Suxamethonium

Acetylcholine nicotinic (LGIC) Na+, K+ and Ca2 + conductance Nicotine, suxamethonium Tubocurarine, a-conotoxins, a-bungarotoxin... 

C4H,N0 108-01-0) see Aclatonium napadisilate Bromazine Chloroquine Deanol acetamidobenzoate Diphenhydramine Medrylamine Orphenadrine Pirisudanol Quinisocaine Suxamethonium chloride Tetracaine Tromanladine... 

CH3CI 74-87-3) see Atropine methonitrate Clobazam Dimethyltubocurarinium chloride Methylmethionine sulfonium chloride Naproxen Suxamethonium chloride methyl chloroacetate... 

To explain the possible differences observed regarding the risk of allergic reactions with the different NMBAs, it has been suggested that the flexibility of the chain between the ammonium ions as well as the distance between the substituted ammonium ions might be of importance in the elicitation of mediator release [16]. Suxamethonium is a linear flexible chain. 

Clinical observations of such inherited differences in drug effects were first documented in the 1950s, as shown by the relationship between prolonged muscle relaxation after suxamethonium and an inherited deficiency of plasma choline esterase [2]. Some psychiatric patients were found to be unusually susceptible to suxametho-... 

Suxamethonium sensitivity, due to atypical serum pseudocholinesterase Frequency 1/2000 Caucasians... 

Consequence prolonged respiratory paralysis on exposure to the drug Suxamethonium (succinylcholine) for muscle relaxation for anesthesia Slow acetylator phenotype, due to mutations in liver N-acetylase transferase,... 

Suxamethonium sensitivity," prolonged paralysis of respiratory muscle function caused by failure to cleave the short-acting muscle relaxant succinylcholine widely used in anesthesia, was made testable with a simple bedside assay in 1968 (Motulsky and Morrow). However, that test was not incorporated widely into practice. Most anesthesiologists felt they could simply monitor all patients and "bag" those not resuming respiratory action, without testing for a trait that would be found in only one of 2000 patients. 

Study participation, treatment development based on, 8 Study populations, describing, 149 Subscriber agreements, 122 Succinylcholine, 60, 165, 168 Survey Questionnaire, General Population, 337-348 Susceptibility alleles, 52 Susceptibility genes, 44, 86 Susceptibility testing, 181, 306-307 Suter, Sonia, 17 Suxamethonium, 89, 139-140 Syphilis study, 68... 

A typical example is succinylcholine (suxamethonium, 7.62), although the discovery of this agent predates by decades the concept of soft drugs. In most individuals, this curarimimetic agent is very rapidly hydrolyzed to choline by plasma cholinesterase with a tm value of ca. 4 min [76] [134],... 

It is certain that pancuronium is but the first of a series of steroids of this type There is l or example, need for an agent with its favourable properties but with the brevity ot action of suxamethonium. Achievement of this aim may not be too distant since quaternary derivatives of the alkaloid conessine, possessing (in cats at least) the required characteristics have recently been described [75], and dacuronium bromide is now under intensive study by the team responsible for the development of pancuronium. 

The place of the dmg in dentistry [153 4] and in electro-convulsive therapy [ 154] (with a description of a technique to surmount difficulties arising from the concurrent use ot suxamethonium) has been evaluated. A refined radio telemetric technique has enabled a detailed study [155] of the cardiovascular effects of propanidid to be made, resulting in strong evidence for a transient procainamide- or quinidine-like depression of myocardial conductive tissue. The above publications [150-5] quote a large number of relevant references. 

The production of a quaternary ammonium salt from a tertiary amine and an alkyl halide forms the synthetic route to decamethonium, the first of a range of synthetic muscle relaxants having an action like the natural materials found in the arrow-poison curare. Decamethonium is actually a di-quaternary salt, as are more modem analogues, such as suxamethonium. Suxamethonium superseded decamethonium as a drug because it has a shorter and more desirable duration of action in the body. This arise because it can be metabolized by ester-hydrolysing enzymes (esterases) (see also Box 6.9). 

Recent developments have led to agents with a built-in functional group that allows more rapid metabolism. Initially, the presence of ester groupings, as in suxamethonium, allowed fairly rapid metabolism in the body via esterase enzymes that hydrolyse these linkages. The enzyme involved appears to be a non-specific serum acetylcholinesterase (see Box 13.4). Even better is the inclusion of functionalities that allow additional degradation via an elimination reaction. Such an agent is atracurium. 

In this drug class, only sucdnylcholine (succinyldicholine, suxamethonium, AJ is of clinical importance. Structurally, it can be described as a double ACh molecule. Like ACh, succinylcholine acts as agonist at endplate nicotinic cholino-ceptors, yet it produces muscle relaxation. Unlike ACh, it is not hydrolyzed by acetylcholinesterase. However, it is a substrate of nonspecific plasma cholinesterase (serum cholinesterase, p. 100). 

Intramuscular injections have been shown to produce elevations in serum enzyme activities presumably due to either inflammatory areas in the muscle or actual breakdown of cells and release of enzyme. In one study, preinjection values of creatine phosphokinase were in the normal range of 24-100 units. Multiple intramuscular injections of penicillin, diuretics, and narcotics every 6 hours caused the creatine phosphokinase values to rise to levels between 160 to 240 units, or up to 2.5 times the upper limit of normal. When the injections were stopped, the creatine phosphokinase values returned to normal within 48 hours (B7). Similar observations of aspartate aminotransferase activities were made in patients receiving intramuscular injections of penicillin every 4 hours. Activities rose to values as high as 200 units. Other workers have reported injection related serum creatine phosphokinase elevations following intramuscular administration of chlorpromazine and suxamethonium (HIO, M11,T6). 

T6. Tummistor, T., and Airaksinen, M. N., Increase of creatine kinase activity in serum caused by intermittently administered suxamethonium. Brit. J. Anaesth. 38, 510 (1966). 

A decrease in stability is often a desirable modification. For example, succinylcholine (suxamethonium 3.25) — a neuromuscular blocking agent used in surgery — has a self-limiting activity, since the ester is hydrolyzed in about 10 minutes, preventing the potential for overdose, which could be fatal with more stable curarizing agents. 

Suxamethonium is the only agent from this class of drugs in current use. Depolarising drugs are agonists at the nicotinic receptor and, like ACh, produce depolarisation at the endplate. However, since the breakdown of suxamethonium is not as rapid as that of ACh, the receptor is held in a prolonged depolarised state which is unresponsive to further stimulation until suxamethonium has been metabolised. 

Suxamethonium produces a typical depolarising block that is characterised by the appearance of fasciculations before the onset of block, absence of fade in response to tetanic and TOP stimulations, and potentiation of block by anticholinesterase drugs. 

Maximum block after suxamethonium develops in 60-90 seconds following a dose of 1 mg-kg-1 (about 3xED95) with a duration of action of 5-10 minutes. This dose provides near ideal intubating conditions in 60-90 seconds. It is because of a rapid onset and a short duration of action that suxamethonium is considered as the ideal agent for facilitating tracheal intubation during rapid sequence induction. 

The pharmacokinetics of suxamethonium are difficult to estimate due to its rapid metabolism. However, its half-life has been indirectly estimated at between 16 seconds and 4 minutes. 

The use of suxamethonium is associated with a range of side effects (Table 6.2). Some of these, such as myalgias, are inconvenient and troublesome while others, such as anaphylaxis... 

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