antiemetics Flashcards

(61 cards)

1
Q

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

A

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

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2
Q

Postoperative Nausea and Vomiting

• Use of _____ to prevent and treat PONV

  • Target various _____ associated with nausea and vomiting
  • ____ acting
  • ____ acting
  • _____ therapies
A

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
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3
Q

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 **

A

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 **

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4
Q

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 _____
A

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
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5
Q

Surgical Risk Factors for PONV

Increased _____ of anesthetic/surgery (each ___ min increase in duration increases PONV risk by___0%)

Surgical type (___, ___, _&_, ___, ___/___)

A

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)

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6
Q

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*

A

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*

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7
Q

Ambulation (especially with ___ analgesics)

_____ hypotension

Uncontrolled ____ (increased ____, endogenous ___ activators such as _____)

Postoperative ____ administration

Early ___ intake

Lower _____ concentration

Reversal agents (____ > _____ mg)

A

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)

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8
Q

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 _____
A

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
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9
Q

Risk Factors for Post-discharge N/V (PDNV)

  • ___ gender
  • Age • History of ____

• PONV in ____

A

Risk Factors for Post-discharge N/V (PDNV)

  • Female gender
  • Age<50 years
  • History of PONV

• PONV in PACU

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10
Q

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

A

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

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11
Q

Apfel score

  • ___
  • ___
  • ___
  • ___

Score of _-_ is high, __-__% risk of postop NV

A

Apfel score

  • Female
  • nonsmoker
  • Hx of PONV
  • Postop opioids

Score of 3-4 is high, 60-80% risk of postop NV

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12
Q

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 ___

A

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

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13
Q

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.

A

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.

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14
Q

Receptors thought to be activated include:

– ___

– ____

– ___

– ____

– _____

A

Receptors thought to be activated include:

– Histamine

– Muscarinic

– Opioid

– Dopamine (D2)

– 5- hydroxytryptamine (serotonin)

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15
Q

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 _____)

A

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)

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16
Q

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

A

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

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17
Q

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 _____

A

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

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18
Q

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 ____

A

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

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19
Q

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

A

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

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20
Q
  • Bioavailability:___%
  • Protein binding: __-____%
  • Metabolism: Liver (CYP___, CYP___, CYP____)

Extensive metabolism in liver by ____ and ____ CYP-450; less than ___% metabolized by kidneys (___renal dose adjustment)

A
  • 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)

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21
Q

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

A

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

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22
Q

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

A

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

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23
Q

Palonosetron (Aloxi)

____ generation serotonin antagonist

Most ____ - greater ___ for serotonin receptor by ___-fold

One of the most effective treatments for ____- induced N/V and PONV

A

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

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24
Q

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

A

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

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25
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
26
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
27
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
28
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
29
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
30
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
31
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
32
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
33
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
34
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
35
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
36
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)
37
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)
38
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
39
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
40
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
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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
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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.)
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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
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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
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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
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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
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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
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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
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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%
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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
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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)
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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