Folic-acid Studies in Megaloblastic Anaemia Due to Primidone

Chanarin, I.; Elmes, P. C.; Mollin, D. L.

doi:10.1136/bmj.2.5088.80

Cited by 46 publications

(15 citation statements)

References 6 publications

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“…The megaloblastic anaemia which occurred during phensuximide and phenobarbitone therapy was refractory to cyanocobalamin but responded promptly to folic acid. This finding is in agreement with the hypothesis of Girdwood and Lenman (1956) and Chanarin et al (1958) that megaloblastic anaemia due to anticonvulsant drugs does not result from tissue depletion of folic acid but arises from an interference with folic acid metabolism.…”

Section: Megaloblastic Anaemia During Combined Phensuximide and Phenosupporting

confidence: 93%

Megaloblastic Anaemia During Combined Phensuximide and Phenobarbitone Therapy

Doig¹,

Stanton²

1961

BMJ

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Section: Megaloblastic Anaemia During Combined Phensuximide and Phenosupporting

confidence: 93%

Megaloblastic Anaemia During Combined Phensuximide and Phenobarbitone Therapy

Doig¹,

Stanton²

1961

BMJ

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“…Although it is well established that megaloblastic haemopoiesis may occur as a complication of anticonvulsant therapy with phenytoin alone (Hawkins & Meynell, 1954), or primidone alone (Chanarin, Elmes & Mollin, 1958) or in combination with other drugs (Kidd & Mollin, 1957;Stokes & Fortune, 1958;Chanarin, Laidlaw, Loughridge & Mollin, 1960) none of the patients in the present study were found to be anaemic (Table 3) Folic acid deficiency in our patients was also assessed by the urinary excretion of FIGLU following histidine loading (Luhby, Cooperman & Teller, 1959). We found that 7 out of 14 patients receiving anticonvulsant drugs, 6 of 15 on phenothiazines, and 1 of 7 treated with tricyclic drugs, excreted amounts of FIGLU that were above the upper limit of the normal range (18 mg/24h).…”

Section: Discussionmentioning

confidence: 99%

The effects of chronic drug administration on hepatic enzyme induction and folate metabolism.

Labadarios¹,

Dickerson²,

Parke³

et al. 1978

Brit J Clinical Pharma

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1 Patients on prolonged treatment with anticonvulsant and phenothiazine drugs exhibited lower than normal concentrations of folate in serum and erythrocytes, and showed increased urinary FIGLU excretion after histidine loading; urinary excretion of D‐glucaric acid was also increased suggesting induction of the hepatic microsomal enzymes. 2 Folate deficiency by enzyme‐inducing drugs was seen to be determined more by the duration of therapy than by the nature of the drugs. Excretion of FIGLU was increased by 70% by 2‐5 years of treatment with anticonvulsant, phenothiazine or tricyclic drugs, and by 200% after 6 or more years. 3 Hepatic microsomal enzyme induction, as measured by D‐ glucaric acid excretion, was greatest after 2‐5 years treatment. 4 It is suggested that the increased requirements for folate, resulting from microsomal enzyme induction, lead to folate deficiency and this subsequently limits enzyme induction, leading to adverse drug side‐ affects. 5 The dietary folate of hospitalized patients would seem to be generally inadequate for patients on long term treatment with enzyme‐ inducing drugs.

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“…Most of these cases responded to folic-acid therapy. More recently Chanarin et al (1958) have studied folic acid utilization by measuring the rate of disappearance of this substance from the plasma in a case of megaloblastic anaemia caused by primidone. They showed that the rate of clearance of intravenously injected folic acid and its oral absorption were normal, and concluded that the anaemia was due to interference with the " tissue metabolism" of folic acid.…”

Section: Discussionmentioning

confidence: 99%