· PC
· PK
· PD
|
Atracurium |
Cisatracurium |
Molecule |
Quaternary amine 4 chiral centres 10 stereoisomers (n2 = 16 but some identical) 15% cisatracurium = 50% activity |
Quaternary amine 1Rcis-1R’cis stereoisomer of atracurium R: stereochemistry of the benzyltetrahydroisoquinoline rings Cis: geometry of the bulky methoxy at C1 and 2-alkylester at N1
|
Needs reconstitution (i.e. easy use) |
N |
N |
Needs refrigeration |
Y 2-8°C |
Y 2-8°C |
Life at room temp (accept 90% potency) |
3/12? |
3/12? |
Compatibility |
No precipitation pH 4 |
No precipitation pH 4 |
|
Atracurium |
Cisatracurium |
Admin: |
|
|
ED95 |
0.25mg/kg |
0.05mg/kg |
Route |
IV only |
Same |
Infusion rate |
5-10mcg/kg/min |
1-2mcg/kg/min |
Time course: |
|
|
-Onset 2x ED95 95% ↓twitch height |
3 mins? |
5 mins? |
-Duration 2x ED95 (mins) |
30-40mins |
20-30mins |
Absorption: |
|
|
|
IV only |
IV only |
Distribution: |
|
|
-VDSS |
0.15L/kg |
0.15L/kg |
-%PPB |
15 |
15 |
Metabolism: |
|
|
-rate |
Cl 5mL/kg/min t1/2β 20 mins (faster offset after long infusion) |
Cl 6mL/kg/min t1/2β 30 mins |
-Hoffman elimination |
30% |
80% |
-Ester hydrolysis |
60% |
15% |
-Active metabolites |
Laudanosine: glycine antagonist -> seizure Tiny amount in man Renally cleared |
Same |
-↓temp |
↓Ester hydrolysis ↓Hoffman elim |
Same |
-↓pH |
↑Ester hydrolysis ↓Hoffman elim (Less impairment) |
Same (more impairment) |
-Liver failure |
Minimal effect on parent (unlikely to ↓esterase level) |
Same |
-Age |
Minimal effect on parent |
Same |
Excretion: |
|
|
-% excreted unchanged |
10% |
5% |
-Renal failure |
Minimal effect on parent Accumulate laudanosine (rarely significant) |
Same |
|
Atracurium |
Cisatracurium |
Effects: |
|
|
Action at NMJ type nAChR |
Competitive antagonist |
Competitive antagonist |
Reversal by AChEi |
Y |
Y |
Side effects: |
|
|
-Histamine release -> bronchospasm, hypotension, rash |
Y ↑Methoxy groups = ↑potency, ↓histamine release ↓risk if slow injection ↓risk with repeat injection |
Rare (↑potency -> ↓dose for 2xED95) |
Factors prolonging effect |
Phys: ↑Mg2+, ↓K+, ↓temp, resp acidosis Pharm: e.g. volatile anaesthetic Path: e.g. myasthaenia gravis |
Same |