Induction agents Flashcards
sedative-hypnotics major functions
- sedative
- hypnotic
- axiolytic
- general anesthetic
In a perfect world….
- stable in aqueous solution: water soluble
- minimal major cardio or resp depression
- rapid metabolism
- steep dose respose curve
- rapdi return to mental baseline
- rapid and smooth onset
- Lack of hypersensitivity
What other substance is added to propofol? Their %
10% Soybean oil
- 25% glycerol
- 2% egg lithecin
Three propofol unique properties
- non-chiral
- pain on injecftion
- rapid return to consciousness
Two brands of propofo
pH, pK and additives
- Diprivan 7-8.5, 11, EDTA
- Propofol 4.5-6.4, 11, sodium metadisulfite or benzyl alcohol
Propofol MOA
Effect on spinal
selective GABA selective modulator
Spinal motor neuron excitability not altered
Propofol unique metabolism mechanism
Clearance exceeds hepatic blood flow:
- Tissue uptake in lungs
- extensive hepatic metabolism CYP450
Propofol metabolite
4-hydroxypropofol
Propofol context sensitive t1/2
<40min
How is propofol affected by hepatic or renal dysfunction?
Not influenced.
for propofol, Decreased rate of plasma clearance in pt over what age?
60.
What does propofol bind to and their %.
Erythrocytes and plasma proteins (50%)
plasma albumin (48%)
Free (2%)
In what population do you see increased free fraction?
- Severe heaptic and renal disease
- pregnant woman
Is propofol an acid or base?
Acid
How is myoclonous induced in propofol?
2ndary to disinhibition of subcortical centers
How does propofol cause moderate BP decrease?
- Primary decrease in sympathetic tone and vasodilation (primary)
- CNS, cardiac and baroreceptor depression
How does propofol affect respiratory depression?
Dose dependent with infusions secondary to decreased sensitivity of respiratory center to CO2
Propofol broncho effect?
minimal bronchodilation
Propofol induction dose?
1.5-2.5mg/kg
- Decrease dose in elderly
- Increase dose in pediatrics
- Effects exaggerated with CV disease
What kind of Monitored Anesthesia Care is porpofol good for?
endoscopy
What is the dose of propofol for monitored anesthesia care?
25-100 mcg/kg/min
Can be used in conjunction with anxiolytic and opioid
What is the dose of propofol for TIVA
100-300 mcg/kg/min
Other applications of propofol and doses
animetics 10-15mg IV, followed by 10mcg/kg/min gtt
antipruritic 10mg IV
anticonvulsant 1mg/kg IV
Attenuante bronchoconstriction, through Ca++ homeostasis
analgesic for neuropathic pain
Propofol contraindications
- olderly, cardiac compromised
- sulfate allergy, more in asthmatic pt
- lecithin alergy
- lipid metabolism disorder
PRIS risk factors
>4mg/kg/hr, >48hrs
critical illness
high fat-low carb intake
concomitant catecholamine infusion, steroid administration and inborn errors of mitochondrial fatty acid oxidation
PRIS signs and symptoms
- high anion gap (AGMA)
- fever
- cardiac failure
- bradycardia refractory to treatment
- severe hepatic and renal disturbances
% of academic centers reporting abuse or diversion of propofol
18
Is etomidate an acid or base? pH, pK?
it is a weak base, 8.1, 4.2
When do you use etomidate?
unstable cardiac pt
What structure does etomidate have?
carboxylated imidazole
R+ isomer 5x more potent
etomidate MOA
selective modulator of GABAa receptors
how much is etomidate bound to lipid?
75% boiund to plasma albumin
rank the three induction agents in terms of protein bound
propofol (98%)>etomidate(75%)>ketamine (12%)
unique metabolism function of etomidate
metabolized by hydrolysis, plasma esterase and microsomal enzymes in liver
etomidate onset and return to conscious time
rapid onset: one arm to brain circulation
return to consciousnewss 5-15 min
What kind of movement happens when given etomidate?
% of pt having this problem?
why?
myoclonus movement common.
happens in 50% of pt
Secondary to deep cerebral and brainstem.
Starting from what dose does etomidate cause changes in HR, stroke volume, or C.O.
And at what dose there is significant change in SBP?
0.3mg/kg and 0.45mg/kg
Which drugs causes apnea during rapid iv injection?
etomidate
etomidate induction dose
0.2-0.4mg/kg
What kind of pt is more prone to myoclonus movement?
Young
giving etomidate, % of patients that will show myoclonus movement.
>50%
how to decrease incidence of myoclonus movement?
given fentanyl and benzo
In etomidate, what causes adrenocortical suppression?
11-Betahydraxylase inhibits cholesterol converting to cortisol
how long does etomidate adrenocortical suppression last?
greater than 8 hrs after induction.
GI effect of etomidate.
Nausea and vomiting
Does etomdiate cause pain on injection?
Minimal. Used to, new solvents not anymore
Which drugs cause porphyria?
Barbs and etomidate, plus, benzos
How does EEG look like for pt on ketamine?
disassociation between thalamocortical and limbic systems
What state do pt get into when given ketamine? How does it look like
cataleptic state. eyes remain open with slow nystagmic gaze.
How does Ketamine disolve?
does not require a lipid “vehicle” for dissolution
ketamine acidity, pH, pk
it is a base, ph 3.5-5.5, pk, 7.5
How is ketamine metabolized?
demethylation of ketamine by cyp450.
- metabolism dependent on hepatic flow
- norketamine is active metabolite, then broken down to water soluble and inactive metabolites
ketamine t1/2
2-3 hrs
how is ketamine lipidphility?
highly lipid soluble, rapid transfer BBB
What does NMDA stand for?
N-methyl-D-apartate
ketamine MOA
binds non-comptetively to phencyclidine site on NMDA receptors to block glutamate, resulting in depressive effect on the medial thalmic nuclei.
receptors ketamine work on
opioid, monoaminergic, muscarinic, voltage gated sodium, L type calcium, and nAchR
Other way ketamine have analgesic effect
directly inhibition of cytokines
which system is activated by ketamine?
limbic system
Does ketamine have effect on GABA?
weak action on GABAa receptors
ketamine eye, airway, muscular skeletal effect
eyes open, pupils reactive, corneal reflex intact, nystagmus present, lacrimation and blinking continue. IOP increases, do not use in eye procedures.
airway reflex intact, increased salivary secretions,
increased skeletal muscle tone
When using ketamine, what other agents should be given as well?
some analgesics or benzos, like fentayl to decrease hallucination and decrease ICP
What type of pt can benefit from ketamine’s bronchodilation effect?
asthmatic
What is patient population is ketamine for?
hypovolemic trauma
ketamine induction doses and response times
How would you describe its response time?
1-2.5mg/kg IV (2-3min)
4-8mg/kg IM (<10min)
10mg/kg PO (10-20min)
They take longer, compared to propofol and etomidate, seconds
Does ketamine cause pain?
no pain on injection
ketamine induction on CAD patient?
it is complicated.
ketamine subanesthetic dose for analgesic effect
0.2-0.5mg/kg
what receptors sensitizes spinal cord?
NMDA receptors
Why is ketamine used in OB anesthesia?
Does not compromise uterine tone, blood flow or neonatal status.
What type of trauma patient is ketamine used for, what procedure?
Burn patients, with extensive dressing changes and grafting procedures.
What is ketamine dart used for
pediatric asthmatic patient.
What can ketamine do to chronic pain mgnt?
opioid induced hyperalgesia, treatment for CRPS and cancer pain.
What effect does ketamine have on sux?
inhibit plasma cholinesterase, prolonged apnea
what effect does ketamine have on non-depolarizing NMBA?
enhancement
what medication should be avoided for pt at risk of MI during preop period if ketamine is given?
medication that block preconditioning
% of pt experience emergence delirium after using ketamine
5-30%, partially dose dependent
how long does the emergence delirium last after ketamine admin?
can occur up to 24 hrs
have morbid and vivid color d/t depression of what part of brain?
inferior coolliculus and medial geniculate nucleus
emergence delirium risk factors
>15 yrs old, female, hx personality problem or frequent dreams.
which benzo used prior to ketamine decrease emergence delirium better
midazolam>diazepam
which agent can increase emergence delirium?
atropine
