2',3'‐Dideoxycytidine (ddC) toxic neuropathy

Abstract

We administered the antiviral agent 2',3'-dideoxycytidine (ddC) to HIV-infected patients with either ARC or AIDS as part of the AIDS Clinical Treatment Group protocol 012 and serially evaluated them with neuropathic symptom questionnaires, neurologic examinations, nerve conduction studies, and quantitative sensory testing (QST). All patients treated with high-dose ddC (0.06 and 0.03 mg/kg every 4 hours) developed a painful, predominantly sensory peripheral neuropathy, with a mean onset of 7.7 weeks, which reached severe intensity over several days. Abnormalities of vibration QST threshold preceded clinical symptoms. Treatment with 0.01 mg/kg every 4 hours produced a similar neuropathy, although of milder severity, later onset (mean, 9.3 weeks), and slower progression. In these patients, the onset of clinical symptoms and QST abnormalities were coincident. Only two of six patients treated with 0.005 mg/kg every 4 hours developed clinical or laboratory evidence of neuropathy; in both cases it was very mild and delayed in onset (26 weeks). All patients treated with high-dose ddC reported progression of symptoms (coasting) for 2 to 3 weeks following discontinuation of therapy. This study documents a painful sensory neuropathy resulting from treatment with ddC. With high-dose treatment, only the rapidity of onset and progression differentiated it from the distal, predominantly sensory neuropathy of AIDS.

Case Files of the New York City Poison Control Center: Paradichlorobenzene-Induced Leukoencephalopathy

“…This has been described with many neurotoxins such as thalidomide, hydrocarbon sniffing with tetraethyl lead, n-hexane (and methyl-n-butyl ketone and 2,5-hexanedione), chemotherapeutic agents, antivirals, and pyridoxine [18][19][20][21][22][23].…”

Mitochondrial DNA Depletion, Oxidative Stress, and Mutation: Mechanisms 0f Dysfunction from Nucleoside Reverse Transcriptase Inhibitors

“…Elimadi et al, 1997 AZT inhibits NADH oxidase Pereira et al, 1998 AZT treatment has no effect on mitochondria Herzberg et al, 1992 DDC Peripheral nerve Painful peripheral neuropathy in 50 -100% of patients Berger et al, 1993Dubinsky et al, 1989Merigan et al, 1989Yarchoan et al, 1990 Inhibition of mtDNA replication in MOLT cells. Mitochondrial structural changes and lipid accumulation in nerves of DDC-treated rabbits.…”

“…Doserelated, painful peripheral neuropathies occur in the majority of patients treated with ddC in doses of 0.03 to 0.09 mg/kg/day (Berger et al, 1993;Dubinsky et al, 1989;Merigan et al, 1989;Yarchoan et al, 1990). Peripheral neuropathy with ddI was unexpected, based upon preclinical data .…”

Pulsatile tinnitus from a redundant arterial loop

“…4,7 Dideoxynucleoside antiretrovirals (d-drug ARV) are neurotoxic and have been demonstrated to increase the risk of PN. [9][10][11] However, other studies have shown that d-drug ARV do not increase the risk or severity of DSP. 6,7,12 It is not clear whether mitochondrial mechanisms are responsible for d-drug ARV neurotoxicity.…”

“…[9][10][11] However, more recent trials have shown that d-drug ARV did not add further risk to the occurrence of HIVassociated PN. [5][6][7]12 Therefore, it is not clear how best to predict which patients are at highest risk for the development of DSP while being treated with d-drug ARV regimens.…”