digoxin and Seizures

Topics: Bacterial Vaccines; Bicarbonates; Brain Edema; Diagnosis, Differential; Diazepam; Digoxin; Fever; Gastrointestinal Hemorrhage; Heparin; Humans; Hydrocortisone; Infant; Infant, Newborn; Isoproterenol; Mannitol; Meningitis; Meningitis, Meningococcal; Meningitis, Viral; Phenytoin; Seizures; Shock, Septic; Vitamin K

The prevalence of epilepsy in the world population together with a high percentage of patients resistant to existing antiepileptic drugs (AEDs) stimulates the constant search for new approaches to the treatment of the disease. Previously a significant anticonvulsant potential of cardiac glycoside digoxin has been verified by enhancing a weak activity of AEDs in low doses under screening models of seizures induced by pentylenetetrazole and maximal electroshock. The aim of the present study is to investigate the influence of digoxin at a sub-cardiotonic dose on the anticonvulsant activity of valproate, levetiracetam, and topiramate in models of primary generalized seizures with different neurochemical mechanisms. A total of 264 random-bred male albino mice have been used. AEDs were administered 30 min before seizure induction once intragastrically at conditionally effective (ED50) and sub-effective (½ ED50) doses: sodium valproate and topiramate - at doses of 300 and 150 mg/kg; levetiracetam - at doses of 100 and 50 mg/kg. Digoxin was administered once subcutaneously at a dose of 0.8 mg/kg body weight (1/10 LD50) 10-15 min before seizure induction. Picrotoxin (aqueous solution 2.5 mg/kg, subcutaneously), thiosemicarbazide (aqueous solution 25 mg/kg, intraperitoneally), strychnine (aqueous solution 1.2 mg/kg, subcutaneously), camphor (oil solution 1000 mg/kg, intraperitoneally) have been used as convulsive agents for seizure induction. It was found that under the conditions of primary generalized seizures induced by picrotoxin, thiosemicarbazide, strychnine, and camphor, digoxin not only shows its own strong anticonvulsant activity but also significantly enhances the anticonvulsant potential of classical AEDs sodium valproate, levetiracetam, and topiramate. The obtained results substantiate the expediency of further in-depth study of digoxin as an anticonvulsant drug, in particular, the in-depth study of neurochemical mechanisms of its action.

Topics: Animals; Anticonvulsants; Camphor; Cardiotonic Agents; Digoxin; Levetiracetam; Male; Mice; Picrotoxin; Seizures; Strychnine; Topiramate; Valproic Acid

An 87-year-old male, prescribed digoxin and furosemide for congestive heart failure and Alzheimer disease, had dehydration and anemia due to poor food intake and hemorrhagic cystitis. Repeated vomiting due to an upper respiratory infection caused disturbance of consciousness and hypotension. The patient was admitted to hospital and diagnosed with digoxin intoxication and hypernatremia. The serum sodium (Na(+)) level was corrected, but the patient died 4 days after admission following uncontrollable seizure. A histologic examination after an autopsy revealed characteristic findings of central pontine myelinolysis (CPM). This is the first autopsy report on CPM triggered by vomiting in association with digoxin administration.

Topics: Aged, 80 and over; Brain; Cardiotonic Agents; Digoxin; Fatal Outcome; Forensic Pathology; Humans; Hypernatremia; Hypokalemia; Male; Myelinolysis, Central Pontine; Respiratory Tract Infections; Seizures; Staining and Labeling; Vomiting

Chan Su, a traditional Chinese medication, and Love Stone, a topical aphrodisiac, are both made from dried venom of the toad bufo bufo gargarizans and contain bufalin, cinobufotalin, cinobufagin, and other cardioactive steroids of the bufadienolide class. Deaths have occurred following ingestion of these products and the clinical course resembles digoxin toxicity. The purpose of this study was to determine the efficacy of digoxin specific Fab fragments in treating Chan Su poisoning. An ethanolic extract was prepared from Chan Su. Digoxin specific Fab fragments were reconstituted in normal saline to a concentration of 80 mg/ml. An approximate LD90 dose was determined in preliminary experiments. Mice were then randomly divided into a treatment group of 15 mice and a control group of 30 mice. The treatment group was pretreated with 20 ml/kg of digoxin specific Fab fragment solution by intraperitoneal injection at t = 0, followed by 10 ml/kg of digoxin specific Fab fragments intraperitoneal at t = 30 min. The control group was pretreated with equal volumes of intraperitoneal normal saline at the same times. Immediately following the 30 min injection, both groups were given the estimated LD90 dose of Chan Su extract by subcutaneous injection. An endpoint of survival at 6 h was chosen after preliminary results showed that all deaths occurred in the first 4 h. All 30 of the control mice had seizures followed by death compared to 11 seizures and 7deaths in the 15 treatment mice. These results were statistically significant by Fisher's exact test (p = 0.00003 for mortality and p = 0.009 for seizures). Digoxin specific Fab fragments are effective in the treatment of Chan Su poisoning in mice and may be effective for poisoning by other cardioactive steroids of the bufadienolide class.

Topics: Amphibian Venoms; Animals; Aphrodisiacs; Bufanolides; Bufonidae; Bufotenin; Cardenolides; Digoxin; Dose-Response Relationship, Drug; Gas Chromatography-Mass Spectrometry; Immunoglobulin Fab Fragments; Medicine, Chinese Traditional; Mice; Poisoning; Seizures; Survival Rate

Experimental evidence suggests that potassium channel openers play an important role in convulsions. In this study, the anticonvulsant activity of BRL 38227, a new potassium channel opener against digoxin-induced convulsions, is reported. Intraventricular administration of digoxin (7.5 micrograms), included "popcorn-type" convulsions in rats. BRL 38227, injected centrally increased the onset time of convulsions and decreased the mortality rate in a dose-dependent manner. Pretreatment with 4-aminopyridine, a potassium channel blocker antagonized the protective effect of BRL 38227. These findings show the involvement of potassium channels in digoxin-induced convulsions. Further these results indicate that in the future potassium channels might be a target for new anticonvulsant drugs.

Topics: 4-Aminopyridine; Animals; Benzopyrans; Brain; Cromakalim; Digoxin; Dose-Response Relationship, Drug; Female; Injections, Intraventricular; Male; Potassium Channels; Pyrroles; Rats; Rats, Wistar; Seizures

Digoxin (7.5 micrograms icv) induced 'pop-corn' type of convulsions and 100% mortality. The GABA-ergic agents produced varying degree of protection against digoxin-induced neurotoxicity. Diazepam (4 mg/kg) offered significant protection whereas pentobarbital (5 mg/kg) and baclofen (5 mg/kg) markedly reduced per cent mortality, but ethanol (2 g/kg), progabide (50 mg/kg) and muscimol (0.5 mg/kg) as well as GABA (50 mg/kg) could not offer significant protection in doses used. GABA-ergic agonists; GABA, baclofen, diazepam and pentobarbital when administered along with MK-801 (0.5 mg/kg) a non-competitive NMDA antagonist, a potentiation of anticonvulsant action of MK-801 was observed. MK-801 showed potent anticonvulsant profile in dose range (0.25-1 mg/kg) studied. A synergistic influence of Mg2+ and K+ ions on NMDA receptor antagonism was also observed. A role of GABA-ergic facilitation and NMDA antagonism as a potential anticonvulsant approach in digoxin-induced convulsions in rats has been suggested.

Topics: Animals; Baclofen; Diazepam; Digoxin; Dizocilpine Maleate; Female; gamma-Aminobutyric Acid; Injections, Intraventricular; Male; Muscimol; Pentobarbital; Rats; Rats, Inbred Strains; Receptors, GABA-A; Receptors, N-Methyl-D-Aspartate; Salts; Seizures

Intraventricular (IVT) administration of digoxin (7.5 micrograms) induced 'popcorn-type' convulsions in rats. Though the convulsions looked similar to morphine-induced seizures, naloxone failed to antagonize these effects. Other anticonvulsants like phenobarbitone, ethosuximide, or GABAergic substances like piracetam and semicarbazide also had no protective effect against digoxin-induced convulsions. While calcium chloride potentiated these effects of digoxin, phenytoin, magnesium chloride, and potassium chloride treatment showed blocking actions. These observations suggest the involvement of Na/K-ATPase system in digoxin-induced convulsions. Clonidine and diazepam also provided protection against digoxin-induced convulsions through an unknown mechanism.

Topics: Animals; Calcium Chloride; Clonidine; Diazepam; Digoxin; Female; gamma-Aminobutyric Acid; Magnesium; Magnesium Chloride; Male; Phenytoin; Piracetam; Potassium Chloride; Rats; Rats, Inbred Strains; Seizures

Topics: Asthma; Blood Circulation; Blood Transfusion; Brain Edema; Child, Preschool; Coma; Digoxin; Heart Massage; Humans; Male; Mannitol; Medication Errors; Respiration, Artificial; Seizures; Tachycardia; Theophylline

Topics: Animals; Behavior, Animal; Cardiac Glycosides; Cerebral Ventricles; Depression, Chemical; Digitoxin; Digoxin; Electrocardiography; Heart; Heart Rate; Injections; Injections, Intravenous; Lethal Dose 50; Mice; Ouabain; Respiration; Seizures