Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of reduced plasma cholinesterase (ChE) activity in response to normothermic cardiopulmonary bypass (CPB) on mivacurium neuromuscular block was studied in nine patients anesthetized with propofol/fentanyl. Mivacurium was injected intravenously as an initial bolus of 150 micrograms/kg; repeat doses of 75 micrograms/kg were given when the evoked twitch tension attained 75% of control. With the institution of CPB, the previously normal ChE activity was reduced by 42% and remained low until the end of the procedure. The times of onset (time from the end of injection to maximum neuromuscular block) of the maintenance doses of mivacurium were 26% longer during than before or after CPB (P < 0.05). Their DUR25% (time from end of injection to recovery of neuromuscular transmission to 25% of control) were 13 +/- 3 min (means +/- SD) before, 14 +/- 4 min during, and 16 +/- 4 min (P < 0.05) after CPB. It is concluded, that, although markedly reducing the patient's previously normal ChE activity, normothermic CPB had little effect on the time characteristics of mivacurium neuromuscular block.
 ...
PMID:Changes in plasma cholinesterase activity and mivacurium neuromuscular block in response to normothermic cardiopulmonary bypass. 776 34

We have studied the pharmokinetics of cis-trans, trans-trans and cis-cis mivacurium in 10 healthy subjects and 11 patients with mild or moderate hepatic cirrhosis, during nitrous oxide-oxygen-isoflurane anaesthesia. Mivacurium 15 micrograms kg-1 min-1 was infused for 10 min (total dose 0.15 mg kg-1) and the plasma concentration of the three isomers measured at regular intervals for 190 min. The electromyographic response to the drug was also measured. Compartmental analysis of the resulting isomer profiles was undertaken: one- and two-compartment models were fitted to derive clearance, volume of distribution and half-life. Clearance of the cis-trans and trans-trans isomers was reduced significantly in the cirrhotic compared with the healthy group: cis-trans (median (range)) 44 (15-121) ml kg-1 min-1 vs 95 (57-213) ml kg-1 min-1 (P < 0.05); trans-trans 32 (12-64) ml kg-1 min-1 vs 70 (34-101) ml kg-1 min-1 (P < 0.05). The difference in the clearance of the cis-cis isomer in the cirrhotic (4.2 (2.9-12.1) ml kg-1 min-1) compared with the healthy group (5.2 (2.9-8.9) ml kg-1 min-1) was not significant with this sample size. Clearance of each isomer correlated significantly with plasma cholinesterase activity: cis-trans r = 0.73, P < 0.001; trans-trans r = 0.69, P < 0.001; cis-cis r = 0.48, P < 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Pharmacokinetics of the three isomers of mivacurium and pharmacodynamics of the chiral mixture in hepatic cirrhosis. 782 89

Although mivacurium is eliminated by plasma cholinesterase, previous investigations have revealed either no relationship or limited correlation between mivacurium infusion rates (IRs) and plasma cholinesterase activity. Assuming that such a relationship should exist, we used a novel approach to better demonstrate the relationship in humans. Fourteen isoflurane-anesthetized adults underwent standard neuromuscular monitoring. Mivacurium was then infused at 1.0 micrograms.kg-1.min-1 until twitch tension stabilized. The IR was then adjusted, using the Hill equation, to produce approximately steady state 50% (n = 14) or 90% (n = 13) twitch depression. Using these values for IR and steady-state twitch depression, the IRs expected to produce 50% and 90% twitch depression (IR50 and IR90, respectively) were estimated by on nonlinear regression. Both IR50 (r2 = 0.51, P < 0.005) and IR90 (r2 = 0.48, P < 0.01) were related to plasma cholinesterase activity; the coefficient of the Hill equation did not vary with plasma cholinesterase activity. We conclude that mivacurium IRs are, as expected, influenced by the activity of the enzyme responsible for its elimination.
 ...
PMID:The effect of plasma cholinesterase activity on mivacurium infusion rates. 789 31

Four neuromuscular blocking drugs, doxacurium, mivacurium, pipecuronium, and rocuronium have been or are about to be introduced into clinical practice. The purpose of this MiniReview is to describe their pharmacology, to consider their place in clinical anaesthetic practice, and to examine whether the needs of the clinician have been met. Two of the agents (doxacurium, mivacurium) are benzylisoquinolines resembling atracurium and two (pipecuronium, rocuronium) are aminosteroids related to pancuronium and vecuronium. Two (doxacurium, pipecuronium) are long-acting compounds, similar in duration of action to pancuronium, although the need for such a profile is questionable. Rocuronium has an intermediate duration of action and produces its maximum effect within two minutes which is much more rapid than any other non-depolarizing relaxant and this is probably a result of its poor potency. However, the onset of paralysis is not as quick as after succinylcholine. Mivacurium is unique because it is metabolized by plasma cholinesterase which produces a rapid recovery although slower than succinylcholine. All of the new drugs are devoid of serious cardiovascular or other side effects. The anaesthetist is now presented with an armamentarium of safe, nondepolarizing muscle relaxants with varying durations of action. However, the rapid onset and recovery associated with succinylcholine are unique and important in the urgent control of a patient's airway and respiration. The indications for succinylcholine will not disappear and the search for a non-polarizing replacement will continue.
 ...
PMID:Newer neuromuscular blocking agents. 815 34

Mivacurium is a benzylisoquinolinium diester. The drug is a nondepolarizing relaxant which is hydrolysed by plasma cholinesterase at 70-88% of the rate of suxamethonium. Enzymatic hydrolysis gives the drug its short duration of action. The length of paralysis is about 2-2.5 times that of suxamethonium and one-half to one-third that of the intermediate-acting nondepolarizers. The development of mivacurium represents a collaboration between industrial pharmacologists and chemists at Burroughs Wellcome Co. (USA) and investigators at the Massachusetts General Hospital, Boston, MA, USA.
 ...
PMID:The clinical and basic pharmacology of mivacurium: a short-acting nondepolarizing benzylisoquinolinium diester neuromuscular blocking drug. 853 38

Mivacurium is a new nondepolarizing muscle relaxant of the benzylisoquinoline type. Its short duration of action is due to rapid breakdown by plasma cholinesterase. The dose of mivacurium which produces 95% inhibition of twitch response (ED95) is between 60 and 80 micrograms/kg. Thus, mivacurium is 0.8 times and four times as potent as vecuronium and atracurium, respectively. With 2-3 x ED95, tracheal intubation can be accomplished within 2.5 min of intravenous injection. The ensuing DUR25% (time from injection to 25% recovery of control twitch tension) is twice as long as with suxamethonium and about half as long as with equipotent doses of atracurium or vecuronium. For muscle relaxation during long surgical procedures, mivacurium has been used as a continuous infusion. The average 6-min recovery index after infusion of mivacurium is particularly favourable for flexible control of muscle paralysis, whereas the recovery indices after infusion of atracurium or vecuronium are 15-30 min. In conclusion, mivacurium will close the pharmacodynamic gap between suxamethonium and the nondepolarizing muscle relaxants of intermediate duration of action. It will probably also be a suitable alternative to suxamethonium in elective cases.
 ...
PMID:Mivacurium chloride--a comparative profile. 853 40

Mivacurium, a new benzylisoquinoline muscle relaxant, appears to be close to the ideal for short to intermediate surgical procedures. Ideal properties of such an agent are discussed, in addition to indications for muscle relaxation in such procedures. Two studies are presented, showing the onset and offset times of mivacurium and its cardiovascular stability in both young and elderly patients. It is concluded that it is a well-tolerated and appropriate agent for use in short to intermediate surgical procedures in those patients with normal plasma cholinesterase function, despite a slight prolongation of action in the elderly.
 ...
PMID:Mivacurium in short to intermediate surgical procedures. 853 42

In special patient groups, drug response may be different from that in the healthy adult patient. Mivacurium dose requirements vary with age, and children require larger doses to obtain any given degree of block, but the elderly often require smaller doses. However, the dose requirements of the neonate do not necessarily differ greatly from those of the adult. There is a relationship between the duration of action of a bolus dose as well as infusion requirements to maintain block and the plasma cholinesterase activity. Patients with renal disease may have a decreased cholinesterase activity and may require smaller doses of mivacurium. Patients with severe liver disease may have a marked decrease in cholinesterase activity, and in these patients a substantially smaller dose of the drug may be needed to obtain and maintain any given degree of block. If the variation in dose requirements is kept in mind and the degree of block appropriately monitored, mivacurium may be used with safety in special patient groups, such as children, the elderly, or those with renal or hepatic impairment.
 ...
PMID:Mivacurium in special patient groups. 853 46

As a consequence of its rapid hydrolysis by plasma cholinesterase, mivacurium has a short duration of action, and recovery from neuromuscular blockade is rapid (5-95% twitch recovery = 13-15 min). Mivacurium is easy to titrate to individual patient requirements; the average infusion rate to maintain neuromuscular blockade at 89-99% twitch suppression during N2O/opioid anaesthesia is 6-7 micrograms/kg per min in adults and approximately 14 micrograms/kg per min in children. There is no evidence of a cumulative effect of mivacurium; recovery is unaffected by dose administered or duration of infusion. These characteristics make mivacurium a very suitable agent for use by infusion.
 ...
PMID:Mivacurium chloride administration by infusion. 853 47

Mivacurium is a new non-depolarizing muscle relaxant consisting of three stereoisomers. The two active isomers (cis-trans and trans-trans) undergo rapid metabolism by plasma cholinesterase (t1/2 beta < 2 min). Due to its rapid elimination, the need for reversal of mivacurium-induced neuromuscular block is controversial, and to date there have been no studies evaluating reversal of deep blocks. The object of the current investigation was to establish the lowest effective dose of edrophonium required to reverse deep mivacurium-induced neuromuscular block. One hundred ASA Class I and II patients undergoing outpatient surgery in two teaching institutions were studied in this randomized, placebo-controlled double-blind trial. Under balanced propofol/nitrous oxide/alfentanil anaesthesia, a continuous infusion of mivacurium was adjusted to maintain between 5-10% of control T1 amplitude. Upon completion of surgery, neuromuscular block was reversed by injecting normal saline (Group PLAC), edrophonium 0.125 mg.kg-1 (Group EDR-1), 0.25 mg.kg-1 (Group EDR-2), or 0.50 mg.kg-1 (Group EDR-3), in addition to a corresponding dose of atropine. Spontaneous recovery, from a T1 response of < 10% to a TOF ratio > or = 0.7, required 13.5 +/- 2.6 min (PLAC Group). In comparison, patients in the EDR-1 group required 9.2 +/- 2.6 min (P < 0.01). Higher doses of edrophonium conferred no advantage. Four patients (4%) had not achieved a TOF ratio of > or = 70%, 20 min after reversal, and required additional edrophonium. Two patients (PLAC group), had dibucaine numbers and cholinesterase levels consistent with an EUEA genotype, whereas the two patients with delayed recovery in the EDR-1 group had characteristics of a normal genotype. We conclude that a very low dose of edrophonium (0.125 mg.kg-1) hastens reversal of deep mivacurium-induced neuromuscular block by approximately four minutes, and that edrophonium doses exceeding 0.125 mg.kg-1 provide no additional benefit. Heterozygous patients with atypical plasma cholinesterase levels, as well as certain individuals with normal dibucaine numbers and plasma cholinesterase activity, are at risk for prolonged neuromuscular block, but the block is easily reversed with edrophonium.
 ...
PMID:Edrophonium requirements for reversal of deep neuromuscular block following infusion of mivacurium. 859 May 11


<< Previous 1 2 3 4 5 Next >>