Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PH3501- Neuropharmacology > General Anaesthetics > Flashcards

General Anaesthetics Flashcards

1
Q

A definition

A
  • Lack of feeling
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Basic principles of anaesthesia

A
  • Anaesthesia- abolition of sensation
  • Analgesia- Abolition of pain
  • Triad of general anesthesia
    • Need for unconsciousness
    • Need for analgesia
    • Need for muscle relaxation
      • We can reduce dose of anaesthetics
      • Stop muscle twitch/contraction
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

History of anaesthesia

A
  • Chinese acupuncture
  • Hindu- Henbane, wine and hemp
  • Greece discordes coined term anaesthesia for effects of drinking mandrake
  • Early arab writing- inhalation via the soporific sponge- sponge soaked in a dissolved solution of opium
  • Manual methods- compression, bleeding, smack on head
  • 1800 Humphry Davy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

General Anaesthetics (GAs)

A
  • Ideal GAs should be
    • Readily controllable
    • So that induction and recovery are rapid
    • Allowing the level of anaesthesia to be adjusted as required
  • Other drugs can produce a state of insensibility and obliviousness to pain (morphine/ethanol)
    • Not used as anaesthetics since they are not readily controllable
  • The discovery of inhalation anaesthetics in 1846 paved the way for safe surgical procedures
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q
A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Stage of anaesthesia

Stage 1- analgesia

A
  • Stage 1- analgesia
    • Patient conscious but drowsy
    • Responses to painful stimuli rediced
    • Degree of analgesia depends upon agent (Ether~ N2O >Halothane)
  • Stage 2- Excitement
    • Very hazardous state
    • Modern anaesthetic procedure are designed to counter effects which include
    • Loss of
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Stage 2- Excitement

A
  • Stage 2- Excitement
  • Very hazardous state
  • Modern anaesthetic procedure are designed to counter effects which include
  • Loss of consciousness, No response to non-painful stimuli but reflex response to painful stimuli
  • Other reflexes (coughing/gagging in response to pharyngeal stimulation) exaggerated
  • May move around, talk incoherently, voluntary apnea, choke, vomit
  • Irregular breathing may affect the of gaseous anaesthetic agents
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Stage 3 and 4

A
  • Stage 3- Surgical anaesthesia
    • Spontaneous movement stops, Respiration become regular
    • While anaesthesia is light, responses to pharyngeal and peritoneal stimulation remain intact
    • Deepening aanaesthesia leads to progressive loss of reflexes, increased muscles relaxation shallowed respiration with intercostal respiratory muscles failing before diaphragm
  • Stage 4- Medullary paralysis
    • Respiratation and vasomotor control cease. Death occurs within minutes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Aims of surgical anesthesia

A
  • Common anaesthetic approaches aim to:
    1. Produce rapid unconsciousness
      • Intravenous injection of a rapid onset, short acting barbiturate (Thiopentone)
    2. Maintain unconsciousness
      • With one of more inhalation agent (e.g. N2O and halothane)
    3. Supplement analgesia
      • With an intravenous analgesic agent (e.g. fentanyl)
    4. Produce muscle paralysis
      • With a neuromuscular blocking agent such as tubocurarine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How do GAs work

2 main theories

A
  1. Lipid theory of overton and Meyer
  2. Protein (receptor) theory
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Lipid theory of anaesthetic action- observations

A
  • Overton and Meyer found
  • The close correlation between anaesthetic potency and lipid solubility
    • Series of a simple and un-reactive organic compound
    • Determined the concentration needed to produce reversible immobilisation of swimming tadpoles
    • Compared with the olive-oil: water partition coefficient
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Lipid theory of anaesthetic action- Hypothesis

A
  • Overton and Meyer- Hypothesis
    • 1937 Meyer formulated the theory
    • Narcosis (anaesthesia) commences when any chemically indifferent substance has attained a certain molar concentration in the lipids of the cell
    • This concentration depends on the nature of the animal or cell but is independent of the narcotic
    • 1989: Halsey confirmed work of Meyer and Overton in man
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Normal v Expanded membrane

A
  • There theory was that the molecules entered the lipids of the cell causing membrane expansion and so prevents the opening of the sodium channel so blocking it
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Lipid theory of anaesthetic action- Evidence

A
  • Minimum Alveolar Concentration (MAC) is inversely proportional to lipid solubility
  • Measure partial pressure of anaesthetic in the lungs and measure pain response gives a measure of potency
  • More lipid soluble the more of an anaesthetic effect
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Lipid theory- Speculations

A
  • The Meyer-Overton hypothesis reveals strong correlation between anaesthetic potency and lipid solubility
    • Does not suggest any mechanism of action of anaesthetics
  • Correlation of potency with solubility in hydrophobic solvents leads to speculation that anaesthesia is caused by an alteration of membrane function
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Testing the lipid hypothesis

A
  1. Volume expansion
    • Supported by the phenomenon of pressure reversal of anaesthesia
17
Q

Membrane expansion hypothesis

A
  • Anaesthesia occurs because when anaesthetics occupy a cell membrane they cause it to expand
  • Evidence for the membrane expansion hypothesis
    • Anaesthetics can expand the area occupied by a mono-molecular layer of phospholipid molecules
    • Anaesthetics can increase the surface area of the erythrocyte cell membrane (2-3%)
    • Anaesthesia can be reversed by hydrostatic pressure
18
Q

Explanations-1

A
  • Is lipid bilayer volume expansion the cause
    • Supported by the phenomenon of pressure reversal of anaesthesia as increased pressure will oppose volume expansion
    • Suggest anaesthesia requires lipid volume expansion of 0.4%
  • BUT
    • Is degree of actual expansion really sufficient
    • Pressure reversal can be seen with other classes of drugs
      • Intravenous agents (barbiturates) and local anaesthetics
    • Therefore an increase in lipid volume is unlikely to explain all the actions of this class of drug s
19
Q

Explanation-2

A
  • Increase in membrane fluidity
    • The intrusion of anaesthetic agents leads to disordering of the regular packing of the hydrophobic tails of membrane phospholipids
  • Evidence
    • Electron spin resonance (ESR) spectroscopy indicate that anaesthetics increase membrane fluidity
    • Correlates with anaesthetic activity
      • Although relatively high concentrations needed
      • Equivalent to an increase in fluidity produced by the 1oC rise in temperature
      • But raising temperature reduces anaesthetic potency
20
Q

Arguments against the lipid theory

A
  • The cut off phenomenon
    • Anaesthetic potency increases steadily through a homologous series of chemical comounds as the length of the hydrocarbon chain is increased
    • Beyond a certain point potency suddenly drops even though lipid solubility continues to increase
  • In-vitro immobilization of halothane during anaesthesia
    • ESR studies in vitro indicarte that halothane molecules in the brain bind to sturable sites, and are immobilized when bound
    • Association of halothane with membrane lipids shows neither saturability nor immobilization
21
Q

Protein theory of anaesthetic action- observation

A
  • Anaesthetics interact with specific membrane proteins
    • Receptors and ligand-gated ion channels
  • Franks and Lieb- 1987
    • The close correlation between anaesthetic potency and the potency of luciferase inhibition for a wide range of anaesthetic compound
    • Luciferase is soluble protein, therefore, interaction with lipid not necessary
    • Suggests anaesthetics bind to a hydrophobic domain of the protein and alter its function
    • Several anaesthetics act in enantio-selective manner isoflurane, barbiturates, etomidate, neuroactive steroids
22
Q

Cellular sites of action

A
  • During surgical anaesthesia, condition along peripheral nerves is largely unaffected- if lipid theory is correct this would be affected
    • I.e. different from actions of local anaesthetics
    • Axonal condution is only affected at concentrations >> than those used for general anaesthesia
  • Synaptic transmission is far more susceptible to anaesthetic action
  • Therefore, at the cellular level, anaesthetics mainly affect synaptic transmission
23
Q

Recording neuronal activity- the brain slice

A

*

24
Q

Recent evidence: Actions at glu and GABA synapses

A
  • We see an increase of GABA activity with the addition of halothane or Propofol
  • Bicucline (GABAA - block GABA A receptor)- effective reversal of propofol
  • Halothane BIC doesn’t reverse as much
  • There is a subtle effect of glutamate
25
Q

Effects on synaptic transmission

A
  1. Reduced Glu release at synapses
  2. Increased GABA release
    • 2b. Increased duration of GABA IPSC
  3. Reduction of the excitability of the post-synaptic cells
26
Q

What sorts of anaesthetics do we use>

A
  • Inhalation
    • Gases or Vapors
    • Usually Halogenated
  • Intravenous
    • Injection
    • Anaesthetics or induction agents
27
Q

Inhaled Anesthetics

A
  • Easy to control
  • Reversible
28
Q

Physical and chemical properties of inhaled anaesthetics

A
  • Although halogenations of hydrocarbons and ethers increase anaesthetic potency, it also increase the potential for inducing cardiac arrhythmias in the following order F<cl>
    </cl><li>Esthers that have an asymmetric hhalogenated carbon tend to be good anesthetics (such as Enflurane)</li><li>Halogenated methyl, ethyl ethers (Enflurane and Isoflurane) are more stable, are more potent and have better clinical profile than halogenated diethyl ethers</li><li>Fluorination decrease flammability and increase sstability of adjacent halogenated carbons</li><li>Complete halogenations of alkane and ethers of full halogenations of end methyl groups decrease potency and enhances convulsant activity
    <ul>
    <li>Flurothyl is a potent convulsant, with a median effective dose (ED50) for convulsions in mice of 0.00122 atm</li>
    </ul>
    </li><li>The presence of double bonds tends to increase chemical reactivity and toxicity</li>

</cl>

29
Q

Intravenous Anesthetics

A
  • Used in combination with inhaled anaesthetics to
    • Supplement general anaesthesia
    • Maintain general anaesthesia
    • Provide sedation
    • Control BP
    • Protect the brain
30
Q

Anaesthetic of the future: Xenon

A
  • Rare gas extracted from the air- synthesised from supernova
    • Very expensive to produce
  • Close to ideal anaesthetic
    • Low blood and tissue solubility- Rapid induction/ recovery
    • Potent
    • Not metabolized
    • Non-flammable
    • Minimal side effects

PH3501- Neuropharmacology (28 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions