Week 4: Induction Agents and Benzos Flashcards
Induction refers to the _______ of anesthesia
Start
During induction, the patient is rendered _______
Unconscious
Intravenous induction allows for patients to experience a _________ loss of consciousness, achieving surgical levels of anesthesia
Rapid
Desirable properties of induction agents (8)
Rapid and smooth onset
Rapid and smooth recovery
Analgesia
Antiemetic actions
Advantageous pharmacokinetics
and pharmaceutics
Bronchodilation
Minimal cardiac and respiratory
depression
Lack of toxicity or histamine release
Has a single IDEAL intravenous anesthesia induction agent been developed?
No
Instead we choose an appropriate drug for the surgical and anesthetic requirements
___________ were introduced in the 1930’s and revolutionized the administration of anesthesia
Use declined in recent years due to the development of __________
Thiobarbiturates
Propofol
Although thiobarbiturate use has declined, the practice of intravenous ______ of sedatives to initiate _______ remains standard of care
boluses, anesthesia
in 2011, decision was made to stop marketing ______ ______ (a barbiturate) in the US and many other countries
Sodium pentothal
Propofol is prepared as a __ % solution in a ______ emulsion
1%, Lipid
Propofol’s lipid emulsion is comprised of:
__ % __________ _____
__ % _________
__ % _________ _____ _______
10% soybean oil
2.25% glycerol
1.2% purified egg lechithin
What kind of contamination is possible in Propofol?
Bacterial and fungal contamination
Propofol
Original trade product contains ______ % ________ ________ (____) as a preservative
0.005% disodium edetate (EDTA)
Propofol
Generic contains _____% ________ ______ or _________ _________
0.025% sodium metabisulfate or benzyl alcohol
Propofol
Open vials or syringes should be discarded within ____ hours if Propofol was transferred from the original container
6
Propofol has a _____ (narrow/wide) therapeutic index
Narrow
Propofol
Hemodynamic and respiratory ________ are problems
Depression
Long term use of propofol can lead to ______ ________ ______
Propofol infusion syndrome
Does propofol have a pharmacologic antagonist?
No
Propofol’s effects are terminated by redistribution
Propofol has a ______ (fast/slow) onset of action
Fast
Propofol
_______ distribution following intravenous bolus into brain and other highly perfused areas
Rapid
Propofol
Rapid ______________ from central to _________ compartments causing brain concentration to ________
Distribution
peripheral
fall
Causes a rapid reawakening after sedative and anesthetic doses
Propofol
Elderly require _______ doses
Children require ______ doses
Lower
Higher
Why do children require higher doses of Propofol?
Children have increased volume of distribution compared to adults
Children’s rate of clearance is higher
Propofol elimination half life
1-2 hours
SLOWER than wake up seen with Propofol (d/t redistribution)
Propofol MOA
Directly stimulates GABA A and potentiates action of exogenous GABA
Propofol
Appears to exert its effects via interaction with _____________ neurotransmitter = ______
Inhibitory
GABA
Propofol
What is GABA A
A protein receptor complex
Propofol
CNS effects
Amnesia
Sedation (unconsciousness in 30
sec)
Rapid/complete awakening with
minimal residual CNS effects
Propofol
CV effects
Decreased BP, CO, SVR
HR unchanged or decreased
Bradycardia/asystole have been
reported
Propofol
Respiratory effects
Respiratory depression
Decreased response to hypoxemia
Propofol
Other pharmacologic actions
Mild antiemetic effects
Risk of infection
Pain on injection
Hypertriglyceridemia (prolonged
administration)
PE
Antipruretic
Anticonvulsant
Reduces bronchoconstriction
Propofol
Hypotension exaggerated in _______, _______, _________
Hypovolemia
Elderly
LV failure
Does propofol cause analgesia?
No
Propofol
Highly ________soluble drug, therefore easily passes placental barrier
lipid
Propofol
Do sedative effects occur in the neonate when propofol is used for cesarean delivery?
Yes
Propofol is lipid soluble and easily passes placental barrier
Propofol
________ (higher/lower) 1 and 5 minute APGAR scores have been noted
Lower
Propofol
In obstetric use, ________ effects may be an advantage
antiemetic
b/c OB patients at high risk for aspiration, nausea common in these patients
Propofol
Controversy exists with propofol avoidance in patients with _____, _____, or ______ allergies
(actually not controversial anymore; no adverse side effects seen in this population)
egg, soy, peanut
Propofol
Is there any striking data that shows problems with use in populations with reported allergies to egg, soy, or peanuts?
No
Propofol infusion syndrome occurs during _______ duration infusions at _______ doses
Long, high
Propofol infusion syndrome is associated with significant morbidity and mortality
True or false?
True
What area is Propofol infusion syndrome usually seen in?
Critical care units
Risk factors for Propofol infusion syndrome (7)
-Doses > 4mg/kg/hr
-Duration > 48 hours
-Critical illness
-High-fat low-carb intake
-Inborn errors of mitochondrial
fatty acid oxidation
-Concomitant catecholamine
infusion
-Steroid administration
Etomidate
Synthesized in ______, introduced into European practice in _____
1965, 1972
Etomidate
IV _______ agent
induction
Etomidate
often used as an alternative to propofol due to little if any __________ effects
Cardiorespiratory
Useful in more hemodynamically unstable patients
Does etomidate have analgesic properties?
No
Etomidate
MOA involves _______ modulation
GABA
Etomidate
Rapidly metabolized in ______ by microsomal enzymes and _______ _______
liver, plasma esterases
Etomidate
What is the primary mode of metabolism in the liver and plasma?
Ester hydrolysis
Etomidate
What accounts for short duration of action?
Rapid redistribution
Etomidate
Lipid or water soluble?
Lipid soluble
Etomidate
Terminal half life
2-5 hours
Etomidate
CNS effects
Reduces ICP, CBF, CMRO2
Myoclonus during onset
Etomidate
CV effects
Hemodynamic stability
HR, PAP, CI, SVR, BP changes not
significant
Aortic/mitral valve dz show
decreased BP (17-19%)
No depression of SNS, baroreceptor
reflex
Agonist at alpha 2B-adrenoceptors
Etomidate
Respiratory effects
Decreased tidal volume
Increased RR
Respiratory depression greater
with propofol
Ventilatory response to C02 reduced
May cause periods of apnea
following induction
Etomidate
Adrenocortical effects
Adrenal cortical suppression limits its clinical use
ex: sepsis = suppressed adrenals, need them to work at maximum function
Etomidate
Other effects
Increased PONV
Burning on injection
Etomidate contraindicated in
Known sensitivity
Adrenal suppression
Acute porphyrias (deficiency in heme building enzymes)
Ketamine
Has a long history of anesthetic use, and its popularity varies through history
True or false
True
Ketamine
Research has led to new uses and renewed interest
true or false
true
Ketamine is extremely useful in ______, _______ and _______ patients
High risk, pediatric, asthmatic
Ketamine provides ________, and can be used to aid in perioperative pain management
Analgesia
Ketamine
Introduced in the ______
1970’s
Ketamine
MOA and pharmacologic effects greatly different from other classic anesthetic drugs
true or false
true
Ketamine
Does it encompass the usual signs and symptoms of anesthesia?
No
Ketamine
Produces a _________ state where the patients feels _________ from environment
Catatonic, separated
Ketamine
The term _________ anesthesia was coined to describe the catatonic state ketamine produces
Dissociative
Ketamine
Produces profound ________ and _______ while maintaining most protective _________
analgesia, amnesia, reflexes
Ketamine
MOA
NMDA receptor antagonist
(N-methyl-D-asparate amino acid)
Noncompetitve antagonist at NMDA receptor
Ketamine inhibits ________
glutamate
Ketamine enhances ____________ analgesia and prevents _________
opioid-induced analgesia, hyperalgesia (ex: as caused by remifentanil)
Ketamine metabolism
__________ enzyme systems responsible for biotransformation
Hepatic microsomal
Ketamine metabolism
Undergoes ______ to produce more ______ compound eliminated by renal system
conjugation, water-soluble
Ketamine metabolism
Metabolite ________ is approximately ____ to ____ activity of ketamine
norketamine
20-30%
Ketamine
Onset of action is _____ (faster/slower) than propofol or etomidate
slower
Ketamine
How long can it take to achieve clinical anesthesia?
3-4 min
Ketamine
Reawakening within ___ min, although wide variability is seen
15 min
depends on how giving (ex: large IM dose = 30-45 min)
Ketamine
Elimination half life: ____
IM onset: _____
PO onset: _____
2-3 hours
5-15 min
10-20 min
Ketamine
CNS effects
-Dissociative state of anesthesia;
amnesia
-Nystagmus
-Skeletal muscle tone increased
-Occasional purposeless
movements
-Analgesic effects
-CBF, CMRO2, ICP increase
-Psychic disturbances on
emergence, nightmares,
hallucinations (reduced by
benzos or other sedatives)
Ketamine
CV effects
Indirect sympathomimetic
Increased BP, HR, inotropy
Ketamine
Respiratory effects
-Potent bronchodilator (indirect
sympathomimetic)
-Increased secretions
-Maintains respirations and airway reflexes (period of initial apnea may
occur)
Ketamine
Intraocular effects
Increased
Ketamine
Can it be used in obstetrics?
Yes, for analgesia or anesthesia
Ketamine is ______ -soluble and crosses _______ into _____ tissue
lipid, placenta, fetal
Ketamine
____- ____mg/kg does not compromise uterine tone, uterine blood flow, or neonatal status at delivery
___ -___mg/kg does result in depressed neonate at delivery
0.5-1mg/kg
2-2.5mg/kg
Ketamine
Popular for neonates and ______
Sedation, analgesia, amnesia, cardiac and respiratory stability, short duration offer advantages in ______ patients
Children
Young
Agent of choice for children with difficult or reactive airways
Ketamine
Ketamine can be given ___ or ____ in uncooperative children
IM or PO
Ketamine has a risk of possible _______ in children
Neurotoxicity
Limit exposure to lowest dose for lowest time
Pharmacologic properties of benzodiazepines (6)
-Sedation
-Hypnosis
-Muscle relaxation
-Anxiolysis
-Anticonvulsant effects
-Amnesia
Benzodiazepines have a ____ (low/high) incidence of side effects
low
Benzodiazepines
Similar compounds first synthesized in ______
1933
_______ was the first benzodiazepine synthesized in 1955, and introduced into clinical practice in ______
Librium, 1960
Diazepam synthesized in ______
1959
Oxazepam synthesized in ______
1961
Lorazepam synthesized in ______
1971
Midazolam synthesized in _______
1976
Remimazolam synthesized in late ______
1990’s
________ was the first benzodiazepine group to be formulated specifically with anesthesia as its target clinical audience
Midazolam
Various benzodiazepines are similar, but vary in ______, ______, and intensities of clinical properties
potencies, pharmacokinetics
______ onset and ______ duration and half life, with relative limited adverse effects make midazolam popular for preoperative medication
Rapid, short
Why is midazolam rarely used to induce anesthesia?
Prolonged effect at high doses
Diazepam and lorazepam used occasionally, usually for inpatients requiring ________ sedation
Prolonged
___________ is an ultra-short acting benzodiazepine developed for procedural sedation as well as induction and maintenance of anesthesia
Remimazolam
Remimazolam is a benzodiazepine like midazolam, but has ______________ metabolism like remifentanil
organ-independent
Remimazolam was approved by the FDA July ______
2020
Benzodiazepines MOA
GABA-A receptor agonist, specifically at the benzodiazepine receptor binding sites
Benzodiazepines work _________ to enhance endogenous GABA binding rather than indirectly, physiologic ______ effect is noted
Allosterically, ceiling
Benzodiazepines are relatively ______ and have low ______
safe, toxicity
d/t ceiling effect
Benzodiazepines
Newer generations focused on chemical alterations to improve chemical ____________
pharmacokinetics
Benzodiazepines
Changes in chemical alterations have resulted in: (3)
Simplified metabolism
Fewer active metabolites
More predictable time course
Remimidazolam has been the result of all this research
Benzodiazepines
CNS effects
Anterograde amnesia
No reliable retrograde amnesia
Anxiolytic
Sedation
Antiepileptic effect
Benzodiazepines
CV effects
Minimal effects
Benzodiazepines
Respiratory effects
-Dose-dependent respiratory depression (Midazolam the most)
-Changes in CO2 sensitivity; caution in obesity, OSA (esp. at high doses)
Midazolam uses
Induction and maintenance of
anesthesia
Sedation
Diazepam uses
Induction and maintenance of
anesthesia
Sedation
Clonazepam uses
Treatment of epilepsy
Alprazolam uses
Anxiolysis
Sole benzodiazepine competitive antagonist available in US
Flumazenil
Flumazenil has a ____ (short/long) duration of action that makes possibility of re-sedation clinically relevant
short
Flumazenil
onset:
duration:
1-2 min
45-90 min
Are withdrawal reactions possible with flumazenil?
______ have been reported
Yes
Seizures
Dexmedetomidine
Drug class
Alpha-2 receptor agonist
_________ developed as a more selective alpha 2 receptor agonist
Dexmedetomidine
Dexmedetomidine causes: (5)
-Sedation
-Analgesia (also ketamine)
-Anxiolysis
-Reduced post-op shivering and
agitation
-Cardiovascular sympatholytic actions (decreased HR, BP)
Dexmedetomidine is highly specific for alpha-2 vs alpha-1 at a ratio of _____:_____
1600: 1
Main site of action for sedative actions of Dexmedetomidine is the _____ ______ _____, the ______ ______
Pontine noradrenergic nucleus, the locus coeruleus
Dexmedetomidine
When alpha-2 receptors are stimulated by an agonist, it results in ________ catecholamine release
decreased
Dexmedetomidine undergoes almost _________ biotransformation with very little unchanged in urine and feces
complete
Dexmedetomidine
Metabolism is direct __________as well as cytochrome p450-mediated
glucuronaidation
Does Dexmedetomidine have active metabolites?
No
Dexmedetomidine
Onset of action:
Duration of action:
10-20 min (slow)
10-30 min (slim)
Dexmedetomidine
CNS
Can be useful in procedures requiring ______ tests
“wake-up”
Dexmedetomidine
CNS effects
Sedation and analgesia, no change in ICP
Antishivering properties
Lowers risk of emergence delirium
Limited effects on evoked potentials
Dexmedetomidine
CV effects
Bradycardia, hypotension
Transient HTN can occur with rapid administration
Dexmedetomidine
Respiratory effects
Preserves respiratory drive
Dexmedetomidine
Other effects (3)
-Mild diuretic effect
-Reduces emergence agitation
in children
-Proposed anti-inflammatory
effect
Dexmedetomidine
Dose for emergence agitation prevention
0.25 mcg/kg
Only anticholinergic drug used primarily for sedation
Scopolamine
Scopolamine
CNS effects
-Restlessness
-Somnolence
Scopolamine CNS effects more likely to occur in ________
elderly
What can reverse CNS symptoms in scopolamine?
Physostigmine 2mg IV
Scopolamine has a __________ effect, which is a benefit
Antisialagogue
__________ used to be the most common intravenous induction agents
Barbiturates
_________ (a barbiturate) was a core medicine in the World Health Organization’s list of essential medicines, but was replaced by propofol
Listed as an acceptable alternative to propofol, depending on local availability and cost
Thiopental
Barbiturates
______ lowers seizure threshold, making it useful when providing anesthesia for electroconvulsive therapy
Methohexital
Methohexital has similar effects to ______
Still used today depending on practice
sodium thiopental
______________ discontinued barbiturate by Eli Lilly in early 80’s
When given intravenously, has a reputation for acting as a truth serum
Amobarbital
Methohexital
CV effects
-Decreased MAP
-Decreased contractility
reflects depression of
medullary vasomotor center
and decreased sympathetic
tone, causing vasodilation
Methohexital
Respiratory effects
Decreased ventilatory drive
Barbiturates usually have more _______ stability than propofol
cardiovascular
Barbiturates have _______ clearance
hepatic
Methohexital uniquely activates ______ foci facilitating electro-convulsion therapy and identification of seizure foci during ablative surgery
epileptic
Methohexital is _____ % protein bound
73%
Methohexital
Onset:
Duration:
15-30 sec (fast)
5-10 min (short)
