2021B09 Discuss the relative advantages and disadvantages of using morphine and fentanyl for post-operative Patient Controlled Analgesia (PCA).

List:

· Summary

· PCA principles

· PC

· PK

· PD

Summary:

	Morphine	Fentanyl
Settings	1mg q5min	20mcg q5min
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

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

Pharmaceutics:

· Both stable in solution

· Both unlikely to precipitate with other drugs

Pharmacokinetics:

Time course:

Parameter

Morphine

Fentanyl

Time to peak effect

Peak effect: ~20 mins*

Peak concentration: ~100mins*

4 mins

Bolus duration

300 mins

5-20 mins

->Morphine provides longer-lasting pain relief, but dose stacking may occur
->Fentanyl is better suited to q5min protocol

*Both these figures are taken from Evers/Maze/Kharasch. I think once the effect site concentration rises to 90% of its maximum, the patient will report peak analgesia. But in truth the concentration keeps rising to a small degree from t=19 to t=100.

Distribution:

Parameter	Morphine	Fentanyl
Lipid solubility	1x	600x
pKa	8	8.4
% unionized	23%	9%
t_1/2ke0	264 min	4 min
% plasma protein bound	35%	83%
VD (L/kg)	3.5	4

Elimination:

Parameter	Morphine	Fentanyl
Speed -Cl (mL/kg/min) -t_1/2b (mins) -Extraction ratio	16 170 0.76	13 210 0.8
Metabolism	Liver: phase 2>1 (Glucuronidation)	Liver: phase 1>2 (CYP3A4)
Metabolites	M6G analgesic M3G neurotoxic	Inactive
Excretion	Renal: parent and metabolites	Renal: metabolites only

->Similar offset time after saturation

->Fentanyl safer in renal failure ± liver failure

Pharmacodynamics:

Parameter	Morphine	Fentanyl
Receptors M/K/D	3:1:1	3:1:0
PONV	↑	↓
Histamine release	↑	↓
Confusion	↑	↓
Abuse potential	↓	↑ (faster onset)

Feedback welcome at ketaminenightmares@gmail.com