Controversies in the Actions of Digitalis Substances: Are all Digitalis Derivatives Alike?

Lathers, Claire M.; Lipka, Leslie J.; Klions, Howard A.

doi:10.1177/009127008502500705

Cited by 6 publications

(2 citation statements)

References 21 publications

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“…19 Explanations for these differences were explored in two in-depth reviews of studies conducted in multiple species with various digitalis glycosides. 20,21 These data suggested that differences existed between the two digitalis glycosides, ouabain and digoxin, in that the nonuniform effect on the peripheral sympathetic neural discharge played a greater role in ouabain-induced arrhythmias.…”

Section: Animal Models Of Ouabain-induced or Coronary Occlusion-inducmentioning

confidence: 98%

“…Interictal activity in spikes/minute is illustrated in the fourth graph, and the duration of ictal activity (prolonged ictal, solid boxes; brief ictal, crosshatched boxes) in seconds is seen in the bottom graph. The arrows along the abscissa indicate injections of pentylenetetrazol (PTZ), 10,20,50,100,200, and 2000 mg/kg intravenously, which were given every 10 minutes. The asterisk indicates the first occurrence of a change in the ECG (discussed in text).…”

Section: Figure 2 Postganglionic Cardiac Sympathetic Neural Dischargmentioning

confidence: 99%

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Clinical Pharmacology: Drugs as a Benefit and/or Risk in Sudden Unexpected Death in Epilepsy?

Lathers

Schraeder

2002

The Journal of Clinical Pharma

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Death may be the consequence of natural or unnatural causes, such as accidents, homicide, and suicide, which have no relationship to the disease of epilepsy. Direct causes of death include status epilepticus, and indirect causes may be head trauma or drowning subsequent to a seizure. When death occurs suddenly and without explanation, the term sudden unexpected unexplained death is used. Unexplained is a term that clinicians and research scientists are working to clarify. Numerous preclinical animal studies have been conducted as models for sudden death and have led to clinical studies in persons with epilepsy. These studies show that sympathetic nerve stimulation, ouabain, or coronary occlusion increased temporal dispersion of recovery of ventricular excitability and led to an underlying electrical instability that predisposed the ventricularmyocardium to arrhythmia. Cardiac arrhythmias in an animal model for ouabain-induced toxicity were associated with neural autonomic dysfunction. Neural discharges were characterized by increases, decreases, or no change in the discharge of postganglionic cardiac sympathetic nerves monitored simultaneously, predisposing to cardiac arrhythmia. Stimulation of the sympathetic ventrolateral cardiac nerve produced a shift in the origin of the pacemaker and tachyarrhythmias because the nerve is not uniformly distributed to the various regions of the heart but is localized to the atrioventricular junctional and ventricular regions. Such nonuniform distribution of sympathetic nerves would also contribute to initiation of arrhythmia as a nonuniform neural discharge occurred. Studies examining the physiology and pharmacology of this finding in multiple animal models found that subconvulsant, interictal discharge was associated with autonomic cardiac neural non-uniform discharge and cardiac arrhythmias. As a result of further investigations, Lathers and Schraeder edited a book in 1990 that summarized the clinical problem of sudden unexpected death and epilepsy (SUDEP). The contributors concluded that there was a paucity of clinical data addressing the mechanism of death. Regulatory response resulting from the consequent increased awareness of SUDEP occurred in 1993, when the FDA focused attention of practitioners and pharmaceutical manufacturers on the question of whether use of anticonvulsant drugs contributes to or prevents sudden unexpected death in epileptic persons. The FDA-convened panel of scientists considered the prevalence of sudden unexpected death in patients involved in studies associated with developing new anticonvulsant drugs and reviewed data on the risk of sudden unexpected death in patients taking lamotrigine. The risk of SUDEP was no different from thatfound in the young epilepsy population in general. Estimated SUDEP rates in patients receiving the new anticonvulsant drugs lamotrigine, gabapentin, topiramate, tigabine, and zonisamide were found to be similar to those in patients receiving standard anticonvulsant drugs, suggesting that SUDEP rates reflect population ...

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Section: Animal Models Of Ouabain-induced or Coronary Occlusion-inducmentioning

confidence: 98%

Section: Figure 2 Postganglionic Cardiac Sympathetic Neural Dischargmentioning

confidence: 99%

Clinical Pharmacology: Drugs as a Benefit and/or Risk in Sudden Unexpected Death in Epilepsy?

Lathers

Schraeder

2002

The Journal of Clinical Pharma

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Does Chlorpromazine Produce Cardiac Arrhythmia Via the Central Nervous System?

Lipka

Lathers

Roberts

1988

The Journal of Clinical Pharma

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The influence of the central nervous system in the production of phenothiazine-induced arrhythmia and death was examined in this study. In a series of cats, spinal cords were transected at the atlanto-occipital junction prior to the 1 mg/kg/min, i.v. infusion of chlorpromazine or thioridazine. No protection against drug-induced arrhythmia or death was afforded by this procedure. In other cats, 6OH-dopamine was administered prior to intravenous injection of atropine and infusion of chlorpromazine, 1 mg/kg/min. In these in situ denervated heart preparations, there was no protection against chlorpromazine-induced arrhythmia or death. In alpha-chloralose anesthetized cats, 0.5 mg chlorpromazine administered intracerebroventricularly did not induce arrhythmia or death, although blood pressure decreased initially. Thus, chlorpromazine or thioridazine do not appear to produce arrhythmia or death via a central locus and may instead be acting directly on myocardial conduction to produce arrhythmia and death.

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Chlorpromazine: Cardiac arrhythmogenicity in the cat

Lathers

Lipka

1986

Life Sciences

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Controversies in the Actions of Digitalis Substances: Are all Digitalis Derivatives Alike?

Cited by 6 publications

References 21 publications

Clinical Pharmacology: Drugs as a Benefit and/or Risk in Sudden Unexpected Death in Epilepsy?

Clinical Pharmacology: Drugs as a Benefit and/or Risk in Sudden Unexpected Death in Epilepsy?

Does Chlorpromazine Produce Cardiac Arrhythmia Via the Central Nervous System?

Chlorpromazine: Cardiac arrhythmogenicity in the cat

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