Peripheral neurotoxicity

Feldman RG, Mayer RM, Taub A. 1970. Evidence for peripheral neurotoxic effect of trichloroethylene. Neurology 20 599-605. 

Isoniazid Adults S mg/kg (300 mg) Children 1 0-1 S mg/kg (300 mg) Asymptomatic elevation of aminotransferases, clinical hepatitis, fatal hepatitis, peripheral neurotoxicity, CNS system effects, lupus-like syndrome, hypersensitivity, monoamine poisoning, diarrhea LFT monthly in patients who have preexisting liver disease or who develop abnormal liver function that does not require discontinuation of drug Dosage adjustments may be necessary in patients receiving anticonvulsants or warfarin... 

New Zealand rabbits exposed to 3,000 ppm -hexane for 8 hours a day, 5 days a week for 24 weeks, showed no signs of peripheral neurotoxicity (hindlimb weakness, foot dragging) (Lungarella et al. 1984). 

In a study where both peripheral and central nervous system effects were measured in rats co-exposed to u-hexane and toluene (Pryor and Rebert 1992), toluene exposure at 1,400 ppm for 14 hours a day for 9 weeks prevented the peripheral neurotoxicity (decreased grip strength and nerve conduction velocities) caused by exposure to 4,000 ppm 77-hcxanc alone. There was no reciprocal action of 77-hexane on the motor syndrome (shortened and widened gait and widened landing foot splay) and hearing loss caused by toluene. Brainstem auditory response amplitudes were decreased by 77-hcxanc, co-exposure to toluene did not block this effect. 

There is no currently accepted experimental model for the peripheral neurotoxicity produced by vincristine in humans. It has been suggested that chronic treatment of rabbits with vincristine might serve as a useful model for neurotoxicity 43). Rabbits were treated with vincristine (0.3 mg/kg) intravenously at weekly intervals for 5 weeks. The treated rabbits experienced little if any growth during the experimental period and had reduced appetite. Alopecia and anemia were observed, and some animals manifested signs of limb paralysis. Vincristine treatment resulted in the reduction of conduction velocity in the sciatic nerve. 

The toxicological profile for vindesine includes effects observed with both vinblastine and vincristine. Among the effects observed with vindesine are bone marrow depression, alopecia, and peripheral neurotoxicity. 

In animal studies, repeated inhalation of chlorpyrifos at 287 Hg/m (near the theoretical maximum vapor concentration) for 13 weeks caused no treatment-related changes in urinalysis, hematology, clinical chemistry, terminal body and organ weights, or pathology. Induction of delayed polyneuropathy in animals occurs only at doses that exceed the LD50." Peripheral neurotoxic effects could occur in humans after massive exposures at almost lethal doses (from which the patient is saved by intensive medical intervention). The possibility that subtle neurobehavioral effects are associated with pesticide exposure cannot be ruled out. ... 

De Haro L, Gastaut J-L, Jouglard J, et ah Central and peripheral neurotoxic effects of chronic methyl bromide intoxication. J Toxicol Clin Toxicol 35(l) 29-34, 1997... 

Adverse effects include depression of bone marrow which gives rise to leukopenia, thrombocytopenia, reticulocytopenia. GI disturbances, oral and anal ulceration, hepatic and renal dysfunction and peripheral neurotoxicity with high doses. 

Nervous system disorders The development of severe peripheral neurotoxicity requires a reduction of dose. Mild to moderate neurosensory signs are characterised by paraesthesia, dysaesthesia or pain including burning. Neuromotor events are mainly characterised by weakness. 

De Wolff, F.A., Treijtel, N., Vermeulen, M. (2002). Mechanisms of peripheral neurotoxicity. In Site-Selective Neurotoxicity (D.S. Lester, W. Slikker, P. Lazarovici, eds), Chapter 15, pp. 282-303. Taylor and Francis, New York, NY. 

Jett, D.A, Lein, P.J. (2006). Noncholinesterase mechanisms of central and peripheral neurotoxicity muscarinic receptors and other targets. In Toxicology of Organophosphate and... 

Delayed peripheral neurotoxicity has been reported in animal studies. Soman produced severe delayed neuropathy in the atropinized hen assay at 1.5 mg/kg (Willems et al. 

By comparing 50 mg/m weekly with 75 mg/m 3 times weekly, using detailed neurological and neurophysiological examination, it has been concluded that cisplatin neuropathy is either of sensory or axonal type, and that both are related to total and single doses (102). However, others have suggested that cisplatin-induced peripheral neurotoxicity is related to dose intensity rather than to the total dose received (103). 

Carbamazepine is a potent sodium channel blocker and has therefore been studied in the prevention of oxaliplatin-induced neuropathy (116). The doses of carbamazepine were adjusted to produce serum concentrations in the range 30-60 pg/ml. None of the patients who took carbamazepine reported symptoms of peripheral neurotoxicity however, two patients (one who forgot to take carbamazepine and one who stopped taking it because he felt tired) developed grade-1 peripheral sensory neurotoxicity. These symptoms were abolished when carbamazepine was restarted. One can therefore speculate that the concomitant use of carbamazepine may allow the use of a higher cumulative dose of oxaliplatin without the occurrence of grade-4 neuropathy. However, a multicenter trial is warranted to confirm these encouraging preliminary results (117). 

Cavaletti G, Marzorati L, Boghun G, Colombo N, Marzola M, Pittelli MR, Tredici G. Cisplatin-induced peripheral neurotoxicity is dependent on total-dose intensity and single-dose intensity. Cancer 1992 69(l) 203-7. 

Cavaletti G, Zanna C. Current status and future prospects for the treatment of chemotherapy-induced peripheral neurotoxicity. Eur J Cancer 2002 38(14) 1832-7. 

Bone marrow depression conjunctivitis megaloblastosis oral ulceration hepatic damage pulmonary edema and central and peripheral neurotoxicity with high doses rhabdomyolysis pancreatitis when used with asparaginase rash... 

Cavaletti G, Pezzoni G, Pisano G, et al. (2002) Gisplatin-induced peripheral neurotoxicity in rats reduces the circulating levels of nerve growth factor. Neuroscience Letters 322 103-106. 

Studies of chronic exposure of those working in dry cleaning plants have reported some CNS effects, some liver function abnormalities, renal dysfunction, and some definite central and peripheral neurotoxicity. Other effects from chronic exposure to PERC include cardiac arrhythmias, reduced color perception, impaired memory, peripheral neuropathy, impaired vision, confusion, disorientation, fatigue, personality changes, and agitation. 

Dideoxycytidine (DDC, zalcitabine), a nucleoside analogue that also inhibits reverse transcriptase, is more active than zidovudine in vitro, and (unlike zidovudine) does not suppress erythro-poiesis. DDC is not without toxicity, however, and a severe peripheral neurotoxicity, which is dose-related, has been reported. The chemical structures of DDC and of another analogue with similar properties, 2 3 -dideoxyinosine (DDI, didanosine), are presented in Fig. 10.25 (G, H, respectively). 

Levine SP, CavenderGD, LangolfGD, etal. 1982. Elemental mercury exposure Peripheral neurotoxicity. Br J Ind Med 39 136-139. 

Valenti F, Agnesi R, Del Vecchio L, et al. Does n-heptane cause peripheral neurotoxicity A case report in a shoemaker. Occup Med 1994 44 102-4. 

A genetic profile on the basis of SNPs would be more than useful for Chemotherapy-Induced Peripheral Neurotoxicity (CIPN) risk stratification, prior to start treatment. CIPN is a potentially severe and long-lasting side effect of commonly employed anticancer drugs platinum compounds, taxanes, proteasome inhibitors, vinca alkaloids, and epothilones they are used every day to treat... 

Argyriou AA, Bruna J, Marmiroli P, Cavaletti G (2012) Chemotherapy-induced peripheral neurotoxicity (CIPN) an update. Crit Rev Oncol Hematol 82 51-77... 

Cavaletti G, Frigcni B, Lanzani F et al (2010) Chemotherapy-induced peripheral neurotoxicity assessment a critical revision of the currendy available tools. Eur J Cancer 46 479-494... 

Oguri T, Mitsuma A, Inada-Inoue M et al (2013) Genetic polymorphisms associated with oxaliplatin-induced peripheral neurotoxicity in Japanese patients with colorectal cancer. Int J Clin Pharmacol Ther 51 475 181... 

Cavaletti G, Frigeni B, Lanzani F et al (2007) The total neuropathy score as an assessment tool for grading the course of chemotherapy-induced peripheral neurotoxicity comparison with the National Cancer Institute-Common Toxicity Scale. J Peripher Nerv Syst 12 210-215... 

Argyriou AA, Cavaletti G, Antonacopoulou A et al (2013) Voltage-gated sodium channel polymorphisms play a pivotal role in the development of oxaliplatin-induced peripheral neurotoxicity - results from a prospective multicenter study. Cancer 119 3570-3577... 

Cisplatin Cancer Nephrotoxicity, peripheral neurotoxicity, and hearing loss TPMT GST COMT [99, 101]... 

Other reactions must be mentioned beside the major reactions described above. These reactions may be responsible for the transformation of a toxic metabolite into the ultimate toxicant. Rearrangements and cyclizations are examples of reactions involved in these processes. In the case of the solvent hexane (Figure 33.19), the toxic metabolite, 2, 5-hexanedione, is formed by four successive oxidations of the molecule. The condensation of the -dicetone with the lysyl amino group of a neurofilament protein is followed by a Paal-Knorr cyclization reaction. This is the initial process that explains the hexane-induced neurotoxicity." A further auto-oxidation of the A-pyrrolyl derivatives leads to the cross-linking of the axonal intermediate filament proteins and the subsequent occurrence of peripheral neurotoxicity." ... 

Neurological Headache, dizziness, weakness, fatigue, cold intolerance, peripheral neurotoxicity... 

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