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Phar 301 > General Anesthesia > Flashcards

General Anesthesia Flashcards

1
Q

What is Nitrous Oxide and what does it do?

A

Inhalational anesthetic
Laughing Gas
Strongly inhibits NMDA receptors

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2
Q

What is halothane and what does it do?

A

Inhalational anesthetic

Potentiates GABA effects at GABA-A receptors

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3
Q

What is isoflurane and what does it do?

A

Inhalational anesthetic

Inhibits output of Thalamocortical neurons

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4
Q

What is ketamine and what does it do?

A

Intravenous anesthetic

Selective inhibitor of NMDA receptors

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5
Q

What is pentobarbital/pentobarbitone and what does it do?

A

Intravenous anesthetic

stereoselectively potentiates GABA

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6
Q

What is luciferase?

A

Luminous protein in fireflies, used for ATP conc assays

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7
Q

What is Kainate?

A

A type of ionotropic glutamate receptor

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8
Q

Where are thalamocortical neurons found?

A

Between the thalamus and the cerebral cortex (convey sensation)

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9
Q

What are the structures of inhalational anesthetics?

A

No clear Structure/Activity relationship
(lots of ethers)
MUST BE GIVEN WITH O2

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10
Q

How can you test the potency of anesthetic agents on an animal model?

A

Tadpole righting reflex loss

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11
Q

Anesthetic potency is predicted by what property of the compound?

A

Solubility in lipid bilayers

Applies mostly to INHALATIONAL anesthetics

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12
Q

What is the Lipid theory, name a possible mechanism, and state a problem with this theory

A

Membrane volume expansion shown to occur in RBCs (disrupts ion channels?) AND pressure reverses anesthesia

Increased membrane fluidity
shown to occur BUT mimicked by 1 degree rise AND correlation breaks down

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13
Q

What is the Lipid theory, name a possible mechanism, and state a problem with this theory

A

Membrane volume expansion shown to occur in RBCs (disrupts ion channels?) AND pressure reverses anesthesia

Increased membrane fluidity
shown to occur BUT mimicked by 1 degree rise AND correlation breaks down

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14
Q

What are exceptions to the disordering/potency rule?

A

Long chain alcohols disorder greatly but are weak anesthetics

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15
Q

What are the 2 critical observations of the lipid theory?

A 
Cut-off phenomenon: 
increasing carbon length
increasing lipid solubility
increasing anesthetic potency
UNTIL cut off is reached

Stereoselective anesthetics:
IV ketamine in rats (+ isomer more potent, not explained by any difference in brain penetration)
Pentobarbital (- is more potent anesthetic)

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16
Q

What is stereoselectively potentiated by Pentobarbital? What is the more potent anesthetic?

A

GABA

(-) isomer

17
Q

True/False? Potency for luciferase inhibition is correlated to potency of general anesthesia

A

True

18
Q

What is the unitary hypothesis, and what is the specific hypothesis? Which is the leading hypothesis? why?

A

Unitary:
One molecular target is common to all general anesthetics
Specific:
The targets (maybe proteins?) differ between anesthetics

19
Q

What are the criteria for identifying an anesthetic target site? (5)

A

Must be affected at appropriate (therapeutic) concnetration
Must show (any) appropriate stereoselectivity
Agonists (or antagonists) must produce anesthesia
“Knockout” animals should not be susceptible to anesthetic
Transgenic animals should be more/less susceptible

20
Q

What is the unitary hypothesis, and what is the specific hypothesis? Which is the leading hypothesis? why?

A

Unitary:
One molecular target is common to all general anesthetics
Specific:
The targets (maybe proteins?) differ between anesthetics

Specific Hypothesis
1) Ketamine acts selectively on NMDA receptors
2) Not all IV anesthetics inhibit NMDA receptors
N2O is an inhalational anesthetic that DOES strongly inhibit NMDA receptors

21
Q

True/False? Voltage-Gated ion channels tend to be very sensitive to general anesthetics

A

False

Completely insensitive

22
Q

What are the three basic ionotropic glutamate receptors?

A

NMDA
AMPA
Kainate

23
Q

What are the three basic ionotropic glutamate receptors?

A

NMDA
AMPA
Kainate

24
Q

True/False? There are only a few ligand gated ion channels

A

EXTREMELY false
Many subunits each produced from a single gene
Subunits can combine in different ways to produce receptor subtypes

25
Q

How might GABA A receptors be important for anesthesia?

A

1) Most gaseous anesthetics can potentiate GABA at surgical concentrations
2) The well-known GABA-potentiating effect of pentobarbital
3) Ketamine and N2O do not potentiate GABA

26
Q

How is anesthesia induced by a GABA A receptor agonist (THIP) measured in rats?

A

Give THIP

measure time until loss of righting reflex

27
Q

General anesthesia and sedation are mediated by what receptors?

A

GABA-A and its isoforms

28
Q

General anesthesia and sedation are mediated by what receptors?

A

GABA-A and its isoforms

29
Q

Which GABA A subunit is relevant to explain etomidate’s anesthedic effect?

A

beta 3 subunit

30
Q

What theory suggests a single anesthesia centre? Where is it?

A

The Mesopontine switch hypothesis

A single anesthesia centre at the junction of midbrain and pons

31
Q

Define the mesopontine switch hypothesis

What are the implications if this theory is true?

A

General (read: GABAnergic) anesthetics produce their effects by targeting a small brain stemp area called the Mesopontine tegmental anesthesia area (MPTA)

If true, it suggests the possibility of more selective drugs that might avoid respiratory depression (and other common side effects of GAs)

32
Q

What are the three arguments for the Mesopontine switch hypothesis?

A

1) Brain mapping with pentobarbital injections - MPTA was anesthetic “hotspot”
2) Extremely low doses of pentobarbital at MPTA were enough to cause sedation
3) Rats with MPTA lesions needed more pentobarbital to receive anesthesia

33
Q

Does intraperitoneal injection of Pentobarbital achieve the same anesthetic effect as direct MPTA injections?

A

Yes

34
Q

What is the hypothesis for multiple distributed anesthetic sites in the brain?

A

General anesthetics DIRECTLY target multiple areas of the CNS in order to produce their various effects

35
Q

What are the three arguments to support the multiple distributed anesthetic site hypothesis?

A

1) GAs distribute throughout the CNS
2) Target receptors (eg NDMA, GABA A) are widespread in the brain
3) DIfferent components of anesthesia are dependent on far-flung regions of the CNS*

  • Suppression of movement and pain - Spinal cord
  • Impaired memory and consciousness - hippocampus/cerebral cortex
36
Q

Is the lipid solubility theory correct?

A

NO

Phar 301 (23 decks)

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