Pharmacology for Anaesthesia and Intensive Care

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Section IICoredrugs in anaesthetic practice

Table 11.1.Characteristics of partial neuromuscular blockade.

Partial depolarizing or

Phase I block

Partial non-depolarizing or

Phase II block

Single twitch reduced reduced

Train-of-four ratio (T 4 :T 1 ) >0.7 <0.7

1Hzstimulus sustained fade

Post-tetanic potentiation no yes

Effect of anticholinesterases block augmented block antagonized

rapidly. It can be thought of as two molecules of ACh joined back to back through

their acetyl groups.

Presentation and uses

Suxamethonium is formulated as a colourless solution containing 50 mg.ml−^1 and

should be stored at 4◦C. It is used to achieve rapid muscle relaxation required during

rapid sequence induction and has also been used by infusion to facilitate short

surgical procedures.

Mechanism of action

Suxamethonium mimics the action of ACh by attaching to the nicotinic ACh receptor

and causing membrane depolarization. However, because its hydrolyzing enzyme

(plasma or pseudo-cholinesterase) is not present at the NMJ its duration of action

is longer than that of ACh. The persistent depolarization produced initiates local

current circuits that render the voltage-sensitive Na+channels within 1–2 mm inac-

tive. This area of electrical inexcitability prevents the transmission of further action

potentials resulting in muscle relaxation.

Initially this depolarizing block is described as a Phase I block; however, if further

doses of suxamethonium are given it may become a Phase II block. The character-

istics of a Phase II block are similar to those of a non-depolarizing block, but the

mechanism is thought to be different (probably a pre-synaptic effect) (Table11.1,

Figure11.3).

Kinetics

Suxamethonium is rapidly hydrolyzed by plasma or pseudo-cholinesterase (an

enzyme of the liver and plasma – none being present at the NMJ), to such an extent

that only 20% of the initial intravenous dose reaches the NMJ, so that the rate of

hydrolysis becomes a critical factor in determining the duration of the neuromus-

cular block. Suxamethonium is hydrolyzed to choline and succinylmonocholine,

which is weakly active. Succinylmonocholine is metabolized further by plasma

cholinesterase to succinic acid and choline. Because metabolism is rapid, less than

10% is excreted in the urine (Figure11.5).