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Probable propafenone-induced transient global amnesia.

Abstract

OBJECTIVE: To describe a probable case of transient global amnesia caused by propafenone. This adverse effect has not been previously described for this agent. CASE SUMMARY: A 61-year old man with a history of sick sinus syndrome with persistent atrial fibrillation and infrequent premature ventricular contractions was admitted to the hospital for symptoms of amnesia and disorientation to time, place, and date. He began taking propafenone only 6 days prior to admission because of uncontrolled atrial fibrillation and symptoms of fatigue. His atrial fibrillation subsequently had converted to normal sinus rhythm while he received propafenone without adverse effects prior to this episode. His symptoms of amnesia resolved approximately 6-7 hours after discontinuing the propafenone therapy. DISCUSSION: Propafenone is a class 1C antiarrhythmic agent that blocks fast sodium channels in heart muscle and Purkinje fibers similar to the action of encainide and flecainide. It also produces weak beta- and calcium-channel blockade. It has a significant adverse effect profile, with 30-45% of patients reporting cardiac adverse effects and 15-20% experiencing noncardiac events. Central nervous system effects that parallel amnesia have been reported in 10-15% of the patients, including dizziness, ataxia, drowsiness, fatigue, confusion, and paranoia. Propafenone's distribution, clearance, and structural similarity to propranolol contribute to its central nervous system effects. CONCLUSIONS: The rapid resolution of this patient's symptoms after discontinuing propafenone therapy and the absence of recurrence lend credence to the probability of this effect. Comparable adverse effects, such as disorientation and temporary amnesia, have been reported in patients in the analogous agent, propranolol. Consequently, this is a likely, although rare, possible adverse effect with propafenone for which patients should be monitored.

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BibTeXRIS

R J Jones, S R Brace, E L Vander Tuin. 1995. Probable propafenone-induced transient global amnesia.. https://doi.org/10.1177/106002809502900606

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Determination of the EC50 amnesic concentration of etomidate and its diffusion profile in brain tissue: implications for in vitro studies.

BACKGROUND: Etomidate is a widely used general anesthetic that has become a useful tool to investigate mechanisms of anesthetic action in vivo and in brain slices. However, the free aqueous concentration of etomidate that corresponds to amnesia in vivo and the diffusion profile of etomidate in brain slices are not known. METHODS: The authors assessed the effect of intraperitoneally injected etomidate on contextual fear conditioning in mice. Etomidate concentrations in brain tissue were obtained by high-performance liquid chromatography. Uptake studies in 400-microm-thick brain slices were used to calculate the diffusion and partition coefficients of etomidate. A diffusion model was used to calculate the expected concentration profile within a brain slice as a function of time and depth. The predicted rate of drug equilibration was compared with the onset of electrophysiologic effects on inhibitory circuit function in recordings from hippocampal brain slices. RESULTS: Etomidate impaired contextual fear conditioning with an ED50 dose of 11.0+/-0.1 mg after intraperitoneal injection, which corresponded to an EC50 brain concentration of 208+/-9 ng/g. The brain:artificial cerebrospinal fluid partition coefficient was 3.35, yielding an EC50,amnesia aqueous concentration of 0.25 microm. The diffusion coefficient was approximately 0.2x10 cm/s. The development of etomidate action in hippocampal brain slices was compatible with the concentration profile predicted by this diffusion coefficient. CONCLUSIONS: The free aqueous concentration of etomidate corresponding to amnesia, as defined by impaired contextual fear conditioning in mice, is 0.25 microM. Diffusion of etomidate into brain slices requires approximately an hour to reach 80% equilibration at a typical recording depth of 100 microm. This information will be useful in designing and interpreting in vitro studies using etomidate.

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