Vecuronium at the nicotinic receptor
Vecuronium
(Norcuron)
3-deacetylated metabolite is
active
Accumulation
is responsible for prolonged neuromuscular blockade in patients
receiving longterm therapy
Metabolites:
3-hydroxy metabolite (Active)
17-hydroxy metabolite (Active)
3, 17-dihydroxy metabolite
(Active)
17 Deacetylated metabolite is active
Pancuronium
Bromide (Pavulon)
Tetrahydroisoquinolines
d-Tubocurarine and metocurine
(Metubine Iodide®)
Cl
Long duration of action
Mostly eliminated unchanged
via kidney and bile, <1% gets demethylated in the liver
CH3I
Long duration of action
4 fold more potent than d-
tubocurarine
Eliminated unchanged via
kidney
Tetrahydroisoquinolines
Atraeurlum
metabolism
och3
ocH3
ocH3
Laudanosine
(Inactive)
ocH3
OCH3
Hofmann
elimination
H3co
оси.
Hofmann
elimination
+
Laudanosine
Mivacurium
and Doxacurium does not undergo hofmann elimination like atracurium
Ester
hydrolysis
иди оно
Structure
Activity Relationships
C
*
Contain
at least one +ve charged quaternary amine (4 C
atoms attached
to nitrogen) like Ach
*
N+
attracted to Alpha sub unit of AChR (-ve charge)
Bis
quaternary amines
*
Succinylcholine,
Pancuronium, Atracurium
Mono
quaternary amines
*
D-Tubocurarine,
Vecuronium, Rocuronium
*
In
acidosis, Tertiary amine protonated ^ + charge increased potency
*
Bridging
structure in between two amines is lipophilic and determines potency
*
10-12 carbon bridge between two nitrogens is optimal for maximal
neuromuscular blockade.
Metabolism
of neuromuscular blockers
|
Duration of action (min) |
Metabolites |
Mode of elimination |
Succinylcholine |
6-8 |
Ester hydrolysis (inactive) |
Hydrolysis by plasma cholinesterases |
d-Tubocurarine |
80-120 |
Mostly unchanged |
Renal elimination, liver clearance |
Vecuronium |
30-40 |
3-hydroxy , 17-hydroxy, 3,17- dihydroxy (all active) |
Liver metabolism and clearance, renal elimination |
Pancuronium |
120-180 |
3-hydroxy (active) 17-hydroxy, 3,17-dihydroxy (inactive) |
Renal elimination, liver metabolism and clearance |
Pipecuronium |
80-100 |
Primarily unchanged |
Renal elimination, liver metabolism and clearance |
Rocuronium |
30-40 |
Primarily unchanged |
Liver metabolism and clearance |
Atracurium |
30-40 |
Ester hydrolysis products, Laudanosine (all inactive) |
Hofmann degradation, hydrolysis by plasma cholinesterases |
Mivacurium |
12-18 |
Ester hydrolysis products (inactive) Hydrolysis by plasma cholinesterases |
|
Doxacurium |
90-120 |
Ester hydrolysis products (Inactive) |
Renal elimination, liver metabolism |
Duration
of action: 0-29 min: Short
acting;
30-40 min: Intermediate
acting;
over 40 min: long
acting
ilWji
QUESTIONS
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