Pharmacopoeias. In China Europe Japan, and US.
European Pharmacopoeia, 6th ed., 2008 and Supplements 6.1 and 6.2 (Tubocurarine Chloride). A white or slightly yellowish crystalline powder. Soluble in water and in alcohol; practically insoluble in acetone; dissolves in solutions of alkali hydroxides. A 1% solution in water has apH of 4.0 to 6.0. Store in airtight containers.
The United States Pharmacopeia 31, 2008, and Supplements 1 and 2 (Tubocurarine Chloride). A white or yellowish-white to greyish-white, crystalline powder. Soluble 1 in 20 of water and 1 in 45 of alcohol. Store in airtight containers.
Adverse Effects, Treatment, and Precautions
As for competitive neuromuscular blockers in general (see Atracurium). A transient fall in blood pressure commonly occurs, due in part to ganglionic blockade and the release of histamine; there may be an increase in heart rate. Tubocurarine has a greater propensity to cause histamine release than other competitive neuromuscular blockers in clinical use. Tubocurarine should be used with caution in patients with renal impairment. Resistance to the effect of tubocurarine may occur in patients with hepatic impairment.
For interactions associated with competitive neuromuscular blockers, see Atracurium.
Tubocurarine chloride is a quaternary ammonium compound and absorption from the gastrointestinal tract is extremely poor. Absorption is slow and irregular when given intramuscularly. After intravenous injection tubocurarine is widely distributed throughout body tissues; less than 50% is bound to plasma proteins.
After a single dose extensive redistribution to tissues is responsible for the termination of activity, but after a large single dose or repeated small doses tissue saturation occurs and renal excretion becomes the main determinant of duration. When given in usual doses it does not pass the blood-brain barrier, and does not appear to cross the placenta in significant amounts. Up to 75% of a dose is excreted unchanged in the urine in 24 hours, and up to 12% in bile. Biliary excretion is increased in renal impairment. A small proportion of a dose is metabolised in the liver.
Uses and Administration
Tubocurarine is a benzylisoquinolinium competitive neuromuscular blocker (see Atracurium). It may be obtained from extracts of the stems of Chondodendron iomeniosum (Menispermaceae) and is one of the active principles of curare, by which name it is sometimes referred to in anaesthetic literature. Tubocurarine chloride is the chloride of (+)-tubocurarine. After intravenous injection of tubocurarine chloride neuromuscular block appears within 1 minute and lasts for about 30 minutes; the maximum effect is attained within 2 to 5 minutes. Tubocurarine chloride has been used similarly to other competitive neuromuscular blockers to produce muscle relaxation in various procedures but has largely been replaced by other drugs with fewer cardiovascular effects and a lower potential for histamine release.
Doses used have varied according to the degree of muscle relaxation required. Doses of neuromuscular blockers need to be carefully titrated for individual patients according to response, and may vary with the procedure, the other drugs given, and the state of the patient; monitoring of the degree of block is recommended in order to reduce the risk of overdosage. An initial dose of 6 to 9 mg intravenously has been suggested followed by 3 to 4.5 mg after 3 to 5 minutes if necessary; additional doses of 3 mg may be given as required for prolonged procedures. Higher doses have been given in some countries. It has also been given intramuscularly but absorption is slow and erratic. Tubocurarine should be given with caution in reduced doses to patients with renal impairment; if large or repeated doses are given neuromuscular block may be prolonged.
Tubocurarine chloride has also been used to control the muscle spasms of tetanus.
The United States Pharmacopeia 31, 2008, and Supplements 1 and 2: Tubocurarine Chloride Injection.
Israel: Curarine; Tubarine