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BIOL2049 S2 > General anaesthetics > Flashcards

General anaesthetics Flashcards

1
Q

LO

A
  • Briefly describe the historical perspective and the systems-based explanation for anaesthesia.
  • Highlight distinct classes of general anaesthetics inhalation and intravenous.
  • Highlight how diverse structures were thought to have a common mode of action through perturbation of lipid membrane.
  • Clarify the important role of ion channel binding sites in mediating general anaesthesia.
  • Describe clinical use and limitations of important general anaesthetics.
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2
Q

Jolly japes through history

A
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3
Q

How many stages are they for controlled anaesthesia for analgesia/surgery?

A

5

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4
Q

Tell me about stage 1 for controlled anaesthesia for analgesia/ surgery

A
  • (Analgesia)
  • During childbirth, some women in labour are administered an analgesic agent (pain relief) and remain conscious and co-operative.
  • Accident victims also need to have some degree of pain relief to lessen the effects of shock.
  • Specifically designed equipment delivers analgesic gas, usually in the proportion 50-50 nitrous oxide and oxygen (entonox).
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5
Q

Tell me about stage 2 for controlled anaesthesia for analgesia/ surgery

A
  • (Unconscious, without reflex depression or delirium)
  • This is too deep for a woman in labour, as she is required to remain conscious.
  • It is not deep enough for a surgeon as it cannot provide the conditions they require.
  • This stage is therefore passed through or bypassed altogether.
  • Confounds are irregular breathing (unpredictable) and gag reflexes avoid when falling into and out of deeper states.
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6
Q

Tell me about stage 3 for controlled anaesthesia for analgesia/ surgery

A
  • (Unconscious, with reflex depression or surgical anaesthesia)
  • This provides at its lightest level, sufficient reflex depression to prevent movement of a limb or muscle if the skin is cut.
  • More anaesthetic agent, and hence more anaesthesia, must be used to depress the more sensitive reflexes, such as those from handling the parietal peritoneum (the abdominal cavity), where inadequate anaesthesia would cause a reflex tightening of the abdominal muscles and prevent the surgeon reaching his objective.
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7
Q

Tell me about stage 4 for controlled anaesthesia for analgesia/ surgery

A
  • (Respiratory paralysis)
  • Respiration becomes progressively paralysed in the deeper planes of stage three, and when it finally ceases, stage four has been reached.
  • Sometimes the anaesthetist has to take the patients near to the brink of this stage in order to meet the surgeon’s requirements.
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8
Q

Tell me about stage 5 for controlled anaesthesia for analgesia/ surgery

A

Death (Loss cardiac reflexes and respiratory reflexes.)

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9
Q

Two sensory pathways are the dorsal column/medial lemnsiscus and the spinothalamic tract, what sensory aspects are they associated with

A
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10
Q

What is the thalamic pathway a relay centre to?

A

The cortex

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11
Q

How does anaesthesia work with the thalamic pathway?

A
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12
Q

Explain what is shown in these graphs

A
  • Red for propofol which is an IV drug
  • Sevoflurane is an inhalation drug
  • Gap between red and green is huge and shows the different concentrations needed for the similar levels of consciousness. Pattern is similar
  • More potent drug (high potency means it evokes a given response at low concentrations) is propofol by between 1000 and 10000-fold
  • Graph b shows that IV are far more potent than inhaled ones
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13
Q

What are the different classes of inhaled anaesthetics?

Tell me about these compared to local anaesthetics

A
  • No common structures with general inhaled anaesthetics, they can be a variety of structures, but they can all inhibit brain activity by some mechanism
  • Compared to local anaesthetics where it’s all very uniform
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14
Q

(Pharmacokinetic aspects)

The speed of induction/recovery is crucial and needs to be controlled, what is this determined by?

A
  1. Blood/ gas pertition coefficient
  2. Oil/gas partition coefficient
  3. Physiological: alveolar ventilation rate, cardiac output…
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15
Q

What is blood/gas partition coefficient (blood solubility) important for?

A

blood/gas partition coefficient (blood solubility)-

important property for drug which determines if induction for recovery is fast or slow. The more the drug partitions into gas the quicker it will happen as it will reach air pressure quickly. If partitioned more in blood, then the slower the induction and recovery as the drug is taken away by the blood by proteins within blood

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16
Q

What does the oil/gas partition coefficient represent?

A

Oil/gas partition coefficient (lipid solubility)- represent efficacy of the drug

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17
Q

What does physiological: alveolar ventilation rate, cardiac output determine?

A

physiological: alveolar ventilation rate, cardiac output- determines how quick the drug is delivered into the brain

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18
Q

Lower solubility in blood leads to what? What does this mean for drug requirement?

A

Lower solubility in blood leads to faster equilibration

–> less drug needs to be transferred via lungs to achieve a given partial pressure.

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19
Q

What are some additional pharmacokinetic considerations?

A

Additional considerations.

  • Effect the clearance.
  • Not so important for inhalation anaesthetic (halothane exception 30% metabolised).
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20
Q

What can drug metabolism generate, provide examples?

A
  • Generate toxic intermediates.
  • Free radicals (chloroform-liver toxicity; fluoride (methoxy fluorane-kidney).
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21
Q

What can lipid distribution lead to?

A

Lipid distribution led to slow redistribution and hangover effect.

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22
Q

Why is ventilation, cardiac output and blood flow key during metabolism?

A
  • Increase sympathetic discharge (e.g., nitrous oxide)
  • Decrease sympathetic discharge (e.g., halothane).
  • Sensitize heart to adrenalin (e.g., halothane).
23
Q

Tell me about the differences in absorption in drugs in fat and lean tissues

A
24
Q

Rate of equilibrium of inhalation anaesthetics

A
  • Different inhalation anaesthetics shown in the graphs
  • Alveolar concentration (reflects arterial blood conc.) as a function of time during induction/recovery
  • Equilibration varies with water solubility
  • Slow phase equilibration most marked for highly lipid soluble drugs (ether, halothane)
25
Q

Summary features of inhalation anaesthetics

A

NB. Highest efficacy is halothane and NO has the lowest efficacy as has the lowest oil/gas

26
Q

What is the minimum alveolar concentration (MAC)?

What is it used to compare?

A

Minimum alveolar concentration or MAC is the concentration of a vapour in the lungs that is needed to prevent movement (motor response) in 50% of subjects in response to surgical (pain) stimulus.

MAC is used to compare the strengths, or potency, of anesthetic vapors.

27
Q

Why do IV anaesthetics tend to have a rapid anaesthesia related travel from site of injection to brain?

A

Theres no BBB constraint

28
Q

What is IV anaesthetics sustained dose dependent reduced by?

A

Sustained dose dependent is reduced by progressive redistribution to tissue with high perfusion (liver, brain) followed by low perfusion (muscle) eventually fat.

29
Q

Different IV drugs and their induction/ recovery

NB. Enzyme induction is a process in which a molecule (e.g. a drug) induces (i.e. initiates or enhances) the expression of an enzyme

A
30
Q

Mechanisms of action…

A
  • Non-specific Pharmacology and Lipid Theory
    1) Structurally unrelated agents with anaesthetic activity -> action via common mechanism
    2) Meyer-Overton rule: strong correlation between potency of drug and their solubility in olive oil!
  • Prediction: non-specific action on hydrophobic lipid components of cells
  • ASS must be controllable with rapid induction and recovery
31
Q

Interpretation of the Meyer/ Overton correlation

A

According to the Meyer-Overton correlation, in a homologous series of any general anaesthetic (e.g. n-alcohols, or alkanes), increasing the chain length increases the lipid solubility, and thereby should produce a corresponding increase in anaesthetic potency.

32
Q

Can anaesthetics bind to proteins?

A

Yes

33
Q

Key failure of all lipid theories: How does lipid perturbation results in dysfunctional membrane proteins?

Explain this experiment

A
  • More likely drug able to inhibit protein luciferase then the more likely/ potent general anaesthetic is
  • Drug can target membrane proteins. If membrane disrupted then function is also disrupted
34
Q

Candidate neuronal (particularly membrane proteins). The clinically relevant general anaesthetic protein binding sites- membrane proteins are targets for general anaesthetics: Give examples of some of these membranes

A
  • Ligand gated ion channels
  • ion channels
  • GPCR (neuromodulators)
  • Transmitter release proteins
35
Q

Tell me some examples of Ligand gated ion channels for general anaesthetics?

A

Ligand gated ion channels.

  • GABA (inhibitory signal) receptor and glycine receptor (generally potentiated).
  • Nicotinic acetylcholine receptors (inhibited).
  • Glutamate receptor NMDA (inhibited).
36
Q

Tell me some examples of ion channels for general anaesthetics

A

Ion channels

  • Voltage gated ion channels (Ca2+ activated K+ channels).
  • K+ Leak Currents (Twin pore channel; ether a go-go).
37
Q

Tell me about GPCR for general anaesthetics

A

G-protein coupled receptors (neuromodulators).

  • Modelled against Rhodopsin and suggestions for other GPCRs
38
Q

Tell me about transmitter release proteins for general anaesthetics

A

Transmitter release proteins.

  • Evidence for direct binding to proteins that control release of neurotransmitters.
39
Q

All membrane proteins work to reduce neural activity in the brain to reduce the brain activity. Excite inhibitor neurons and inhibit excitatory neurons

A
40
Q

What are some effects on the nervous system for inhibitory and excitatory synapses?

A
  • GABA with general anaesthetics shifts curve left which represents potentiation
  • Excitatory shift curve to the right side which represents the inhibition effect
41
Q

Tell me about the structure of the GABA receptor and some drugs that bind to each site

A
42
Q
A
43
Q

Based on the data provided, N265 is important for the binding with…

A. Propofol

B. Alphaxalone

C. Both propofol and Alphaxalone

D. Neither Propofol or alphaxalone

A

A. Propofol

44
Q

Based on the data, M159 is important for the binding with…

A. Halothane

B. Isoflurane

C. Both halothane and Isoflurane

D. Neither Halothane nor isoflurane

A

C. Both halothane and isoflurane

45
Q

Which of the following is NOT a general anaesthetic

A. Thipental

B. Propofol

C. Ketamine

D. Midazolam

E. Prilocaine

A

E. prilocaine

46
Q

Sedation by which of the following routes can be reversed most rapidly?

A. oral

B. inhalation

C. Intravenous

D. intramuscular

A

B. inhalation

47
Q

All of the following factors influence the rate of induction of anaesthesia with an inhaled anaesthetic EXCEPT:

A. aqueous solubility of the anaesthetic

B. Patient history of malignant hyperthermia

C. Ventilation rate

D. Tension of gas administration

E. pulmonary blood flow rate

A

B. patient history of malignant hyperthermia

48
Q

The blood/gas partition coefficients for Ether, Halothane, Nitrous oxide and isoflurane are 12, 2.4, 0.5 and 1.4, respectively. Which one has the quickest induction and recovery?

A

Nitrous oxide

49
Q

The oil/gas partition coefficients, for ether, halothane, nitrous oxide and isoflurane and 65, 220, 1.4 and 91 respectively. Which one has the greatest anaesthetic potency?

A

Halothane

50
Q

State some clinical uses of general anaesthetics

A
  1. Anaesthesia for surgical reasons requires combined control
  2. clinical anaesthesia use combinations
  3. Peri-operative
  4. Fast induction and recovery
51
Q

Tell me why anaesthesia for surgical reasons requires combined control?

A
  1. Loss of consciousness
  2. Analgesia.
  3. Muscle relaxation.
52
Q

Tell me about clinical anaesthesia using combinations

A
  • Propofol (rapidly induced Anaesthesia-more reduced side effects).
  • Inhalation anaesthetic (sevoflurane) maintain a sustained 1 and support 2).
  • Where 2 is required supplement with intravenous analgesic (opiates).
  • Muscle relaxants (nerve blocking agents atracurium via Ach receptor and is a competitive inhibitor).
  • Parasympathetic block atropine reduces bradycardia and bodily secretions like urine for example
53
Q

Tell me about Peri-perative (period of time of patients procedure) and general anaesthetics

A

Peri-operative.

  • Pre: reduce anxiety (with additional amnesiac) using benzodiazepine
  • Post: control of emesis using droperidol, metaclopramide).
54
Q

Tell me about fast induction and recovery of general anaesthetics

A
  • Avoiding STAGE 2.
  • Allow the maintenance of the homeostatic reflexes that are lost when in STAGE 4.

BIOL2049 S2 (10 decks)

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