Effect of Griseofulvin in Acute Intermittent Porphyria

Redeker, Allan G.; Sterling, Rex E.; Bronow, Ronald S.

doi:10.1001/jama.1964.03060310066017

Cited by 29 publications

(5 citation statements)

References 3 publications

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“…Elevations in faecal protoporphyrins were found in patients receiving griseofulvin, but this was not related to sex, age or duration of therapy and its occurrence in any individual patient was not predictable. However, in patients with prior metabolic errors in their porphyrin metabolism 335 (Rimington et al 1963), precipitation of attacks such as acute intermittent porphyria (Berman & Franklin 1965;Redeker et al 1964) and porphyria cutanea tarda have been documented.…”

Section: Metabolic Effectsmentioning

confidence: 99%

Adverse Drug Reactions to Systemic Antifungals Prevention and Management

1992

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Systemic administration of antifungal agents for invasive mycoses has dramatically increased over the past 10 years in many fields of medicine. The increase has been due both to an increasing immune compromised population and to potent antibacterial agents which allow these fungi to invade tissue. It is apparent that our understanding of the use of both the old and new antifungal agents has significantly increased in the last few years. In this review, we attempt to document our extensive knowledge of the adverse effects of the polyenes, flucytosine, griseofulvin and azoles when given systemically for treatment. Interwoven in this documentation of the adverse reactions to these agents is the attempt to help clinicians potentially avoid some of these adverse effects and if they do occur, to be able to identify and successfully manage them.

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Section: Metabolic Effectsmentioning

confidence: 99%

Adverse Drug Reactions to Systemic Antifungals Prevention and Management

1992

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“…In the mouse liver, griseofulvin is metabolized by cytochrome P450 enzymes to produce griseofulvin-PPIX adducts and N -MPP; N -MPP inhibits FECH and causes the accumulation of hepatotoxic heme precursors 15 . Similar toxicity is observed in humans with congenital deficiencies in heme biosynthetic enzymes 16 , although the drug is well-tolerated in healthy individuals.…”

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confidence: 62%

Griseofulvin impairs intraerythrocytic growth of Plasmodium falciparum through ferrochelatase inhibition but lacks activity in an experimental human infection study

Smith

Jerkovic

Truong

et al. 2017

Sci Rep

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Griseofulvin, an orally active antifungal drug used to treat dermatophyte infections, has a secondary effect of inducing cytochrome P450-mediated production of N-methyl protoporphyrin IX (N-MPP). N-MPP is a potent competitive inhibitor of the heme biosynthetic-enzyme ferrochelatase, and inhibits the growth of cultured erythrocyte stage Plasmodium falciparum. Novel drugs against Plasmodium are needed to achieve malaria elimination. Thus, we investigated whether griseofulvin shows anti-plasmodial activity. We observed that the intraerythrocytic growth of P. falciparum is inhibited in red blood cells pretreated with griseofulvin in vitro. Treatment with 100 μM griseofulvin was sufficient to prevent parasite growth and induce the production of N-MPP. Inclusion of the ferrochelatase substrate PPIX blocked the inhibitory activity of griseofulvin, suggesting that griseofulvin exerts its activity through the N-MPP-dependent inhibition of ferrochelatase. In an ex-vivo study, red blood cells from griseofulvin-treated subjects were refractory to the growth of cultured P. falciparum. However, in a clinical trial griseofulvin failed to show either therapeutic or prophylactic effect in subjects infected with blood stage P. falciparum. Although the development of griseofulvin as an antimalarial is not warranted, it represents a novel inhibitor of P. falciparum growth and acts via the N-MPP-dependent inhibition of ferrochelatase.

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“…These workers demonstrated a porphyrin-like syndrome in mice as a result of griseofulvin administration, characterized in its early stages by increases in urinary ALA, PBG and coproporphyrin output, followed by increases in free erythrocyte protoporphyrin content. Griseofulvin is known to provoke an acute attack, as well as an increase in urinary uroporphyrin and coproporphyrin output, in patients suffering from acute intermittent hepatic porphyria (Redeker and Sterling 1964).…”

Section: Discussionmentioning

confidence: 99%

Porphyria in Childhood Following Transient Neonatal Quadriplegia

Gatfield

Haust

Durrant

1972

Develop Med Child Neuro

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SUMMARY A patient is described who had had transient severe paralysis in the neonatal period, followed by the discovery seven years later of increases in urinary ala and coproporphyrin and red‐cell protoporphyrin. The possibility that the metabolic defect could be due to lead poisoning is considered and rejected in favor of an unusual form of porphyria. Since the type of porphyrin abnormality found is unique, conclusions regarding its relationship to the neonatal illness are speculative. The presence of mental retardation and delayed bone development in this patient may also have been fortuitous. RÉSUMÉ Les auteurs rapportent le cas d'un mdlade ayant présenté une quadriplégie transitoire sévère durant la période néonatale suivie sept ans plus tard par la découverte d'une augmentation de Iala et des coproporphyrines urinaires et une protoporphyrie globulaire. L'éventualité que le défaut métabolique ait été provoqué par un empoisonnement par le plomb a été envisagée et rejetée en faveur d'une forme inhabituelle de porphyrie. Du fait que le type d'anomalie porphyrique est unique, les hypothèes sur les relations avec la maladie néonatale ne peuvent êre que spéculatives. L'association d'un retard mental et d'un retard de développement osseux peut également être fortuite. ZUSAMMENFASSUNG Es wird über einen Patienten berichtet, der in der Neugeborenenzeit vorübergebend eine schwere Tetraplegie hatte, und bei dem dann sieben Jahre später eine erhöhte Ausscheidung im Urin von Aminolävulinsäure, Coproporphyrin und Protoporphyrin TX festgestellt wurde. Die Möglichkeit, daß der metabolische Defekt durch eine Bleivergiftung bedingt ist, wird erwogen, jedoch glaubt man eher an das Vorliegen einer seltenen Form der Porphyrie. Da dieser Typ der Porphyrinabnormität einmalig ist, sind die Erwägungen bezüglich seiner Beziehung zu der Erkrankung in der Neugeborenenperiode spekulativ. Die zusätzlich bestehende geistige Retardierung und die verzögerte Knochenentwicklung kann eben falls zufällig sein. RESUMEN Se describe un paciente que había tenido una grave cuadriplegia transitoria en el período neonatal, seguida 7 años después por el descubrimiento de aumentos en orina de ala, coproporfirina y protoporfiria de células rojas. La posibilidad de que el defecto metabólico pudiera ser debido a intoxicación por el plomo es considerada y rechazada en favor de una forma no usual de porfiria. Puesto que el tipo de anormalidad de la porfirina encontrada aquí es úmico, las condiciones con respecto a su relación con la enfermedad neonatal son especulativas. La presencia adicional de retraso mental y retraso en el desarrollo óseo, puede haber sido tambión fortuita.

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Effect of Griseofulvin in Acute Intermittent Porphyria

Cited by 29 publications

References 3 publications

Adverse Drug Reactions to Systemic Antifungals Prevention and Management

Adverse Drug Reactions to Systemic Antifungals Prevention and Management

Griseofulvin impairs intraerythrocytic growth of Plasmodium falciparum through ferrochelatase inhibition but lacks activity in an experimental human infection study

Porphyria in Childhood Following Transient Neonatal Quadriplegia

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