The effect of liver damage on the action of some barbiturates

Cameron, G. R.; Saram, G. S. W. De

doi:10.1002/path.1700480107

Cited by 25 publications

(5 citation statements)

References 5 publications

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“…Three points are advanced in support of this belief: First, patients with advanced liver disease have remained comatose for long periods of time after receiving a barbiturate; second, animals after chloroform induced hepatic damage or partial liver extirpation have shown an increased sensitivity to anesthetic doses of barbiturates (1,2); and third, animals are alleged to show a greater than normal retention of pentobarbital and barbital in their blood and tissues after chloroform anesthesia (3). These points of evidence, however, are far 'from conclusive.…”

mentioning

confidence: 98%

The Effect of Barbiturates in Patients With Liver Disease 1

Sessions¹,

Minkel²,

Bullard³

et al. 1954

J. Clin. Invest.

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Although sedatives are frequently required in the treatment of patients with liver disease, barbiturates are believed to be contraindicated in the face of impaired hepatic function. Three points are advanced in support of this belief: First, patients with advanced liver disease have remained comatose for long periods of time after receiving a barbiturate; second, animals after chloroform induced hepatic damage or partial liver extirpation have shown an increased sensitivity to anesthetic doses of barbiturates (1, 2); and third, animals are alleged to show a greater than normal retention of pentobarbital and barbital in their blood and tissues after chloroform anesthesia (3). These points of evidence, however, are far 'from conclusive. The natural progression of hepatic coma from a stage of restlessness to one of somnolence, and the spontateous fluctuations that occur in the course of liver disease reduce the significance of temporal correlations in determining the part any single factor plays in causing hepatic coma. As far as animal experiments are concerned, they are not necessarily applicable to man, particularly if the type of liver damage and the barbiturate dosage are not comparable to the usual clinical situation. Finally, methods of barbiturate analysis are difficult and non-specific. Since the evidence incriminating the use of barbiturates in liver disease seemed circumstantial, a study to obtain direct evidence was undertaken. Three questions in particular seemed worthy of consideration:

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mentioning

confidence: 98%

The Effect of Barbiturates in Patients With Liver Disease 1

Sessions¹,

Minkel²,

Bullard³

et al. 1954

J. Clin. Invest.

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“…Generally speaking, the long-acting compounds are eliminated from the body almost entirely by the kidneys, the liver playing a minor role. This certainly appears to be the case with barbital (Pratt et aE., 1932;Pratt, 1933; Cameron and de Saram, 1939). The short-acting barbiturates are mainly destroyed by the liver, although small amounts may be eliminated by the kidneys or dealt with by other tissues (Pratt, 1933 Goodman and Gilman, 1941; Richards and Appel, 1941).…”

Section: Discussionmentioning

confidence: 98%

The effect of castration on the action of some barbiturates

Cameron

Cooray

1948

J. Pathol.

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“…Cameron and De Saram (1939) found that there was no significant prolongation of its action in rats after acute liver damage caused by carbon tetrachloride. Masson and Beland (1945) stated that the anaesthetic effect of phenobarbitone was not increased by partial hepatectomy, whereas after bilateral nephrectomy rats slept for over twice as long as the controls.…”

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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The effect of liver damage on the action of some barbiturates

Cited by 25 publications

References 5 publications

The Effect of Barbiturates in Patients With Liver Disease 1

The Effect of Barbiturates in Patients With Liver Disease 1

The effect of castration on the action of some barbiturates

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

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