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Diploma in Anaesthesia > Intravenous induction agents > Flashcards

Intravenous induction agents Flashcards

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1
Q

What can be added to propofol to reduce pain on injection?

A

Lidocaine: 1 -2 mls 1% IV solution

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2
Q

What is meant by one “arm brain circulation time”?

A

The time it takes for the drug to travel from the injection site to the brain ± 30 seconds

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3
Q

What physicochemical property allows a drug to get into the brain?

A

Lipid solubility

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4
Q

What challenge is presented by highly lipid soluble agents?

A

Preparation - if they are highly lipid soluble they cannot readily be presented as an aqueous solution

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5
Q

How is propofol presented?

A

1-2% lipid-water emulsion (soya bean oil and purified egg phosphatide)

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6
Q

How is Thiopental presented?

A

It is a weak acid and can be dissolved in water as long as it is in its ionized form.

pKa of 7.4
Acids ionize at pH above their pKa

So if thiopental is in its ionized form at a pH above its pKa it will be soluble in water.

Stored in NaCO3 powder –> when mixed with 20 mL of water a 2.5% solution of thiopental with a pH of 10.5 is made.

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7
Q

How is Etomidate presented?

A

It is soluble in water but is stabilized by 35% propylene glycol to give a 0.2% solution

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8
Q

At what plasma concentration of propofol is there risk of awareness? And how long does it take for propofol to decline to this level after a single induction dose?

A
  1. 5ug/ml
  2. 5 minutes

However, propofol is synergistic with volatile agents meaning that there is an overall effect during the ‘cross-over’ phase that will prevent awareness unless volatile is started later than 2 minutes after IV dose of propofol

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9
Q 
List the doses of the following IV induction agents:
Propofol
Thiopentone
Etomidate
Ketamine
A

Propofol: 1 - 2.5 mg/kg
Thiopentone 3 - 7
Etomidate 0.3
Ketamine 0.5 - 2

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10
Q

When should the doses of the induction agent be reduced

A

Specific clinical scenarios: e.g. shock

Adjuvant drugs used (benzodiazepines/opioids)

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11
Q

With the exception of RSI, how are IV induction agents administered?

A

Slowly and titrated to effect (loss of eyelash reflex).

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12
Q

What is the onset and offset time of propofol

A

Onset: 30 s
Offset: 3 - 7 minutes

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13
Q

Describe the metabolism of propofol

A

Conjugated (liver) –> glucuronide

Hydroxylated (liver) –> quinol –> glucuronidated

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14
Q

CVS effects of propofol

A 
Direct myocardial depression
Decreased SVR
Hypotension
Possible bradycardia
(i.e. reduction in CO)
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15
Q

RSP effects of propofol

A

Dose-dependent respiratory depression

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16
Q

Effects of propofol vs thiopentone on the airway reflexes

A

Propofol obtunds the airway reflexes more than thiopental – allowing earlier placement of LMA

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17
Q

What are the miscellaneous effects of propofol

A

Pain on injection (reduced with lidocaine)

LESS PONV

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18
Q

Is propofol licensed for children under 3 years

A

No

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19
Q

Summarise the physicochemical properties of propofol

A

Phenol derivative
Highly lipid soluble
pKa of 11 ( weak acid so almost entirely unionized at pH of 7.4)
Plasma protein binding: 98%

20
Q

What is in the ampoule of propofol

A 
Lipid-water emulsion containing 1% propofol (10mg/ml)
Emulsifying agent
- Purified egg phosphatide
- Glycerol
- Soya-bean oil
21
Q

What is the onset and offset of Thiopental

A

Onset: 30 s
Offset: 5-10 mins

22
Q

What is the metabolism of thiopental

A

Liver –> active oxybarbiturate derivative PENTOBARBITAL and two other inactive metbolites

23
Q

What are the effects of Thiopental on the CVS

A

Direct myocardial depression –? low BP and decreased CO

24
Q

What are the effects of thiopental on the RSP

A

Dose dependent reduction in Ve

25
Q

What are the problems with the use of thiopental

A
  1. Intra-arterial injection – extreme pain and limb threatening
    (Urgent Rx –> saline dilution and papaverine 40mg to dilate artery and SNS blockade to improve blood flow locally.
  2. Hypersensitivity 1 in 15 000
26
Q

What is an absolute contraindication to the use of thiopental

A

Porphyria

27
Q

What are the physicochemical properties of thiopental

A

Thiobarbiturate
Weak acid with pKa 7.6 (60% exists in unionized form)
Highly lipid soluble
Protein binding 80%

28
Q

What is in the vial of thiopental

A

Thiopentone sodium salt 500mg
NaCO3
Stored under Nitrogen

When mixed with 20 ml of water it forms a 25mg/ml solution at pH 10.5 - high pH stops the insoluble acid from precipitating out of solution

Acids ionize above their pH (want solution form for administration. Physiological pH lipid soluble form increases

29
Q

What is the onset and offset time of etomidate?

A

Onset: 30 s
Offset: 3-7 minutes

30
Q

How is etomidate metabolized

A

Its an ester so undergoes ester hydrolysis in plasma and liver

31
Q

CVS effects of etomidate

A

Minimal effect on HR
Minimal effect on CO
Minimal effect on SVR

32
Q

RSP effects of etomidate

A

Minimal and transient dose-dependent respiratory depression

33
Q

What are other important effects of etomidate

A

Pain on injection (reduced by use of preparation with lipid i.e. etomidate-lipuro)

N and V common compared with propofol

Adrenocortical suppression - especially if used by infusion

Hypersensitivity rxns 1:75 000

34
Q

What are the physicochemical properties of etomidate

A

Carboxylated imidazole derivative
High lipid solubility and water soluble
pKa 7.4
Protein binding: 70%

35
Q

Dose of etomidate

A

0.3 mg/kg

36
Q

What is in the ampoule of etomidate

A

Etomidate 2mg/ml
Aqueous solution of etomidate pH of 8.1
Stabilized by propylene glycol 35%

37
Q

Define pharmacokinetics

A

The study of how and why plasma concentrations of drugs change with time

38
Q

Concerning the negative exponential decline of plasma propofol concentration after a single dose, why is the propofol concentration decreasing?

A
  1. Some drug is distributing to other tissues (Brain, fat, muscle)
  2. Some drug is being metabolized and/or excreted from the body
39
Q

What determines to which tissues the drug is INITIALLY distributed

A

Blood flow

  • Blood vessel rich tissues take up drug more quickly
  • Eventually the blood vessel poor tissue (fat) take up the drug as it recirculates
40
Q

What causes the initial rapid decline in plasma concentration after a single IV dose of an induction agent

A

distribution to other tissues

41
Q

How does the metabolism differ between propofol, thiopental and etomidate

A

Etomidate is an ester and is rapidly broken down by plasma and hepatic esterases

Propofol is more rapidly broken down than thiopental without active metabolites. Thiopental is metabolized more slowly and has an active metabolite pentobarbital.

42
Q

What impact does the active metabolite of thiopental, pentobarbital, have on the clinical effect and duration of action of pentobarbital

A

Single IV dose of thiopental for induction leads to a very low and clinically insignificant level of pentobarbitol which does not influence the duration of action of thiopental.

However, the effects of pentobarbital become more important if thiopental is given by continuous infusion

43
Q

How is pentobarbital structurally different from thiopental

A

The Sulfur group is substituted for an Oxygen

44
Q

What are absolute contraindications to thiopental and etomidate

A

Previous hypersensitivity

Porphyria

45
Q

Which induction agent is faster thiopental, propofol or etomidate

A

Thiopental is slightly faster than propofol which is faster than etomidate

46
Q

Which agent should be avoided in a patient with egg allergy

A

Propofol (but there is no evidence for this)

47
Q

Which induction agent should be used in epilepsy

A

Thiopental -antiepileptic (or propofol)

Diploma in Anaesthesia (73 decks)

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