General Anesthesia Flashcards
wakefulness
following fire:
- noradrenergic neurons in locus ceruleus
- histaminergic neurons in the tubomammilary nucleus
- serotonergic neurons in the dorsal and median raphe nuclei
- dopaminergic neurons in the periqueductal grey matter
- orexinergic neurons stimulate directly and support monoaminergic neurons
NREM/REM sleep
NREM = firing decreases; REM = quiescent
General Anesthesia
pharmacologically induced state of:
- Amnesia
- unconsciousness-hypnosis
- skeletal muscle relaxation
- reduction in autonomic responses
benzodiazepines
-sedation, anziolysis, anticonvulsant effects, spinal cord mediated muscle relaxation, anterograde amnesia; at high doses: unconsciousness and resp depression
-NO ANALGESIA
Examples: diazepam (long 1/2 life); madazolam (short 1/2 life); lorazepam
action: BZD facilitates action of GABA at the alpha subunit–> enhanced opening of Cl- channels, hyperpolarization of postsynaptic membrane
propofol
- presumed interaction with GABA, delays dissociation of GABA from receptors (increasing GABA activated opening of chloride ion channels and Na channel blocker)
- hyperpolarization of cell membranes
- 95-99% PRO bound
- T1/2 30-60 min
- tissue uptake and redistribution are imp factors in term of action
- met via glucoronidation in liver; excreted by kidneys
fospropofol
prodrug of propofol in H20 base s’ln if allergic to solvent in propofol
propofol CV, pulm, CNS effects
CV: decreased SBP, MAP, SVR. no change in HR
Pulm- resp depression, dose dependent
CNS: decreased CBF, ICP, CMRO2
propofol induction dose; cont infusion dose
induction: 1.5 to 2.5 mg/kg IV, unconscious in 30-60 sec, decreased PONV/PDNV
cont infusion sedation: 25 to 100 mcg/kg/min
anesthesia: 100 to 300 mcg/kg/min
etomidate mech of action; pharmacokinetics
MOA: rapid onset of sleep (30-60s), assumed to enhance effects of GABA, rapid awakening
PK: 75% PRO bound, hydrolyzed to inactive metabolites via ester hydrolysis
t1/2 = 75 mins
excretion 85% renal, 15% biliary
etomidate effects (CV, Pulm, CNS)
CV: minimal overall; min BP drop, min HR inc, min SVR drop
Pulmonary: min resp depression
CNS: decreased CBF, ICP, CMRO2
etomidate induction dose, SE
0.2-0.4 mg/kg; myoclonus, adrenal suppression (not enough to really cause a problem), increased PONV
ketamine MOA/PK
MOA: dissociative anesthetic: NMDA/opioid/monoaminergic/muscarinic receptors and VGCa channels
PK: v. lipid soluble, met in liver to norketamine
t1/2 2-3 h
excretion: >90% renal
ketamine effects (CV, Pulm, CNS)
CV: incr HR, SBP, SVR
Pulm: no resp depression
CNS: incr CBF, ICP, CMRO2 (not good for neuro pt)
ketamine doses
induction: 1-3 mg/kg IV or 4-8 mg/kg IM
adjunctive analgesia
0.2-0.5 mg/kg
ketamine SE
emergence delirium
-premed with midazolam seems to help
barbituates MOA/PK
MOA: interact with GABA-A receptor, directly activates Cl- ion channels, increase duration open, hyperpolarize membrane), blocks AMPA receptors
PK: 83% PRO bound, highly lipid soluble, achieve CNS uptake in 30 seconds, prompt awakening after 1 dose; hepatic metabolism and renal excretion
barbituates SE (CV, CNS, Pulm, Renal)
Cv: decreased SBP, SVR, incr HR
Pulm: profound resp depression, apnea, return with slow resp and low TV
CNS: decr CBS, ICP, CMRO2
renal: modes decrease in BP and GFR
barbituates induction doses
NaP: 3-5 mg/kg
methohexital 1-1.5 mg/kg
rectal methohexital: 20-30 mg/kg (1st pass effect)
barbituates SE
- extravasation causes tissue sloughing
- contraindicated in pt with acute intermittent porphyria
dexmedetomidine MOA
nonselective alpha2 agonist (G Pro)–> casues inhibition of adenylate cyclase and modulation of ion channels
alpha2B and C in brain/SC cause sympatholysis, sedation and antinociception
sedation (locus cereleus)
analgesia (LC and SC)
decreased activity of LC to VLPO, increases GABAergic and galanin release in the TMN which results in a decrease in histamine release in cortical and subcortical areas
-inhib ion conductance via VG calcium activated K channels
dexmedetomidine CV, Pulm, CNS effects
CV: decreased HR, SV, (CO, SBP/Contractility dec. indirectly)
CNS: not well defined
Pulm: decreased MV, but maintains CO2 response
-similar to natural sleep
Dexmedetomidine Anesthetic uses
premed: 0.33-0.67 mcg/kg 15 mins before surgery–> decreases MAC, induction agent dose
MAC: 1 mcg/kg over 10 mins (slower than propofol), similar CV effects
0.7 mcg/kg/min keeps BIS 70-80 (40-70 is GA)
Maintenance of GA: reduces MAC of inhaled agent, reduces post of opioid req, not useful as a solo GA
volatile anesthetics MOA
- inhibit excitatory NT glutamate
- enhance inhib NT GABA/Glycine
volatile anesthetics why fluorinated
- reduces or elim toxicity
- reduce or elim anesthetic flammability
- allow increased speed of induction and recovery
MAC & MAC levels
partial pressure (Vol%) of an agent that must be present in the brain to result in GA
MAC incision: level of anesthesia at which 50% of patients will not move to a surgical stimulus (1 MAC)
MAC awake: is a proportion of MAC at which patients will wake up and respond to commands (0.4 MAC)
MAC BAR: deep anesthesia in which no CV response to BP (1.3 MAC)
isoflurane
-irritating to breathe
-MAC 1.15
B:G coefficient: 1.4
B:B 2.6
Fat:B 45
Metabolized 0.2%
dose dep hypotension d/t mod peripheral vasodilation
-neg cardiac chronotrop, but may also inc HR 2/2 hypotension
desflurane
MAC: 6 B:G 0.4 BB 1.3 F:B 27 v. irritating to breathe metabolized 0.02% min myocardiac depression, direct SNS stim: tachy, hypertension (when turn up quickly) -fast in and out
sevoflurane
MAC: 2 B:G 0.69 BB 1.7 F:B 48 non-irritating metabolized 2-5% min myocardial depression -fast in and out -incorrectly linked to renal failure
nitrous oxide
MAC 105
B:G 0.47 BB 1.1 FB 2.3
non-irritating to breathe
min metabolism (
pulm effects of inhaled anesthetics
-decreased TV (dose dependent)
-decreased residual O2 in lungs at end of expiration
-bronchodilate
-alter pulm vascular resistance
-alter hypoxic pulm vasoconstriction
depress response to hypercapnia at 0.2 MAC
attenuate vent reponse to hypoxia at 0.1 MAC
CV effects of inhaled anesthetics
dose dep depression of myocardiac contractility
- dose dep decrease in SBP
- dose depen decrease in SVR
- neg chronotropy
- sometimes tachy response to dec BP
Neuro effects of inhaled anesthetics
-inc cerebral BP b/c of vasodilation which leads to increased ICP
-decreased CMRO2
centrally mediated muscle relaxant
-can trigger MH
