Antiarrhythmic Agents

AMIODARONE

Amiodarone is a di-ionated benzofurane derivative used primarily in the treatment of refractory ventricular and atrial arrhythmias. Amiodarone can be toxic for almost every organ in the body, including the central and peripheral nervous systems, especially when taken at high doses for long periods of time. The most common neurotoxic findings include tremor, ataxia, proximal muscle weakness, and wasting. Tremor usually appears early in the course of therapy and is usually a bilateral 6-to 10-Hz action tremor of the arms, which is indistinguishable from essential tremor. It can involve all limbs and may be asymmetrical, although to date it has not been reported to be unilateral. Rarely, the tremor is associated with parkinsonian features. Other manifestations of basal ganglia dysfunction that have been reported in association with amiodarone include myoclonus, hemiballismus, and dyskinesias of the extremities and orofacial area. Basal ganglia dysfunction associated with amiodarone is dose related, and reversibility is inversely related to duration of therapy. y

LIDOCAINE

Lidocaine is widely administered parenterally and topically. It is oxidized to active and inactive metabolites by hepatic enzymes in the cytochrome P-450 mixed oxidase system. Toxic effects of lidocaine occur frequently and involve the cardiovascular system and CNS. Although lidocaine-associated CNS effects can be seen with other local anesthetics, lidocaine is far more common as the causative drug, and this relates to its rapid absorption across the blood-brain barrier. The high frequency of toxicity is probably due to a diffuse excitation of neuronal systems and begins as altered behavior. '1] At concentrations less than 6 pg/ml, dizziness, drowsiness, paresthesias, and visual disturbances predominate; confusion, dysarthria, coma, convulsions, cardiac arrhythmias, and respiratory arrest are more often seen at concentrations greater than 6 pg/ml. The toxicity of lidocaine can be viewed as a self-enhancing phenomenon: If administration is not terminated immediately, a marked respiratory acidosis results, which creates more of the active, ionized form of the drug. y Treatment focuses on adequate oxygenation and support because the half-life of bolus lidocaine given immediately is 6 to 8 minutes. However, because repeated injections change the kinetics of lidocaine and prolong its half-life to approximately

1140

90 minutes, more long-lasting effects can be seen.y Although most reports of adverse reactions involve intravenous lidocaine, toxic signs have also been reported with topical or oral use.

QUINIDINE

Quinidine is present in the cinchona bark, along with quinine and other alkaloids. Nervous system manifestations are usually not significant, but with overdosage or in susceptible individuals, quinidine causes a type of intoxication similar to that of quinine. The corresponding clinical syndrome, namely cinchonism, is manifested as headache, nausea, vomiting, blurring of vision, transient visual obscurations, and ringing of the ears. [i] The visual symptoms are short lived but can be confused with visual transient ischemic attacks or the visual accompaniments of migraine. More persistent quinidine amblyopia is the result of direct damage to the retinal ganglion cells. [62] Finally, there have been two case reports of dementia associated with chronic quinidine use, which reversed after drug discontinuation. y

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