Megaloblastic Anæmia Due to Phenytoin Sodium

Rhind, E.G.; Varadi, S.

doi:10.1016/s0140-6736(54)92647-1

Cited by 25 publications

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“…Two cases of megaloblastic anaemia occurring in epileptics who had been taking phenobarbitone and phenytoin were reported by Badenoch (1954), who suggested that the anticonvulsants-might have played a part in the production of the anaemia. Other cases have been reported by Hawkins and Meynell (1954), Chalmers and Boheimer (1954), and Rhind and Varadi (1954).…”

mentioning

confidence: 71%

“…In only one case, that of Rhind and Varadi, has there been evidence of malabsorption, and even this was inconclusive. The normal vitamin B12 serum levels in those cases in which this has been determined (Badenoch, 1954;Chalmers and Boheimer, 1954;Rhind and Varadi, 1954), and the excellent response to folic acid, suggest that this anaemia is essentially a folic acid deficiency, whatever its precise mechanism. It is extremely difficult to produce a folic acid deficiency in the experimental animal, but, in man, megaloblasts have occasionally been found in the bone marrow in cases of acute leukaemia treated by aminopterin (Stickney, 1952).…”

Section: Discussionmentioning

confidence: 91%

“…Recently, megaloblastic anaemia has been reported in patients who had been receiving anticonvulsants (Badenoch, 1954;Hawkins and Meynell, 1954;Chalmers and Boheimer, 1954;Rhind and Varadi, 1954).…”

Section: Discussionmentioning

confidence: 99%

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Megaloblastic Anaemia Following Anticonvulsants

Berlyne¹,

Levene²,

Mcglashan³

1955

BMJ

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confidence: 71%

Section: Discussionmentioning

confidence: 91%

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Megaloblastic Anaemia Following Anticonvulsants

Berlyne¹,

Levene²,

Mcglashan³

1955

BMJ

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“…Since that time I have had three other examples of anaemia of a similar character resulting from phenytoin, though one of these has also received primidone, and my experience adds nothing, except numbers, to that of Gydell andothers (Hawkins andMeynell, 1954, 1956;Chalmers and Boheimer, 1954;Rhind and Varadi, 1954;Webster, 1954;Berlyne et al, 1955;Ryan and Forshaw, 1955). In a few of these recorded examples extensive investigation has shown that the serum B12 level and the absorption of folic acid were normal; all have responded to folic acid by mouth and only four to vitamin B12 by injection, though in the case of two of the latter the withdrawal of phenytoin may have been responsible for the improvement (Webster, 1954; Ryan and Forshaw, 1955) whilst one other (Chalmers and Boheimer, 1954) may have had coincidental pernicious anaemia.…”

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confidence: 89%

Discussion on the Toxic Effects of Drugs Used in Neurological and Psychiatric Practice

1957

Proceedings of the Royal Society of Medicine

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Drugs Used in the Management of Epilepsy It would be of some interest to know how many patients are being treated for epilepsy at any one moment, the incidence of epilepsy, very broadly defined, in Great Britain usually being considered to be about 250,000 persons. Through the kind cooperation of the Leeds Executive Council a group of general practitioners was circularized and information obtained relating to a population of about 300,000. 800 epileptic patients were reported to be under treatment, an incidence of 2-5 patients per 1,000 population. This suggests that the number of epileptics under treatment in Great Britian (population approx. 50,000,000) is about 125,000, which is perhaps only half of all epileptics. My personal figures relate to a survey of over 2,000 epileptic patients seen in the Neurological Department of the General Infirmary at Leeds, and in private practice, between the years 1948 and 1956. The dominant problems arose in connexion with the hydantoins, the bromides, primidone and the diones. In this group only two examples of barbiturate intoxication were seen, which illustrates the wide margin of safety between the therapeutic and toxic doses of the barbiturates. The hydantoins.-During the initial stages of treatment the signs and symptoms of intoxication with sodium phenytoin are the result of gastric irritation, giving rise to anorexia, nausea and vomiting, or to individual idiosyncrasy reflected in the skin by rashes which may resemble those of measles or scarlet fever. The former may be avoided by giving the drug after meals, whilst, if small doses are given initially and later increased, the incidence of dermatological complications is said not to exceed 5% (Tullidge and Fox, 1942; Symonds, 1950) and in my experience the incidence has been even less. The most important toxic phenomena are referable to dysfunction of the cerebellum with resulting dysarthria, nystagmus and ataxia, with or without disturbance of mentation and behaviour. In 31 patients symptoms and signs of this nature occurred and were of sufficient severity to warrant admission to hospital. It was possible in only 4 to incriminate overdosage and in another 3, who developed their disability within the first few days of treatment, individual hypersensitivity seemed to be the predominant factor. The greater proportion, however, had received sodium phenytoin and phenobarbitone or phemitone (Prominal) for many years in unvarying quantities and had developed evidence of toxicity for no apparent reason. This would seem to indicate that either detoxication or excretion varies from time to time in any one individual and may occasionally lead to the accumulation of an excessive quantity of phenytoin. In others it is clear that there is a very narrow margin between the therapeutic and the toxic doses, and 6 patients developed toxic symptoms after their daily intake was increased from 3 to 4j grains. More rarely the addition of primidone may provoke phenytoin toxicity although the dose of the latter drug is not altered. Mental dis...

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“…In [953 primidone, one gramme per day, was commenced, and in 1954 to this was added phenytoin and :\leynell, 1954 .. Rhind and Varadi, 1954Berlyne, Levene and :\IcClashan, '955 Vaishnava, 1955Hurwitz, 1956Girdwood, 1956 ----- Girdwood and Lenman, 1956 I Phenobarbitone…”

Section: Case Reportmentioning

confidence: 99%

Megaloblastic Anæmia Associated With Anticonvulsant Drug Therapy

Stokes

Fortune

1958

Australasian Annals of Medicine

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Summary An epileptic boy of 16 years developed megaloblastic anæmia while being treated with primidone and phenytoin. There was an optimal hæmatological response to folic acid therapy. Laboratory investigations showed a normal serum concentration of vitamin B12 and normal radioactive vitamin B12 absorption. This is the thirty‐third reported case of megaloblastic anæmia associated with anticonvulsant therapy. Certain features common to the majority of these cases suggest that a folic acid deficiency or a derangement of folic acid metabolism is responsible for the megaloblastic anæmia. All 20 patients treated with folic acid responded optimally. Eight patients are reported to have responded to vitamin B12, one to liver extract and four to a combination of folic acid and vitamin B12. It is suggested that the anticonvulsant drugs have an antifolic acid action which is too mild to produce megaloblastic anæmia in the majority of epileptics unless one or more co‐factors operate. A suboptimal folic acid intake is postulated as the main co‐factor in at least five of the 20 cases in which there was a response to folic acid and perhaps also in some of the cases in which a response has been reported to vitamin B12. In one case repeated hæmorrhage, in another pregnancy and in a third case a possible latent steatorrhœa are postulated as additional co‐factors.

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Megaloblastic Anæmia Due to Phenytoin Sodium

Cited by 25 publications

References 0 publications

Megaloblastic Anaemia Following Anticonvulsants

Megaloblastic Anaemia Following Anticonvulsants

Discussion on the Toxic Effects of Drugs Used in Neurological and Psychiatric Practice

Megaloblastic Anæmia Associated With Anticonvulsant Drug Therapy

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