Pharmacology for Anaesthesia and Intensive Care

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9780521704632c11 CUFX213A/Peck 9780521618168 December 28, 2007 12:5

Section IICoredrugs in anaesthetic practice

Table 11.4.Properties of some non-depolarizing muscle relaxants.

Intubating

dose

(mg.kg−^1 )

Speed of

onset Duration

Cardiovascular

effects

Histamine

release

Vecuronium 0.1 medium medium none/bradycardia rare

Rocuronium 0.6 rapid medium none rare

Pancuronium 0.1 medium long tachycardia rare

Atracurium 0.5 medium medium none slight

Cis-atracurium 0.2 medium medium none rare

Mivacurium 0.2 medium short none slight

Gallamine 2.0 fast medium tachycardia rare

Tubocurarine 0.5 slow long hypotension common

the liver by de-acetylation to 3- and 17-hydroxy and 3,17-dihydroxy-pancuronium,

the former of which is half as potent as pancuronium. Unchanged drug is eliminated

mainly in the urine while its metabolites are excreted in bile.

Tubocurarine (dTC)

Curareis a generic term used to describe various alkaloids from the plant species

Chondrodendron.Itwas used in South America to poison the tips of hunting arrows.

Tubocurarine, which was first used as an aid to anaesthesia in 1942, is a mono-

quaternary alkaloid with a tertiary amine group, which is largely protonated at body

pH.

Presentation and uses

Tubocurarine is presented as a colourless solution containing 10 mg.ml−^1 .At

0.5 mg.kg−^1 intubating conditions are reached within 3 minutes. Its duration of action

is about 40 minutes, but this is variable.

Other effects


Cardiovascular – dTC causes the greatest degree of autonomic ganglion blockade

and histamine release of all the non-depolarizing muscle relaxants, which results

in a fall in blood pressure. Reflex tachycardia is uncommon due to the ganglion

blockade. It appears to protect against arrhythmias.


Gut–itincreases salivation.


Toxicity – anaphylaxis is associated with its use.

Kinetics

dTC is 30–50% protein bound. Under acidic conditions the tertiary amine group (pKa

8.0) becomes increasingly protonated, resulting in increased potency. However, as

pH varies, [K+]also varies, which alters the membrane potential and may offset