inhalation agents: Unitary, Lipid-Based Theories: Meyer-Overton Theory
- chemically indifferent substance that are soluble in fat are anesthetics
- there relative potency depends on their affinity for water and their affinity for fat–there fat/water partition
inhalation agents: Unitary, Lipid-Based Theories: Unitary theory
cell membranes were mostly lipid therefore the majority of anesthetics effects must come from the effects on cell membranes
inhalation agents: The Concept of MAC
- MAC is analogous to plasma EC50
- universal measure for inhaled anesthetic potency
inhalation agents: Protein Centered Theory
signaling proteins (ion channels and receptors) are the molecular site of action
inhalation agents: Plasma EC50
non-paralyzed patients don’t respond to stimuli
inhalation agents: Alcoholics and MAC requirements
need more MAC inhaled agent
inhalation agents: normal person MAC requirements
Start with MAC and adjust
inhalation agents: Commorbidities MAC requirements
Start at lower MAC
inhalation agents: Site of Action of inhaled anesthetics: Proteins
- site: amphilic binding sites
- effect: conformational flexibility, ligand binding
- target: ion channels, receptors, signaling proteins
inhalation agents: Site of Action of inhaled anesthetics: Action Potential
- site: Nervous system
- effect: small reduction in amplitude
- target: Na channels
- site: Cardiovascular system
- effect: reduced amplitude, duration
- target: Ca channels, K channels
inhalation agents: Site of Action of inhaled anesthetics: inhibitory synaptic transmission
- site: presynaptic
- effect: enhanced transmitter
- site: post synaptic
- effect: enhanced transmitter effects
- target: glycine, GABA-a receptors
Site of Action of inhaled anesthetics: excitatory
- site: pre synaptic
- effect: reduced transmitter release
- target: Na channels, K2P channels
- site: post synaptic
- effect: reduced transmitter release
- target: NMDA receptors, HCN channels, K2P channels, extrasynaptic GABA-a receptors
Site of Action of inhaled anesthetics: Neuronal Networks
- site: neuronal circuit neuronal integration
- effect: altered LTP/LTD, altered rhythmicity, coherence
Site of Action of inhaled anesthetics: central nervous system
- site: neocortex
- effect: sedation, amnesia
- target: gamma rhythms, synchony
- site: diencephalon
- effect: unconsciousness
- target: gamma-band transfer entropy
- site: spinal cord
- effect: immobility
- target: thalamic deafferentation, nocifensive reflex
Site of Action of inhaled anesthetics: cardiovascular system
- site: myocardium
- effect: negative inotropy
- target: excitation-contraction coupling
- site: conduction system
- effect: dysthymias
- target: action potential
- site: vasculature
- effect: vasodilation
- target: direct and indirect vasoregulation
Molecular targets of inhaled anesthetics: ligand dated ion channels
potentiation of GABA and Glycine
Molecular targets of inhaled anesthetics: voltage gated ion channels
Na, Ca, K channels
Molecular targets of inhaled anesthetics: intracellular signaling mechanisms
G-protein coupled receptors, protein phophorlaytion, gene expression
inhalation agents: Cellular mechanisms: neuronal excitability
determined by resting membrane potential, threshold, and input resistance
inhalation agents: Cellular mechanisms: presynaptic effects
inhalation agents alter transmitter release
inhalation agents: Cellular mechanisms: post synaptic effects
inhalation agents neurotransmitter responses
Desired Effects of inhalation agents: immobility
- mediated by spinal cord NMDA receptors
- requires 2.5-4x MAC for amnesia and unconsciousness
Desired Effects of inhalation agents: unconsciousness
- hyperpolarization of thalamic sites
- dimmer-switch than off/on
- depends on interrupting synchrony between multiple neural networks
Desired Effects of inhalation agents: learning and memory
hippocampal and amygdala dependent
