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Pharmacology for Anaesthetists > Inhaled anaesthetic agents > Flashcards

Inhaled anaesthetic agents Flashcards

1
Q

Why is Xenon not used for general anaesthesia

A

Expensive to extract from the atmosphere

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2
Q

Define MAC

A

Minimum Alveolar Concentration is a measure of potency and is defined as the minimum alveolar concentration at STEADY STATE that prevents MOVEMENT to a SURGICAL STIMULUS (skin incision) in 50% of subjects at 1 atmosphere.

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3
Q

List the 14 attributes of the ideal volatile agent. Use mnemonics..

A

PHYSICAL PROPERTIES: LIPOCAFE (because cafe’s are physical and sleepy…)

Light/heat stable
Inert: Metal/Rubber/Soda lime
Preservative-free
Odourless
Cheap
Atmosphere friendly
Flammable - NO !
Explosive - NO !

BIOCHEMICAL PROPERTIES: MEATBOM -> ‘Biochemical weapon of general anaesthesia….

Metabolized - NO
Epileptiogenic - NO
Analgaesic - YES
Toxic - NO
B:G - LOW
O:G - HIGH i.e.
MAC low
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4
Q

List the factors that increase and decrease the MAC

A

INCREASED MAC | DECREASED MAC
Chronic Opioid | Acute OPIOID
Chronic ETOH | Acute ETOH
Acute amphetamines | Chronic amphetamines
Catecholamines ± SNS + | alpha 2 agonists

——————————— | Sedatives

Hyperthermia | Hypothermia
Hyperthyroidism | Hypothyroidism
Hypernatraemia | Lithium

————————————- | Hypotension

Infancy | Neonates

  • ———————————— | Elderly
  • ————————————- | Pregnancy
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5
Q

What does steady state mean with regard to volatile anaesthetics and what ratio is used to determine when steady state has been reached

A

PA = Pa = PB
Very rarely achieved as it takes a long time
Ratio is FA: Fi –> Fraction of volatile in Alveoli to fraction of inspired volatile.
Interpretation –> the faster an volatile agent approaches an FA:Fi of 1 the faster the onset of anaesthesia.

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6
Q

What 5 factors impact the rate at which the FA:Fi ratio approaches 1 (and hence speed of onset of anaesthesia). Draw a graph demonstrating the various FA:Fi versus time for: N2O, Desflurane, Sevoflurane, Isoflurane, Halothane.

A

Faster approach of FA:Fi to 1
1. Increased alveolar ventilation
2. Small FRC (Large FRC will dilute volatile)
3. High FiAG
4. Low cardiac output –> faster FA:Fi to 1.
(If gas keeps moving away due to high CO then equilibrium not reached) –> less significant for modern volatiles as minimal volatile dissolved.
5. Low B:G –> less gas dissolved in blood –> less carried away by CO

Graph
X axis: Time to infinity
Y axis: Fa:Fi
Physiological build up negative exponential
Asymptotes: y axis and FA:Fi of 1
Top to bottom
N2O
Desflurane
N2O 
Sevoflurane
Isoflurane
Halothane
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7
Q

Define the Blood: Gas partition co-efficient

A

The ratio of the amount of anaesthetic agent in blood and gas when the two phases are of equal volume and pressure and in equilibrium at 37 deg C.

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8
Q

How is nitrous oxide manufactured

A

Heat ammonium nitrate to 240 degrees C

NH4NO3 –> N2O + 2H2O

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9
Q

How are contaminates formed during the process of N2O manufacture

A

Temperature not carefully monitored contaminates are formed

NH3
N2
NO
NO2
HNO3

–> These are actively removed by passage through scrubbers, water and caustic soda.

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10
Q

convert 1 atm to bar/kPa/mmHg/psi

A

1 atm =

1 bar
14.5 psi
101.325 kPa
760 mmHg

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11
Q

How is N2O stored? What is the filling ratio, gauge pressure at 20 degrees, critical temperature and critical pressure

A

As liquid in French Blue cylinders
C = 450 L
G = 9000 L

Filling ratio (mass of N2O in cylinder/mass of water cylinder can hold) = 0.75. But reduced to 0.67 in temperate regions to avoid cylinder explosions

Gauge pressure 51 kPa at 20 deg C

Critical temperature: 36.5 deg C
Critical P: 72 bar

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12
Q

Describe N2O

Relate P1DODSS P2MMMVI TBC to volatiles

Presentation --> Storage + Manufacture
Dose              --> MAC
Onset            --> B:G
Duration        --> O:G
Systems        --> Systems
Specifics       --> Specifics

Protein bound –> ‘Pounds’ of Molecular Weight
pKa/Percent unionized –> Point of boiling
Mechanism –> mechanism
Metabolism –> Metabolism
Metabolites –> Metabolites
Vol distribution –> Vapour pressure (saturated) at 20deg
Interactions –> ? Irritant and odour

Telim –> N/A
Bioavail –> N/A
Clearance –> N/A

A

Storage and Manufacture

Manufacture
Heat Ammonium nitrate to 240 (250) deg C.
NH4NO3 –> N2O + 2H2O
Poor temp. control –> impurities (NH3, N, NO, NO2, HNO3) removed by scrubbers, water and caustic soda.

Storage
C cylinders = 450L
G cylinders = 9000L
Gauge pressure 51 kPa at 20 deg C

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13
Q

Describe the percentage metabolism and the metabolites of the volatile anaesthetic agents

A

N2O < 0.01 % ———> N2
Halothane 20% ——-> Cl-, Br-, Trifluoroacetic acid

Sevoflurane 3.5% —–> Compound A (presence of soda lime and heat), Inorganic and organic fluorides.

Enflurane 2% ————-> Inorganic and organic fluorides

Isoflurane 0.2%———–> F- Trifluroracetic acid

Desflurane 0.02 ———-> Trifluoroacetic acid

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14
Q

A full cylinder of O2 has a gauge pressure of 137 x 100 kPa

A full cylinder if N2O has gauge pressure of 51 x 100 kPa

Why is this

A

N2O is usually stored at 20 deg C

The critical temperature of N2O is 36.5 deg C

Therefore, N2O is stored at temperatures below its critical temperature meaning that it can be compressed by increasing pressure into the liquid phase. The gauge pressure in the N2O cylinder therefore does not correlate with amount N2O remaining as much is in liquid form.

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15
Q

What is the filling ratio and why does this vary for N2O in different regions

A

The filling ratio is the:

mass of N2O in the cylinder / mass of water the cylinder can hold.

Temperate regions: 0.75
Tropical regions: 0.67 –> to avoid cylinder explosions should the ambient temperature rise

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16
Q

What is critical pressure

A

The pressure required to liquify a gas at its critical temperature

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17
Q

How does N2O affect the RSP, CVS,CNS

A

RSP:

  1. decrease Vt
  2. increase RR –>
  3. Ve and PaCO2 unchanged

CVS:
1. MYOCARDIAL DEPRESSANT offset by
2. increases SNS output centrally.
There is no sensitisation to catecholamines.

CNS:
1. Increases CBF

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18
Q

Define the concentration effect. Why does this affect only apply to one agent. Which agent is this

A

The observed phenomenon that describes the disproportionate rise in alveolar fraction compared with inspired fraction when high concentrations of N2O are inspired.

The fundamental driving force for this effect is thought to be the large gradient which HIGH concentrations of N2O generate

The concentration effect only applies to N2O as it is the only agent used at sufficiently high concentration.

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19
Q

Define the second gas effect

A

The second gas effect is a direct result of the concentration effect. O2 ± volatile agent used alongside HIGH concentrations of N2O will be concentrated by the rapid uptake of N2O and augmented alveolar ventilation. This leads to increased concentrations of O2 and volatile agents, resulting in a reduced induction time.

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20
Q

Define diffusion hypoxia

A

This is the reverse of the second gas effect. At the end of anaesthesia when N2O /O2 is replaced with air N2/O2 the reverse of the second gas effect is seen. The volume of N2O entering the alveolus will be greater than the volume of N2 entering the pulmonary capillaries resulting in dilution of all alveolar gases. (FiO2 of 1.0 prevents diffusion hypoxia)

21
Q

Describe N2O toxicity

A

Cobalamin = B12 contains cobalt. Cobalt is oxidised and inhibited by N2O. Methionine synthetase requires B12 as cofactor and hence is inhibited by N2O. This leads to reduced Methionine, Thymidine, THF and DNA synthesis. Exposure for a few hours can lead to megaloblastic bone marrow changes. Exposure for days can lead to agranulocytosis.

22
Q

is N2O teratogenic

A

Under exp. conditions this has been shown in rats but this effect is prevented by administration of folinic acid

Avoid in first trimester

23
Q

What is the Poynting effect?

A

The poynting phenomenon is demonstrated by entonox - 50:50 O2 N2O.

The two gases dissolve effectively into each other and do not behave in a way that would be predicted from their individual properties.

Gas A and Gas B mix together to form mixture C. Mixture C does not behave in a way that would be predicted from the individual properties of gas A and Gas B

24
Q

How is entonox stored?

A
  1. Stored as a gas at 137 x 100 kPa (pseudo-critical temperature is - 7)
  2. French blue cylinders with white-blue checkered shoulders

NB to ensure temperature does not fall below the pseudo-critical temperature or separation will occur with overlying gas 80% O2 and underlying liquid of 20% O2. First gas expelled from this will be 80% O2 but as the oxygen is depleted the end gas will be hypoxic with high concentration of N2O

25
Q

What is pseudo-critical temperature. Give an example

A

Pseudo-critical temperature is the temperature at which a mixture of gases separate out into their constituents at a specific pressure.

Example
Entonox is a mixture of O2:N2O 50:50 which has a risk of separating out into O2 and Nitrous Oxide a temperature of -7 deg C. This separation is found to be more likely when the pressure of the mixture before cooling is 117 bar and is less likely at higher and lower pressures.

26
Q

Compare the pseudocritical temperature of entonox in pipelines to that in cylinders

A

Cylinder pressure = ± 117 x 100 kPa then pseudocritical temperature is -7 deg C

Pipeline pressure = ± 4.1 x 100 kPa then pseudocritical temperature is - 30

Therefore, gas mix separation is possible during alpine mountain rescue but less likely in hospital gas pipelines.

27
Q

Consider the event that entonox separates at its pseudocritical temperature. What are the practical implications of this

A

Initially –> no analgaesia as 100% O2

Then as use continues the gas will become progressively hypoxic until N2O 100%

28
Q

List the O:G, | MAC of the volatile anaesthetic agents

A

N2O ————> 1.9 | 105

Xenon ———> 1.4 | 71

Desflurane —-> 29 | 6.6

Sevoflurane —> 80 | 2.0

Enflurane ——-> 98 | 1.68

Isoflurane ——-> 98 | 1.2

Halothane ——-> 224 | 0.75

Methoxyflurane –> 950 | 0.16

29
Q

List the B:G for the volatile agents

A

N2O ————> 0.47

Xenon ———> 0.14

Desflurane —-> 0.45

Sevoflurane —> 0.7

Enflurane ——-> 1.8

Isoflurane ——-> 1.4

Halothane ——-> 2.4

Methoxyflurane –> 12

30
Q

Describe the the boiling point and saturated vapour pressure at 20 deg C of Desflurane differs from the other volatile agents

A

Desflurane:

  1. Boiling Point = 23.5 deg C
  2. SVP @ 20 deg C = 89.2 kPa

Other volatile agents:

  1. Boiling Points = ± 50 deg C
  2. SVPs @ 20 deg C = ± 25 kPa
31
Q

Describe the effects of the volatile agents on cardiac contractility

A

All decrease contractility except

  1. Desflurane –> minimal effect
  2. Halothane –> significant effect
32
Q

Describe the effects of volatile anaesthetics on heart rate

A

N2O ——————–> decrease

Desflurane ————> increase (^^ at 1.5 MAC)

Sevoflurane ———-> Minimal effect

Isoflurane ————-> Increase

Halothane ————-> Decrease

33
Q

Describe the effect of volatile agents on SVR

A

All decrease except N2O

34
Q

Describe the effects of volatile anaesthetics on blood pressure

A

All decrease
(Sevoflurane = minimal)
(Nitrous –> no effect)

35
Q

Describe how the volatile agents affect the sensitivity to catecholamines

A

Halothane –> increase sensitivity to CATS

Enflurane –> mild increase sensitivity to CATS

36
Q

Describe the effects of the volatile agents on the respiratory rate

A

All increase

37
Q

Describe the effects of the volatile agents on tidal volume

A

All decrease (especially enflurane)

38
Q

Describe the effects of the volatile agents on PaCO2

A

All increase

Except Halothane and N2O

39
Q

Describe the effects of the volatile agents on airway reacitvity

A

BRONCHODILATATION
Sevoflurane
Isoflurane
Halothane

IRRITANT
Desflurane

40
Q

Describe the effects of the volatile agents on cerebral blood flow

A

All mild increase CBF

  1. Most significant increase: halothane
  2. Sevoflurane preserves autoregulation
  3. Isoflurane increases CBF at MAC > 1
41
Q

Describe the effects of volatile anaesthetic agents on Cerebral metabolic rate of O2 consumption

A

All decrease

42
Q

Describe the effects of volatile anaesthetics on the UTerus

A

All cause some relaxation

43
Q

Describe the effects of the volatile anaesthetics on muscle relaxation

A

All cause significant muscle relaxation except halothane (some)

44
Q

Describe the analgaesic effects of the volatile anaesthetics

A

Mild analgaesic effects –> all

45
Q

Describe the EEG findings during use of the volatile anaesthetic agents

A

All burst suppression

Except enflurane –> epileptiform activity

46
Q

List the major specific problems with each of the volatile agents

A

N2O ————–> oxidises cobalt ion on B12

Desflurane —–> requires complex vaporizer

Sevoflurane —-> Compound A renal toxicity. Increased incidence of post op delirium in children vs halothane

Isoflurane ——-> Coronary steal?

Halothane ———-> Hepatotoxicity. 20% metabolized

Enflurane ————> Epileptiform activity: Neurotoxic, Hepatotoxic, nephrotoxic

47
Q

What is the coronary steal phenomena and which volatile agent has this been associated with

A

Isoflurane may cause coronary steal.

Vasodilation of healthy vessels. No vasodilation of diseased and narrowed vessels. This leads to diversion of blood away from already diseased vessels, resulting in ischaemia

48
Q

What is the problem with regards to the -CHF2 group in the structure of isoflurane, enflurane and desflurane

A

-CHF2 might react with DRY soda lime to produce Carbon Monoxide (CO)

Pharmacology for Anaesthetists (37 decks)

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