Sedative/Hypnotics Flashcards
not barbs not Benzes
deprival edta has
preservative in it. hence edta
propofol generic preservative =
sodium metabisulfite. Which can cause bronchospasm
ampofol-low preservative
has no preservative r/t Lower lipid concentration
aqua-van prodrug
hydrolysis in plasma
can be unpredictable
slower onset, higher VD, higher potency
propofol MOA
Acts at GABAa (major)
glycine (minor)
reduces rate of dissociation of GABA from GABAa
NO SPINAL CORD DEPRESSION (despite glycine)
volume of distribution of propofol is
HUGE
Vd 3.5 - 4.5 L/Kg
metabolism of propofol is
CAPACITANCE dependent
because clearance exceeds hepatic blood flow. -
Relies on enzyme activity
elimination half time of propofol
0.5 to 1.5 hours
CNS effects of propofol
cerebroprotective
(decreses CBF, ICP, CMRO2, and CPP)
EEG burst suppression
antioxidant effects (vitamin E)
highest dose of propofol is usually in
toddlers r/t increasing circulation
must reduce propofol dose in
elderly, neonates
propofol + bronchodilation
in COPD Patients, except when using generic with sodium bisulfate
hypercarbia and hypocarbia respones in propofol
decreased ventilatory response to arterial hypoxemia /hypercarbia, intact ventilatory response to hypoxic pulmonary vasoconstriction
potential for bronchodilator in COPD
CV effects of propofol
25 - 40 % decrease in BP up to 40%
dose dependent myocardial depression and vasodilation
decrease in SV, CO, SVR
heart rate unchanged - inhibition of baroreceptors?
antipruritic and anti-emetic at
sub hypnotic doses
mechanism unknown.
doses of propofol:
induction 1 to 2.5 mg/kg or to 3 mg/kg in toddlers
GA maintenance: 100-300 mcg/kg/min
sedation infusion: 25 - 100 mcg/kg/min
metabolites of propofol
4-hydroxypropofol is 1/3 as potent
Etomidate/Amidate is
carboxylated imidazole derivative
Etomidate is ____ Lipid soluble
HIGHLY LIPID SOLUBLE.
pKa = 6.9
at physiological pH becomes highly lipid soluble hence fast onset.
MOA etomidate:
binds to a specific site on the receptor
increases the affinity of GABA to GABAa
onset of etomidate:
rapid, one arm to brain
etomidate redistribution:
terminates hypnotic effect
elimination half time of etomidate is
3-5 hours
metabolism of etomidate is
PERFUSION dependent
etomidate is a weak
base
but is water soluble in bottle. which is why we cant give it with a barb cause precipitates
etomidate dose:
induction: 0.2 to 0.6 mg/kg (0.3 mg/kg)
maintenance: 10 mcg/kg/min c opined and n2o
sedation: 5-8 mcg/kg/min
rectal: 6.5 mg/kg
CNS effects of etomidate
decrease IOP, ICP, CMRO2, CBF.
Can INCREASE EEG at epileptic foci. Good in ECT, may cause seizure.
MYOCLONUS
CV effects of etomidate
MINIMAL! distinguishing feature
Resp effects of etomidate
minimal decrease in response to Co2.
minimal decrease in TV.
INCREASE IN RR.
hiccups/coughing.
metabolism of etomidate
perfusion decedent liver. CYP 450
also some ester hydrolysis
notable features of etomidate outside of CV/CNS/RESP
depression of synthesis of cortisol and aldosterone.
4-8 hours corticosuppresion
C/I in PROPHYERIA
PONV 30-40% highest incidence
ketamine MOA
- glutamate antagonist at NMDA
- Muscarinic agonsit?
- weak actions at GABA
- agonist at opiod (Mu, sigma, kappa, delta)
- inhibition at Ca++ channel, vgNa like LA.
ketamine CNS:
dissociative. nystagmus pupil dilation salvation myoclonus
INCREASED CMRO2, CBF, IOP, ICP
ketamine RESP:
minimal effects, bronchodilator!
increased secretions
ketamine: CV
inhibits reuptake of NE so increased BP, SVR, HR, CO but directly is a cardiac depressant.
ketamine metabolism:
CYP 450
perfusion depedent
INDUCES ENZYME METABOLISM, so tolerance develops
ketamine metabolites:
NORKETAMINE
1/3 to 1/5 as potent
ketamine doses:
spinal: 0.2 to 0.5 mg/k
sedation/analgesia: 0.2 to 0.5 mg/kg
induction: 1-2 mg/kg IV
4-8 mg/kg IM
PO/intranasal: 60 mg/kg
precedex MOA:
potent alpha 2 agonist
large density of alpha 2 at
pontine locus cerealus -> does sleep
precedex CNS:
uncoupling!!! decrease CBF with no effect on ICP or CMRO2
precedex thermoregulation:
depresses thermoregulation and also inhibits shivering.
precedex CV
bolus = initial hypertension
then! decrease HR, SVR, BP, Bradycardia, risk for heart block asystole.
ATTENUATES CV responses -> sympatholytic, decrease catecholamines
precedex resp:
minimal changes in RR, mod decrease in TV.
No change in Co2 response.
UPPER AIRWAY OBSTRUCTION POSSIBLE.
metabolism of precedex
RAPID metabolism, but also inhibits CYP450.
MAY INTERFERE WITH METABOLISM OF OTHER DRUGS
specific antagonist for precedex =
atipamezol
precedex dose
bolus: 1 mcg/kg over 10 min
infusion 0.2 - 1 mcg/kg/hr
