Beruflich Dokumente
Kultur Dokumente
Oleh
Ayu Ika Gustati Nurrahmah, S.Ked
70 2010 019
Pembimbing
dr. Achmad Marwan, Sp.An, M.Kes
Dose
The traditional intravenous dose of SCh to facilitate tracheal intubation is 1mg/kg.
Conceptually, it is anticipated that administration of 1mg/kg IV to a preoxygenated patient
would be associated with the return of spontaneous breathing before arterial hypoxemia
became significant. Considering the variability inresponse to SCh among patients,it is
concluded that no single perfect intubating dose of SCh exists.
Mechanismof Action
SCh attaches to one or both of the -subunits of nAChRs and mimics the action of
acetylcholine (partial agonist), thus depolarizing the post junctional membrane. Compared
with acetylcholine, the hydrolysis of SCh is slow, resulting insustained depolarization
(opening) ofthe receptor ion channels. Neuromuscular blockade develops because a
depolarized post junctional membrane can not respond to subsequent release of acetylcholine
(depolarizing neuromuscular blockade). Depolarizing neuromuscular blockade is also
referred to as phase I blockade. A single large intravenous dose of SCh (>2mg/kg), repeated
doses, or a prolonged continuous infusion of SCh may result in post junctional membranes
that do not respond normally to acetylcholine even when the post junctional membranes have
become repolarized (desensitization neuromuscular blockade). The mechanism for the
development of desensitization neuromuscular blockade is unknown and, for this reason,
designation as phase II blockade, which does not imply a mechanism, is the preferred
terminology.
Duration of Action
The brief duration of action of SCh (3 to5minutes) is principally due to its hydrolysis by
plasma cholinesterase (pseudocholinesterase) enzyme. Plasma cholinesterase has an
enormous capacity to hydrolyze SC hat a rapid rate so that only a small fraction of the
original intravenous dose of drug actually reaches the NMJ. Because plasma cholinesterase is
not present in significant amounts at the NMJ, the neuromuscular blockade produced by SCh
is terminated by its diffusion away from the NMJ and into extracellular fluid. Therefore,
plasma cholinesterase influences the duration of action of SCh by controlling the amount of
neuromuscular-blocking drug that is hydrolyzed before reaching the NMJ.
Atracurium
Atracuriumis abisquaternary benzylisoquinolinium nondepolarizing neuromuscular-blocking
drug (mixture of tengeometric isomers) with an ED95 of 0.2mg/kg that produces an onset in
3 to5minutes and a duration of neuromuscular blockade lasting 20 to 35 minutes.
Clearance
Atracurium undergoes spontaneous non enzymatic degradation at normal body temperature
and pH by a base catalyzed reaction termed Hofmann elimination. A second and
simultaneously occurring route of metabolism is hydrolysis by non specific plasma esterases.
Hofmann elimination represents a chemical mechanism of elimination, where as ester
hydrolysisis a biologic mechanism. These two routes of metabolism are independent of
hepatic and renal function as well as plasma cholinesterase activity (duration of atracuriuminduced neuromuscular blockade is similar in normal patients and those with absent or
impaired renal or hepatic function or those with atypical plasma cholinesterase). The absence
of prolonged neuromuscular blockade after the administration of atracurium to patients with
atypical cholinesterase emphasizes the dependence of atracurium's ester hydrolysis on non
specific plasma esterases that are unrelated to plasma cholinesterase. Hofmann elimination
and ester hydrolysis also account for the lack of cumulative drug effects with repeated doses
or continuous infusions of atracurium. Overall, ester hydrolysis accounts for an estimated
two-thirds of degraded atracurium, where as Hofmann elimination provides a safety
net,especially in patients with impaired hepatic and/or renal function.
Laudanosine
Laudanosine is the major metabolite of both pathways of metabolism of atracurium.
Laudanosine depends on the liver for clearance, with approximately 70% excreted in the bile
and there mainder in urine. Despite increases in plasma laudanosine concentrations during
each stage of liver transplantation in patients receiving atracurium, these levels are
considered to be far below clinically significant concentrations. Although in active at the
NMJ (in contrast to metabolites of many other non depolarizing neuromuscular-blocking
drugs), animal studies have shown laudanosine to be a CNS stimulant, to increase the MAC
of volatile anesthetics, and to cause peripheral vasodilation. In patients receiving a full
paralyzing dose of atracurium (0.5mg/kg IV), the resulting peak plasma concentrations of
laudanosine are approximately 0.3g/mL, which is approximately 20 times less than the
plasma concentrations producing cardiovascular effects in animals. Laudanosine resulting
from the metabolism of atracurium probably will not produce seizure activity in anesthetized
patients, because skeletal muscle paralysis from atracurium would prevent movement.
Acid-Base Changes
Despite pH-dependent Hofmann elimination (accelerated by alkalosis and slowed by
acidosis), it is unlikely that the range of pH changes encountered clinically is sufficiently
great to alter the rate of Hofmann elimination and, thus, the duration of atracurium induced
neuromuscular blockade.
Cumulative Effects
Consistency of onset to recovery intervals after repeated supplemental doses of atracurium is
characteristic of this drug and reflects the absence of significant cumulative drug effect.
Cardiovascular Effects
Systemic blood pressure and heart rate changes do not accompany the rapid intravenous
administration of atracurium in doses u pto2 ED95 with background anesthetics including
nitrous oxide, fentanyl, and isoflurane. Facial and truncal flushing in some patients suggests a
release of histamine as the mechanism for the circulatory changes accompanying the rapid
administration of high doses (3 ED95 ) of atracurium. It is estimated that the plasma
histamine concentration must double before cardiovascular changes manifest clinically.
Pediatric Patients
Effective doses of atracurium are similar in adults and children (2 to 16 years old), when
differences in extracellular fluid volume are minimized by calculating the dose on a mg/m2
rather than a mg/kg basis.
Elderly Patients
Increasing age has no effect on the continuous rate of atracurium infusion necessary to
maintain a constant degree of neuromuscular blockade. This most likely reflects the
independence of clearance mechanisms (Hofmann elimination and ester hydrolysis )from
age-related effects on renal and hepatic function.
Sumber :
Pharmacology And Physiology In Anesthetic Practice, Robert K. Stoelting