2015A11 Discuss the relative advantages and disadvantages of using morphine vs fentanyl for post-operative
patient-controlled analgesia (PCA).

 

List:

·      PCA principles

·      Typical settings

·      Comparison summary

·      Pharmaceutics

·      Pharmacokinetics

·      Pharmacodynamics

 

PCA principles:

Definition

·  User controlled, locked, IV analgesic pump

·  Usually opioid

Indication

·  High opioid requirement

·  Unreliable gut function

·  Risk of overdose (OSA, OHS, severe COPD, sedated)

Toxicity

·  Respiratory depression

·  Sedation

·  Airway obstruction

·  Death

 

Typical settings:

 

Morphine (M)

Fentanyl (F)

Bolus dose

0.5-2mg

10-40mcg

Lockout

5 minutes

5 minutes

 

Comparison summary:

 

Morphine

Fentanyl

Onset

Slower

Faster

Offset

Slower

Faster

Intra-op loading dose

Not needed

Needed

Side effects

More

Less

Suitable patient

Young, large, athletic

Older, OSA, risk of sedation

 

Pharmaceutics:

·         Both stable in solution

·         Both unlikely to precipitate with other drugs

 

Pharmacokinetics:

Parameter

Morphine

Fentanyl

Implication

Time course:

 

 

 

Time to peak effect (TTPE)

30min

5mins

M: risk of dose stacking

Duration of single small bolus

2-3 hours

5-20mins

M: prolonged analgesia but higher risk of toxicity

F: brief analgesia but lower risk toxicity

Distribution

 

 

 

Lipid solubility

1x

600x

F crosses blood-brain barrier (BBB) more easily

pKa

8

8.4

More M in BBB-diffusible form

% unionised

23%

9%

 

t1/2ke0

17min

7min

F has shorter TTPE

%plasma protein binding

35%

83%

If ↓ [plasma protein] -> greater ↑free [F] than ↑free [M]

VD (L/kg)

3.5

4

Similar

Metabolism:

 

 

 

Organ

Liver

Liver

 

Hepatic extraction ratio

0.76

0.8

 

Mode

Phase 2>1

(glucuronidation)

Phase 1&2 liver

(CYP3A4)

M metabolism in theory less affected in liver failure

Speed

Cl mL/kg/min

t1/2β (mins)

 

16

170

 

13

210

Similar offset after long infusion

Active metabolites

M6G analgesic

M3G neurotoxic

Nil

F safer with prolonged use

Excretion:

 

 

 

Route:

Renal – drug and metabolites

Renal - metabolites

F safer in renal failure


Pharmacodynamics:

Parameter

Morphine

Fentanyl

Implication

Nausea and vomiting

↑risk

↓risk

F preferable esp in GIT surgery patients

Histamine release

Y

N

F preferable if haemodynamic instability

Confusion

↑risk

↓risk

F preferable if elderly or confused

Opioid-induced hyperalgesia (OIH)

↓fluctuation [M] -> ↓ OIH

↑fluctuation [F] -> ↑OIH

 

Abuse potential

↑ (faster peak effect)

 

 

 

 

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