adjustment <5% metabolized by kidneys
Half-life 4hrs
Excreted via urine/feces
Ondansetron Dose
PO 4-8mg pre-op prophylaxis 16mg 1x prior to induction IV 4mg Do not administer > 16mg IV FDA warning based on 32mg QT prolongation risk
Ondansetron SE
Headache (mild to moderate) Dizziness Diarrhea Constipation QTc prolongation
Palonosetron
Selective serotonin type 3 receptor antagonist
Newest & most selective agent
Effective treatment for chemotherapy induced N/V
No safety/efficacy data in patients <18yo
NOT safe for pediatric patients
Palonosetron PK
Increased serotonin receptor affinity 100x
Half-life 40hrs
Therapeutic effects for 72hrs (long-acting)
80% excreted in urine over 6 days
Palonosetron Dose
0.75mg PONV
0.25mg chemo-induced N/V
No dosage adjustments for elderly, renal, or hepatic patients
Dolasetron (Anzemet)
Selective serotonin type 3 receptor antagonist
Dolasetron MOA
Reduce vagus nerve activity to limit vomiting center activation in the medulla oblongata
Dolasetron PK
Immediate onset (fast-acting) 75% protein binding Peak plasma ≈ 40min Duration 4-9hrs Elimination half-life 8hrs Metabolism: CYP450 & kidneys Active metabolite - hydrodolasetron Excreted in urine/feces
Dolasetron SE
Headache
Dizziness
Constipation
Potential QT prolongation
Dolasetron Dose
12.5mg IV
4x dose needed to reach = efficacy to 4mg Zofran
Administer 15min prior to anesthesia off
Single PO 100mg 1-2hrs pre-op effective
Droperiol
Butyrophenone/dopamine receptor antagonist
Derivative structurally similar to Haloperidol
Anxiolytic, sedative, hypnotic, & antiemetic properties
Droperiol MOA
Blocks dopamine receptors (D2)
Antagonist
Droperiol PK
Onset 3-10min (fast-acting) Peak 30min Duration 2-4hrs Metabolism: Liver Excreted via urine 10% unchanged & feces
Droperiol PD
QT prolongation FDA black box warning (5-15mg) Do NOT administer to patients w/ QT interval prolongation Obtain baseline EKG Monitor EKG 2-3hrs after surgery (PACU)
Droperiol Dose
0.625-1.25mg IV/IM
Prochlorperazine (Compazine)
Phenothiazine
Antipsychotic/antiemetic
PONV prophylaxis
Prochlorperazine MOA
Dopaminergic D2 blockade (antagonist)
Histaminergic
Muscarinic
Prochlorperazine PK
Duration 3-4hrs High protein binding 90-99% Peak 2-4hrs Metabolism: Liver primarily Elimination half-life 6-10hrs Excreted via biliary & inactive metabolites in urine
Prochlorperazine PD
Extrapyramidal & anticholinergic SE
Antipsychotic working on muscarinic receptors
Sedation, blurred vision, hypotension, dizziness, restlessness, dystonia
Neuroleptic malignant syndrome NMS
S/S ↑HR, arrhythmias, irregular BP, fever, stiff muscles, diaphoresis, spasms
→ LIFE THREATENING
Prochlorperazine Dose
5-10mg IV/IM prior to induction
IM onset 5-10min
Metoclopramide (Reglan)
Dopamine receptor antagonist, antiemetic, upper GI motility stimulant
Pro-kinetic stimulates motility (gastric emptying) & ↑ lower esophageal sphincter tone
1° choice aspiration risk patients
Gastroparesis, GERD, aspiration pneumonia prophylaxis patients
Metoclopramide MOA
Centrally acting
Dopamine receptor antagonist in CTZ or vomiting center
Peripherally acting as cholinomimetic in GI tract (facilitates ACh transmission at muscarinic receptors)
Metoclopramide PK
Onset 3-5min
Peak 1-2hrs
Duration 1-2hrs
Elimination half-life 5-6hrs
Metabolism: Liver
Excreted via kidneys (modify dose for impaired renal function) urine/feces
Lack sedative properties - does not ↑ PACU stay
Metoclopramide SE
Higher dosages or chronic medication as pro-kinetic → extrapyramidal SE
Contraindicated in seizure, GI obstruction, & Parkinson’s
Avoid in pheochromocytoma - hypertension crisis by releasing catecholamines from tumor
Metoclopramide Dose
10mg IV (5-20mg) 0.1-0.25mg/kg IV Q6-8hrs Slow push over 1-2min to prevent abdominal cramping, anxiety, & restlessness
Aprepitant (Emend)
Neurokinin-1 receptor antagonist
Inhibit substance P at central & peripheral receptors
Aprepitant PK
Elim 1/2 life 9-13hr
Hepatic CYP3A4 metabolism
Aprepitant Dose
40-80mg PO preop
Aprepitant SE
Non-sedative
Fatigue, dizziness, hiccups, heartburn, hypoesthesia, diarrhea, disorientation, anorexia, constipation, dyspepsia, abdominal pain, gastritis, duodenal ulcer
Birth control ineffective for 28 days
Patient teaching use back-up birth control 1mos
Dexamethasone (Decadron)
Long-acting corticosteroid
Exact MOA unknown
Possibly vomiting center but not area postrema
Dexamethasone PK
Onset 2hr Earlier administration more effective Elim 1/2 life 36-54hr Plasma 4-5hr Hepatic metabolism
Dexamethasone Dose
4-10mg
Dexamethasone SE
Perineal pruritis
Contraindicated in uncontrolled infections
Immediate
Dimehydrinate (Dramamine)
Histamine receptor antagonist
Competes w/ histamine at H1 receptors
Blocks CTZ, depresses labyrinthine function, & vestibular stimulation
Dimehydrinate PK
Hepatic metabolism w/ metabolites excreted via urine
Dimehydrinate Dose
1-2mg/kg
50-100mg IV/IM Q4H
Max 100mg
Dimehydrinate Onset & DOA
Immediate
DOA 4-6hr
Dimehydrinate SE
Anticholinergic
Drowsiness, urinary retention, dry mouth, blurred vision, extrapyramidal effects
Sedation common
Promethazine (Phenergan)
Antihistamine H1 antagonist
Anticholinergic
Muscarinic
Avoid in patients >65yo
Promethazine PK
Glucuronidation
Sulfoxidation
Elim 1/2 time 10-19hr
Promethazine Dose
12.5-25mg Q4-6H
IM route preferred
6.25-12.5mg IV
Promethazine Onset & DOA
IM 20min
IV 5min
DOA 4-6hr
IV dilute in 10 or 20mL NS
Admin over 10-15min
Promethazine SE
Confusion, dizziness, dry mouth, constipation Significant sedation (especially w/ opioids) Hypotension
Scopolamine
Muscarinic antagonist
Tertiary amine
Inhibits ACh at PSNS site in CNS, smooth muscle, & secretory glands
Blocks communication b/w vestibule nerves & vomiting center
Avoid in patients w/ closed-angle glaucoma or >65yo
Place night before surgery & keep on at least 24hrs
Scopolamine PK
Onset 2-4hr
DOA 72hr
Elim 1/2 life 4.5hr
Hepatic metabolism
Scopolamine Dose
1.5mg patch
Lipid solubility allows transdermal absorption
Scopolamine SE
Tachycardia (blocks SA node), ↓secretions, relaxes bronchial smooth muscle, ↓GI motility, prolonged gastric emptying, mydriasis, blurred vision, urinary retention
CNS cerebral depression, sedation, & amnesia
Scopolamine Reversal
Physostigmine 0.01-0.03mg/kg IV repeat after 15-30min
Ephedrine
Indirect acting sympathomimetic
Recommended to treat N/V associated w/ postural hypotension
Ephedrine Dose
10-25mg
Midazolam (Versed)
Benzodiazepine
GABA receptor antagonism
Inhibit dopamine release
Midazolam Dose
2mg IV
Pediatric 50-75mcg/kg
