Drug treatment in acute porphyria

Gorchein, A.

doi:10.1046/j.1365-2125.1997.t01-1-00609.x

Cited by 50 publications

(39 citation statements)

References 15 publications

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“…34 It is well known that drugs are one of the most important precipitating factors of acute porphyric attacks, so that the acute porphyrias are also considered to be pharmacogenetic or toxicogenetic diseases. 8,34,35,38 The capacity of a drug to induce an APA (ie, drug porphyrogenicity) depends mostly on its ability to directly activate the synthesis of ALA-S1 or to block its negative regulatory feedback control by reducing the hepatic free heme pool ( Figure 2). 7…”

Section: Drugs and Acute Porphyrias: A Hazardous Relationshipmentioning

confidence: 99%

“…4 Drugs frequently play a pivotal role among the environmental triggering factors of acute porphyrias. 3,28,35,37 In the presence of an inherited enzymatic deficiency of heme metabolism potentially responsible for an acute porphyria (acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, or delta-aminolevulinic acid dehydratase porphyria; Table 2), many environmental factors can trigger the serious (and potentially fatal) clinical manifestations of the disease. 34 It is well known that drugs are one of the most important precipitating factors of acute porphyric attacks, so that the acute porphyrias are also considered to be pharmacogenetic or toxicogenetic diseases.…”

Section: Drugs and Acute Porphyrias: A Hazardous Relationshipmentioning

confidence: 99%

“…For this reason, the identification of harmful substances for patients with porphyria is still incomplete. 13,35 The classification of drugs as safe or unsafe in cases of acute porphyria is based mostly on anecdotal reports of the effects observed in patients with acute porphyrias, on clinical reports of induction of an APA by other agents, or on the measurement of porphyrins or porphyrin precursors (ALA and PBG) in urine and feces after drug consumption. Drugs may also be tested in vitro (on cellular cultures) in order to assess their ability to induce ALA-S1 activity or to determine their effects on the synthesis of porphyrins.…”

Section: Drugs and Acute Porphyrias: A Real Issue In Drug Prescribingmentioning

confidence: 99%

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Drugs and Acute Porphyrias: Reasons for a Hazardous Relationship

Roveri

Nascimbeni

Rocchi

et al. 2014

Postgraduate Medicine

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The porphyrias are a group of metabolic diseases caused by inherited or acquired enzymatic deficiency in the metabolic pathway of heme biosynthesis. Simplistically, they can be considered as storage diseases, because the partial enzymatic defect gives rise to a metabolic "bottleneck" in the biosynthetic pathway and hence to an accumulation of different metabolic intermediates, potentially toxic and responsible for the various (cutaneous or neurovisceral) clinical manifestations observed in these diseases. In the acute porphyrias (acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, and the very rare delta-aminolevulinic acid dehydratase ALAD-d porphyria), the characteristic severe neurovisceral involvement is mainly ascribed to a tissue accumulation of delta-aminolevulinic acid, a neurotoxic nonporphyrin precursor. Many different factors, both endogenous and exogenous, may favor the accumulation of this precursor in patients who are carriers of an enzymatic defect consistent with an acute porphyria, thus contributing to trigger the serious (and potentially fatal) clinical manifestations of the disease (acute porphyric attacks). To date, many different drugs are known to be able to precipitate an acute porphyric attack, so that the acute porphyrias are also considered as pharmacogenetic or toxygenetic diseases. This article reviews the different biochemical mechanisms underlying the capacity of many drugs to precipitate a porphyric acute attack (drug porphyrogenicity) in carriers of genetic mutations responsible for acute porphyrias, and addresses the issue of prescribing drugs for patients affected by these rare, but extremely complex, diseases.

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Section: Drugs and Acute Porphyrias: A Hazardous Relationshipmentioning

confidence: 99%

Section: Drugs and Acute Porphyrias: A Hazardous Relationshipmentioning

confidence: 99%

Section: Drugs and Acute Porphyrias: A Real Issue In Drug Prescribingmentioning

confidence: 99%

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Drugs and Acute Porphyrias: Reasons for a Hazardous Relationship

Roveri

Nascimbeni

Rocchi

et al. 2014

Postgraduate Medicine

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“…Antineoplastic drugs have been generally administered safely to patients with AIP and advanced cancer (24). There is disagreement, however, regarding the safety of several antibiotics such as chloramphenicol, cephalosporins, erythromycin and vancomycin (25).…”

Section: ) Endocrine Factorsmentioning

confidence: 99%

Gene-Environmental Interactions: Lessons from Porphyria

Sassa

2003

Environ. Health Prev. Med.

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The porphyrias are uncommon, complex, and fascinating metabolic conditions, caused by deficiencies in the activities of the enzymes of the heme biosynthetic pathway. Two cardinal symptoms of the porphyrias are cutaneous photosensitivity and neurologic disturbances. Molecular analysis of gene defects has shown that there are multiple and heterogeneous mutations in each porphyria. Patients with symptomatic porphyria can suffer greatly, and, in rare cases, may die. While congenital porphyrias are inherited, other forms of porphyria occur as acquired diseases. In addition, not all gene carriers of inherited porphyrias develop clinical disease and there is a significant interplay between the gene defect and acquired or environmental factors. The variable response of porphyrias to acquired factors may likely reflect genetic polymorphisms in drug metabolism. The lessons from acute hepatic porphyria, such as acute intermittent porphyria, are very useful in clarifying the complex nature of the clinical expression of metabolic disorders.

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“…Unfortunately, information for most drugs is insufficient to allow them to be classified as definitely harmful or safe, even as other drugs have been labeled harmful on the basis of inadequate evidence (4,6,30,46). Little information exists about the safety of many psychotropic drugs, especially the newer antidepressants and atypical antipsychotics (30).…”

Section: Treatment and Prophylaxismentioning

confidence: 99%

Acute Porphyrias: A Case Report and Review

Gonzalez-Arriaza¹,

Bostwick²

2003

AJP

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As befits a hematologic class of disorders, the word "porphyria" derives from the Greek word porphuros, which means red or purple (1). The porphyrias (Table 1 and Table 2) are a group of rare metabolic disorders arising from reduced activity of any of the enzymes in the heme biosynthetic pathway. The disorders may be either acquired (for instance, through a toxin acting on one of the enzymes) or inherited through a genetic defect in a gene encoding these enzymes. These deficiencies disrupt normal heme production, with symptoms especially prominent when increased heme is required. Porphyrin precursors, overproduced in response to synthetic pathway blockages, accumulate in the body (1-31), cause diverse pathologic changes, and become the basis for diagnostic tests.In this review we focus on the two neuroporphyrias (acute intermittent porphyria and plumboporphyria) and the two neurocutaneous porphyrias (hereditary coproporphyria and variegate porphyria). These four entities, of all the porphyrias, are the only ones with neuropsychiatric manifestations. We use a case of variegate porphyria to illustrate how the manifestations may be broad, the relevance in neuropsychiatric disorders overlooked, and the diagnosis unsuspected. Given the variable and nonspecific clinical features, we emphasize the need to carefully interpret excretion patterns and concentrations of porphyrin precursors in urine and stool to make a specific diagnosis. The workup of any potential case needs to be individualized, taking into consideration both the history and the symptoms at the time of evaluation. We discuss the complexities of making a diagnosis of porphyria. Without carefully gathering a history and having a clear understanding of what laboratory tests can and cannot show, making the diagnosis will be delayed, possibly resulting in increased morbidity and use of medical and financial resources. When evaluating complicated neuropsychiatric cases of uncertain cause, we advocate maintaining a high degree of awareness for porphyria. Case PresentationMr. A, a 47-year-old, married, male florist with no significant previous medical or psychiatric history, presented to a local neurologist with a 3-month history of symptoms of apparent neurologic origin. He had had progressive loss of memory and concentration, spells of confusion, and indeterminate jerking spasms of the upper extremities and facial muscles that lasted only seconds but occurred up to 30 times per day. The neurologic examination was normal; the neurologist did not make a specific diagnosis but did prescribe nefazodone, an antidepressant.A few weeks later, psychiatric symptoms developed that were serious enough to warrant admission to a local hospital. Mr. A had paranoid delusions and auditory hallucinations. He heard animals in his room and thought the police wanted to harm him. He had hyponatremia, so before his transfer to the psychiatric ward, an internist evaluated him but offered no specific explanation for the hyponatremia. A psychiatric mood disorder was diagnosed, and Mr...

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Drug treatment in acute porphyria

Cited by 50 publications

References 15 publications

Drugs and Acute Porphyrias: Reasons for a Hazardous Relationship

Drugs and Acute Porphyrias: Reasons for a Hazardous Relationship

Gene-Environmental Interactions: Lessons from Porphyria

Acute Porphyrias: A Case Report and Review

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