Optic neuropathy

Isoniazid is bactericidal against growing M. tuberculosis. Its mechanism of action remains unclear. (In the bacterium it is converted to isonicotinic acid, which is membrane impermeable, hence likely to accumulate intracellu-larly.) Isoniazid is rapidly absorbed after oral administration. In the liver, it is inactivated by acetylation, the rate of which is genetically controlled and shows a characteristic distribution in different ethnic groups (fast vs. slow acetylators). Notable adverse effects are peripheral neuropathy, optic neuritis preventable by administration of vitamin Be (pyridoxine) hepatitis, jaundice. 

CNS toxicity occurs because isoniazid has structural similarities to pyridoxine (vitamin Be) and can inhibit its actions. This toxicity is dose-related and more common in slow acetylators. Manifestations include peripheral neuropathy, optic neuritis, ataxia, psychosis and seizures. The administration of pyridoxine to patients receiving INH does not interfere with the tuberculostatic action of INH but it prevents and can even reverse neuritis. Hematological effects include anaemia which is also responsive to pyridoxine. In some 20% of patients antinuclear antibodies can be detected but only in a minority of these patients drug-induced lupus erythematosus becomes manifest. 

Anti-CRMP5/CV2 CRMP5 Cytoplasm of oligodendrocytes Encephalomyelitis, cerebellar degeneration, LE, chorea, sensory neuronopathy, sensorimotor neuropathy, optic neuritis, gastrointestinal pseudo-obstruction SCLC, thymoma, gynecological tumors... 

Polyneuropathy with both sensory and motor involvement is much more common among cancer patients than pure SN [83, 110, 111]. SCLC is the most common associated tumor, although other solid tumors may be found [112]. Sensory-motor neuropathy is a quite common paraneoplastic feature in patients with onconeural antibodies, especially Hu and CRMP-5 antibodies. The CRMP-5 antibody is particularly associated with SCLC and thymoma [30]. The CRMP-5 antibody binds to oligodendrocytes as well as to neurons in specific brain regions and the retina and Schwann cells of the peripheral nervous system. In accordance with this, the clinical characteristics are heterogeneous. Many patients exhibit mixed axonal and demye-linating sensory-motor neuropathy, optic neuritis, or cerebellar dysfynction [85, 113], as well as extrapyramidal symptoms (Chapter 5.3). 

Bi2 Meat, dairy, eggs, seafood Toxic optic neuropathy Optic nerve atrophy (in Leber s disease)... 

Side effects caused by isoniazid, rifampin, pyrazinamide, and ethambutol are common and can include hepatotoxic-ity, peripheral neuropathy, optic neuritis, and Gl side effects. All four agents can potentially be hepatotoxic, but this side effect is most frequently associated with isoniazid and rifampin. Peripheral neuropathy is most commonly associated with isoniazid, whereas optic neuritis is associated with ethambutol. The metabolism of isoniazid is genetically predetermined. Patients of Scandinavian, European, and African descent metabolize isoniazid slower (slow acetylators) and are therefore more predisposed to hepatotoxicity and peripheral neuropathy due to isoniazid. Fast acetylators include people of Asian or American Indian descent and are less predisposed to these adverse effects. 

Extrapyramidal syndrome Cerebellar syndrome, visual dysfunction, encephalopathy, CNS teratogenicity Peripheral neuropathy, encephalopathy Encephalopathy, neuronopathy (trimethyltin) leukoencephalopathy, vacuolar myelinopathy (triethyltin) Peripheral neuropathy, optic neuropathy Peripheral neuropathy Acute, chronic encephalopathy, CNS teratogenicity (fetal alcohol syndrome) Peripheral neuropathy Optical neuropathy... 

Acute encephalopathy, peripheral neuropathy, optic neuropathy... 

Disulfiram produces a variety of adverse effects, which commonly include drowsiness, lethargy, and fatigue (Chick 1999). Other more serious adverse effects, such as optic neuritis, peripheral neuropathy, and hepatotoxicity, are rare. Psychiatric effects of disulfiram are also uncommon. They probably occur only at higher dosages of the drug and may result from the inhibition by disulfiram of a variety of enzymes in addition to ALDH. Included among the enzymes inhibited by disulfiram is dopamine P-hydroxylase, inhibition of which increases dopamine levels, which in turn can exacerbate psychotic symptoms in patients with schizophrenia and occasionally may result in psychotic or depressive symptoms in patients without schizophrenia. 

Applanation tonometry elevated IOP (greater than 21 mm Hg) may be present however, a patient can have signs of optic neuropathy without elevated IOP. 

Linezolid Myelosuppression monitor CBC once weekly if more than 2 weeks of therapy Peripheral and/or optic neuropathy has been reported with long-term therapy Mild MAO inhibitor evaluate for potential drug-drug or drug-food interactions... 

Complex I deficiency due to mtDNA mutations (seven subunits of complex I are encoded by mtDNA) can be divided into encephalomyopathies and myopathies. The most important encephalomyopathy is Leber s hereditary optic neuropathy, characterized by acute or subacute loss of vision due to severe bilateral optic atrophy, with onset usually between 18 and 30 years and marked predominance in men. Three mutations (in ND1, ND4 and ND6)... 

Much of the toxicological interest in cyanide relating to mammals has focused on its rapid lethal action. However, its most widely distributed toxicologic problems are due to its toxicity from dietary, industrial, and environmental factors (Way 1981, 1984 Gee 1987 Marrs and Ballantyne 1987 Eisler 1991). Chronic exposure to cyanide is correlated with specific human diseases Nigerian nutritional neuropathy, Leber s optical atrophy, retrobulbar neuritis, pernicious anemia, tobacco amblyopia, cretinism, and ataxic tropical neuropathy (Towill etal. 1978 Way 1981 Sprine etal. 1982 Beminger et al. 1989 Ukhun and Dibie 1989). The effects of chronic cyanide intoxication are confounded by various nutritional factors, such as dietary deficiencies of sulfur-containing amino acids, proteins, and water-soluble vitamins (Way 1981). 

Amiodarone Tremor, ataxia, pareslfresia, insomnia, corneal microdeposits, optic neuropathy/neuritis, nausea, vomiting, anorexia, constipation, TdP (<1%), bradycardia or AV block (IV and oral use), pulmonary fibrosis, liver function test abnormalities, hepatitis, hypothyroidism, hyperthyroidism, photosensitivity, bluegray skin discoloration, hypotension (IV use), phlebitis (IV use)... 

In open-angle glaucoma, the specific cause of optic neuropathy is unknown. Increased intraocular pressure (IOP) was historically considered to be the sole cause. Additional contributing factors include increased susceptibility of the optic nerve to ischemia, reduced or dysregulated blood flow, excitotoxicity, autoimmune reactions, and other abnormal physiologic processes. 

Clioquinol Subacute myelo-optic neuropathy Approx 1930 51... 

The nervous system is the most sensitive target for cyanide toxicity, partly because of its high metabolic demands. High doses of cyanide can result in death via central nervous system effects, which can cause respiratory arrest. In humans, chronic low-level cyanide exposure through cassava consumption (and possibly through tobacco smoke inhalation) has been associated with tropical neuropathy, tobacco amblyopia, and Leber s hereditary optic atrophy. It has been suggested that defects in the metabolic conversion of cyanide to thiocyanate, as well as nutritional deficiencies of protein and vitamin B12 and other vitamins and minerals may play a role in the development of these disorders (Wilson 1965). 

Lessell S. 1971. Experimental cyanide optic neuropathy. Arch Ophthalmol 86 194-204. 

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