Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

General anesthetics, ganglionic blocking agents, anticonvulsants, and antioxidants have been shown to afford protection from seizures caused by exposure to hyperbaric oxygen. In the present study cats were exposed to 5 ATA oxygen in pairs in a hyperbaric chamber until both the control and pretreated cat convulsed or for a maximum 120 min exposure. Small amounts of four common antiepileptic agents and propylene glycol in amounts far less than previously reported (0.1 to 0.2 ml/kg) were initially tested for potential anticonvulsant activity. Two agents, clonazepam and propylene glycol, offered significant protection in delaying the onset of seizures whereas carbamazepine, valproic acid, and trimethadione appeared to hasten the onset of seizure activity. The time to seizures was increased nearly five times by clonazepam and over three times by very small amounts of propylene glycol.
 ...
PMID:Protection from oxygen-induced seizures by clonazepam and propylene glycol. 679 72

Hyperosmolality complicating the management of burned patients has multiple etiologies. Sepsis, hyperglycemia, renal failure, electrolyte disturbances, shock, and substances absorbed from the burn wound may be contributing factors. Chemicals, such as propylene glycol, within bacteriostatic topicals may also lead to hyperosmolality. This report describes a patient who developed severe hyperosmolality after 5% Betadine-glycerin therapy for a 60% partial-thickness burn. Status epilepticus developed 36 hours later, and triglycerides were 9,700 mg/dl. After Betadine-glycerin was stopped the central nervous system status slowly improved but pre-seizure function was never regained.
 ...
PMID:Hyperosmolality caused by percutaneously absorbed glycerin in a burned patient. 706 13

The development of tolerance to the anticonvulsant effects of clonazepam (CZP) was investigated using a pentylenetetrazol (PTZ)-induced kindled rat seizure model. PTZ kindled rats received twice daily injections, either 0.3 mg/kg of CZP for 3 weeks, 2.0 mg/kg of CZP for 2 weeks or vehicle (propylene glycol) as maintenance doses. PTZ injections (30 mg/kg) were given once weekly both prior to and after the initiation of maintenance doses. The protective effect of CZP against PTZ-induced seizures was examined by determining the protective effect of a single dose of CZP (0.1 or 0.3 mg/kg) given once weekly 30 min prior to 30 mg/kg PTZ injection. CZP treatment continued to protect the rats from kindled seizures during the CZP maintenance period in both experiments. No significant differences were found in seizure responses between rats receiving either dose of CZP maintenance and the vehicle maintenance control group (p > 0.05). We were unable to demonstrate tolerance to the protective effects of CZP against PTZ-induced kindled seizures in this rat seizure model.
 ...
PMID:Lack of tolerance to anticonvulsant effects of clonazepam in a rat pentylenetetrazol (PTZ) induced kindled seizure model. 808 52

Fosphenytoin is a water-soluble disodium phosphate ester of phenytoin that is converted in plasma to phenytoin. Fosphenytoin is compatible with most common i.v. solutions and can be administered safely through the i.m.route. An additional safety factor is the absence of propylene glycol in the fosphenytoin formulation. Propylene glycol is used as a vehicle in the i.v. phenytoin preparation and by itself may produce serious cardiovascular complications. Studies of the pharmacokinetics, safety, and tolerance of i.v. fosphenytoin have demonstrated that fosphenytoin produces phenytoin plasma concentrations similar to those achieved with oral and i.v. phenytoin, but without significant cardiovascular effects and only minimal discomfort at the injection site. Aside from local reactions, the most common adverse events associated with fosphenytoin have been pruritus and reactions typical of phenytoin (e.g., dizziness, somnolence, and ataxia). Fosphenytoin represents a significant advance in the treatment of patients with seizures who require parenteral therapy.
 ...
PMID:Intravenous administration of fosphenytoin: options for the management of seizures. 864 9

These studies investigate whether the neurosteroid and 5 alpha-reduced metabolite of testosterone (T), 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-Diol), has anti-seizure effects similar to its parent compound. In experiment 1, ovariectomized (ovx) Long-Evans rats (n = 20) were subcutaneously (s.c.) administered 32 mg/kg kainic acid or saline vehicle 10 min following 0.0, 3.0, or 7.5 mg/kg 3 alpha-Diol in 10% ethanol, propylene glycol vehicle (veh). During 2 h of observation of ictal activity, 3 alpha-Diol (3.0 and 7.5 mg/kg) prior to kainic acid significantly decreased the number and duration of partial and full seizures compared to the 0.0 3 alpha-Diol conditions and produced ictal activity that was comparable to 0.0 mg/kg 3 alpha-Diol no kainic acid controls (procedure controls). Animals that received 7.5 mg/kg 3 alpha-Diol prior to kainic acid had shorter latencies and distances to the hidden platform in a Morris Water Maze task than those that received 0.0 3 alpha-Diol, 1 week following ictal activity. Administration of 3 alpha-Diol (3.0 or 7.5 mg/kg) prior to kainic acid stimulation resulted in a greater number of identifiable neurons in the hilar region of the hippocampus, compared to 0.0 3 alpha-Diol condition. Experiment 2 was conducted to ascertain whether 3 alpha-Diol's anti-seizure effects were comparable to T and possibly a result of metabolism from T. Ovx rats (n = 36) were stereotaxically implanted with bipolar electrodes into the perforant pathway. One hour prior to perforant pathway stimulation, six rats were s.c. injected with either T (7.5 mg/kg), 3 alpha-Diol (7.5 mg/kg), 7.5 mg/kg T + 4MA (a 5 alpha-reductase inhibitor, 17 beta-N,N-diethylcarbamoyl-4-methyl-4aza,5 alpha-androstan-3-one), 4MA alone, 10% propylene glycol vehicle (veh) with perforant pathway stimulation, or veh without perforant pathway stimulation. 3 alpha-Diol and T produced similar seizure activity, water maze performance, and neuronal integrity in the hilar region of the hippocampus that were comparable to unstimulated controls. Because the T and 3 alpha-Diol groups were not different from T + 4MA but tended to be different from 4MA alone on these measures, this suggests that 3 alpha-Diol and T can have similar anti-seizure effects which may be due to actions of neurosteroids.
 ...
PMID:Androgenic neurosteroids: anti-seizure effects in an animal model of epilepsy. 969 38

First developed in 1950, parenterally administered phenytoin offered substantial advantages over parenterally administered phenobarbital and paraldehyde, which were the treatments for status epilepticus until the 1960s. During the 1950s, clinical research established the pediatric dosage of parenteral phenytoin for the treatment of seizures, which was based on the adult dosage adjusted to each child's weight. Studies in the late 1970s and early 1980s established more appropriate dosing for neonates and children on a milligram-per-kilogram basis. Scientifically derived dosing guidelines have been available only for the past 12 years. Side effects associated with parenteral phenytoin, caused primarily by its high pH level and the propylene glycol content needed to increase its solubility, were frequently reported during the 1970s and 1980s, after 25 years of clinical use. Intravenous administration of phenytoin caused burning at the infusion site and was associated with severe local cutaneous reactions following infiltration into surrounding tissue, leading to a recommendation that intravenous phenytoin be avoided in young children and the elderly. The propylene glycol solvent was linked to seizures, arrhythmia, asystole, and hepatic and renal damage. When administered intramuscularly, phenytoin is poorly absorbed and can cause hemorrhagic necrosis of the soft tissues at the injection site. Many of these side effects can be avoided in children with the use of fosphenytoin.
 ...
PMID:Pediatric use of intravenous and intramuscular phenytoin: lessons learned. 979 46

Intranasal (IN) administration is a promising approach for rapid-onset delivery of medications. In order to assess the feasibility of this approach for the emergency treatment of status epilepticus, three anticovulsants, i.e. diazepam (DZ), clonazepam (CZ), and a monocarbamate-based new compound (MCA) were studied in rabbits for the pharmacokinetics (PK) and pharmacodynamic (PD) response following intravenous (IV) and IN administrations. The animals were intranasally dosed with DZ (1 mg/kg), CZ (0.2 mg/kg), and MCA (5 mg/kg), dissolved in 200 microl of vehicle consisting of propylene glycol (PG), ethanol (EtOH), and water in the presence or absence of 1% sodium glycocholate (SGC) using single and repeated dosing schedules. Both DZ and CZ were absorbed very rapidly from 1% SGC/60% PG-30% EtOH-10% Water after IN single application; the T(max)'s were less than 2 min. The absorption rate of MCA was relatively slower with the peak time of 13-32 min. The bioavailability of single IN administration for DZ, CZ, and MCA determined over the first 2 or 4 h was found to be 77, 45, and 79%, respectively. The peak plasma level of DZ increased linearly with increasing the volume fraction of EtOH in the ternary cosolvent (20% to 60%). A repeated IN application of DZ, 5 min after the first dose, doubled the C(max) and AUC(0-2 h) values of the first one, whereas those of CZ and MCA resulted in an increase of 73-94% of the first dose. A single IN application of DZ- and CZ-containing formulations produced a PD response within 1.5 min, which was comparable to that of an IV injection. These results suggest that single or repeated IN applications of DZ, CZ, and MCA in a hydroalcohol-glycolic formulation might represent a viable approach to achieving a rapid systemic absorption of these anticonvulsants during the emergency treatment of status epilepticus and other types of seizures.
 ...
PMID:Rapid-onset intranasal delivery of anticonvulsants: pharmacokinetic and pharmacodynamic evaluation in rabbits. 1079 28

Effects of a solvent mixture commonly used to dissolve antiepileptic drugs on the anticonvulsive effect as well as serum and brain concentrations of zonisamide (ZNS), a sulfonamide derivative, were investigated. The solvent mixture consisted of propylene glycol (PG, 40%) and ethanol (10.5%) in saline (PES). Intraperitoneal administration of ZNS at 25, 50, and 75 mg/kg dissolved in PES suppressed seizures in the EL strain of mice more effectively than the same doses of ZNS in saline. Serum and brain concentrations of the drug were significantly higher with PES than with saline as the vehicle for administration. At a dose of 75 mg/kg ip, both serum and brain ZNS concentrations in mice treated with ZNS in PES remained significantly higher than concentrations in mice treated with ZNS in saline from 1 to 6 hours after injection. PES mixtures including PG may not be suitable solvents for antiepileptic drugs in experiments investigating anticonvulsive effects.
 ...
PMID:A solvent used for antiepileptic drugs increases serum and brain zonisamide concentrations in seizure-susceptible el mice. 1260 13

Oral droplet formulations of clonazepam (CZ) were developed to examine their potentials as an alternative to i.v. administration for the treatment of acute epileptic seizures. Propylene glycol containing 2.5% (wt/wt) CZ with or without 5.0% (wt/wt) oleic acid (OA) was prepared as a solution by heating at 90 degrees C and subsequently lowering the temperature to 30 degrees C. The droplet (20 microL) was administered to the oral cavity between the lower gum and bottom lip before CZ precipitation started. With a droplet of propylene glycol loaded with 2.5% (wt/wt) CZ and 5.0% (wt/wt) OA, the plasma concentration reached 20 ng/mL (minimal effective concentration) within 10 min and was maintained between 20 and 60 ng/mL, less than a toxic level, for a period of 60 min. For a droplet of propylene glycol loaded only with CZ at 2.5% (wt/wt), it took more than 15 min for the plasma concentration to reach 20 ng/mL. It is suggested that a droplet of CZ/OA/propylene glycol (2.5:5.0:92.5, wt/wt) might be useful as an alternative to i.v. injection of CZ for the treatment of acute epileptic seizures.
 ...
PMID:Clonazepam oral droplets for the treatment of acute epileptic seizures. 1872 Jan 41

Alcohol withdrawal syndrome (AWS) is a major cause of morbidity and mortality in the acute care setting. We describe a 28-year-old man who was brought to the emergency department with a new-onset seizure and clinical signs and symptoms consistent with advanced delirium tremens. A symptom-triggered intensive care unit treatment protocol consisting of a benzodiazepine and antiadrenergic agents was started. The manifestations of delirium tremens persisted with titration of a lorazepam infusion in excess of 40 mg/hour. Intravenous phenobarbital was administered in escalating doses of 65 mg followed by 130 mg 15 minutes later, resulting in control of severe agitation in the face of benzodiazepine resistance. Subsequent scheduled phenobarbital administration allowed for a successful and orderly weaning of the continuous benzodiazepine infusion and adjunctive agents used in AWS management. With continued clearing of consciousness, the patient was successfully discharged. The administration of phenobarbital in this patient allowed improved symptom control, minimized the potential for propylene glycol toxicity, was not associated with respiratory depression, and facilitated successful weaning of benzodiazepines. Barbiturates offer a mechanism of action that is different from that of benzodiazepines. Although the cornerstone of treatment for AWS remains benzodiazepines, this case highlights the potential utility of phenobarbital in patients with resistant AWS.
 ...
PMID:Phenobarbital treatment in a patient with resistant alcohol withdrawal syndrome. 1955 62


<< Previous 1 2 3 Next >>