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Biomedical subjects

B K Alldredge

Publications and source records attributed to B K Alldredge.

At least 19 recordsLinked to original sources
PubMed2001

A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus.

BACKGROUND: It is uncertain whether the administration of benzodiazepines by paramedics is an effective and safe treatment for out-of-hospital status epilepticus. METHODS: We conducted a randomized, double-blind trial to evaluate intravenous benzodiazepines administered by paramedics for the treatment of out-of-hospital status epilepticus. Adults with prolonged (lasting five minutes or more) or repetitive generalized convulsive seizures received intravenous diazepam (5 mg), lorazepam (2 mg), or placebo. An identical second injection was given if needed. RESULTS: Of the 205 patients enrolled, 66 received lorazepam, 68 received diazepam, and 71 received placebo. Status epilepticus had been terminated on arrival at the emergency department in more patients treated with lorazepam (59.1 percent) or diazepam (42.6 percent) than patients given placebo (21.1 percent) (P=0.001). After adjustment for covariates, the odds ratio for termination of status epilepticus by the time of arrival in the lorazepam group as compared with the placebo group was 4.8 (95 percent confidence interval, 1.9 to 13.0). The odds ratio was 1.9 (95 percent confidence interval, 0.8 to 4.4) in the lorazepam group as compared with the diazepam group and 2.3 (95 percent confidence interval, 1.0 to 5.9) in the diazepam group as compared with the placebo group. The rates of respiratory or circulatory complications (indicated by bag valve-mask ventilation or an attempt at intubation, hypotension, or cardiac dysrhythmia) after the study treatment was administered were 10.6 percent for the lorazepam group, 10.3 percent for the diazepam group, and 22.5 percent for the placebo group (P=0.08). CONCLUSIONS: Benzodiazepines are safe and effective when administered by paramedics for out-of-hospital status epilepticus in adults. Lorazepam is likely to be a better therapy than diazepam.

Adult↗
PubMed2001

The prehospital treatment of status epilepticus (PHTSE) study: design and methodology.

Status epilepticus is a neurological emergency that is typically first encountered and managed in the prehospital environment. Although aggressive pharmacological treatment of status epilepticus is well established in the emergency department and hospital settings, the relative risks and benefits of active therapy for status epilepticus in the prehospital setting are not known. The Prehospital Treatment of Status Epilepticus (PHTSE) study is a prospective, randomized, double-blind, placebo-controlled study designed to address the following aims: (1) to determine whether administration of benzodiazepines by paramedics is an effective and safe means of treating status epilepticus in the prehospital setting and whether this therapy influences longer-term patient outcome, (2) to determine whether lorazepam is superior to diazepam for the treatment of status epilepticus in the prehospital setting, and (3) to determine whether control of status epilepticus prior to arrival to the emergency department influences patient disposition. The initial phase of the PHTSE study began in January 1994 and was completed in February 1999 after the successful enrollment of 205 patients into the three treatment arms. In this paper, we describe the rationale for the conceptualization of the study and details of the study design and methodology, and emphasize some aspects of study implementation that are unique to research involving the emergency medical system.

Adult↗
PubMed1999

Prehospital stability of diazepam and lorazepam.

Injectable benzodiazepines are commonly stocked on ambulances for use by paramedics. We evaluated the stability of lorazepam and diazepam as a function of storage temperature. Diazepam (5 mg/mL) and lorazepam (2 mg/mL) injectable solutions were stored for up to 210 days in clear glass syringes at three conditions: 4 degrees C to 10 degrees C (refrigerated); 15 degrees C to 30 degrees C (on-ambulance ambient temperature); and 37 degrees C (oven-heated). High-performance liquid chromatography (HPLC) analyses of syringe contents were performed at 30-day intervals. After 210 days, the reduction in diazepam concentration was 7% refrigerated, 15% at ambient temperature, and 25% at 37 degrees C. The reduction in lorazepam concentration was 0% refrigerated, 10% at ambient temperature, and 75% at 37 degrees C. Whereas diazepam retained 90% of its original concentration for 30 days of on-ambulance storage, lorazepam retained 90% of its original concentration for 150 days. The decrease in lorazepam concentration correlated with an increase in the maximum ambient temperature in San Francisco. These results suggest that diazepam and lorazepam can be stored on ambulances. When ambient storage temperatures are 30 degrees C or less, ambulances carrying lorazepam and diazepam should be restocked every 30 to 60 days. When drug storage temperatures exceed 30 degrees C, more frequent stocking or refrigeration is required.

Ambulances↗
PubMed1999

Status epilepticus: new concepts.

Generalized convulsive status epilepticus is a neurological emergency characterized by abnormally prolonged seizures. This review emphasizes recent developments that bear on our understanding of the pathophysiology and management of status epilepticus. Topics include GABAA receptor modulation during prolonged seizures, the role of genetics in susceptibility to status epilepticus, neuron-specific enolas, the Veterans Administration Cooperative Study Group trial comparison of various drug regimens, utility of the electroencephalogram in patient monitoring, emerging drug therapies and patient management in out-of-hospital settings.

Anticonvulsants↗
PubMed1999

Pharmacokinetics of fosphenytoin in patients with hepatic or renal disease.

PURPOSE: The pharmacokinetic behavior of fosphenytoin (FOS), the water-soluble prodrug of phenytoin (PHT), has been characterized in normal subjects. This is the first study of the effect of hepatic or renal disease on the rate and extent of conversion of FOS to PHT. METHODS: A single dose of fosphenytoin (250 mg over a period of 30 min) was administered to subjects with hepatic cirrhosis (n = 4), renal disease requiring maintenance hemodialysis (n = 4), and healthy controls (n = 4). Serial plasma concentrations were measured, and pharmacokinetic parameters were calculated. RESULTS: The mean time to reach the peak plasma FOS concentration was similar for each of the three groups. However, the mean time to achieve peak plasma concentrations of PHT tended to occur earlier in the hepatic or renal disease groups than in healthy subjects. The half-life of FOS was 4.5, 9.2, and 9.5 min for the three groups, respectively. There was a trend toward increased FOS clearance and earlier peak PHT concentration in subjects with hepatic or renal disease. This finding is consistent with decreased binding of FOS to plasma proteins and increased fraction of unbound FOS resulting from decreased plasma protein concentrations associated with these disease states. The conversion of FOS to PHT was equally efficient in subjects with hepatic or renal disease and healthy subjects. CONCLUSIONS: Although the differences in pharmacokinetic parameters between the three groups were not statistically significant, these data suggest the need for close clinical monitoring during FOS administration to patients with hepatic or renal disease. To minimize the incidence of adverse effects in this patient population, FOS may need to be administered at lower doses or infused more slowly.

Adult↗
PubMed1999

Seizure risk associated with psychotropic drugs: clinical and pharmacokinetic considerations.

Psychiatric co-morbidity with epilepsy is common and often requires the combined use of psychotropic and antiepileptic drugs (AEDs). Antidepressants and antipsychotic agents are believed to lower the threshold for new-onset seizures and recurrent seizures in epilepsy patients. Factors that influence the risk for seizures during psychotropic drug therapy include the intrinsic convulsant potential of the drug, the drug dosage and plasma concentration, and patient-related risk factors for seizure occurrence. Available evidence supports an increased risk for seizures associated with antidepressant and antipsychotic agents in overdose and during therapeutic use of high doses of selected drugs. However, a clear differentiation in seizure risk between most antidepressants and antipsychotics used at low to moderate therapeutic doses is not often possible. Limited studies of psychotropic drug use in patients with epilepsy demonstrate that these agents usually have a positive effect on the underlying psychiatric condition without an adverse effect on seizure occurrence. Pharmacokinetic interactions between AEDs and psychotropic drugs are common. Plasma concentration monitoring is often useful for minimizing the adverse consequences of these drug-drug interactions.

Anticonvulsants↗
PubMed1997

New pharmacotherapy for Parkinson's disease.

OBJECTIVE: To summarize the development, pharmacology, pharmacokinetics, efficacy, and safety of five investigational antiparkinsonian drugs that are in or have recently completed Phase III trials: three dopamine agonists, pramipexole, ropinirole, and cabergoline; and two catechol-O-methyltransferase (COMT) inhibitors, entacapone and tolcapone. The pathophysiology and the role of dopamine in Parkinson's disease are also reviewed. DATA SOURCES: A MEDLINE search of relevant English-language literature, clinical studies, abstracts, and review articles pertaining to Parkinson's disease was conducted. Manual searches of 1996/1997 meeting abstracts published by the American Academy of Neurology and the Movement Disorders Society were also performed. Manufacturers provided unpublished Phase III trial efficacy and pharmacokinetic data. STUDY SELECTION AND DATA EXTRACTION: Clinical trial investigations selected for inclusion were limited to human subjects. Interim analyses after 6 months for long-term clinical studies in progress were included. Pharmacokinetic data from animals were cited if human data were unavailable. Statistical analyses for all studies were evaluated. DATA SYNTHESIS: By selectivity targeting D2 receptors, the newer dopamine agonists (i.e., cabergoline, pramipexole, ropinirole) may delay the introduction of levodopa and thus the occurrence of levodopa-induced dyskinesias. In addition, they are efficacious as adjunctive therapies in patients with advanced Parkinson's disease. Unlike the currently available dopamine agonists, pramipexole and ropinirole are non-ergot derivatives and do not cause skin inflammation, paresthesias, pulmonary infiltrates, or pleural effusion. The COMT inhibitors, tolcapone and entacapone, improve the pharmacokinetics of levodopa by preventing its peripheral catabolism and increasing the concentration of brain dopamine; thus, these agents may reduce the incidence of "wearing-off" effects associated with the short half-life of levodopa and the progression of Parkinson's disease. CONCLUSIONS: Interim 6-month analyses of pramipexole, ropinirole, and cabergoline for symptomatic treatment of early Parkinson's disease have shown these drugs to be efficacious and relatively well-tolerated when used as monotherapy. Their role in delaying the development of motor fluctuations and delaying the addition of levodopa is the subject of long-term clinical studies. In advanced stages of Parkinson's disease, these medications were also efficacious; however, the main adverse effects included dyskinesias, somnolence, and hallucinations. The COMT inhibitors, entacapone and tolcapone, have also demonstrated efficacy in improving on-time in patients with stable disease. Tolcapone has also demonstrated efficacy in patients with motor fluctuations. Both drugs are relatively well-tolerated, with the exception of dyskinesias that require reduction of the levodopa dosage and occasional diarrhea.

Benzophenones↗
PubMed1995

Effect of prehospital treatment on the outcome of status epilepticus in children.

Diazepam is administered to children in status epilepticus by paramedics in many Emergency Medical Services systems throughout the United States despite the lack of clear evidence that this therapy is safe and effective when employed in the prehospital environment. We reviewed the clinical course of 45 episodes of generalized convulsive status epilepticus (SE) in 38 children to determine the effect of prehospital diazepam therapy (given rectally or intravenously) on the clinical course of SE and subsequent patient management. Nineteen SE episodes were treated with prehospital diazepam therapy--9 episodes with rectal diazepam (mean dose: 0.6 mg/kg) and 10 episodes with intravenous diazepam (mean dose: 0.2 mg/kg). Prehospital diazepam therapy was associated with SE of shorter duration (32 min vs 60 min; P = .007) and a reduced likelihood of recurrent seizures in the emergency department (58% vs 85%; P = .045). There were no significant differences between rectal and intravenous diazepam therapy with regard to SE duration, intubation, or recurrent seizures in the emergency department. These data suggest that prehospital administration of diazepam may shorten the duration of SE in children and simplify the subsequent management of these patients in the emergency department.

Administration, Rectal↗
PubMed1994

Antiepileptic drug hypersensitivity syndrome: in vitro and clinical observations.

Four patients who manifested symptoms of the antiepileptic drug (AED) hypersensitivity syndrome during therapy with carbamazepine are reported. In 3 patients, the syndrome was exacerbated after conversion of therapy to another antiepileptic drug with an aromatic ring chemical structure. In vitro lymphocyte transformation studies confirmed cross-reactivity to one or more aromatic AEDs in 3 patients. In all patients, discontinuation of aromatic AEDs resulted in resolution of symptoms and in 3 patients who required continued AED therapy, valproic acid was well tolerated.

Adolescent↗
PubMed1994

Drug-induced seizures.

Drug-induced seizures are a commonly encountered problem for physicians. In this article, drugs that cause seizures are discussed with regards to the incidence of seizures, associated clinical factors, risk factors, and special treatment considerations. This information should help physicians determine appropriate evaluation and treatment strategies when their patients experience a seizure while using drugs.

Analgesics↗
PubMed1993

Status epilepticus at an urban public hospital in the 1980s.

We retrospectively reviewed the clinical course of adult patients treated for generalized status epilepticus (SE) at the San Francisco General Hospital (SFGH) from 1980 to 1989. The review was designed to determine whether the etiologies of SE at our hospital have changed over the last two decades, and to investigate the relationships between etiology, response to anticonvulsant therapy, and short-term clinical outcome. Of 154 patients reviewed, the four leading etiologies for SE were anticonvulsant drug withdrawal (39), alcohol-related (39), drug toxicity (14), and CNS infection (12). This pattern was essentially unchanged from observations made at SFGH in the 1970s. Sixty percent of all patients responded to first-line drug treatment (usually phenytoin +/- diazepam), and the remainder required an additional agent (usually phenobarbital) for control of SE. The best response to anticonvulsants occurred in patients with SE related to tumor, anticonvulsant drug withdrawal, or refractory epilepsy, and the poor responders had anoxia, drug toxicity, CNS infection, or other metabolic abnormalities. Seventy-six percent of the patients had good outcomes. Of the 22 patients who died, SE was a likely cause of death in only two (ie, 1.3% of the entire study group). Metabolic abnormalities, stroke, and anoxia were associated with particularly poor outcomes compared with other etiologies. These observations show that the etiologies of SE have remained similar over two successive decades, and that the etiology of SE may help predict both the initial response to drug therapy and the short-term outcome.

Adolescent↗
PubMed1993

Pharmacoepidemiology of adverse drug reactions in hospitalized patients with human immunodeficiency virus disease.

To evaluate the incidence, characteristics, and risk factors of adverse drug reactions (ADRs) in patients with human immunodeficiency virus (HIV) disease, we conducted was a prospective observational study of inpatients with HIV disease. The study was conducted in a public teaching hospital affiliated with the University of California, San Francisco. We reviewed daily the hospital records of all eligible inpatients throughout their hospitalization for potential ADRs. Potential ADRs were independently evaluated by two of the authors with regard to the extent of their causal association(s) with implicated drug(s) using a previously validated algorithm. Type (A, augmented; B, bizarre) and severity (mild, moderate, severe) were also evaluated. Among 495 patient admissions involving 390 eligible patients, 173 potential ADRs were identified, of which 118 (68.2%) had a probable or definite causal relationship to the implicated drugs. These probable or definite ADRs occurred among 79 (20%) eligible patients; 82 ADRs (69.5%) were classified as augmented (type A) and 36 (30.5%) were classified as bizarre (type B) reactions. Skin rash was the most frequent (17%) ADR encountered. Of the medications causing ADRs, 70% were antimicrobial drugs. Significant independent risk factors for developing ADRs included advanced stage of HIV disease, intake of a greater number of medications, and longer hospital stay. A high percentage of patients with HIV disease developed ADRs. Skin rash was the single most common kind of ADR. Advanced stage of illness and prolonged drug exposure were the only risk factors for ADRs.

Adult↗
PubMed1990

Perphenazine-induced priapism.

A 29-year-old man experienced four episodes of prolonged painful erection while being treated with perphenazine for paranoid schizophrenia. Each episode of priapism lasted five hours or longer. On two occasions, aspiration of blood from the corpora cavernosa resulted in detumescence; the other episodes were successfully managed with operative shunting of blood from the congested cavernosa. Perphenazine was discontinued after the fourth episode of priapism and antipsychotic treatment with thiothixene was subsequently initiated. During 16 months of follow-up, the patient has reported normal erections without repeat episodes of priapism.

Adult↗
PubMed1989

Placebo-controlled trial of intravenous diphenylhydantoin for short-term treatment of alcohol withdrawal seizures.

PURPOSE: Despite conflicting experimental and clinical evidence, diphenylhydantoin continues to be used for the treatment of alcohol withdrawal seizures in emergency departments and alcohol detoxification centers. Our goal was to evaluate the effectiveness of intravenous diphenylhydantoin for prevention of alcohol withdrawal seizures in high-risk patients using a prospective, randomized, double-blind, placebo-controlled study design. PATIENTS AND METHODS: Ninety alcoholic patients, enrolled within six hours of the initial alcohol-related seizure in a withdrawal episode, were randomly assigned to treatment with intravenous diphenylhydantoin (1,000 mg) or placebo. Seventy-one patients had a history of seizures during prior alcohol withdrawal episodes. Patients with a history of seizures unrelated to alcohol withdrawal were excluded. Drugs known to affect the seizure threshold or demonstrating cross-tolerance with alcohol were withheld. For each patient, the study endpoint was either (1) seizure recurrence or (2) a minimum 12-hour seizure-free observation period after completion of the study drug infusion. RESULTS: During the postinfusion observation period, six of 45 diphenylhydantoin-treated patients and six of 45 placebo-treated patients experienced at least one recurrent seizure. Equivalent diphenylhydantoin serum levels were measured in patients with and without subsequent seizures. There was no statistically significant difference between the response rates for the two treatments (p greater than 0.05). The 95% confidence interval for the difference in response probabilities was -14.0%, 14%. CONCLUSION: When administered to non-epileptic patients within six hours of the onset of alcohol withdrawal seizures, intravenous diphenylhydantoin failed to show a significant benefit over placebo in the prevention of subsequent seizures. We suggest that the well-documented risks of intravenous diphenylhydantoin therapy outweigh the potential benefit in the short-term treatment of alcohol withdrawal seizures.

Adult↗
PubMed1989

Seizures associated with recreational drug abuse.

We retrospectively identified 49 cases of recreational drug-induced seizures in 47 patients seen at the San Francisco General Hospital between 1975 and 1987. Most patients experienced a single generalized tonic-clonic seizure associated with acute drug intoxication, but 7 patients had multiple seizures and 2 patients developed status epilepticus. The recreational drugs implicated were cocaine (32 cases), amphetamine (11), heroin (7), and phencyclidine (4). A combination of drugs was responsible in 11 cases. Seizures occurred independent of the route of administration, and occurred in both first-time and chronic abusers. Ten patients (21%) reported having had prior seizures, all with a close temporal association with drug abuse. Other than 1 patient who developed prolonged status epilepticus that caused a fixed neurologic deficit, most patients had no obvious short-term neurologic sequelae.

Adult↗
PubMedDate not supplied

Pharmacologic management of epilepsy in the elderly.

OBJECTIVE: To review the epidemiology and pharmacologic management of epilepsy in elderly patients. DATA SOURCES: Controlled trials, case studies, and review articles identified via MEDLINE using the search terms epilepsy, seizures, elderly, phenobarbital, primidone, phenytoin, carbamazepine, valproic acid, felbamate, gabapentin, lamotrigine, topiramate, tiagabine, levetiracetam, oxcarbazepine, and zonisamide. Recently published standard textbooks on epilepsy were also consulted. DATA SYNTHESIS: Epilepsy is a common neurologic disorder in the elderly. Cerebrovascular and neurodegenerative diseases are the most common causes of new-onset seizures in these patients. Alterations in protein binding, distribution, elimination, and increased sensitivity to the pharmacodynamic effects of antiepileptic drugs (AEDs) are relatively frequent, and these factors should be assessed at the initiation, and during adjustment, of treatment. Drug-drug interactions are also an important issue in elderly patients, because multiple drug use is common and AEDs are susceptible to many interactions. In addition to understanding age-related changes in the pharmacokinetics and pharmacodynamics of AEDs, clinicians should know the common seizure types in the elderly and the spectrum of AED activity for these seizure types. AEDs with activity against both partial-onset and generalized seizures include felbamate, lamotrigine, levetiracetam, topiramate, valproic acid, and zonisamide. Other AEDs discussed in this review (carbamazepine, gabapentin, phenobarbital, phenytoin, primidone, and tiagabine) are most useful for partial-onset seizures. CONCLUSION: The provision of safe and effective drug therapy to elderly patients requires an understanding of the unique age-related changes' in the pharmacokinetics and pharmacodynamics of AEDs as well as an appreciation of common seizure types and the drugs that are effective for the specific types seen in the elderly.

Absorption↗