Receptor classification

DOP/delta/OP1
KOP/kappa/OP2
MOP/mu/OP3
NOP/orphan/ORL1

Mechanism of action

G-protein coupled receptors
Spinal and supraspinal
Overall effect is inhibition of excitatory neurotransmitter (glutamate) release from presynaptic terminals and hyyperpolarization of postsynaptic membranes
α subunit spits from β and y and combines with GTP to inhibit adenyl cyclase so less cAMP formed from ATP
yβ subunits block inward flow of Ca and enhance outward flow K
SC opioid recs in C-fibres in lamina 1 and substantia gelatinosa

Opioid classification

Functional
Full agonists (morphine, fentanyl etc)
Partial agonists (buprenorphine)
Mixed action (tramadol, pethidine)

Traditional
Strong
Intermediate (partial agonists)
Weak

Structural


Morphine

Uses
Analgesia
Premed
LVF

Chemical
Phenanthrene derivative
Base

Presentation
Tablets
Syrup
Suppositories
Clear colourless solution
Must be preservative free for neuraxial

Mode of action
See above

Routes of admin/doses
Po up to 20mg initially
IM/SC 0.1-0.2mg/kg initially – peaks at 60 mins
IV up to 0.1mg/kg initially – 30 mins

Effects
CNS
Analgesia
Sedation
N+V
Miosis
Euphoria/dysphoria
CVS
BP (SVR - abolishes high sympathetic tone from hypovolaemia or vasodilatation)
bradycardia
RS
Respiratory depression
Antitussive
Bronchospasm
GI
gastric emptying
intestinal motility
N+V
GU
bladder and uterine tone
retention urine
Other
ADH
Muscle rigidity
Itching
Histamine release

Kinetics

Absorption
50% bioavailability PO
Distribution
40% protein bound
pKa 7.9; 25% unionized 7.4
Vd 250
Metabolism
Phase 2 conjugation in liver to morphine 3 and 6 glucuronide
Excretion
Metabolites excreted in urine. 6 is active 10x more potent than morphine
Clearance 1000mls/min
T1/2 2-3h

Fentanyl

Pethidine derivative
7-10mcg/kg needed to obtund pressor response
15-25mcg spinal
50mcg epidural
Up to 100mcg/kg has been used in cardiac
6h recovery if >50mcg/kg used
Does not
ADH
Wooden chest (abolished with muscle relaxant)
Bradycardia

Kinetics
Absorption
Bioavailability 33% PO; 94% transdermal after 72h
Distribution
Vd 330L
85% protein bound
X1000 more lipid soluble than morphine so more rapid
Short duration of action due to redistribution
pKa 8.4; 9% unionized 7.4
Metabolism
Phase 1 and 2
Metabolites inactive
Excretion
Clearance 1200mls/min

Alfentanil

Derived from fentanyl
X10 more potent than morphine
Works in 90s; lasts 10mins
50mcg/kg to obtund pressor response (3-4mg)
Up to 125mcg/kg used in cardiac (10mg; 20mls)
Infusion 0.5-1mcg/kg/min

Kinetics
Distribution
Vd 30L
130X more lipid soluble than morphine
90% protein bound
pKa 6.5; 90% unionized at 7.4
Less lipid soluble than fentanyl but works quicker because:
  • Greater concentration gradient
    • Smaller Vd
    • Less potent so bigger dose used
  • Less ionized
Metabolism
Phase 1 and 2
Excretion
Clearance 300mls/min
T1/2 50-70mins

Remifentanil

Induction up to 3mcg/kg
Maintenance 0.1-0.3mcg/kg/min (or effect site 5-7ng/ml if TCI)
Onset 1 min
Offset 5 mins
Distribution
Vd 30
80% protein bound
pKa 7.3
60% unionized
Metab
Ester hydrolysis by non specific plasma esterases within RBCs
Metabolite excreted renally (virtually inactive)