General Anesthesia

Question 1

wakefulness

Answer 1

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

Question 2

NREM/REM sleep

Answer 2

NREM = firing decreases; REM = quiescent

Question 3

General Anesthesia

Answer 3

pharmacologically induced state of:

• Amnesia
• unconsciousness-hypnosis
• skeletal muscle relaxation
• reduction in autonomic responses

Question 4

benzodiazepines

Answer 4

-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

Question 5

propofol

Answer 5

• 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

Question 6

fospropofol

Answer 6

prodrug of propofol in H20 base s’ln if allergic to solvent in propofol

Question 7

propofol CV, pulm, CNS effects

Answer 7

CV: decreased SBP, MAP, SVR. no change in HR
Pulm- resp depression, dose dependent
CNS: decreased CBF, ICP, CMRO2

Question 8

propofol induction dose; cont infusion dose

Answer 8

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

Question 9

etomidate mech of action; pharmacokinetics

Answer 9

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

Question 10

etomidate effects (CV, Pulm, CNS)

Answer 10

CV: minimal overall; min BP drop, min HR inc, min SVR drop
Pulmonary: min resp depression
CNS: decreased CBF, ICP, CMRO2

Question 11

etomidate induction dose, SE

Answer 11

0.2-0.4 mg/kg; myoclonus, adrenal suppression (not enough to really cause a problem), increased PONV

Question 12

ketamine MOA/PK

Answer 12

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

Question 13

ketamine effects (CV, Pulm, CNS)

Answer 13

CV: incr HR, SBP, SVR
Pulm: no resp depression
CNS: incr CBF, ICP, CMRO2 (not good for neuro pt)

Question 14

ketamine doses

Answer 14

induction: 1-3 mg/kg IV or 4-8 mg/kg IM
adjunctive analgesia
0.2-0.5 mg/kg

Question 15

ketamine SE

Answer 15

emergence delirium

-premed with midazolam seems to help

Question 16

barbituates MOA/PK

Answer 16

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

Question 17

barbituates SE (CV, CNS, Pulm, Renal)

Answer 17

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

Question 18

barbituates induction doses

Answer 18

NaP: 3-5 mg/kg
methohexital 1-1.5 mg/kg
rectal methohexital: 20-30 mg/kg (1st pass effect)

Question 19

barbituates SE

Answer 19

• extravasation causes tissue sloughing

- contraindicated in pt with acute intermittent porphyria

Question 20

dexmedetomidine MOA

Answer 20

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

Question 21

dexmedetomidine CV, Pulm, CNS effects

Answer 21

CV: decreased HR, SV, (CO, SBP/Contractility dec. indirectly)
CNS: not well defined
Pulm: decreased MV, but maintains CO2 response
-similar to natural sleep

Question 22

Dexmedetomidine Anesthetic uses

Answer 22

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

Question 23

volatile anesthetics MOA

Answer 23

• inhibit excitatory NT glutamate

- enhance inhib NT GABA/Glycine

Question 24

volatile anesthetics why fluorinated

Answer 24

• reduces or elim toxicity
• reduce or elim anesthetic flammability
• allow increased speed of induction and recovery

Question 25

MAC & MAC levels

Answer 25

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)

Question 26

isoflurane

Answer 26

-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

Question 27

desflurane

Answer 27

``` 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 ```

Question 28

sevoflurane

Answer 28

``` 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 ```

Question 29

nitrous oxide

Answer 29

MAC 105 B:G 0.47 BB 1.1 FB 2.3 non-irritating to breathe min metabolism (

Question 30

pulm effects of inhaled anesthetics

Answer 30

-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

Question 31

CV effects of inhaled anesthetics

Answer 31

dose dep depression of myocardiac contractility - dose dep decrease in SBP - dose depen decrease in SVR - neg chronotropy - sometimes tachy response to dec BP

Question 32

Neuro effects of inhaled anesthetics

Answer 32

-inc cerebral BP b/c of vasodilation which leads to increased ICP -decreased CMRO2 centrally mediated muscle relaxant -can trigger MH