amiodarone neurotoxicity

INTRODUCTION: Aconitine and related alkaloids found in the Aconitum species are highly toxic cardiotoxins and neurotoxins. The wild plant (especially the roots and root tubers) is extremely toxic. Severe aconite poisoning can occur after accidental ingestion of the wild plant or consumption of an herbal decoction made from aconite roots. In traditional Chinese medicine, aconite roots are used only after processing to reduce the toxic alkaloid content. Soaking and boiling during processing or decoction preparation will hydrolyze aconite alkaloids into less toxic and non-toxic derivatives...

PURPOSE: A case of amiodarone-induced neurotoxicity is reported. SUMMARY: A 76-year-old man arrived at the emergency department with complaints of increasing imbalance over the past 2.5 months after a recent discharge from the hospital. He reported that his balance had worsened over the past week and that he now must use a cane to walk. His medical history included coronary artery disease, peripheral vascular disease, hypertension, hyperlipidemia, and paroxysmal atrial fibrillation...

BACKGROUND: Amiodarone is commonly used in the treatment of refractory paroxysmal atrial fibrillation. Much of the literature focuses on the toxic effects of this medication in the setting of rapid loading or long-term therapy with high maintenance doses. However, patients have been known to develop multi-organ toxicities with long-term low-dose therapy. CASE REPORT: We present a 90-year-old man with paroxysmal atrial fibrillation undergoing low-dose amiodarone therapy for a period of 18 months without medical follow-up who developed signs and symptoms consistent with neurotoxicity and hepatotoxicity in association with hyperammonemia...

INTRODUCTION: Drug-induced neuropathies are mainly sensory and subacute. The pathophysiological mechanisms associated with them are not clearly established and few pharmacoepidemiologic studies are available. METHOD: This study investigated spontaneous reports of peripheral neuropathies reported to the French Adverse Drug Reaction (pharmacovigilance) database over a ten-year period. RESULTS: Between January 1995 and April 2005, 1110 cases were reported, predominantly among men (60%)...

Amiodarone chlorhydrate is a diiodated benzofuran derivative, and it is used to treat cardiac rhythm abnormalities. Hepatotoxicity is a relatively uncommon side effect of amiodarone, and symptomatic hepatic dysfunction occurs in fewer than 1% of the patients taking amiodarone. Cirrhosis is a rare complication that's been confirmed in 12 cases. Peripheral neuropathy occurs in 10% of patients taking aminodarone. We report here on an unusual case of amiodarone-induced hepatotoxicity and peripheral neurotoxicity...

Grape seed proanthocyanidins have been reported to possess a broad spectrum of pharmacological and medicinal properties against oxidative stress. We have demonstrated that IH636 proanthocyanidin extract (GSPE) provides excellent protection against free radicals in both in vitro and in vivo models. GSPE had significantly better free radical scavenging ability than vitamins C, E and beta-carotene and demonstrated significant cytotoxicity towards human breast, lung and gastric adenocarcinoma cells, while enhancing the growth and viability of normal cells...

Grape seed proanthocyanidins have been demonstrated to exhibit a broad spectrum of pharmacological, therapeutic and chemoprotective properties. In our previous studies, IH636 grape seed proanthocyanidin extract (GSPE, commercially known as ActiVin) demonstrated excellent concentration- and dose-dependent free radical scavenging abilities in both in vitro and in vivo models and provided significantly better protection than vitamins C, E and beta-carotene. GSPE demonstrated significant cytotoxicity towards human breast, lung and gastric adenocarcinoma cells, while enhancing the growth and viability of normal human gastric mucosal cells and macrophage J774A...

Amiodarone, a benzofuranic derivative, iodine-rich drug, has been used in pregnancy for either maternal or fetal tachyarrhythmias. Amiodarone, its main metabolite (desethylamiodarone) and iodine are transferred, albeit incompletely, through the placenta, resulting in a relevant fetal exposure to the drug and iodine overload. Since the fetus acquires the capacity to escape from the acute Wolff-Chaikoff effect only late in gestation, the iodine overload may cause fetal/neonatal hypothyroidism and goiter. Among the reported 64 pregnancies in which amiodarone was given to the mother, 11 cases (17%) of hypothyroidism in the progeny (10 detected at birth, 1 in utero) were reported, 9 non-goitrous (82%) and 2 (18%) associated with goiter...

It is not known whether amiodarone is neurotoxic to the fetus, as it is to adults. We evaluated neurodevelopment of a historical cohort (N = 10) of children exposed transplacentally to amiodarone. Scores on standardized tests of cognitive and language skills were compared (by Wilcoxon signed rank test) between eight toddlers and matched controls. It was not possible to obtain controls for older amiodarone-exposed children (aged 9.7 and 12.0 years), whose test results were compared descriptively with normative data...

This report describes two patients with recent stroke who, upon transfer to the rehabilitation medicine service, were noted to have extrapyramidal features. Both patients were receiving amiodarone for management of atrial fibrillation. When this medication was discontinued, there was slow resolution of extrapyramidal features and an improvement in function. Physicians managing acute stroke patients should be alert for features of amiodarone neurotoxicity, because these side effects may occur more readily in patients with recent neurologic impairment and may impede their progress in rehabilitation...

PATIENTS: Three patients complained of proximal weakness and paraesthesia of the legs and difficulties in walking during amiodarone treatment. Examination showed signs of a predominantly distal sensory neuropathy, a proximal myopathy, and a cerebellar gait disorder. All had amiodarone dosages of 600 mg per day, amiodarone serum levels above 2.7 mg/l and a total amount of amiodarone ingestion of 300 to 500 g. The clinical symptoms subsided within six to eleven months after treatment was stopped...

Although amiodarone is the most effective antiarrhythmic agent for maintaining sinus rhythm in patients with atrial fibrillation, it is generally used as the drug of the last resort in the United States. This is because long-term amiodarone therapy can potentially cause serious noncardiac side effects, such as pulmonary fibrosis, thyroid dysfunction, hepatitis, and neurotoxicity. Furthermore, it may also cause adverse interaction with digoxin, coumadin, and other antiarrhythmic drugs. Atrial fibrillation is frequently associated with a variety of cardiac disease, and its triggering factors vary among patients...

A series of antiarrhythmic drugs was studied on spontaneous spike activity and depolarizing outward potassium current in leech Retzius nerve cells. Propafenone (0.7 microM/ml) produced a cardiac-like action potential with a rapid depolarization followed by a sustained depolarization or plateau, which is terminated after 250 msec by a rapid repolarization. The effect of lidocaine (0.7 microM/ml) on spontaneous spike activity was less pronounced, and early afterdepolarization has been recorded. Amiodarone at the same and much higher concentrations (3 microM/ml) did not generate either a cardiac-like action potential or an early afterdepolarization...

Rats were treated with amiodarone (20 mg/kg/day) up to 6 weeks and the neurotoxicity was assessed by determining changes in motor coordination, pain-threshold and rectal temperature every week during treatment. Body weight gain was decreased during amiodarone treatment and it was significant at and after 5 weeks. Food intake and water consumption were significantly reduced during treatment. After the first week of treatment with amiodarone, rats showed decreased ability to balance on horizontal rods. In the hot plate test (paw-lick), the amiodarone treated rats showed increased pain-thresholds throughout the treatment...

One hundred two patients with recurrent, drug-refractory tachyarrhythmias were treated with amiodarone for nine +/- eight months (mean +/- SD) (range, one to 50 months). Forty-five patients exhibited some form of neurotoxic reaction that was severe enough in nine patients to require discontinuation of treatment or reduction in dosage of the drug. The most frequent neurotoxic findings were tremor (44 patients), peripheral neuropathy (ten patients), and ataxia (seven patients). Five patients developed unusual neurotoxic manifestations: brainstem dysfunction characterized by downbeat nystagmus, hemisensory loss and ataxia, severe dyskinesia, jaw tremor, and proximal myopathy...

Sural nerve changes are described in 2 cases of amiodarone neuropathy. Clinically, 1 patient developed a sensorimotor neuropathy, whereas in the other it was predominantly motor. Examination of sural nerves showed demyelination with only mild axonal loss. Cytoplasmic changes developed in Schwann cells of myelinated and unmyelinated axons, and involved loss of most recognizable organelles. These changes were associated with, and possibly preceded, myelin sheath breakdown. Inclusions, mainly of a lamellated type, were found in all cell types in the nerves...

Rats and mice were given amiodarone by mouth at doses of 50 mg/kg/day. The drug induced accumulations of lipids within lysosomes, leading to the formation of cytoplasmic bodies. These were found in many tissues, both nervous and nonnervous, but were excluded from regions with blood-brain or blood-nerve barriers. Of nervous system regions lying outside a vascular barrier, autonomic ganglia were the most affected, with large accumulations of lysosomal bodies in nerve cells and processes, and evidence of degenerative changes...

Amiodarone has been implicated in the pathogenesis of optic neuropathy in several cases. However, that relationship is unclear, as subjects placed on amiodarone represent a high-risk group for various vasoocclusive accidents. In order to investigate the effect of amiodarone on the optic nerve, we examined histopathologically sections of the retrobulbar optic nerve obtained from an asymptomatic subject taking amiodarone. Lamellar inclusions were selectively found in the large axons. Amiodarone may have a chronic neurotoxic effect on the optic nerve via a drug-induced lipidosis...

Three patients were investigated due to neurological symptoms induced by amiodarone used to treat refractory cardiac arrhythmia. Chronic polineuritis was found in two and dyskinesia in one. The light and electromicroscopical studies (cases 1 and 2) of a N. Suralis (neuropathic cases) display a loss of large myelinated fibers and marked reduced unmyelinated axons associated with osmiophilic inclusions in Schwann cells and endothelial venulae. The EEG was abnormal in the case of dyskinesia (n.3). The interruption of amiodarone improved the neurological symptoms...

Five patients developed neurological adverse effects as they were treated with amiodarone for 2 to 18 months. The daily maintenance dose did not exceed 400 mg. The neurological manifestations included tremor, ataxia, peripheral neuropathy, dyskinesia, myoclonic jerks, extrapyramidal hypertony, and altered mental status. These side effects resolved within 3 days to 3 months after amiodarone withdrawal. Advanced age, renal failure, diabetes mellitus, and alcoholism seemed to be risk factors for development of amiodarone neurotoxicity...