General Anesthesia Flashcards

1
Q

anesthetic state components

A

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

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2
Q

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

A

MAC

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3
Q

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

A

protein
lipid

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4
Q

T/F
Neuronal excitability is more affected by VAs than general anesthetics.

A

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.

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5
Q

most likely relevant site of anesthetic action

A

The synapse

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6
Q

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

A

presynaptic inhibition of NT release

inhibit excitatory neurotransmission

enhancement inhibitory neurotransmission

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7
Q

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

A

Activation of background K+ channels

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8
Q

ligand-activated ion channel family receptors

A

GABA
glycine
neuronal nicotinic
5-HT3 receptors

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9
Q

anesthetic action to produce immobility occurs largely at the

A

spinal cord

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10
Q

specific molecular targets for amnesia lie in the

A

hippocampus

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11
Q

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

A

brainstem
hypothalamus
thalamus
cerebral cortex

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12
Q

Anesthetic ablation of arousal relies on

A

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

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13
Q

Why have mechanisms of anesthesia been so difficult to elucidate?

A

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.

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14
Q

Anesthesia, by definition, is

A

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

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15
Q

General anesthesia can be broadly defined as

A

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

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16
Q

T/F
can only be defined and measured in the intact organism

A

True
rapid and reversible drug-induced changes in behavior or perception are essential to anesthesia

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17
Q

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 “

A

emergence occurs at a significantly lower concentration than induction

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18
Q

neural inertia

A

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)

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19
Q

neural inertia suggests that…

A

mechanisms of induction & emergence may be different

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20
Q

Minimum alveolar concentration (MAC)

A

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

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21
Q

T/F
MAC represents a dose

A

True

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22
Q

MAC represents the average response of

A

the whole of the population

not one person!

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23
Q

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

A

End-tidal concentration of gas

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24
Q

the end-tidal gas concentration is in equilibrium with

A

the free plasma concentration & BIS monitoring

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25
Q

T/F
BIS monitoring has also become a standard of care

A

True

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26
Q

T/F
MAC can account for the amount of other adjuncts that we have given

A

FALSE
MAC only refers to the concentration of agent

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27
Q

Meyer-Overton Rule

A

potency of gases as anesthetics was strongly correlated with their solubility in olive oil

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28
Q

The unitary theory of anesthesia

A

Structurally unrelated compounds obey the Meyer–Overton rule so all anesthetics are likely to act at the same molecular site

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29
Q

MAC as a measure of anesthetic potency
two major advantages

A

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)

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30
Q

There is a ___ relationship between the oil/gas partition coefficient and anesthetic potency

A

linear

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31
Q

Anesthetic agents must disrupt the function of neurons mediating (3)

A

behavior, consciousness & memory

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32
Q

Anesthesia alters neuronal communication by:

A

-alter neuron excitability (hyperpolarize to decrease action potential)

-synaptic transmission- most likely subcellular site of general anesthetic action

33
Q

Where in the CNS do Anesthetics work?

A

Suppress circuits in the spinal cord & brainstem

Induce immobility & disrupt autonomic homeostasis

34
Q

Autonomic Control:
Anesthetics can profoundly affect cardiopulmonary & thermoregulatory homeostatic circuitry without affecting …

A

autonomic centers in the brainstem & hypothalamus

35
Q

drives the phrenic motor neurons to activate diaphragmatic contraction

A

Inspiratory neurons in the medulla

36
Q

How does Halothane affect inspiratory neurons in the medulla?

A

suppresses the spontaneous activity of these neurons

37
Q

Mediates the anesthetic affect on CV reflexes

A

nuclei in the brainstem

38
Q

T/F
olive oil/gas partition coefficients can be determined for liquid anesthetics

A

False
oil/gas partition coefficients can be determined for gases and volatile liquids, but not for liquid anesthetics

39
Q

Which coefficient best correlates with anesthetic potency?

A

octanol/water partition coefficient

40
Q

solvent octanol properties suggest that the anesthetic site is likely to be ___

A

amphipathic
(having both polar and nonpolar characteristics)

41
Q

anesthetic potency & chain length

A

potency increases with chain length until a certain critical chain length is reached.

Beyond this = unable to produce anesthesia regardless of [ ]

42
Q

T/F
Enantiomers show a weak point in the Myer-Overton rule.

A

True
difference in potency between enantiomers can only be explained by a protein-binding site

size and shape also determine sites of action

43
Q

The functional unit of the CNS

A

neuron

44
Q

Neuronal excitability

A

propensity of a neuron to generate and propagate action potentials from the cell body to their nerve terminals

45
Q

Intrinsic neuronal excitability is chiefly determined by three parameters:

A

resting membrane potential
threshold potential
size/propagation of the action potential

46
Q

ability to hyperpolarize neurons correlates with

A

anesthetic potency

47
Q

Which IA has been shown to hyperpolarize thalamic neurons, leading to an inhibition of tonic firing of action potentials

A

Iso

48
Q

T/F
General anesthetics greatly alter neurotransmission across both excitatory and inhibitory synapses

A

True

49
Q

Places where general anesthetics inhibit excitatory synaptic transmission

A

sympathetic ganglia
olfactory cortex
hippocampus
spinal cord

50
Q

Presynaptic Effects on excitatory NTs

A

Inhibits NT release at glutamatergic synapses

51
Q

Anesthetics alter the two fundamental determinants of neuronal communication:

A

neuronal excitability
synaptic transmission

52
Q

Voltage-dependent calcium channels (VDCCs) are located (pre/post) synaptically.

A

PRE
located at presynaptic terminals
respond to action potentials by opening
calcium enters
activates calcium-dependent secretion of NT into the synaptic cleft

53
Q

most diverse of the ion channel types

A

K channels
(voltage-gated, background, or leak channels )

54
Q

Background or leak K+ channels are activated by (2)

A

both volatile and gaseous anesthetics

55
Q

Fast excitatory and inhibitory neurotransmission is mediated by

A

the actions of ligand-gated ion channels

56
Q

Glutamate-activated ion channels
3 categories:

A

AMPA receptors
kainate receptors
NMDA receptors

57
Q

Which Glutamate receptor is involved in long term potentiation?

A

NMDA

58
Q

the most important inhibitory neurotransmitter in the mammalian CNS

A

GABA

59
Q

How do GABA(A) receptors work?

A

mediate the postsynaptic response to synaptically released GABA by selectively allowing chloride ions to enter, and thereby hyperpolarize neurons

60
Q

T/F
Convulsants act on GABA(A) receptors.

A

True

61
Q

GABAA structure

A

pentameric
various combinations of α, β, δ, and ε subunits
many subtypes of each subunit

62
Q

Which drugs modulate GABAA fxn?

A

Barbiturates
anesthetic steroids
benzodiazepines
propofol
etomidate
volatile anesthetics

63
Q

Which drugs inhibit NMDA-type glutamate receptors?

A

Ketamine, N2O, and xenon

64
Q

diffuse collection of brainstem neurons that mediate arousal

A

RETICULAR ACTIVATING SYSTEM (RAS)

65
Q

major site for generating awareness of the external environment

A

CEREBRAL CORTEX

66
Q

primary sensory areas

A

CEREBRAL CORTEX

67
Q

CEREBRAL CORTEX
___ ___ by anesthetics may contribute to impaired consciousness

A

Disruption feedback

68
Q

Awareness

A

ability to process and store information in order to interact with internal or external environment

69
Q

arousal/wakefulness

A

state of receptivity to the external environment

70
Q

arousal/wakefulness
likely mediated through

A

subcortical structures such as the reticular activating system (RAS) and other arousal centers

71
Q

RAS includes

A

reticular formation
tuberomammillary nucleus (TMN)
ventral tegmental area (VTA)
thalamic intralaminar nucleus

72
Q

heterogeneous collection of neurons in the midbrain and pons involved in the regulation of arousal and sleep

A

reticular formation (RF)

73
Q

Lesions of the midbrain RF can induce

A

coma

74
Q

The thalamus regulates….

A

widespread cortical excitability
relays info to specialized cortical regions

75
Q

likely target for anesthetic ablation of arousal and awareness

A

Thalamus

76
Q

Anesthetics suppress circuits in the spinal cord and brainstem to …

A

induce immobility and disrupt autonomic homeostasis

77
Q

T/F
The hippocampus is a major site of anesthetic action for retrograde amnesia.

A

False
anterograde

78
Q

T/F
no single anatomic site is responsible for anesthetic-induced unconsciousness

A

True
arousal and awareness are distributed across brainstem, subcortical, and cortical structures