General Anesthesia Flashcards by Veronica Robinson

anesthetic state components

-unconsciousness
-amnesia
-analgesia
-immobility
-attenuation of ANS response to noxious stimulation

How well did you know this?

Not at all

Perfectly

most robust measurement and the standard for determining the potency of volatile anesthetics.

MAC

How well did you know this?

Not at all

Perfectly

Current evidence strongly indicates ___ rather than ___ as the molecular target for anesthetic action.

protein
lipid

How well did you know this?

Not at all

Perfectly

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.

How well did you know this?

Not at all

Perfectly

most likely relevant site of anesthetic action

The synapse

How well did you know this?

Not at all

Perfectly

Possible actions an anesthetic may elicit at the synapse (3)

presynaptic inhibition of NT release

inhibit excitatory neurotransmission

enhancement inhibitory neurotransmission

How well did you know this?

Not at all

Perfectly

important and general mechanism through which volatile and gaseous anesthetics regulate neuronal resting membrane potential and excitability

Activation of background K+ channels

How well did you know this?

Not at all

Perfectly

ligand-activated ion channel family receptors

GABA
glycine
neuronal nicotinic
5-HT3 receptors

How well did you know this?

Not at all

Perfectly

anesthetic action to produce immobility occurs largely at the

spinal cord

How well did you know this?

Not at all

Perfectly

specific molecular targets for amnesia lie in the

hippocampus

How well did you know this?

Not at all

Perfectly

arousal and awareness are mediated by targets distributed across the… (4)

brainstem
hypothalamus
thalamus
cerebral cortex

How well did you know this?

Not at all

Perfectly

Anesthetic ablation of arousal relies on

disruption of redundant subcortical systems that regulate sleep and patterns of cortical activity

How well did you know this?

Not at all

Perfectly

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.

How well did you know this?

Not at all

Perfectly

Anesthesia, by definition, is

a change in the responses of an intact animal to external stimuli

How well did you know this?

Not at all

Perfectly

General anesthesia can be broadly defined as

drug-induced reversible CNS depression
⬇️
loss of response to & perception of all external stimuli.

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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)

How well did you know this?

Not at all

Perfectly

neural inertia suggests that…

mechanisms of induction & emergence may be different

How well did you know this?

Not at all

Perfectly

Minimum alveolar concentration (MAC)

partial pressure of gas at which 50% of humans do not respond to surgical stimulation

How well did you know this?

Not at all

Perfectly

T/F
MAC represents a dose

True

How well did you know this?

Not at all

Perfectly

MAC represents the average response of

the whole of the population

not one person!

How well did you know this?

Not at all

Perfectly

Provides an index of the free [ ] required to produce anesthesia

End-tidal concentration of gas

How well did you know this?

Not at all

Perfectly

the end-tidal gas concentration is in equilibrium with

the free plasma concentration & BIS monitoring

How well did you know this?

Not at all

Perfectly

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