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Study of the fate of curare (dextro-tubocurarine chloride) in the body

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AalMMA_1949redux.pdf (13.60Mb)
Date
1949
Author
Aal, Mohamed Mahfouz Abdel
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Abstract
 
 
1. The method described by Jalon for estimating tubocurarine by its action on the frog's rectus abdominus, was adopted for determining the drug equivalent of tissue extracts and biological fluids. This method was used to follow the fate of the drug in man and animals.
 
2. The immediate volume of distribution on intravenous injection corresponds to the plasma volume. The drug does not enter the blood cells. It disappears from the plasma exponentially with a halving time of about thirteen minutes. These conclusions apply both to man and to rabbits.
 
3. In the conscious human subject, a concentration of 4μg. per ml. in the plasma causes complete paralysis. A concentration of 1µg. per ml. has very little effect.
 
4. About 20-40% of the drug appears in the urine. This percentage may be increased by water diuresis. Excretion continues for several hours, even when the paralysis only lasts about half an hour.
 
5. The main route of disappearance of the drug from the body does not depend on the kidneys, since double nephrectomy in rats did no more than slightly delay full recovery from paralysis. By extracting whole mice, it was shown that about 60% of the dose was inactivated in the body within four hours.
 
Since subtotal hepatectomy in rats did not appreciably affect the duration of paralysis, the liver is probably not the main site of inactivation. It is possible that inactivation occurs in voluntary muscles, which were found to contain 40% of the dose in an experiment on rabbits.
 
6. The effective dose by oral administration in rats is about 100 times the effective dose by intramuscular administration. Absorption occurs in the small intestine but not in the stomach. On intravenous injection, appreciable quantities (12% of the dose) may be excreted in the stomch.
 
7. A rapid intravenous injection of tubocurarine usually causes bronchoconstriction in guinea-pigs.
 
A second injection has no such effect.
 
The effect may be prevented or interrupted by neoantergan and is probably due to the release of histamine. The best way to avoid this effect in the clinical use of tubocurarine is to give the injection slowly. Slow injections of large doses in guinea -pigs had no effect on the bronchi, although a dose ten to fifteen times smaller caused bronchoconstriction when given rapidly.
 
URI
http://hdl.handle.net/1842/26052
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