Pharmacology for Anaesthesia and Intensive Care

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11 Muscle relaxants and anticholinesterases

Safedrugs

These include opioids, thiopental, propofol, etomidate, ketamine, benzodiazepines,

atropine, local anaesthetics and N 2 O.

Patients suspected of having MH should be referred to the UK MH investigation

unit in Leeds.

Dantroleneis used in the treatment (and prophylaxis) of MH, neuroleptic malig-

nant syndrome, chronic spasticity of voluntary muscle and ecstacy intoxication. It

is available as capsules and in vials as an orange powder containing dantrolene

20 mg, mannitol 3 g and sodium hydroxide. Each vial should be reconstituted with

60 ml water producing a solution of pH 9.5. It is highly irritant when extravasated

and a diuresis follows intravenous administration reflecting its formulation with

mannitol. Chronic use is associated with hepatitis and pleural effusion.

Mechanism of action

Dantrolene uncouples the excitation contraction process by binding to the ryanodine

receptor thereby preventing the release of Ca^2 +from the sarcoplasmic reticulum in

striated muscle. As vascular smooth muscle and cardiac muscle are not primarily

dependent on Ca^2 +release for contraction, they are not usually affected. It has no

effect on the muscle action potential and usually has little effect on the clinical dura-

tion of the non-depolarizing muscle relaxants. It may, however, produce respiratory

failure secondary to skeletal muscle weakness.

Kinetics

Oral bioavailability is variable and it is approximately 85% bound in the plasma to

albumin. It is metabolized in the liver and excreted in the urine.

Prolonged block (suxamethonium apnoea)

Plasma cholinesterase activity may be reduced due to genetic variability or acquired

conditions, leading to prolonged neuromuscular block. Single amino acid sub-

stitutions are responsible for genetically altered enzymatic activity. Four alleles –

usual (normal), atypical (dibucaine-resistant), silent (absent) and fluoride-resistant

• have been identified at a single locus of chromosome 3 and make up the 10 geno-
  types.
  Ninety-six percent of the population is homozygous for the normal Eu gene and
  metabolize suxamethonium rapidly. Up to 4% may be heterozygotes resulting in a
  mildly prolonged block of up to 10 minutes while a very small fraction may have
  agenotype that confers a block of a few hours. This prolonged block may be
  reversed by administration of fresh frozen plasma, which provides a source of plasma
  cholinesterase. Alternatively the patient may be sedated and ventilated while the
  block wears off naturally.