Specific Pharmacology

Here, units used (unless stated separately) are:

Volume of distribution at steady state (Vd) (ml/kg) Clearance (Cl) (ml/kg/min) Terminal half life (t1/2) (min)

Non Depolarizing Drugs

Atracurium Dibesylate

Structure—bisquaternary nitrogenous plant derivative

Presentation—clear, colourless, aqueous solution of pH 3.5 (10 mg/ml, 2.5, 5,25 ml ampoules). Storage—in fridge at 2-8° C, protect from light

Dose—IV bolus 0.3-0.6 mg/kg, infusion 0.3-0.6 mg/kg/h. Initial dose lasts 30 min, ED95 = 0.2 mg/kg Pharmacokinetics

Protein binding Vd Cl

CNS—no increase in intra-ocular pressure (IOP) or intracranial pressure (ICP). Laudanosine, a metabolite and stimulant crosses the blood brain barrier and can cause convulsions if plasma concentration > 20 pg/ml

CVS—the small amount of histamine release may lower systemic vascular resistance, central venous pressure and pulmonary capillary wedge pressure

RS—paralysis of respiratory muscles; small risk of bronchospasm due to histamine release

Other—no effect on lower oesophageal sphincter pressure; placental transfer insufficient to cause an effect in the foetus

Elimination—non cumulative. Hofmann elimination is the spontaneous fragmentation of atracurium at the bond between the quaternary nitrogen and the central chain. This occurs at body temperature and pH, producing inactive products—laudanosine (t1/2 = 234 min) and a quaternary monoacrylate (t1/2 = 39 min). Atracurium is also metabolized by ester hydrolysis producing a quaternary alcohol and a quaternary acid. These two mechanisms account for 40% of the elimination of atracurium, the remainder being by a variety of other mechanisms

Metabolites—55% excreted in the bile within 7 H, 35% excreted in the urine within 7 H

Side effects—histamine release may cause bronchospasm, hypotension, and erythema and wheals generally or along the vein of injection

CIS-Atracurium Besylate

Atracurium contains a mixture of isomers. One of these, cis-cis-atracurium is marketed as cis-atracurium. The features are as for atracurium except:

Dose—IV bolus 0.15 mg/kg; infusion 3 mcg/kg/min

This single isomer of atracurium avoids the histamine release but is similar to atracurium in other respects.

Doxacurium Chloride

Structure—bisquaternary benzylisoquinolinium Presentation—not available in the UK

Dose—IV bolus 0.05 mg/kg. Initial dose lasts 80-90 min. Can be antagonized within 10 min. ED95 30 mcg/kg

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