Pharmacology of Anaesthesia Flashcards

1
Q

What is the most common method of induction?

A

Intravenous induction: used in adults almost universally rather than inhalation

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2
Q

When is inhalation more commonly used as an induction method?

A

In children

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3
Q

What are 3 advantages of intravenous induction of anaesthetic?

A
  1. Pleasant for patients (once cannula is in)
  2. Rapid loss of consciousness under control of anaesthetist
  3. Loss and recovery of consciousness are dependent upon passive pharmacokinetic processes so relatively predictable
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4
Q

What are 2 disadvantages of intravenous induction of anaesthesia?

A
  1. May be adverse CVS and RS effects, especially if given rapidly in elderly, those in pain or shocked
  2. Easy to overdose if cardiac output is low and slow arm-brain circulation time - nothing happens so inject more
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5
Q

Why is it important to induce anaesthesia slowly in those who are unwell?

A

Can lead to overdose due to low cardiac output/ slow arm-brain circulation time: nothing happens so inject more, as the medication is slower to act

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6
Q

Why do people recover consciousness after IV induction of anaesthesia?

A

Due to redistrubtion of drug to fat in muscle, causing fall in blood concentration

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7
Q

What happens to the concentration of an anaesthetic agent injected for IV induction?

A
  • Concentration over time shows rapid rise in concentration to peak
  • then rapid fall due to redistribution, predominantly into fat - especially fat in muscle
  • Drug is then slowly cleared from the body through liver or kidneys (or both), resulting in a fall from the peak to wake-up concentration
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8
Q

What are 5 examples of drugs that can be used as anaesthetic induction agents via IV induction?

A
  1. Propofol
  2. Etomidate
  3. Thiopentone
  4. Ketamine
  5. Benzoddiazepines: midazolam
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9
Q

Which IV induction is most commonly used?

A

Propofol

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10
Q

What is the chemical structure of propofol?

A

2, 6 di-isopropyl phenol (hindered phenol) - simple drug

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11
Q

How does the propofol drug exist?

A

Suspended in a soybean oil and egg phosphatide emulsion

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12
Q

What is the solubility of propafol in fat and water?

A

Insoluble in water; all anaesthetic agents have to dissolve in fat, if totally fat soluble then insoluble in water

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13
Q

What is the appearance of propafol?

A

One of the few white drugs

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14
Q

What is the wake-up like after propafol and why?

A

Rapid wake up - due to redistribution, there’s no accumulation

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15
Q

What type of drug is etomidate?

A

An imidazole and ester

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16
Q

What is the accumulation like of etomidate?

A

No accumulation

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17
Q

What is a key advantage of etomidate as an IV induction agent?

A

Little effect on CVS - cardiovascularly stable

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18
Q

What will happen with an infusion of etomidate and why isn’t this usually an issue?

A

Leads to severe adrenal suppression; no problem with single injection (but in 70s led to marked rise in death from sepsis when used in emergency care)

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19
Q

How does the drug etomidate exist?

A

Dissolved in propylene glycol, new emulsion form

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20
Q

Which drug is known as the grandfather of modern induction agents?

A

Thiopentone

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21
Q

When is thiopentone used now?

A

Not often used now apart from in obstetrics for C-sections

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22
Q

In what form does thiopentone come as?

A

Powder

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23
Q

What type of drug is thiopentone?

A

Barbiturate

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24
Q

What is a key advantage of thiopentone?

A

Extremely cheap

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25
Q

What is the effect of thiopentone if given as an infusion and when is this done?

A

Long terminal half life (several hours) if given by infusion, such as for status epilepticus and controlling raised ICP. Can take several days to wear off

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26
Q

What is a key disadvantage of thiopentone as an IV induction agent?

A

Potent myocardial depressant (?killed more American soldiers in WWII than Japanese did at Pearl Harbour as dose wasn’t understood)

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27
Q

What type of drug is ketamine?

A

Phencyclidine, acts on NMDA receptor

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28
Q

What are the two routes via which ketamine can be administered?

A

IV and IM

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29
Q

What is the disadvantage of giving ketamine IM?

A

Painful as large dose

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30
Q

Which is the only IV induction agent that can be given IM?

A

Ketamine

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31
Q

What happens to the airway when ketamine is used as an IV induction agent?

A

Partial maintenance of airway

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32
Q

What is the appearance of a patient who has receive IV induction with ketamine?

A

Produces srange dissociated state - sit with eyes open, appear to be looking at you

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33
Q

What is the key disadvantaeg of ketamine as an IV induction agent?

A

Gives patients lots of dreams, associated with horrible nightmares

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34
Q

How can the dreams/nightmares associated with ketamine as an IV induction agent by treated sometimes?

A

Suppressed with benzodiazepines

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35
Q

What are 3 ways that ketamine is sometimes used?

A
  1. IV induction in children
  2. Analgesic benefit e.g. for burns
  3. Occasionally in shocked/ hypovolaemic patients as can give small rise in blood pressure
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36
Q

Which of the induction agents an be argued isn’t really an induction agent and why?

A

Midozolam/ benzodiazepines: if you give enough midazolam will induce anaesthesia, but it is more commonly used for sedation

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37
Q

What is the water solubility like of midazolam vs. diazepam and why?

A

Midazolam is water soluble but diazepam is not, due to midazolam’s cyclic imidazole structure attached to the diazepine ring

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38
Q

How does the structure of midazolam give it a unique physiochemical characteristic?

A

at pH <4.0 the ring opens so it becomes water soluble. at pH >4.0 the ring closes, so it becomes lipipd soluble. Therefore at physiological pH, the molecule an cross the blood brain barrier

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39
Q

In what form is diazepam often given and why?

A

It is given as diazemules as it’s water insoluble

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40
Q

What are 5 advantages of inhalational induction?

A
  1. Slower and gentle onset of hypnotic effects
  2. More control over unwanted side effects (CVS and RS)
  3. If problems arise, patient can be allowed to be woken
  4. Good in paediatrics - don’t have to give a cannula
  5. Useful in adults in special circumstances e.g. difficult airways, difficult veins, needle phobia
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41
Q

What are 4 disadvantages of inhalational induction?

A
  1. Requires skill and attention to technique to do it well
  2. Needs skilled assistant
  3. Needs good co-operation from patient
  4. Speed of action depends upon drug solubility (less soluble the drug, the more rapid its onset), respiratory rate and depth, and cardiac output
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42
Q

How common is inhalational maintenance of anaesthesia?

A

Widely used

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43
Q

What are the two types of breathing circuits that can be used for inhalational maintenance of anaesthesia?

A
  1. Open circle breathing system
  2. Closed circle breathing system
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44
Q

How long-lasting are the effects of modern inhalational maintenance agents?

A

short-acting

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45
Q

What must be done when providing inhalational maintenance of anaesthesia and why?

A

Scavenging: method of controlling waste anaesthetic gases. This gathers gas after exhaled/ left area of patient

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46
Q

What are the 4 Guedel’s stages of anaesthesia?

A
  1. Amnesia and analgesia
  2. Excitement or delirium
  3. Surgical anaesthesia, divided into 4 planes
  4. Anaesthetic overdose
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47
Q

What happens during Guedel stage 1 of anaesthesia?

A

From amnesia to analgesia to loss of consciousness. Respirations present and quiet, reflexes intact

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48
Q

What happens during Gueldel stage 2 of anaesthesia?

A
  • From loss of consciousness to onset of total anaesthesia.
  • Respirations irregular, increased muscle tone, involuntary movements, dilated pupils.
  • Disconjugate gaze, increased risk of vomiting, aspiration, laryngospasm, and bronchospasm.
  • Best not to stimulate patient at this time.
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49
Q

How many planes is stage 3 of Guedel’s stages of anaesthesia divided into, and what do these represent?

A

4 planes

  • 1 and 2: from total loss of consciousness with regular aspirations, decreased muscle tone, absent cough/swallow/gag reflexes, pupils normal size and reactive
  • 3 and 4: onset of total muscle relaxation, non-reactive pupils, cessation of spontaneous respirations
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50
Q

What happens during Guedel stage 4 of anaesthesia?

A
  • anaesthetic overdose
  • pupils fixed and dilated, cardiac arrest imminent, no respirations
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51
Q

What 3 things must be done if Guedel stage 4 anaesthesia is reached?

A
  1. immediate cessation of all anaesthetics
  2. ventilation with 100% oxygen
  3. supportive measures
52
Q

What are 7 physical properties of the ideal inhalational agent?

A
  1. Non-flammable and non-explosive at room temperature
  2. Stable in light
  3. Liquid and vaporisable at room temperature i.e. low latent heat of vaporisation
  4. Stable at room temperature, with a long shelf life
  5. Stable with soda lime, as well as plastics and metals
  6. Environmentally friendly - no ozone depletion (currently responsible for a degree)
  7. Cheap and easy to manufacture
53
Q

How did previous inhalational agents create issues in terms of flammability and explosivity and what is done to avoid this?

A

Previously: ether in air burns, ether in oxygen explodes. All are now ethers which are heavily halogenated to stop them from burning/ exploding

54
Q

What are 6 biological properties of the ideal inhalational agent?

A
  1. Pleasant to inhale, non-irritant, induces bronchodilation
  2. Low blood to gas (blood : gas) solubility - i.e. fast onset
  3. High oil : water solubility - i.e. high potency
  4. Minimal effects on other systems - e.g. cardiovascular, respiratory, hepatic, renal or endocrine
  5. No biotransformation - should be excreted unchanged, ideally via the lungs
  6. Non-toxic to operating theatre personnel
55
Q

What is an example of an inhalted anaesthetic agent that can affect organ systems negatively? What negative effects have many had in the past?

A
  • Halothane can cause hepatitis
  • Others in the past have been nephrotoxic, thought to have effects on endocrine organs
56
Q

What is an example of a modern inhalational agent that is largely unchanged when exhaled?

A

Sevoflurane

57
Q

What is the definition of minimum alveolar concentration or MAC?

A

The concentration that prevents movement in response to skin incision in 50% of un-premedicated animals. Subjects studied at sea level (1 atmosphere) in 100% oxygen

58
Q

What is MAC (minimum alveolar concentration) inversely related to?

A

Potency: the more potent the agent, the less you need i.e. smaller MAC

59
Q

What are 6 advantages of using MAC?

A
  1. Alveolar concentration can be easily measured
  2. Near equilibrium, alveolar and brain tensions are virtually equal
    • The high cerebral blood flow produces rapid equilibrium across the brain, and the agent can get into the brain quickly
  3. MAC is invariant with a variety of noxious stimuli
  4. Individual variability is small
  5. Sex, height, weight and anaesthetic duration do not alter MAC
  6. Doses of anaesthetics in MACs are additive
60
Q

What is an example of an effect that occurs because doses of anaesthetics in MACs are additive?

A

Opioids reduce amount needed

61
Q

What are 7 examples of inhalational anaesthetic agents?

A
  1. Nitrous oxide
  2. Entonox
  3. Halothane
  4. Enflurane
  5. Isoflurane
  6. Sevoflurane
  7. Desflurane
62
Q

What is the chemical formula for nitrous oxide?

A

N2O

63
Q

What is the appearance of nitrous oxide?

A

Colourless, odourless gas

64
Q

Why is nitrous oxide ineffective as a sole inhalational anaesthetic agent?

A

It has a predicted MAC of 105%, so you would be receiving no oxygen and would die

65
Q

What property is possessed by nitrous oxide in addition to being an anaesthetic agent?

A

Analgesic properties

66
Q

How does the solubility of nitrous oxide compare to nitrogen and what implication does this have?

A

Much more soluble than nitrogen - therefore if given to baby, will diffuse into stomach and make it much larger - diffuses into air spaces.

67
Q

What is another name for entonox?

A

Gas and air

68
Q

What is the composition of entonox?

A

50:50 mix of N2O (nitrous oxide) and oxygen

69
Q

What are 3 uses for entonox?

A
  1. labour
  2. trauma
  3. children
70
Q

What are 4 examples of old inhalational anaesthetic agents?

A
  1. cholorform
  2. ether
  3. oxyflurane
  4. trichlorethylene
71
Q

When did halothane become a population inhalational anaesthetic agent and why?

A

Seen to be big advance from ether in the 50s as not flammable

72
Q

What type of chemical is halothane?

A

Halogenated hydrocarbon

73
Q

What is the MAC of halothane?

A

0.75%

74
Q

What are 3 disadvantages of halothane as an inhalational anaesthetic agent?

A
  1. Chemically unstable in light
  2. Increases vagal one - causes bradycardia
  3. Halothane hepatitis
75
Q

What is a benefit of using halothane as a inhalational anaesthetic agent?

A

Non-irritant

76
Q

Why is halothane no longer used as an inhalational anaesthetic agent?

A

due to halothane hepatitis - very high mortality

77
Q

What is the frequency of halothane hepatitis?

A

1 in 30 000, 1 in 3500 if repeat exposure

78
Q

What is the mechanism that causes halothane hepatitis?

A

Immune mechanism - trifluoroacetyl group

79
Q

In which patient group is halothane still sometimes used and why?

A

Children - halothane hepatitis is less common in children

80
Q

When did isoflurane and enflurane become popular?

A

Both in late 70s/ early 80s

81
Q

What type of chemicals are enflurane and isoflurane?

A

Fluorinated ethers - optical isomers of each other

82
Q

Are enflurane and isoflurane irritants or not?

A

Yes, irritant

83
Q

What effect do enflurane and isoflurane have on blood vessels?

A

Vasodilators

84
Q

How common is hepatitis with enflurane and isoflurane?

A

very rare

85
Q

What is the MAC of enflurane?

A

1.68% (low)

86
Q

What is the MAC of isoflurane?

A

1.15%

87
Q

Why is isoflurane still widely used as an inhalational anaesthetic agent?

A

relatively insoluble, clean agent, low MAC

88
Q

Which 3 inhalational agents are most widely used today?

A
  1. Desflurane
  2. Sevoflurane
  3. Isoflurane
89
Q

What type of chemical is sevoflurane?

A

Fluorinated methyl-isopropyl ether

90
Q

What is the MAC of sevoflurane?

A

2%

91
Q

What are 4 advantages of using sevoflurane?

A
  1. non-irritant (unlike isoflurane)
  2. very little odour
  3. rapid inductino as very insoluble (also wears off quickly)
  4. cardiovascular stability
92
Q

How is sevoflurane decomposed?

A

soda lime - some concerns

93
Q

What is it good practice to do after using sevoflurane?

A

flush circular breathing system after using so sevoflurane doesn’t remain

94
Q

What type of chemical is desflurane?

A

fluorinated methyl-ethyl ether

95
Q

What are 4 key properties of desflurane?

A
  1. Rapid onset (low blood solubility)
  2. pungent
  3. low potency - MAC 6%
  4. Low boiling point - 22.8oC
96
Q

What is a distinctive property of desflurane?

A

pungent

97
Q

Why does desflurane have a rapid onset?

A

Low blood solubility

98
Q

What is the MAC of desflurane?

A

6% (low potency)

99
Q

Why is the low boiling point of desflurane - 22.8oC - important?

A

Heated vaporiser is used - plugged into mains supply and mixed as a gas. Comes in a special bottle

100
Q

What are 2 advantages of maintenance of anaesthesia with inhaled agents?

A
  1. Easy to administer
  2. Predictable behaviour
101
Q

What are 4 disadvantages of maintenance of anaesthesia with inhaled agents?

A
  1. take up in fat depots - affects recovery
  2. potential toxicity
  3. recovery dependent upon ventilation
  4. need to ‘wash out’ circle systems
102
Q

What is the only drug that can be used to perform total intravenous anaesthesia (TIVA)?

A

propofol

103
Q

What are 3 advantages of total intravenous anaesthesia (TIVA)?

A
  1. easy to continue from induction
  2. titratable, smooth anaesthesia
  3. flow rates for hypnosis predictable, based on weight and age
104
Q

What are 5 disadvantages of of TIVA?

A
  1. Can be unpredictable wake up time - dependent on elimination half life
  2. No perfect context-sensitive properties
  3. Unsuitable for short cases
  4. Dependent upon action of syringe pumps
  5. IV cannula can become displaced/ detached
105
Q

When is an intermittent bolus approach to anaesthetic sometimes used?

A

Short procedures

106
Q

What happens to intermittent bolus concentration over time?

A

Initial spike above threshold for side effects - patient usually given too much, wears off quickly then starts to move; second bolus given which goes just above threshold, then continuous dips and peaks as more boluses given (graph)

107
Q

What are 2 different types of total intravenous anaesthesia (TIVA)?

A
  1. Intermittent bolus
  2. Target-controlled infusional (TCI) anaesthesia: computer controlled pump
108
Q

Why won’t a fixed infusion work to provide total intravenous anaesthetic (TIVA)?

A

see graph: either increases too much to produce side effects, or too slow to produce effects so patient is awake

109
Q

How does TCI (target controlled infusional) anaesthesia work?

A
  • computer controlled pump gives bolus early on (often slight overshoot)
  • turns off until achieves infusion it wants then starts again and can try and achieve concentration you want
  • see graph
110
Q

What is the mechanism of action of propofol?

A

GABA receptor agonist

111
Q

How quickly does propofol take to produce the onset of anaesthesia?

A

Rapid onset of anaesthesia (not as quick as sodium thiopentone)

112
Q

Which IV anaesthetic agent can produce pain on IV injection?

A

propofol

113
Q

What is the metabolism of propofol like?

A

rapidly metabolised with little accumulation of metabolites

114
Q

Which type of IV anaesthetic agent has proven anti-emetic properties?

A

propofol

115
Q

Which IV anaesthetic agents produce myocardial depression?

A
  • Propofol produces moderate myocardial depression, sodium thiopentone may cause myocardial depression
  • (etomidate has favourable cardiac safety profile with little haemodynamic instability, ketamine is suitable for those who are haemodynamically unstable)
116
Q

What is the IV induction agent of choice in patients who are haemodynamically unstable?

A

ketamine (etomidate usually unsuitable due to prolonged and also brief using causing adrenal suppression)

117
Q

When is propofol used as an IV induction agent? (3 key things)

A

widely used, especially for -

  1. maintaining sedation on ITU
  2. total IV anaesthesia
  3. daycase surgery
118
Q

What is the IV induction agent of choice for rapid sequence induction (emergencies)?

A

Sodium thiopentone - extremely rapid onset of action

119
Q

What are 4 negative properties of sodium thiopentone?

A
  1. Marked myocardial depression may occur
  2. Metabolites build up quickly
  3. Unsuitable for maintenance infusion
  4. Little analgesic effects
120
Q

Which IV induction agents have no analgesic properties and which has considerable analgesic effects?

A
  • sodium thiopentone and etomidate have little/ no analgesic properties
  • ketamine has moderate to strong analgesic properties
121
Q

What is the mechanism of action of ketamine?

A

NMDA receptor antagonist

122
Q

Why is etomidate unsuitable for maintaining sedation?

A

prolonged (and even brief) use may result in adrenal suppression

123
Q

What is a common side effect of etomidate?

A

post-operative vomiting

124
Q

What is an agent which reverses the action of midazolam and how?

A

Flumazenil: antagonises effects of benzodiazepines by competition at GABA binding sites

(many benzos have longer half lives than flumazenil, so patinets still require close monitoring after receiving)

125
Q

What are 3 key adverse effects of halothane?

A
  1. Hepatotoxicity
  2. Myocardial depression
  3. Malignant hyperthermia
126
Q

What is a key adverse effect of thiopental (intravenous anaesthetic)?

A

Laryngospasm

127
Q

Why does thiopental (an intravenous anaesthetic) affect the brain quickly?

A

highly lipid soluble