Volatile Anesthetic Agents Flashcards
Meyer-Overton correlation theory
- chemically different substances that are soluble in fat
- potency of VA depends on affinity for water & fat
- fat:water partition coefficient
The concept of MAC
- analogous to plasma ED50
- universal measure of potency
- non-paralyzed pt do not respond to surg stimuli in 50% of pt
Protein centered theory
- signaling proteins (channels/receptors) are molecular site of action
- bind directly to amphiphilic cavity in proteins
molecular target- ligand gated ion channel
- potentiates/enhance synaptic transmission of GABA/glycine
- extrasynapically by enhancing GABA receptors/leak channels
- presynaptically by enhancing basal GABA release
- inhibits ACh/glutamate
- presynaptically reduce glutamate release
- postsynaptically by inhibiting glutamate receptors
molecular target- VG ion channel
Na+, Ca++, K+ channels
molecular target- intracellular signaling mechanisms
- G-protein coupled receptors
- protein phosphorylation
- gene expression
neuronal excitability
- IA hyperpolarize neurons
- determined by resting membrane potential, threshold potential, input resistance
presynaptic effects
-IA alter transmitter release
postsynaptic effects
-IA alter NT responses
Immobilizing site of action
spinal cord
sedation, hypnosis, & amnesia site of action
supra-spinal mechanisms
Immobility
SC NMDA receptors requires high (2.5-4x MAC) to achieve
unconscious
- hyperpolarization of thalamic sites via “dimmer switch” effect
- interrupts synchronicity b/t neural networks
Desired effects of IA
- immobility
- unconsciousness
- learning/memory
- sedation
- neuroprotection
- CV/respiratory
learning/memory
hippocampus/amygdala dependent
0.3-0.4 MAC amnesia
sedation
potent VA- stimulate GABA
N2O- antagonize NMDA
neuroprotection
- prevents apoptosis
- decrease CMRO2 via increase inhibitory & decrease excitatory transmission
neurotoxicity
irreversible cell damage by N2O??
CV/respiratory
- dose dependent myocardial depression & hypotension d/t decrease Ca++ availability/sensitivity
- respiration depression via central depression -> decrease Tv, increase RR, increase EtCO2
VA fluorination
- reduce toxicity d/t metabolism
- eliminate flammability
- increase speed of induction/recovery
pulmonary effects- TV
-decrease TV -> inadequate increase RR -> increase EtCO2
pulmonary effects- irritant receptors
- increase laryngeal irritant receptors
- decrease pulmonary irritant receptors
pulmonary effects- FRC
- loss of intercostals
- altered resp pattern
- cephalad movement of diaphragm
- altered thoracic blood volume
pulmonary effects- smooth muscle
bronchodilation via direct depression of sm. musc contractility
- bronchial epithelium/sm musc cells
- indirect inhibition of reflex neural pathways
pulmonary effects- PVR
- resistance is lowest at lung vol equivalent to FRC
- increase PVR -> increase PAP -> interstitial fluid transudation
increase PVR
- PEEP
- alveolar hypoxia
- alveolar hypercapnia
- critical closing pressure
hypoxic pulmonary vasoconstriction
- altered with VA
- all VA vasodilate the pulmonary vascular bed
- all VA cause a dose dependent myocardial depression
central control of respiration
- located near ventrolateral medulla/brainstem
- respond to changes in [H+] in CSF
- affected by resp alterations in arterial CO2 tension
peripheral control of respiration
- located in carotid bodies
- responds to changes in arterial CO2 tension, pH, and arterial O2 tension
post-op effects on breathing
-dose dependent depression of ventilatory response to hypercapnia
<0.2 MAC- depress peripheral chemoreflex loop and inhibit ventilatory response to hypercapnia
0.1 MAC attenuate ventilatory response to hypoxia in dose-dependent manner
-diffusion hypoxia
CV effects- contractility
dose dependent depression of myocardial contractility d/t intracellular Ca++ homeostasis, inhibition of Na+Ca++ exchange, LB diastolic dysfunction, LV after load effects, LA myocardial depression
CV effects- SBP
dose dependent decrease SBP
CV effects- SVR
dose dependent decrease in SVR
CV effects- chronotropic
negative chronotropic effects d/t SA node depression and blunt baroreceptor reflex -> bradycardia, AV conduction abnormalities
CV effects- coronary
vitro- vasodilation
vivo- vasoconstriction- reduce MVO2 via decrease HR, preload, afterload, inotropic state
neuro effects- CBF
increase CBF d/t decrease cerebrovascular resistance -> increase ICP
neuro effects- CMRO2
decrease CMRO2- neuro protective
neuro effects- SSEP/MEPs
depress SSEP/MEP monitoring
NM effects
centrally mediated muscle relaxant properties- synergistic effects with IV muscle relaxants
hepatic effects
liver receives blood from hepatic artery & portal vein
decrease hepatic blood flow
hepatic metabolism
phase 1 rxn (CYP450_
phase 2 rxn (uridine 5’ diphosphate transferase enzymes)
-affected by age, gender, disease, genetics
hepatic metabolite
trifluoroacetylated protein -> liver injury in “susceptible” patients
renal effects
decrease blood flow, GFR, and UOP
OB effects
decrease uterine blood flow and uterine contractility
N2O concentration effect
N2O is taken up fast -> leaves space in FRC for fresh gas saturated with VA inflow to occur -> concentration of VA in FRC increases faster
N2O second gas effect
second gas (VA) rises to a higher concentration more quickly d/t N2O concentration effect
N2O diffusion hypoxia
N2O washes out of tissues fast -> as N2O rushes into lungs it drags other gases with it -> displaces O2
