Effect of Nephrectomy on Duration of Action of Barbitals

Hirschfelder, Arthur D.; Haury, Victor G.

doi:10.3181/00379727-30-6792

Cited by 7 publications

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“…Similarly, Hirschfelder and Haury (1933) found that bilateral nephrectomy markedly increased the effect of phenobarbitone in rabbits. These and other workers, therefore, consider that soluble phenobarbitone is eliminated through the kidney and not detoxicated to a significant extent by the liver.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Hepatectomy on the Action of Certain Anaesthetics in Rats

Walker

Parry

1949

British Journal of Pharmacology and Chemotherapy

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To investigate the role of the liver in the detoxication of anaesthetics, two main methods are available. First, the liver may be damaged by some drug such as carbon tetrachloride; if the anaesthetic has a greater effect than before, it is probable that it is normally detoxicated by the liver. This method is open to at least two objections. In the first place, it is impossible accurately to assess the amount of liver damaged by this means; and further it is possible that the carbon tetrachloride has some action of its own on the central nervous system. The second method, which we have used, is to remove by operation a large proportion of the liver and observe whether the effect of the anaesthetic is increased. This method has the advantage that the amount of liver tissue removed can be estimated fairly accurately, and it is unlikely that the operation has g.6 any complicating sideeffects.Higgins and - Anderson (1931) quent intervals the rat was laid on its side, and when it remained in this position it was considered to be asleep. As soon as it got to its feet it-was considered awake, and the sleeping-time was thus determined. At least five days later partial hepatectomy was carried out by the method of Higgins and Anderson (1931). The animals withstood the operation well, the mortality being about 10 per-cent, and by the third day after operation appeared perfectly normal. For 24 hours after operation they were fed on bread and milk and 20 per cent glucose. Thereafter they were given the normal laboratory diet. On a chosen day after hepatectomy, the rat was given the same dose of drug as before, and the sleeping-time again determined in the same way. The experiment was planned to give at least 10 results on each of the following days after hepatectomy: 6th-7th, 8th-9th, 10th, 12th, 15th, 17th-18th, 20th, 22nd, and 26th-28th. The mean sleeping-time of the rats on each of these days after

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Section: Discussionmentioning

confidence: 99%

The Effect of Hepatectomy on the Action of Certain Anaesthetics in Rats

Walker

Parry

1949

British Journal of Pharmacology and Chemotherapy

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“…The rate of elimination was 18-25 % per 24 h and it was about 75 % per 24 h in rats (3,7). Functioning kidneys seem to be essential for the detoxification of phenobarbital (12). Eleven to twenty-five per cent of the dosage given are excreted unchanged in the urine (for references see 20).…”

Section: Findings In Animal Experimentsmentioning

confidence: 99%

“…Most of the phenobarbital is converted to an inactive compound, 5-ethyl-5-(p-hydroxyphenyl) barbituric acid which appears in the urine of dogs as the glucuronide (4, 5). Functioning kidneys seem to be essential for the detoxification of phenobarbital (12).…”

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confidence: 99%

Aspects of the Pharmacology of Phenytoin (Dilantin®) and Phenobarbital Relevant to their Dosage in the Treatment of Epilepsy

Buchthal

Svensmark

1959

Epilepsia

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SUMMARY AND CONCLUSIONS Findings are reviewed concerning the distribution and fate of phenytoin and pheno‐barbital in animals and in man. The serum concentration of these drugs can be considered an adequate expression of their concentration in the brain and hence of their anticonvulsant effect. The serum level increased approximately linearly with increasing dose, 1 mg/kg phenytoin by mouth giving about 3 μg/ml in the serum and 1 mg/kg phenobarbital giving about 10 μg/ml in the serum. The scatter of the ratio of level to dosage was greater for phenytoin than for phenobarbital. In most of the patients who had taken phenytoin for several years the serum level per mg/kg given was above 3 μg/ml per mg/kg. In the individual patient it may therefore be difficult to predict the serum concentration from the amount given and the determination of serum phenytoin has proved of considerable value for the institution and maintenance of therapy. In patients who were given only phenytoin, clinical and electroencephalographic improvement was not observed with serum concentrations below 10 μg/ml. Convulsions in most patients with severe grand mal epilepsy were controlled or significantly reduced in number when the dosage was adjusted so that the serum concentration was about 15 μg/ml (0.3–0.4 g daily to a 70 kg patient). For patients who were on phenobarbital only no information is available as to the correlation between serum level and anticonvulsant effect. In institutionalized patients who had been given combined phenytoin and phenobarbital medication for years serum levels averaged 18 μg/ml of phenytoin and 20 μg/ml of phenobarbital. In patients who had not previously received phenytoin it took about a week to reach a level of 10–15 μg/ml. The time required for the serum concentration to become at equilibrium increased with increasing dosage. With phenobarbital it took still longer, a level of 20 μg/ml being reached after about 1 month. The rate of fall after withdrawal of the drug was about proportional to the serum concentration, the rate of elimination being 35–55 % for phenytoin and 11–25 % for phenobarbital per 24 h. When a serum level had been attained the maximum variation between two daily doses given by mouth at twelve hour intervals did not exceed 10% for phenytoin and was still less for phenobarbital. Thus the administration of phenytoin more often than twice a day and of phenobarbital more often than once a day is unnecessary. Toxic side‐effects (fatigue and signs of incoordination) were not seen with phenytoin serum concentrations below 14 μg/ml. Half of the patients with phenytoin serum levels of 30 μg/ml showed side‐effects. Gum hyperplasia is not included in this compilation. Its occurrence was not correlated to the phenytoin concentration in saliva. The development of an increased tolerance to phenytoin is indicated by the more frequent occurrence of side‐effects in patients who had been given phenytoin treatment for less than six months as compared with those who had been given a longer treatment. With pheno...

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Surgical Treatment for Cirrhosis

Cates¹

1943

Arch Intern Med (Chic)

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Effect of Nephrectomy on Duration of Action of Barbitals

Cited by 7 publications

References 0 publications

The Effect of Hepatectomy on the Action of Certain Anaesthetics in Rats

The Effect of Hepatectomy on the Action of Certain Anaesthetics in Rats

Aspects of the Pharmacology of Phenytoin (Dilantin®) and Phenobarbital Relevant to their Dosage in the Treatment of Epilepsy

Surgical Treatment for Cirrhosis

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