antiemetics Flashcards
Postoperative Nausea and Vomiting
PONV is associated with _____ and ______
Most common complication observed in PACU
– Identify_____ for PONV
– Identify high-risk ______
Most ____ reason (along with _____) for hospitalization following ambulatory surgery
May result in _____ and _____ problems
Postoperative Nausea and Vomiting
PONV is associated with delayed recovery and patient dissatisfaction
Most common complication observed in PACU
– Identify risk factors for PONV
– Identify high-risk populations/surgical patients
Most common reason (along with pain) for hospitalization following ambulatory surgery
May result in incisional stress and postoperative problems
Postoperative Nausea and Vomiting
• Use of _____ to prevent and treat PONV
- Target various _____ associated with nausea and vomiting
- ____ acting
- ____ acting
- _____ therapies
Postoperative Nausea and Vomiting
• Use of antiemetics to prevent and treat PONV
- Target various pathways associated with nausea and vomiting
- Centrally acting
- Peripherally acting
- Combination therapies
Postoperative Nausea and Vomiting
PONV occurs in ____% of general surgical population (___% in children)
Increases to _____% in patients with risk factors
Increased ______ duration leads to increased risk
_______ (SAMBA) Guidelines – ____ scoring system
Multifactorial: ____, ____ and ____l risk factors
** At-risk patients benefit from _____ measures **
Postoperative Nausea and Vomiting
PONV occurs in 20-30% of general surgical population (25-39% in children)
Increases to 70-80% in patients with risk factors
Increased anesthetic duration leads to increased risk
Society of Ambulatory Anesthesia (SAMBA) Guidelines – simplified scoring system
Multifactorial: anesthetic, surgical and individual risk factors
** At-risk patients benefit from one or more prophylactic measures **
Patient Risk Factors for PONV
- ____ gender (overall ____ predictor)
- History of ___ or ____ (___ predisposition)
- ___-smoker
- Age < ___ years (risk decreases by ___% per decade in adults)
- _____ (r/t s____ air and abdominal ____ and increased ____)
- Gastro_____
- Recent food _____
Patient Risk Factors for PONV
- Female gender (overall strongest predictor)
- History of PONV or motion sickness (genetic predisposition)
- Non-smoker
- Age < 50 years (risk decreases by 10% per decade in adults)
- Apprehension (r/t swallowed air and abdominal distention and increased catecholamines)
- Gastroparesis
- Recent food ingestion
Surgical Risk Factors for PONV
Increased _____ of anesthetic/surgery (each ___ min increase in duration increases PONV risk by___0%)
Surgical type (___, ___, _&_, ___, ___/___)
Surgical Risk Factors for PONV
Increased duration of anesthetic/surgery (each 30 min increase in duration increases PONV risk by 60%)
Surgical type (laparoscopy, eye, T&A, breast, GU/GYN)
Anesthesia Risk Factors for PONV
____ analgesics(____ receptor site stimulation and release of ____)
____ induction–gastric ___ from _____
_____ anesthetic agents(____-dependent and ____ among all agents)
___ __(increased __ ____ pressure,____distention and ____ nerve activation)
Maintenance:___ anesthesia time, _____,____ administration
* _____ found to result in less postoperative vomiting than other ___ agents*
Anesthesia Risk Factors for PONV
Opioid analgesics(opioid receptor site stimulation and release of serotonin)
Inhalational induction–gastric distention from PPV
Volatile anesthetic agents(dose-dependent and equivocal among all agents)
Nitrous oxide(increased middle ear pressure,GI distention and sympathetic nerve activation)
Maintenance:Longer anesthesia time,GA,opioid administration
* Propofol found to result in less postoperative vomiting than other hypnotic agents*
Ambulation (especially with ___ analgesics)
_____ hypotension
Uncontrolled ____ (increased ____, endogenous ___ activators such as _____)
Postoperative ____ administration
Early ___ intake
Lower _____ concentration
Reversal agents (____ > _____ mg)
Postanesthetic Risk Factors for PONV
Ambulation (especially with opioid analgesics)
Postural hypotension
Uncontrolled pain (increased catecholamines, endogenous nociceptor activators such as serotonin)
Postoperative opioid administration
Early oral intake
Lower Fi02 concentration
Reversal agents (neostigmine > 2.5 mg)
Strategies to reduce baseline risk
- avoidance of ____ by the use of ____ anesthesia
- Use of ___ for ___ and ____ of anesthesia
- Avoidance of ____ in surgeries lasting over ___ hr
- Avoidance of ____ anesthetics
- Minimization of intraoperative and postoperative ____
- Aquedate ____
- Using _____ rather than ____ for reversal of _____
Strategies to reduce baseline risk
- avoidance of GA by the use of regional anesthesia
- Use of propofol for induction and maintenance of anesthesia
- Avoidance of Nitrous Oxide in surgeries lasting over 1 hr
- Avoidance of volatile anesthetics
- Minimization of intraoperative and postoperative opioids
- Aquedate hydration
- Using Suggamadex rather than neostigmine for reversal of NMBD
Risk Factors for Post-discharge N/V (PDNV)
- ___ gender
- Age • History of ____
• PONV in ____
Risk Factors for Post-discharge N/V (PDNV)
- Female gender
- Age<50 years
- History of PONV
• PONV in PACU
SAMBA Guidelines
Identify ____ at risk for PONV
Employ ____ ______ to reduce PONV risk
Employ ___or ___ ____ measures in ___ at ____ risk
Use ____ interventions in patients at ___ PONV risk
Administer ____ antiemetic therapy to ____ at high risk using ____ therapy
Provide ____ therapy to patients with PONV who did not receive ____ therapy or in whom ______ failed
SAMBA Guidelines
Identify patients at risk for PONV
Employ management strategies to reduce PONV risk
Employ one or two prophylactic measures in adults at moderate risk
Use multiple interventions in patients at high PONV risk
Administer prophylactic antiemetic therapy to children at high risk using combination therapy
Provide antiemetic therapy to patients with PONV who did not receive prophylactic therapy or in whom prophylaxis failed
Apfel score
- ___
- ___
- ___
- ___
Score of _-_ is high, __-__% risk of postop NV
Apfel score
- Female
- nonsmoker
- Hx of PONV
- Postop opioids
Score of 3-4 is high, 60-80% risk of postop NV
Combination Therapy
Antiemetic drugs should be administered ____ or in ____ based on ___ factors
Combination therapy targets ____ receptors
___-onset agent + ____ duration of action
Patients at ____ risk will benefit from ___ therapy
Postop nausea and vomiting treat with ____ pharmacological ____ than the ______ antiemetic administered
Also consider combo therapy for certain surgical procedures: ___, ___, ___, ___, ____, increased ___
Combination Therapy
Antiemetic drugs should be administered singularly or in combination based on risk factors
Combination therapy targets multiple receptors
Rapid-onset agent + longer duration of action
Patients at high risk will benefit from combination therapy
Postop nausea and vomitingàtreat with different pharmacological class than the prophylactic antiemetic administered
Also consider combo therapy for certain surgical procedures: gastric, esophageal, plastic, eye, mandibular jaw wiring, increased ICP
Anatomy and Physiology
Vomiting triggered ____ or via ____pathway
– Directly: ___stimuli, __, ___, ____
– ____ pathway: stimulation of vomiting center in ____ _____
- Cerebral ___/____
- ______ apparatus
- ____ afferent ____ tracts
- ______ (CTZ)
– Once activated, efferent motor nerves travel through cranial nerves (_, ___, ___, ___, ___), _____, and ____ nerves to stimulate various parts of body
****You need to remember the stimulation of vomiting center is in ___ ___ and
the _____() is important part of vomiting trigger pathway.
Anatomy and Physiology
Vomiting triggered directly or via indirect pathway
– Directly: noxious stimuli, toxins, drugs, irritants
– Indirect pathway: stimulation of vomiting center in medulla oblongata
- Cerebral cortex/thalamus
- Vestibular apparatus
- Vagal afferent GI tracts
- Chemoreceptor trigger zone (CTZ)
– Once activated, efferent motor nerves travel through cranial nerves (V, VII, IX, X, XII), sympathetic, and spinal nerves to stimulate various parts of body
****You need to remember the stimulation of vomiting center is in medulla oblongata and
the chemoreceptor trigger zone (CTZ) is important part of vomiting trigger pathway.
Receptors thought to be activated include:
– ___
– ____
– ___
– ____
– _____
Receptors thought to be activated include:
– Histamine
– Muscarinic
– Opioid
– Dopamine (D2)
– 5- hydroxytryptamine (serotonin)
Serotonin Receptor Antagonists
Serotonin (5-HT): ___ and ____ tract
Important _____ in CNS
______ inactivates serotonin
At least _____ receptor subtypes
******_____ receptor mediates vomiting and is found in ___ tract (abdominal ____ afferents) and ____ (____ zone of area ___ and _____)
Serotonin Receptor Antagonists
Serotonin (5-HT): platelets and GI tract
Important neurotransmitter in CNS
Monoamine oxidase inactivates serotonin
At least seven receptor subtypes
*****5-HT3 receptor mediates vomiting and is found in GI tract (abdominal vagal afferents) and brain (chemoreceptor trigger zone of area postrema and nucleus tractus solitarius)
Serotonin
Effects of 5-HT3 receptor mediated via ____ channel (other 5-HT receptors are _____ receptors)
5-HT3 receptors in area ___ ___ BBB
Trigger zone activated by ____ and _____
Signals ______ resulting in PONV
GI emetogenic stimuli simulate development of PONV in ____ way
Serotonin
Effects of 5-HT3 receptor mediated via ion channel (other 5-HT receptors are G-protein coupled receptors)
5-HT3 receptors in area postrema outside BBB
Trigger zone activated by anesthetics and opioids
Signals nucleus tractus solitarius resulting in PONV
GI emetogenic stimuli simulate development of PONV in similar way
Serotonin
Systemic Effects
CV: powerful ____ (exceptin ___/____), ____ effect in heart is ____ dependent, may lead to increases in _____ and ____ with reflex ____ after
Resp: increased ___ _____
GI: release of ____ in ______ increases _____
Serotonin
Systemic Effects
CV: powerful vasoconstrictor (exceptin heart/skeletal muscle), vasodilator effect in heart is endothelium dependent, may lead to increases in cardiac contractility and heart rate with reflex bradycardia after
Resp: increased airway resistance
GI: release of Ach in myenteric plexus increases peristalsis
Serotonin Receptor Antagonists
5-HT3 receptors are gated ____channels that can be found in the ___/____
– Especially in ____, and ___ fibers of ___ nerve in ___ tract/___
Serotonin receptor antagonists inhibit ___ and ____ stimulation of 5-HT3 receptors
Effective, do not cause ___ and well ___
Generally administered at the ____ of surgery
Side effects: (Well tolerated) ___, prolonged ____
****Medications: ___, ___ and ____
Serotonin Receptor Antagonists
5-HT3 receptors are gated Na+/K+ channels that can be found in the CNS/PNS
– Especially in CTZ, and afferent fibers of vagus nerve in GI tract/CNS
Serotonin receptor antagonists inhibit central and peripheral stimulation of 5-HT3 receptors
Effective, do not cause sedation and well tolerated
Generally administered at the end of surgery
Side effects: (Well tolerated) Headache, prolonged QT interval
****Medications: Ondansetron, Palonosetron and Dolasetron
Ondansetron (Zofran)
Selective Serotonin Type___ Receptor Antagonist
Dose PO: __or ____mg (For PONV prophylaxis, ___ mg PO dose x 1 ___ hour before ___ of ___)
Dose: ___ mg single dose___(___ mg/kg if < ____ kg)
Half-life:____ hours (dose towards end of surgery)
Onset: ____minutes
Peak plasma: almost immediate
Ondansetron (Zofran)
Selective Serotonin Type 3 Receptor Antagonist
Dose PO: 4 or 8 mg (For PONV prophylaxis, 16 mg PO dose x 1 one hour before induction of anesthesia)
Dose: 4 mg single dose IV (0.1 mg/kg if < 40 kg)
Half-life: 4 hours (dose towards end of surgery)
Onset: 30 minutes
Peak plasma: almost immediate
- Bioavailability:___%
- Protein binding: __-____%
- Metabolism: Liver (CYP___, CYP___, CYP____)
Extensive metabolism in liver by ____ and ____ CYP-450; less than ___% metabolized by kidneys (___renal dose adjustment)
- Bioavailability:60%
- Protein binding: 70-76%
- Metabolism: Liver (CYP3A4, CYP1A2, CYP2D6)
Extensive metabolism in liver by hydroxylation and conjugation CYP-450; less than 5% metabolized by kidneys (no renal dose adjustment)
Ondansetron (Zofran)
Elimination half-life: 3-7 hours
Excretion:urine(30-70%)/feces(25%)
Severe ____ impairment will decrease clearance due to increase in plasma half-life (daily dose not to exceed ___mg)
Side effects (mild to moderate): headache, dizziness, diarrhea, constipation, QTc prolongation
Ondansetron (Zofran)
Elimination half-life: 3-7 hours
Excretion:urine(30-70%)/feces(25%)
Severe hepatic impairment will decrease clearance due to increase in plasma half-life (daily dose not to exceed 8 mg)
Side effects (mild to moderate): headache, dizziness, diarrhea, constipation, QTc prolongation
Ondansetron (Zofran)
Effective _____ in preventing vomiting ____
Effective in treating ____ vomiting
Most effective when administered at the ____ of the surgical procedure
Studies have shown ___ mg = ____mg IV in PACU as ___ for N/V
Ondansetron (Zofran)
Effective preoperatively in preventing vomiting intraoperatively
Effective in treating postoperative vomiting
Most effective when administered at the end of thesurgical procedure
Studies have shown 4 mg = 8 mg IV in PACU as rescue for N/V
Palonosetron (Aloxi)
____ generation serotonin antagonist
Most ____ - greater ___ for serotonin receptor by ___-fold
One of the most effective treatments for ____- induced N/V and PONV
Palonosetron (Aloxi)
Second generation serotonin antagonist
Most selective - greater affinity for serotonin receptor by 100-fold
One of the most effective treatments for chemotherapy- induced N/V and PONV
Palonosetron (Aloxi)
Half-life: ____ hours (therapeutic effects for ____ hours)
Dosing:____ mg PONV; _____ chemo-induced N/V
Excretion: more than ___% excreted in ____ over ___days and ____amount is unchanged
____ dosage adjustments for ___, ___, ____ pts.
No __/___ data in patients < ____years of age
Palonosetron (Aloxi)
Half-life: 40 hours (therapeutic effects for 72 hours)
Dosing: 0.75 mg PONV; 0.25mg chemo-induced N/V
Excretion: more than 80% excreted in urine over 6 days and 1⁄2 amount is unchanged
No dosage adjustments for elderly, renal, hepatic pts.
No safety/efficacy data in patients < 18 years of age
