Toxicity peripheral neuropathy

Vincristine (Oncovin) Dose limiting toxicity peripheral neuropathies, paresthesias, constipation, alopecia Given in combination with doxorubicin and dexamethasone (VAD)... 

Because of the toxicity of lead, special care must be taken when working with lead ahoys. Lead and its inorganic compounds are neurotoxias which may produce peripheral neuropathy. Eor an overview of the effects of lead exposure, see Occupational Exposure to Lead, Appendix A (29 CRE 1910.1025) (see... 

The incidence of adverse reactions appears to be higher when larger doses of isoniazid are prescribed. Adverse reactions include hypersensitivity reactions, hematologic changes, jaundice, fever, skin eruptions, nausea, vomiting, and epigastric distress. Severe, and sometimes fatal, hepatitis has been associated witii isoniazid tiierapy and may appear after many months of treatment. Peripheral neuropathy (numbness and tingling of the extremities) is the most common symptom of toxicity. 

Before an antiviral agent becomes a drug, advanced toxicity testing, pharmacological combination, and drug-interaction studies are needed. The use of new cell-based assays that can predict mitochondrial toxicity, lactic acidosis, peripheral neuropathy, anemia, hypersensitivity, lipodystrophy, and other potential side effects can alleviate these issues (Stuyver et al. 2002). 

The phenotype and clinical presentation of antiretroviral toxic neuropathy (ATN) are similar to those of HIV-associated DSP. However, ATN is more likely to be painful, and has an abrupt onset and rapid progression. The main diagnostic clue is the temporal relationship of peripheral neuropathy to the start of NRTI therapy and stabilization, or at least the partial resolution when therapy is interrupted (Moyle and Sadler 1998). ATN most often develops after a mean of 16 to 20 weeks of treatment, unless there are other conditions that lower the threshold. Symptomatic improvement over weeks to months has been reported in two thirds of patients after discontinuation of the offending drug, but may be preceded by an initial period of worsening symptoms, also known as coasting (Berger et al. 1993). Despite the improvement, most patients do not return to a completely asymptomatic state (Hoke and Comblath 2004). 

NRTls are structural analogues of the natural nucleotides that form the building blocks of RNA and DNA in human cells. Their use as part of HAART has dramatically modified the natural history of HIV infection. They, however, cause a range of drag- or tissue-specific toxicides zidovudine (AZT) causes myopathy zalcitabine (ddC), didanosine (ddl), and lamivudine (3TC) cause neuropathy stavudine (d4T) causes neuropathy or myopathy and lactic acidosis (Dalakas 2001). During phase 1 and 11 trials, the dose-limiting toxicity of didanosine, zalcitabine, and stavudine was identified as peripheral neuropathy (Dalakas 2001). 

Zalcitabine (ddC) Hivid (anticipated discontinuation of distribution in 2006) 0.375-, 0.75-mg tab 0.75 mg tid CrCI Dose (mL/minute) 10-40 0.75 mg bid less than 10 0.75 mg qday No data on hemodialysis None Peripheral neuropathy stomatitis, lactic acidosis with hepatic steatosis (rare but potentially life-threatening toxicity with use of NRTIs) pancreatitis Renal excretion... 

Docetaxel asthenia, peripheral neuropathy, alopecia, cardiovascular Fatigue, nausea, vomiting, skin toxicity, neuropathy, anemia, Mild (on administration days... 

Peripheral neuropathy primary dose-limiting toxicity motor sensory, autonomic, and cranial nerves may all be affected (paresthesias, ileus, urinary retention, facial palsies) may be irreversible mild emetogen SIADH vesicant extravasation injury... 

Organophosphate Ester Hydraulic Fluids. The biomarkers of effects after exposure to organophosphate ester hydraulic fluids are well established in cases of delayed neuropathy (clinical signs of peripheral neuropathy). Further study would be helpful to determine whether certain effects (such as diarrhea after oral exposure) are due to direct action of the toxic agent on the target organ or to inhibition of acetylcholinesterase at the acetylcholine nerve receptor site on the organ. 

Effect of Dose and Duration of Exposure on Toxicity. No studies were located where -hexane concentration was measured in workplace air before workers became ill, so no dose-response relationship can be defined for human neurotoxicity as the result of -hexane exposure. Information on duration of exposure leading to toxicity is available from some case series reports. An occupational exposure caused sensory disturbances in the lower extremities after approximately 2 months (Herskowitz et al. 1971). A case of peripheral neuropathy after 7 months of exposure was reported among press-proofing workers in Taipei (Wang et al. 1986) a serious case resulting in quadriplegia after 8 months of exposure was reported among sandal workers in Japan (Yamamura 1969). Based on case reports, it can be estimated... 

Route-dependent Toxicity. w-Hexane toxicity does not appear to be route-dependent. Peripheral neuropathy can be produced in rats by the oral route (Krasavage et al. 1980) at high doses (4,000 mg/kg/day). The clinical and histopathological signs were similar to those seen after inhalation exposure. No reports of neurotoxicity after dermal exposure were located. 

No information is available as to whether the mechanism of action of -hexane toxicity in children differs from that of adults. Weanling rats (21 days old) were more resistant to the development of -hexane peripheral neuropathy than young adults (80 days old) during an exposure to 1,000 ppm -hexane (Howd et al. 1983). The authors suggested that the relative resistance of the weanling rats may have been due to shorter, smaller-diameter axons, or to a greater rate of growth and repair in their peripheral nerves compared to those of adults. 

Human toxicity associated with -hexane was first recognized in the 1960s and early 1970s in Japan and Italy. Workers in the shoe industries in these countries developed a peripheral neuropathy that started with numbness in the feet and hands, followed by weakness in the lower legs and feet. In severe cases,... 

Peripheral neuropathy has also occurred in humans as the result of solvent abuse of products containing -hexane (Altenkirch et al. 1977 Chang et al. 1998 Spencer et al. 1980). Clinical signs were very similar to those seen after occupational exposure however, signs of central nervous system toxicity may also be present due to other components in the inhaled mixtures, e.g., toluene (Spencer et al. 1980). 

Neurological examinations of humans with M-hexanc-induced peripheral neuropathy have not shown clinical signs of central nervous system toxicity (Herskowitz et al. 1971 Yamamura 1969). There have been reports of altered evoked potentials recorded in the brain (increased latency, decreased amplitude) in humans occupationally exposed to -hexane (Mutti et al. 1982c Seppalainen et al. 1979). There has been one report of an individual occupationally exposed to -hexane for 38 years who developed Parkinsonism (Pezzoli et al. 1995), although the etiology of this case is complicated by the fact that the patient had a sister who was probably affected by Parkinsonism. Further studies, particularly prospective... 

Cases of -hexane toxicity in humans have occurred as the result of workplace exposure and solvent abuse (Spencer et al. 1980). Some of these cases of peripheral neuropathy have occurred in teenagers (particularly with solvent abuse) however, none of the clinical reports indicate differences in physical signs or functional tests between this group and adults (Altenkirch et al. 1977 Yamamura et al. 1969). While no reports of -hexane toxicity in young children were located, it is probable that similar toxicity would occur if exposure was comparable to that in affected adults. Specific information is not available on whether children are more susceptible than adults to the effects of -hexane. 

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