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
Dolasetron (Anzemet)
___ serotonin type 3 receptor antagonist (highly ___ and ___)
MOA: reduce activity of ____ nerve to limit activation of the ___ center in ___ ___
Dose: ____ mg IV
DOA: ___ hours
Protein binding: ___-____%
Elimination half-life: _____ hours
Elimination: ___, ___
***Onset: ____
Peak plasma: ____minutes
Dolasetron (Anzemet)
Selective serotonin type 3 receptor antagonist (highly specific and selective)
MOA: reduce activity of vagus nerve to limit activation of the vomiting center in medulla oblongata
Dose: 12.5 mg IV
DOA: 4-9 hours
Protein binding: 69-77%
Elimination half-life: 8.1 hours
Elimination: liver (CYP450), kidneys
Onset: ~immediate
Peak plasma: 36 minutes
Dolasetron (Anzemet)
Administer within ____minutes before the end of anesthesia
Single oral dose ___mg ____ hours preop is effective also
One study: ____mg IV shown to have equal efficacy as ___mg ____ in preventing PONV
Adverse effects: ___, ___, ___, potential for ___
Active metabolite: ____
Excretion: ___/_____
Dolasetron (Anzemet)
Administer within 15 minutes before the end of anesthesia
Single oral dose 100 mg 1-2 hours preop is effective also
One study: 50 mg IV shown to have equal efficacy as 4 mg ondansetron in preventing PONV
Adverse effects: headache, dizziness, constipation, potential for QT prolongation
Active metabolite: hydrodolasetron
Excretion: urine/feces
Droperidol
_____ derivative structurally similar to ____
Class: ___/____ receptor antagonist
MOA: blocks ____ receptors that contribute to development of PONV
___, ___, __ and ___ properties
Dosing: ___-____ mg ___(slow) or ___
Droperidol
Butyropheone derivative structurally similar to haloperidol
Class: Butyrophenone/dopamine receptor antagonist
MOA: blocks dopamine receptors that contribute to development of PONV
Anxiolytic, sedative, hypnotic and antiemetic properties
Dosing: 0.625-1.25 mg IV (slow) or IM
Droperidol
Onset:__ to ___ minutes
Peak: ____minutes
Duration of action: _-__hours
Metabolism: ___
Excretion: ___ (___% unchanged) and ___
***_____
Doses in FDA black box warning __-___ mg
No ____ that use of droperidol at doses used for PONV prophylaxis increases risk of sudden ____ in perioperative population
Droperidol
Onset: 3 to 10 minutes
Peak: 30 minutes
Duration of action: 2-4 hours
Metabolism: Liver
Excretion: Urine (10% unchanged) and feces
***QT interval prolongation
Doses in FDA black box warning 5-15 mg
No evidence that use of droperidol at doses used for PONV prophylaxis increases risk of sudden cardiac death in perioperative population
Droperidol
__-___ mcg/kg IV effective in reducing vomiting
___ mcg/kg IV immediately after induction superior to __ __-___ mg PO in reducing PONV
______dose causes prolonged sedation (increased PACU _____)
High dose (____) – increased side effects: __, __, __, __, ___ side effects
FDA: ____ monitoring of patients for ___hours after administration (clinical relevance?)
Decreased use in clinical practice because of _____
Dropedridol
10-20 mcg/kg IV effective in reducing vomiting
20 mcg/kg IV immediately after induction superior to metoclopramide 5-10 mg PO in reducing PONV
20 mcg/kg dose causes prolonged sedation (increased PACU LOS)
High dose (50-75 mcg/kg) – increased side effects: anxiety, dizziness, drowsiness, hypotension, extrapyramidal side effects
FDA: 12-lead EKG monitoring of patients for 2-3 hours after administration (clinical relevance?)
Decreased use in clinical practice because of FDA advisory
Dopamine receptor antagonists
___ receptors in ____ tract sends signal to ___ to induce n___ in ____ center
___ side effects
Contraindicated in patients with ____ disease
Dopamine receptor antagonists
D2 receptors in GI tract sends signal to CNS to induce nausea and vomiting in vomiting center
Extrapyramidal side effects
Contraindicated in patients with Parkinson’s disease
Prochlorperazine (Compazine)
belongs to: _____
Class: ___/____
MOA: affects multiple receptors - ____, ___ (___ blockade), ____
Used for PONV ___
Dose: _____ IM/IV before induction
IM onset____ minutes
DOA ____ hours
Protein binding: ___%
Peak: _____ hours
Prochlorperazine (Compazine)
Phenothiazine
Class: Antipsychotic/antiemetic
MOA: affects multiple receptors - histaminergic, dopaminergic (D2 blockade), muscarinic
Used for PONV prophylaxis
Dose: 5-10 mg IM/IV before induction
IM onset 5-10 minutes
DOA 3-4 hours
Protein binding: 91-99%
Peak: 2-4 hours
Prochlorperazine (Compazine)
Metabolism: Primarily ____
Elimination half-life: _-___ hours (IV)
Excretion: ___, __ metabolites in ___
May cause ___ and ____ side effects
Adverse effects: ___, ___, __, ___, ____, ___, ___
Prochlorperazine (Compazine)
Metabolism: Primarily liver CYP2D6/CYP3A4
Elimination half-life: 6-10 hours (IV)
Excretion: Biliary, inactive metabolites in urine
May cause extrapyramidal and anticholinergic side effects
Adverse effects: sedation, blurred vision, hypotension, dizziness, neuroleptic malignant syndrome, restlessness, dystonia
Metoclopramide (Reglan)
____ receptor antagonist, antiemetic, ____motility stimulant
MOA: ___ acting as ____ receptor antagonist in ____ center (peripherally acting as ____ in GI tract (facilitates ____ transmission at ____ receptors))
Increases _____tone, speeds ____ time, lowers ____ fluid volume
Metoclopramide (Reglan)
Dopamine receptor antagonist, antiemetic, upper GI motility stimulant
MOA: centrally acting as dopamine receptor antagonist in CTZ/vomit center (peripherally acting as cholinomimetic in GI tract (facilitates Ach transmission at muscarinic receptors))
Increases LES tone, speeds gastric emptying time, lowers gastric fluid volume
Metoclopramide (Reglan)
Efficacious for ___, ____, ____ pneumonia prophylaxis
Dose: ___ mg IV (Range __-___ mg) or___-____ mg/kg IV q __-___hours (Chemotherapy: __-___ mg/kg large doses)
Route: __, ___ push, ___ infusion, ___
IV: Give ___mg slowly over __-___ minutes
Rapid injection->_______
Metoclopramide (Reglan)
Efficacious for gastroparesis, GERD, aspiration pneumonia prophylaxis
Dose: 10 mg IV (Range 5-20 mg) or 0.1-0.25 mg/kg IV q 6-8 hours (Chemotherapy: 1-2 mg/kg large doses)
Route: PO, IV push, IV infusion, IM
IV: Give 10 mg slowly over 1-2 minutes
Rapid injection->abdominal cramping
Metoclopramide (Reglan)
Studies show metoclopramide is ineffective at ___ doses (i.e. ___ IV) unless used in combination with other antiemetics (i.e. ____)
Alone, even ____mg/kg dose is not as effective as ____
Advantage: lack of ___ properties
Sedated PACU patient – ____mg/kg IV
Metoclopramide (Reglan)
Studies show metoclopramide is ineffectiveat lower doses (i.e. 10 mg IV) unless used in combination with other antiemetics (i.e. dexamethasone)
Alone, even 0.5 mg/kg dose is not as effective as ondansetron
Advantage: lack of sedative properties
Sedated PACU patient – 0.15 mg/kg IV
Metoclopramide (Reglan)
Onset: __-___ minutes IV
Peak: ___-____ hours
Duration: ___-____ hours
Metabolism: ____
Elimination: ____excretion (modify for impaired ___ function); elimination half-life __-___ hours
Excretion: urine (__-___%)/feces (___%)
Adverse effects: May cause____side effects in higher doses; contraindicated in ___, ___, ____
**Avoid in ______ (can cause ____ crisis by releasing ____ from tumor)
Metoclopramide (Reglan)
Onset: 3-5 minutes IV
Peak: 1-2 hours
Duration: 1-2 hours
Metabolism: Liver
Elimination: renal excretion (modify for impaired renal function); elimination half-life 5-6 hours
Excretion: urine (70-85%)/feces (2%)
Adverse effects: May cause extrapyramidal side effects in higher doses; contraindicated in Parkinson’s disease, seizure, GI obstruction
**Avoid in pheochromocytoma (can cause HTN crisis by releasing catecholamines from tumor)
Neurokinin 1 Receptor Antagonists
Medications: []
NK receptors are found in ____ and regulate ____ function
NK1 receptor antagonists provide antiemetic activity by suppressing activity at____
___ approved for PONV
Rolapitant half-life of ___ hours(CINV and possible PDNV)
Neurokinin 1 Receptor Antagonists
Medications:Aprepitant(Emend),Fosaprepritant (Emend), Netupitant/palonosetron (Akynzeo), Rolapitant (Varubui)
NK receptors are found in nucleus of solitary tract and regulate visceral function
NK1receptor antagonists provide antiemetic activity by suppressing activity at NST
Aprepitant approved forPONV
Rolapitant half-life of 180 hours(CINV and possible PDNV)
Aprepitant (Emend)
___ receptor antagonist
___ is a neuropeptide that interacts at ___ receptors
MOA: ____ antagonists inhibit ____ at ___ and ___ receptors
Non-___ effects
Aprepitant (Emend)
Neurokinin-1 receptor antagonist
Substance P is a neuropeptidet hat interacts at neurokinin-1 (NK-1) receptors
MOA: NK-1 antagonists inhibit Substance P at central and peripheral receptors
Non-sedative effects
Aprepitant (Emend)
Long half-life: ____hours
Originally used for ___ patients, now available for PONV ____
Dose: _____ PO preoperatively
Recommended for ___ ____patients
Aprepitant (Emend)
Long half-life: 9-13 hours
Originally used for chemotherapy patients, now available for PONV prophylaxis
Dose: 40-80 mg PO preoperatively
Recommended for high-risk non-pregnant patients
Aprepitant (Emend)
Metabolism: ____
Bioavailability:__%
Protein binding: ___%
Elimination half-life ____hours
Excretion:Feces(__%)/urine(___%)
____adjustment for renal failure patients
Aprepitant (Emend)
Metabolism: Liver (mostly CYP3A4)
Bioavailability:60-65%
Protein binding: >95%
Elimination half-life 9-13 hours
Excretion:Feces(86%)/urine(5%)
No dose adjustment for renal failure patients
Aprepitant (Emend)
Adverse effects seen in >___% patients: ___, __, __, ___, N/D, ___, ___, diarrhea, ___, heartburn, abdominal pain, gastritis, p___, ___, etc.
Shown to be more effective than ___ for preventing PONV (esp. in first ____ hours)
If administered with ____, ___ dose by ___ to maintain ___ plasma concentrations
Aprepitant (Emend)
Adverse effects seen in >3% patients: fatigue, dizziness, hypoesthesia, disorientation, N/D, anorexia, constipation, diarrhea, dyspepsia, heartburn, abdominal pain, gastritis, perforating duodenal ulcer, hiccups, etc.
Shown to be more effective than ondansetron for preventing PONV (esp. in first 48 hours)
If administered with dexamethasone, reduce dose by half to maintain dexamethasone plasma concentrations
Dexamethasone (Decadron)
MOA: ____-acting corticosteroid
____ glucocorticoid with ___ and ____ properties
MOA as antiemetic is ____ (possibly acts on ___ center, but not area ___)
Protein binding: ___%
Bioavailability: ____%
Metabolism: ___
Excretion: Urine (___%)
Elimination half-life: Biological ____hr. (plasma half- life _____hrs.)
Dexamethasone (Decadron)
MOA: Long-acting corticosteroid
Synthetic glucocorticoid with anti-inflammatory and immunosuppressant properties
MOA as antiemetic is unknown (possibly acts on vomit center, but not area postrema)
Protein binding: 77%
Bioavailability: 80-90%
Metabolism: Liver
Excretion: Urine (65%)
Elimination half-life: Biological 36-54 hr. (plasma half- life 4-5 hrs.)
Dexamethasone (Decadron)
Dose:____ mg IV for PONV at induction
Minimum ____ to be effective
Peds: ____ mg/kg IV
Onset: ___hours
Peak: ____minutes
Metabolism:____(no adjustment for hepatic/renal failure)
Half-life: ___hours
DOA:____
Dexamethasone (Decadron)
Dose: 4-10 mg IV for PONV at induction
Minimum 5mg to be effective
Peds: 0.2-0.5 mg/kg IV
Onset: 2 hours
Peak: 5-10 minutes
Metabolism:Hepatic(no adjustment for hepatic/renal failure)
Half-life: 1-5 hours
DOA:Short
Adverse effects rare with _____dose
Timing: _____ administration shown to be more effective
Caution:_____ if patient is awake
Absolute contraindications: []
Relative contraindication in ____ patients
Adverse effects rare with one-time dose
Timing: earlier administration shown to be more effective
Caution:perineal pruritis if patient is awake
Absolute contraindications: uncontrolled infections, known hypersensitivity, cerebral malaria, systemic fungal infection, concurrent treatment with live virus vaccine
Relative contraindication in diabetic patients
Dimenhydrinate (Dramamine)
MOA: ___ antagonist – competes with ___ at ____ receptor sites in the ___, ___ and ____; blocks ____, depresses ___ function and ____ stimulation
Histamine found in ___, ____ and in _____
Dimenhydrinate (Dramamine)
MOA: H1 antagonist – competes with histamine at H1 receptor sites in the GI tract, blood vessels and respiratory tract; blocks CTZ, depresses labyrinthine function and vestibular stimulation
Histamine found in CNS, gastric mucosa and in peripheral tissue
Dimenhydrinate (Dramamine)
Histamine ___ arterial BP, ____ HR and myocardial _____, ____ capillary _____, H1 constricts ______/H2 mild ____, increases ____
____dosage adjustment for hepatic/renal failure
Adverse reactions: ___, ____, ___, ____, ____
Commonly causes _____
Dimenhydrinate (Dramamine)
Histamine reduces arterial BP, increases HR and myocardial contractility, increases capillary permeability, H1 constricts bronchiolar smooth muscle/H2 mild bronchodilation, increases gastric acid secretion
No dosage adjustment for hepatic/renal failure
Adverse reactions: drowsiness, urinary retention, dry mouth, blurred vision, extrapyramidal effects
Commonly causes sedation
Dimenhydrinate (Dramamine)
Dose: _____ IV/IM q___h (max dose ___mg q___h)
Onset:____
Duration: ____hours
Peak ___
Metabolism:____
Excretion: metabolites excreted in ___
Dimenhydrinate (Dramamine)
Dose: 50-100 mg IV/IM q4h (max dose 100 mg q4h)
Onset:Immediate
Duration: 4-6 hours
Peak unknown
Metabolism:Liver
Excretion: metabolites excreted in urine
Promethazine (Phenergan)
MOA: ____ (___ antagonist) and __/___- blocking effects responsible for antiemetic activity
Dose: __-__ mg q__-__h
____ route preferred (onset ___ minutes)
IV avoided when possible (onset ___ minutes)
DOA: ___-____ hours
Promethazine (Phenergan)
MOA: Antihistamine (H1 antagonist) and anticholinergic/muscarinic- blocking effects responsible for antiemetic activity
Dose: 12.5-25 mg q4-6h
IM route preferred (onset 20 minutes)
IV avoided when possible (onset 5 minutes)
DOA: 4-6 hours
Promethazine (Phenergan)
Metabolism: ____ (____ and ___)
Excretion:__/___
Elimination half-life: __-___ hours
No dosage adjustment for renal impairment
Bioavailability: ____(decreases to ___% absolute bioavailability after ____ metabolism)
Protein binding: ___%
Promethazine (Phenergan)
Metabolism: Hepatic (glucuronidation and sulfoxidation)
Excretion:kidney/biliary
Elimination half-life: 10-19 hours
No dosage adjustment for renal impairment
Bioavailability: 88% (decreases to 25% absolute bioavailability after first-pass metabolism)
Protein binding: 93%
Promethazine (Phenergan)
Common side effects: __, ___, ___, ___ (avoid in patients > ___years)
Risk of significant ___ (esp. with ___) – ___ utility
____-dose promethazine ____ mg IV recommended for prophylaxis/rescue due to ____ properties
Promethazine___mg more effective than ____ for treating PONV after failed ___ prophylaxis
Promethazine (Phenergan)
Common side effects: confusion, drowsiness, dry mouth, constipation (avoid in patients > 65 years)
Risk of significant sedation (esp. with opioids) – limited utility
Low-dose promethazine 5-10 mg IV recommended for prophylaxis/rescue due to antihistamine properties
Promethazine 6.25 mg more effective than ondansetron for treating PONV after failed ondansetron prophylaxis
Anticholinergics
Scopolamine
MOA: ___ antagonist; inhibits action of __ at ____ sites in __ muscle, ___ and ___ glands
____ amine
Lipid solubility allows for ____ absorption
Blocks communication between nerves of ___ and ___ center in brain (may also directly block ____ center)
Anticholinergics
Scopolamine
MOA: Muscarinic antagonist; inhibits action of Ach at parasympathetic sites in smooth muscle, CNS and secretory glands
Tertiary amine
Lipid solubility allows for transdermal absorption
Blocks communication between nerves of vestibule and vomit center in brain (may also directly block vomiting center)
Scopolamine
Anticholinergics: esters of an aromatic acid combined with organic base – ____ is essential for effective binding of anticholinergics to ____ receptors
_____ blocks binding of Ach at ____ receptors
Blockade of muscarinic receptors with lead to ____cardia (blocks ___ node), inhibits secretions in ____ tract, relaxes ____ smooth muscle, ____ GI motility, _____ gastric emptying time, ___asis and ___plegia, decreased ___ and ___ tone
Scopolamine
Anticholinergics: esters of an aromatic acid combined with organic base – ester linkage is essential for effective binding of anticholinergics to Ach receptors
Competitively blocks binding of Ach at muscarinic receptors
Blockade of muscarinic receptors with lead to tachycardia (blocks SA node), inhibits secretions in respiratory tract, relaxes bronchial smooth muscle, decreased GI motility, prolonged gastric emptying time, mydriasis and cycloplegia, decreased ureter and bladder tone
Many CNS side effects
Scopolamine can cause ____ depression, ____ and ____
Remember _____ (cholinesterase ___) crosses _____ and reverses _____ actions on the brain
– Anticholinergic poisoning: ___, ____, ___, ___, ___, ____, ____
– Physostigmine: dose? IV (repeat after ____ minutes)
Avoid in patients with ______
Many CNS side effects
Scopolamine can cause cerebral depression, sedation and amnesia
Remember physostigmine (cholinesterase inhibitor) crosses BBB and reverses anticholinergic actions on the brain
– Anticholinergic poisoning: agitation, delirium, dry mouth, tachycardia, impaired vision, hallucinations, unconsciousness
– Physostigmine: 0.01-0.03 mg/kg IV (repeat after 15-30 minutes)
Avoid in patients with closed-angle glaucoma
Scopolamine
Dose: (Pre-op) dose? topical patch behind ear the evening before surgery (keep on for ___hours postop)
Onset: ____hours (transdermal)
DOA: _____ hours
Metabolism: ____
Elimination half-life: ____hours
Excretion: _____
Scopolamine
Dose: (Pre-op) 1.5 mg topical patch behind ear the evening before surgery (keep on for 24 hours postop)
Onset: 2-4 hours (transdermal)
DOA: 72 hours
Metabolism: Liver
Elimination half-life: 4.5 hours
Excretion: kidneys
Scopolamine
Avoid in patients over _____years of age due to ___ properties
Adverse Effects: ____, ____, ___ skin, ____, ___, ____, ___ vision, ___ pupils, ___ sensitivity
Toxic ____ reported in __/__ patients
Scopolamine
Avoid in patients over 65 years of age due to anticholinergic properties
Adverse Effects: dry mouth, increased thirst, dry skin, constipation, drowsiness, dizziness, blurred vision, dilated pupils, light sensitivity
Toxic psychosis reported in pediatric/elderly patients
Ephedrine
Class: ____-acting ____ agent
Dose: dose? IV recommended for N/V associated with ____ hypotension in PACU
_____ IM at the end of surgery shown to have equivalency to ____
______ IM shown to minimize N/V with less sedation
Ephedrine
Class: Indirect-acting sympathomimetic agent
Dose: 10-25 mg IV recommended for N/V associated with postural hypotension in PACU
0.5 mg/kg IM at the end of surgery shown to have equivalency to droperidol
40 mcg/kg IM shown to minimize N/V with less sedation
Midazolam
Pediatric dose: ____mcg/kg IV
Adult dose: ____ IV
Effective in reducing PONV when given as ___, ___ or as ___ therapy
Possible MOA related to ____receptor antagonism, inhibition of ___ release and ____ effects
___ + ____ in pediatric patients undergoing ____ surgery = ____ incidence of PONV
Midazolam
Pediatric dose: 50-75 mcg/kg IV
Adult dose: 2 mg IV
Effective in reducing PONV when given as premedication, intraoperatively or as rescue therapy
Possible MOA related to GABA receptor antagonism, inhibition of dopamine release and anxiolytic effects
Midazolam + dexamethasone in pediatric patients undergoing strabismus surgery = ZERO incidence of PONV
Pain management
Uncontrolled postoperative pain causes triggering of stress response=>____ release, ____ oxygen consumption, increased ___ workload and ___cardia
Neurohumoral response (increased production of ___ hormone, ___, ___, __, FSH, GH, LH, plasma renin activity and prolactin)
Increased ___
Pain management
Uncontrolled postoperative pain causes triggering of stress response=>catecholamine release, increased oxygen consumption, increased cardiac workload and tachycardia
Neurohumoral response (increased production of adrenocortical hormone, aldosterone, ADH, cortisol, FSH, GH, LH, plasma renin activity and prolactin)
Increased N/V
Pain Management
Psychological ____, ____ delays, ____ hospital admission
Use pain management techniques: wound ___, nerve ___, ___ __ catheters, __ and ____ analgesics
**Goal:decrease postop ____, reduced ____ and decreased___
Pain Management
Psychological distress, discharge delays, unanticipated hospital admission
Use pain management techniques: wound infiltration, nerve blocks, local anesthesia catheters, opioid and non-opioid analgesics
**Goal:decrease postop analgesic requirements, reduced pain scores and decreased PONV
Nonpharmacological Management
_____ acupuncture point stimulation (___ release vs. ___ changes?)
Acupuncture, ___ and ___
Isopropyl ____ inhalation
Reduction of baseline risk factors for PONV:
– Avoid ____ with ___ Agent
– Minimize ____ use
– Preferential use of ____ infusion
– Avoid ____
– Adequate ____
Nonpharmacological Management
P6 acupuncture point stimulation (endorphin release vs. serotonin changes?)
Acupuncture, acupressure and TENS
Isopropyl alcohol inhalation
Reduction of baseline risk factors for PONV:
– Avoid General Anesthesia with Inhalational Volatile Agent
– Minimize opioid use
– Preferential use of Propofol infusion
– Avoid nitrous oxide
– Adequate hydration
Dopamine receptor antagonists
___ receptors in ___ tract sends signal to CNS to induce nausea and vomiting in vomiting center
_____ side effects
Contraindicated in patients with _____ disease
Dopamine receptor antagonists
D2 receptors in GI tract sends signal to CNS to induce nausea and vomiting in vomiting center
Extrapyramidal side effects
Contraindicated in patients with Parkinson’s disease
