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E-lfh Basic Sciences Pharmacology > Inhalational Agents > Flashcards

Inhalational Agents Flashcards

1
Q

What is the definition of MAC?

A

The alveolar concentration of a gaseous volatile agent needed to ensure that 50% of a test population at sea level does not respond to a standard surgical skin incision.

Ths is a proxy for suppression of spinal cord reflexes and it cannot be assumed to ensure lack of awareness.

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2
Q

What determines the MAC?

A

The partial pressure of the agent (at 1 atmosphere the conc in kPa and partial pressure in kPa are virtually the same)

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3
Q

What is the dose-response curve for inhalational agents like?

A

Very steep so:

  • at 20% below MAC almost all patients move in response to surgical stimulus
  • at 20% above MAC less than 5% of patients move

(different to propofol which has a flat dose-response curve so has a massive variation in effector site conc to prevent movement)

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4
Q

What is the MAC-awake?

A

The concentration of vapour in the lungs required to block voluntary reflexes and control perceptive awareness.

50% of patients respond to commands at this MAC.

Usually 0.3 x MAC-asleep.

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5
Q

What is the MAC-awake of isoflurane, desflurane and sevoflurane?

A

Isoflurane 0.3%

Des 2%

Sevoflurane 0.4% (highly fat-soluble)

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6
Q

What is MAC-BAR?

A

The concentration of vapour in the lungs required to block autonomic reflexes to nociceptive stimuli.

It’s 1.8 x MAC asleep.

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7
Q

What is the MAC of halothane, isoflurane, enflurane, sevoflurane, desflurane?

A

Halothane - 0.8

Isoflurane - 1.2

Enflurane - 1.7

Sevoflurane - 1.8

Desflurane - 6.6

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8
Q

What is the O:G coefficient for desflurane, sevoflurane, enflurane, isoflurane and halothane?

A

Des - 29

Sevo - 80

Enflurane - 98

Isoflurane - 98

Halothane - 224

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9
Q

What are the B:G coefficients for desflurane, sevoflurane, isoflurane, enflurane and halothane?

A

Des - 0.4

Sev - 0.7

Iso - 1.4

Enflurane - 1.9

Halothane - 2.2

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10
Q

What does a high O:G mean?

A

The higher the O:G coefficient, the lower the MAC.

High O:G means the substance is MORE lipid soluble, and stays in an “oily” state. Tends to pass readily into oily organs eg brain -rich in lipids and fat stores.

Therefore, the dose needed is lower than for a substance with a low O:G value.

Wake up is slower because of the mass of agent in fat stores.

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11
Q

What is a partition coefficient?

A

The ratio of concentrations of a compoound in the 2 phases of a mixture of 2 immiscible liquids at equilibrium.

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12
Q

What does a high B:G value mean?

A

If B:G is high the substance will pass easily into the blood from gas form in alveoli.

Slower onset and offset of anaesthesia

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13
Q

What does a low B:G value mean?

A

Low B:G means less initial movement of volatile from alveoli into blood.

Fast onset and offset of anaesthesia due to high diffusion gradient from alveoli to blood. So the blood’s concen of volatile is higher.

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14
Q

What is the formula for the wash-in curves of the volatiles?

A

The lower the B:G coefficient, the faster the volatile takes effect.

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15
Q

What is the formula for the wash-out curve for the volatiles?

A

The lower the B:G coefficient, the faster the volatile wears off.

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16
Q

What is the structure of desflurane?

A
17
Q

What is the structure of enflurane?

A
18
Q

What is the structure of halothane?

A
19
Q

What is the structure of isoflurane?

A
20
Q

What is the structure of sevoflurane?

A
21
Q

What are the undesirable effects of the volatiles on the CNS?

A
  • cerebral metabolic rate is decreased
  • O2 consumption is decreased
  • EEG burst suppression occurs
  • sev/enflurane may cause epileptiform activity if >2 MAC
  • precondition of neurones to hypoxia
  • cerebral blood flow less reactive to pCO2
  • cerebral vasodilatation that increases ICP
  • excitatory phenomena
22
Q

What are the SEs of the volatiles in the RS?

A
  • dose-dependent respiratory depression - increased pCO2 and impaired response to hypercapnia
  • increased dead space ventilation as tidal volume decreases
  • increased RR (usually counteracted by surgical stimulation)
  • blunts the hypoxic pulmonary vasoconstriction response -through pulmonary artery dilatation (usually insignificant)
  • increased airway resistance secondary to reduced lung volume counterbalanced by bronchodilation
  • desflurane irritates the ariways causing laryngospasm and coughing
23
Q

What effects do volatiles have on the CVS?

A
  • decrease in MAP in dose-dependent manner
  • all agents reduce SVR except halothane - reduces CO
  • all volatiles reduce baroreceptor reflex
  • sevo can lengthen QT
  • all volatiles slow SA discharge and decrease ventricular muscle action potential duration
  • cardiac dysrhythmia is uncommon, except with halothane
24
Q

What effects do volatiles have on the liver?

A
  • reduces hepatic blood flow minimally
  • halothane can cause halothane hepatitis, due to formation of protein which activates T-cells and induces inflammation of the liver
    • the protein is formed by oxidative phosphorylation of halothane (25% metabolised in P450 system)
    • risk factors - female, duration of exposure, repeated exposure
    • 1:10,000
    • can get this with iso, en and desflurane but not sevo
25
Q

What effects do volatiles have on the kidneys?

A
  • inorganic fluoride production is a mode of direct nephrotoxicity
  • levels needed are >50 micromols/L for methoxyflurane
  • isoflurane less nephrotoxic than enflurane due to higher defluorination resistance
  • Des and halothane are not defluorinated
  • sevo is significantly defluorinated
  • Compount A (triflurormethyl vinyl ether) is renal toxic in rats but no real clinical impact on humans
26
Q

What is MH?

A

Malignant hyperpyrexia, is an uncommon pharmacogenetic disorder of skeletal muscle induced by exposure to suxamethonium and any volatile anaesthetic agents.

It’s autosomal dominant with variable penetrance and incidence of 1:10000.

27
Q

What are the characteristics of MH?

A
  • hypermetabolism
  • muscle rigidity
  • muscle injury
  • initial signs:
    • unexplained increased CO2 production
    • tachycardia
  • late signs:
    • unstable BP, decreased sats
    • increased body temp
    • raised CK, myoglobinuria
    • cardiac arrhythmias
    • hyperkalaemia
    • DIC
28
Q

What is the cause of MH?

A
  • Unregulated calcium flux from the muscle SR to the muscle fibres themselves
  • due to a mutation in ryanodine receptor, RYR1, chromosome 19 on the SR surface
  • RYR1 receptors are linked to the L-type calcium channel, which is voltage dependent
  • RYR2 receptors in the heart open by calcium ions inducing their activity
29
Q

How is MH confirmed by testing?

A

In vitro contracture testing (IVCT) at specialist centres.

The tension in muscle from MH-susceptible patients increases at lower halothane and caffeine concentrations.

30
Q

What is the treatment for MH?

A

Dantrolene 2.5 mg/kg bolus with further 1mg/kg boluses to a maximum of 10mg/kg.

31
Q

How should you manage patients that are susceptible to MH?

A
  • consider regional anaesthesia
  • avoid sux and all volatiles
  • TIVA
  • use a clean machine - no volatiles used by the machine beforehand (or O2 at 10L/min for 30mins through anaesthetic machine and ventilator)
  • have dantrolene ready
  • monitor temp and end-tidal CO2 closely
32
Q

What disease is associated with MH?

A

Central core disease, a rate congenital myopathy

33
Q

Why does the vapour concentration not change the clinical effect when changing altitude?

A

MAC is expressed as a percentage, but the clinical effect of volatiles is determined by their partial pressure in tissues.

Eg. the output of a vapour is calibrated to atmospheric pressure (101.325 kPa). So 1% on the dial is a vapour pressure of 1% of atmospheric. Sevo’s SVP = 22.7 kPa (22.7% of atmospheric pressure)

If you half atmospheric pressure, the SVP of Sevo is still 22.7kPa, but atmospheric pressure is now 50kPa = Sevo = 45.4% of atmospheric pressure.

So now 1% on the vapouriser is no longer 1% of atmospheric pressure (101kPa) it’s 2% because the pressure has halved because it hasn’t been recalibrated.

The resultant partial pressure is 2% of 50kPa ie 1kPa - same as sea level.

34
Q

What is the calcuation for the agent concentration delivered when altitude is being changed?

A

Where:

  • %1 is the agent % delivered
  • p1 is the pressure at a given altitude
  • %cal is the agent % dialled on the vaporizer
  • p cal is the pressure at an altitude where the vaporizer is calibrated
35
Q

What is the overall effect of altitude on partial pressure of vapour delivered?

A

The partial pressure and therefore clinical effect does not change because the concentration delivered is increased.

36
Q

How does temperature affect vaporizers?

A

Temperature decreases with altitude - this is “lapse rate” and varies according to the moisture content of the air.

International standard is 6.49 degrees C per 1000m from sea level to 11000m.

This reduces the saturated vapour pressure with altitude and therefore the clinical effect of the agent.

However, modern vapourizers are temperature compensated, so can essentially be used at altitude/sea level/hyperbaric conditions without temperature correction.

37
Q

Why doesn’t temperature affect the desflurane Tec 6?

A

The desflurane vapourizer is pressurized to 2 atmospheres, there is no compensation for ambient pressure.

So, concentration delivered is stable, regardless of ambient pressure.

Eg. if ambient pressure halved to 50kPa but dial constant at 2% - the partial pressure is 2% of 50 = 1kPa so the dial must be increased to maintain partial pressure of 2kPa at altitude

38
Q

What % of sevoflurane is metabolised?

A

3.5%

39
Q
A

E-lfh Basic Sciences Pharmacology (3 decks)

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