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Exam Prep MCQs > IV agents and sedatives > Flashcards

IV agents and sedatives Flashcards

1
Q

How does propofol produce vasodilatation?

A

By nitric oxide production.

It causes hypotension (reduction in SVR + CO) without tachycardia.

Bradycardia is common, esp with opiate co-administration.

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2
Q

How unionized is propofol at physiological pH?

A

pKa of propofol is 11, therefore at pH 7.4 is almost entirely unionized

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3
Q

Where is the hydroxyl group situated in propofol?

A

1st carbon.

Phase 1 metabolism into a quinol derivative involves hydroxylation of the 4th carbon.

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4
Q

What phases of metabolism does propofol undergo?

A

Phase 1 and 2.

Glucuronidation is the predominant metabolic pathway, hydroxylation by cytochrome P450 to a quinol derivative prior to conjugation is also an important pathway.

The relative importance of each pathway varies amongst patients.

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5
Q

What is the paediatric dose of propofol for IV paediatric induction?

A

Approx double that of adults.

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6
Q

How does propofol cause a reduction in cardiac output?

A

Reduces HR, myocardial contractility and sympathetic tone.

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7
Q

How is propofol cleared?

A

Hepatic metabolism but extra-hepatic metabolism is significant suggested by the fact that clearance is higher than hepatic blood flow.

Sites for extra-hepatic metabolism: kidneys (1/3) and lungs (to 2,6-diisopropyl- 1,4-quinol)

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8
Q

How is the anti emetic effect of propofol mediated by?

A

Dopamine receptor antagonism

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9
Q

What can happen in children with a prolonged infusion of propofol?

A

Propofol infusion syndrome

  • hypertriglyceridaemia
  • organ fatty infiltration
  • severe bradycardias
  • metabolic acidosis
  • increased mortality
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10
Q

What is the VoD of propofol, ketamine, etomidate and thiopentone?

A

Propofol 4 L/kg

Ketamine 3 L/kg

Etomidate 3 L/kg

Thiopentone 2.5 L/kg

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11
Q

Which of the IV induction agents has the highest clearance rate?

A

Propofol (30-60 ml/kg/min)

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12
Q

What are the clearance rates of the IV induction agents?

A

Propofol 30-60 ml/kg/min

Etomidate 10-20 ml/kg/min

Ketamine 17 ml/kg/min

Thiopentone 3.5 ml/kg/min

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13
Q

Which has a higher percentage of protein binding, thiopentone or methohexitone?

A

Thiopentone 80%

Methohexitone 60%

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14
Q

What is the pKa of thiopentone?

A

7.6

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15
Q

How protein bound is midazolam?

A

98%

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16
Q

What % of midazolam is unionized at physiological pH?

A

Midazolam is a tautomeric molecule consisting of benzene and diazepine rings.

In a pH > 4 the diazepine ring closes producing a lipid soluble unionized molecule.

With a pKa of 6.5 around 89% of molecules are unionized at physiological pH.

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17
Q

What is midazolam metabolised to?

A

The phase 1 metabolite 1-alpha-hydroxy-midazolam is active. This may then be conjugated (glucuronidation) prior to excretion.

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18
Q

Which enzyme system is midazolam metabolised by?

A

CP450 3A3/4.

The action of midazolam may be prolonged by co-administration of alfentanil.

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19
Q

What dose of midazolam can you give to children as a pre-medication?

A

Oral dose of up to 1mg/kg 30 mins prior to induction.

Monitoring is required if doses >0.5 mg/kg are used.

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20
Q

What receptors does ketamine act on?

A

It is a non-competitive antagonist of NMDA

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21
Q

Which isomer is more potent in the racemic mixture of ketamine?

A

S+ is 2-3 times more potent than the R- isomer. It may also produce less intense emergence phenomena.

22
Q

What dose can you give of ketamine as an oral premedication?

A

2-5 mg/kg

It has 20% bioavailability. Dose of up to 10mg/kg have been used in extreme cases.

23
Q

Using ketamine, who is less likely to get emergence phenomena?

A

Young/elderly

24
Q

What is the metabolism of ketamine?

A

Undergoes cytochrome P450 demethylation to norketamine which is active, this then undergoes glucuronidation to an inactive metabolite which is excreted.

25
Q

What is ketamine stored as?

A

As acidic solution of pH 3.5-5.5

26
Q

What EEG activity does ketamine produce?

A

Dissociative anaesthesia with predominant theta and delta activity

27
Q

What effects on cerebral circulation does ketamine have?

A

Cerebral O2 consumption, blood flow and intracranial pressure are all increased by ketamine.

28
Q

How protein bound is ketamine?

A

25-50%

29
Q

Does ketamine have direct myocardial depressant effects?

A

Ketamine increases sympathetic tone and circulating levels of adrenaline and noradrenaline. This produces the cardiovascular effects seen clinically of tachycardia, increased cardiac output, increased / maintained blood pressure and elevated CVP.

However, ketamine also produces a mild direct myocardial depressant effect that is masked, less so for the S+ isomer.

30
Q

How is etomidate prepared?

A

With 35% propylene glycol

31
Q

What % of people feel pain on injection of etomidate?

A

25%

32
Q

Is N+V a SE of etomidate?

A

Yes

33
Q

What is the induction dose of etomidate?

A

The IV induction dose is 0.2-0.3 mg/kg

34
Q

Which is the most likely IV induction agent to cause excitatory movements with epileptiform activity on EEG?

A

Etomidate is the most likely IV induction agent to cause myoclonic movements and epileptiform activity on EEG - in around 20% of cases.

35
Q

What is etomidate?

A

Etomidate is an imidazole derivative and an ester.

36
Q

What happens if you give a patient with porphyria etomidate?

A

Porphyric crisis

37
Q

How highly protein bound is etomidate?

A

75%

38
Q

How does etomidate affect aldosterone and cortisol synthesis?

A

Etomidate has been shown to inhibit 11-beta and 17-alpha hydroxylase function and impair aldosterone and cortisol synthesis for up to 24 hours after administration. Steroidogenesis occur in the adrenal cortex.

39
Q

What does etomidate have the same volume of distribution as?

A

Ketamine, both 3L/kg

40
Q

What is thiopentone prepared as?

A

Hygroscopic yellow powder in 6% sodium carbonate

41
Q

What % solution does thiopentone produce when reconstituted with water?

A

2.5%

42
Q

What % of thiopentone is unionized in blood?

A

60%

43
Q

What is thiopentone metabolized to?

A

Pentobarbitone (active metabolite)

44
Q

What is thiopentone predominantly when it’s in solution?

A

It is predominantly in its enol form when in solution. The enol form is soluble. Thiopentone is tautomeric and alkaline conditions promote the switch from keto to enol.

45
Q

Where is the sulphur group on thiopentone?

A

On 2nd carbon

46
Q

What effects does thiopentone have on the RS?

A

It can cause laryngospasm and bronchospasm

47
Q

Why does thiopentone cause reduced urine output?

A

It stimulates ADH release

48
Q

Is thiopentone an enzyme inhibitor or inducer?

A

Inducer

49
Q

Is thiopentone more active in acidic or alkalotic conditions?

A

Acidotic conditions.

Acidosis + hypoalbuminaemia increases the amount of free unionized drug. So a lower dose should be used in critically ill patients.

50
Q
A

Exam Prep MCQs (19 decks)

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