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Neurotoxic Drugs (neurotoxic + drug)

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Medical Sciences60%

Selected Abstracts

Peripheral neuropathy associated with leflunomide: is there a risk patient profile?,

PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 1 2007
Karin Martin pharmD
Abstract Purpose (i) To monitor the potential clinical neurotoxic symptoms in patients treated with leflunomide in daily practice and (ii) to describe the characteristics of patients presenting with this peripheral nervous system symptoms. Method All patients treated with leflunomide between May 2000 and April 2003 and followed in the rheumatology department of the University Hospital participated in the study. Data concerning treatment patterns with leflunomide, demographic and disease characteristics were obtained from clinical charts. Neuropathy was diagnosed with nerve conduction study (NCS). Cases of neuropathy were described and then compared to other patients using univariate analyses. Results One hundred and thirteen patients were included in the study. M/F sex ratio was 0.45. Mean age at start of treatment was 55.6 years (range,=,27,81). During the study period, eight incident cases of peripheral neuropathy and two cases of worsening of preexisting neuropathy were reported (incidence: 9.8%). Compared with other patients, neuropathy cases were older (69 vs. 54 years, p,=,0.0006), more often diabetic (30% vs. 2.9%, p,=,0.009) and more often treated with potentially neurotoxic drugs (20% vs. 1.9%, p,=,0.039). At least one risk factor (potentially neurotoxic drug or diabetes) was found in 50% of patients with neuropathy versus 4% of patients without neuropathy (56% PPV, 96% NPV). Conclusion Cases of toxic neuropathy have been observed during treatment of rheumatoid arthritis with leflunomide. Their occurrence seems to be associated with known risk factors. Careful monitoring of the patient's neurological status during leflunomide treatment is therefore mandatory. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Effects of Xenobiotic Compounds on Cell Activities in Euplotes crassus

THE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 2 2005
FRANCESCA TRIELLI
It is now widely accepted that Protists are relevant bioassays to be exploited for the study of environmental modifications due to the presence of xenobiotic compounds. In this work, we evaluated the possibility of utilizing Euplotes crassus, an interstitial marine ciliate, for the pre-chemical screening of environmental sites, such as estuarine and coastal sediments. With this aim, we tested the sensitivity of E. crassus to exposure to three classes of pollutants: an organophosphate neurotoxic drug, basudin, largely used for pest control in agricultural sites, a toxic heavy metal, mercury (HgCl2), and an aromatic polycyclic hydrocarbon, benzopyrene (BP). We found a dose-dependent effect of these compounds on cell viability at concentrations ranging from 1/102 v/v to 1/107 v/v for basudin, from 5 ,M to 0.1 ,M for HgCl2, and from 50 ,M to 1 ,M for BP. In particular, 100% mortality was caused by a 1-h exposure to 1/105 v/v basudin, or 2 ,M HgCl2, or 25 ,M BP, and by a 24-h exposure to 1/106 v/v basudin, 0.5 ,M HgCl2, or 5 ,M BP. A significant decrease in the daily mean fission rate (P<0.001) was found after exposure to 1/107 v/v basudin, or 0.25 ,M HgCl2, or 1 ,M BP. Moreover, as it is well known that the inhibition of acetylcholinesterase (AChE) activity represents a specific biomarker for neurotoxic drugs, we first detected this enzyme activity in E. crassus, using cytochemical, spectrophotometric, and electrophoretic methods; then, AChE activity was characterized by its sensitivity to specific AChE inhibitors and to variations in pH and temperature. Like AChE present in higher organisms, the AChE activity detected in E. crassus was inhibited by exposure to basudin. Conversely, exposure to HgCl2, or PB did not inhibit AChE activity, but caused a significant reduction in lysosomal membrane stability. [source]

PREVALENCE AND RISK FACTORS IN CHRONIC POLYNEUROPATHY IN THE ELDERLY

JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2002
E. Scarpini
The elderly are a population at high risk of polyneuropathy because there is a correlation between age and impairment of the peripheral nervous system and because the number of agents that can damage peripheral nerves, including chronic systemic disorders and neurotoxic drugs, increases with age. The Italian Longitudinal Study on Aging (ILSA), a multicenter project designed to study age-associated diseases, collected data from 8 Italian municipalities. For this study, the definition of peripheral neuropathy by P.J. Dyck (1982) was used. However, only peripheral neuropathies with distal and symmetrical involvement of lower limbs were considered. Diagnosis was articulated in two phases: Phase 1 or screening, administered to all participants. The criteria were: a) self reported diagnosis; b) presence of at least one neurological symptom; and c) presence of at least one positive test at short neurological evaluation. A validation of the screening instruments was performed. Phase 2 or clinical confirmation by a neurologist, based on: a) review of the clinical records; b) a neurological examination; c) a clinical history of the disease; and, d) when available, EMG, blood and spinal fluid examination, and a sural nerve biopsy. Three diagnostic categories were identified: possible, probable and definite DSNLL. The neuropathy was classified as definite only when confirmation by a positive EMG was available. A random sample of 5632 subjects aged 65,84 years was evaluated. A total number of 337 DSNLL were identified (possible, probable, defined). The prevalence is 6.5% (95% C.I. 5.8,7.2) in men and women; the rates by age, geographic area, and clinical severity are described, and the prevalence in the different groups of diabetic patients and non-diabetic subjects is analyzed. The prevalence obtained in our study is slightly lower than that in a similar recent multicentric study (IGPSG, 1995), but the diagnostic criteria were different. Diabetes is the most common associated disorder with the 20.8% of association, followed by toxic/drug exposure (5% of association). [source]

Peripheral neuropathy associated with leflunomide: is there a risk patient profile?,

PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 1 2007
Karin Martin pharmD
Abstract Purpose (i) To monitor the potential clinical neurotoxic symptoms in patients treated with leflunomide in daily practice and (ii) to describe the characteristics of patients presenting with this peripheral nervous system symptoms. Method All patients treated with leflunomide between May 2000 and April 2003 and followed in the rheumatology department of the University Hospital participated in the study. Data concerning treatment patterns with leflunomide, demographic and disease characteristics were obtained from clinical charts. Neuropathy was diagnosed with nerve conduction study (NCS). Cases of neuropathy were described and then compared to other patients using univariate analyses. Results One hundred and thirteen patients were included in the study. M/F sex ratio was 0.45. Mean age at start of treatment was 55.6 years (range,=,27,81). During the study period, eight incident cases of peripheral neuropathy and two cases of worsening of preexisting neuropathy were reported (incidence: 9.8%). Compared with other patients, neuropathy cases were older (69 vs. 54 years, p,=,0.0006), more often diabetic (30% vs. 2.9%, p,=,0.009) and more often treated with potentially neurotoxic drugs (20% vs. 1.9%, p,=,0.039). At least one risk factor (potentially neurotoxic drug or diabetes) was found in 50% of patients with neuropathy versus 4% of patients without neuropathy (56% PPV, 96% NPV). Conclusion Cases of toxic neuropathy have been observed during treatment of rheumatoid arthritis with leflunomide. Their occurrence seems to be associated with known risk factors. Careful monitoring of the patient's neurological status during leflunomide treatment is therefore mandatory. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Effects of Xenobiotic Compounds on Cell Activities in Euplotes crassus

THE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 2 2005
FRANCESCA TRIELLI
It is now widely accepted that Protists are relevant bioassays to be exploited for the study of environmental modifications due to the presence of xenobiotic compounds. In this work, we evaluated the possibility of utilizing Euplotes crassus, an interstitial marine ciliate, for the pre-chemical screening of environmental sites, such as estuarine and coastal sediments. With this aim, we tested the sensitivity of E. crassus to exposure to three classes of pollutants: an organophosphate neurotoxic drug, basudin, largely used for pest control in agricultural sites, a toxic heavy metal, mercury (HgCl2), and an aromatic polycyclic hydrocarbon, benzopyrene (BP). We found a dose-dependent effect of these compounds on cell viability at concentrations ranging from 1/102 v/v to 1/107 v/v for basudin, from 5 ,M to 0.1 ,M for HgCl2, and from 50 ,M to 1 ,M for BP. In particular, 100% mortality was caused by a 1-h exposure to 1/105 v/v basudin, or 2 ,M HgCl2, or 25 ,M BP, and by a 24-h exposure to 1/106 v/v basudin, 0.5 ,M HgCl2, or 5 ,M BP. A significant decrease in the daily mean fission rate (P<0.001) was found after exposure to 1/107 v/v basudin, or 0.25 ,M HgCl2, or 1 ,M BP. Moreover, as it is well known that the inhibition of acetylcholinesterase (AChE) activity represents a specific biomarker for neurotoxic drugs, we first detected this enzyme activity in E. crassus, using cytochemical, spectrophotometric, and electrophoretic methods; then, AChE activity was characterized by its sensitivity to specific AChE inhibitors and to variations in pH and temperature. Like AChE present in higher organisms, the AChE activity detected in E. crassus was inhibited by exposure to basudin. Conversely, exposure to HgCl2, or PB did not inhibit AChE activity, but caused a significant reduction in lysosomal membrane stability. [source]