General Anesthesia Flashcards
anesthetic state components
-unconsciousness
-amnesia
-analgesia
-immobility
-attenuation of ANS response to noxious stimulation
most robust measurement and the standard for determining the potency of volatile anesthetics.
MAC
Current evidence strongly indicates ___ rather than ___ as the molecular target for anesthetic action.
protein
lipid
T/F
Neuronal excitability is more affected by VAs than general anesthetics.
True
Current data:
neuronal excitability is only slightly affected by general anesthetics, this small effect may nevertheless contribute significantly to the clinical actions of volatile anesthetics.
most likely relevant site of anesthetic action
The synapse
Possible actions an anesthetic may elicit at the synapse (3)
presynaptic inhibition of NT release
inhibit excitatory neurotransmission
enhancement inhibitory neurotransmission
important and general mechanism through which volatile and gaseous anesthetics regulate neuronal resting membrane potential and excitability
Activation of background K+ channels
ligand-activated ion channel family receptors
GABA
glycine
neuronal nicotinic
5-HT3 receptors
anesthetic action to produce immobility occurs largely at the
spinal cord
specific molecular targets for amnesia lie in the
hippocampus
arousal and awareness are mediated by targets distributed across the… (4)
brainstem
hypothalamus
thalamus
cerebral cortex
Anesthetic ablation of arousal relies on
disruption of redundant subcortical systems that regulate sleep and patterns of cortical activity
Why have mechanisms of anesthesia been so difficult to elucidate?
1) link between effects observed in vitro and in vivo is difficult.
2) No structure–activity relationships among anesthetics. (many diff structures can cause anesthesia = multiple mechanisms)
3) work at HIGHER [ ] > drugs, NTs, & hormones. (low affinity & very short binding time). Low-affinity binding is harder to observe & characterize than high.
Anesthesia, by definition, is
a change in the responses of an intact animal to external stimuli
General anesthesia can be broadly defined as
drug-induced reversible CNS depression
⬇️
loss of response to & perception of all external stimuli.
T/F
can only be defined and measured in the intact organism
True
rapid and reversible drug-induced changes in behavior or perception are essential to anesthesia
What is wrong with this ideaology?
“anesthesia is a state that is achieved when an anesthetic agent reaches a specific concentration at its effect site in the brain “
emergence occurs at a significantly lower concentration than induction
neural inertia
it takes a higher anesthetic brain concentration to induce anesthesia than to maintain anesthesia
(i.e., emergence occurs at a significantly lower concentration than induction)
neural inertia suggests that…
mechanisms of induction & emergence may be different
Minimum alveolar concentration (MAC)
partial pressure of gas at which 50% of humans do not respond to surgical stimulation
T/F
MAC represents a dose
True
MAC represents the average response of
the whole of the population
not one person!
Provides an index of the free [ ] required to produce anesthesia
End-tidal concentration of gas
the end-tidal gas concentration is in equilibrium with
the free plasma concentration & BIS monitoring
T/F
BIS monitoring has also become a standard of care
True
T/F
MAC can account for the amount of other adjuncts that we have given
FALSE
MAC only refers to the concentration of agent
Meyer-Overton Rule
potency of gases as anesthetics was strongly correlated with their solubility in olive oil
The unitary theory of anesthesia
Structurally unrelated compounds obey the Meyer–Overton rule so all anesthetics are likely to act at the same molecular site
MAC as a measure of anesthetic potency
two major advantages
reproducible & constant over a wide range of species
end-tidal gas [ ] provides an index of the “free” concentration of drug required to produce anesthesia (end-tidal gas [ ] is in equilibrium w/ the free [ ] in plasma)
There is a ___ relationship between the oil/gas partition coefficient and anesthetic potency
linear
Anesthetic agents must disrupt the function of neurons mediating (3)
behavior, consciousness & memory
Anesthesia alters neuronal communication by:
-alter neuron excitability (hyperpolarize to decrease action potential)
-synaptic transmission- most likely subcellular site of general anesthetic action
Where in the CNS do Anesthetics work?
Suppress circuits in the spinal cord & brainstem
Induce immobility & disrupt autonomic homeostasis
Autonomic Control:
Anesthetics can profoundly affect cardiopulmonary & thermoregulatory homeostatic circuitry without affecting …
autonomic centers in the brainstem & hypothalamus
drives the phrenic motor neurons to activate diaphragmatic contraction
Inspiratory neurons in the medulla
How does Halothane affect inspiratory neurons in the medulla?
suppresses the spontaneous activity of these neurons
Mediates the anesthetic affect on CV reflexes
nuclei in the brainstem
T/F
olive oil/gas partition coefficients can be determined for liquid anesthetics
False
oil/gas partition coefficients can be determined for gases and volatile liquids, but not for liquid anesthetics
Which coefficient best correlates with anesthetic potency?
octanol/water partition coefficient
solvent octanol properties suggest that the anesthetic site is likely to be ___
amphipathic
(having both polar and nonpolar characteristics)
anesthetic potency & chain length
potency increases with chain length until a certain critical chain length is reached.
Beyond this = unable to produce anesthesia regardless of [ ]
T/F
Enantiomers show a weak point in the Myer-Overton rule.
True
difference in potency between enantiomers can only be explained by a protein-binding site
size and shape also determine sites of action
The functional unit of the CNS
neuron
Neuronal excitability
propensity of a neuron to generate and propagate action potentials from the cell body to their nerve terminals
Intrinsic neuronal excitability is chiefly determined by three parameters:
resting membrane potential
threshold potential
size/propagation of the action potential
ability to hyperpolarize neurons correlates with
anesthetic potency
Which IA has been shown to hyperpolarize thalamic neurons, leading to an inhibition of tonic firing of action potentials
Iso
T/F
General anesthetics greatly alter neurotransmission across both excitatory and inhibitory synapses
True
Places where general anesthetics inhibit excitatory synaptic transmission
sympathetic ganglia
olfactory cortex
hippocampus
spinal cord
Presynaptic Effects on excitatory NTs
Inhibits NT release at glutamatergic synapses
Anesthetics alter the two fundamental determinants of neuronal communication:
neuronal excitability
synaptic transmission
Voltage-dependent calcium channels (VDCCs) are located (pre/post) synaptically.
PRE
located at presynaptic terminals
respond to action potentials by opening
calcium enters
activates calcium-dependent secretion of NT into the synaptic cleft
most diverse of the ion channel types
K channels
(voltage-gated, background, or leak channels )
Background or leak K+ channels are activated by (2)
both volatile and gaseous anesthetics
Fast excitatory and inhibitory neurotransmission is mediated by
the actions of ligand-gated ion channels
Glutamate-activated ion channels
3 categories:
AMPA receptors
kainate receptors
NMDA receptors
Which Glutamate receptor is involved in long term potentiation?
NMDA
the most important inhibitory neurotransmitter in the mammalian CNS
GABA
How do GABA(A) receptors work?
mediate the postsynaptic response to synaptically released GABA by selectively allowing chloride ions to enter, and thereby hyperpolarize neurons
T/F
Convulsants act on GABA(A) receptors.
True
GABAA structure
pentameric
various combinations of α, β, δ, and ε subunits
many subtypes of each subunit
Which drugs modulate GABAA fxn?
Barbiturates
anesthetic steroids
benzodiazepines
propofol
etomidate
volatile anesthetics
Which drugs inhibit NMDA-type glutamate receptors?
Ketamine, N2O, and xenon
diffuse collection of brainstem neurons that mediate arousal
RETICULAR ACTIVATING SYSTEM (RAS)
major site for generating awareness of the external environment
CEREBRAL CORTEX
primary sensory areas
CEREBRAL CORTEX
CEREBRAL CORTEX
___ ___ by anesthetics may contribute to impaired consciousness
Disruption feedback
Awareness
ability to process and store information in order to interact with internal or external environment
arousal/wakefulness
state of receptivity to the external environment
arousal/wakefulness
likely mediated through
subcortical structures such as the reticular activating system (RAS) and other arousal centers
RAS includes
reticular formation
tuberomammillary nucleus (TMN)
ventral tegmental area (VTA)
thalamic intralaminar nucleus
heterogeneous collection of neurons in the midbrain and pons involved in the regulation of arousal and sleep
reticular formation (RF)
Lesions of the midbrain RF can induce
coma
The thalamus regulates….
widespread cortical excitability
relays info to specialized cortical regions
likely target for anesthetic ablation of arousal and awareness
Thalamus
Anesthetics suppress circuits in the spinal cord and brainstem to …
induce immobility and disrupt autonomic homeostasis
T/F
The hippocampus is a major site of anesthetic action for retrograde amnesia.
False
anterograde
T/F
no single anatomic site is responsible for anesthetic-induced unconsciousness
True
arousal and awareness are distributed across brainstem, subcortical, and cortical structures
