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Epilepsia 1999This article describes a flexible, dynamic system for comparing antiepileptic drugs (AEDs) as monotherapy, taking into account the needs of the patient and the... (Review)
Review
This article describes a flexible, dynamic system for comparing antiepileptic drugs (AEDs) as monotherapy, taking into account the needs of the patient and the characteristics of the treatment. Because differences in efficacy between AEDs cannot readily be demonstrated in regulatory clinical trials, safety is of paramount importance. Each drug has been judged across 11 criteria. These include knowledge of mechanism of action, suitable pharmacokinetics, drug interactions, delineated range of efficacy, ease of titration, idiosyncratic reactions, sedative burden, neuropsychiatric profile, teratogenic potential, and the likelihood of producing long-term side effects. The final consideration relates to how "comfortable" the doctor is with prescribing the drug as monotherapy. Scores of -1 (drawback), 0 (neutral/unknown), or +1 (advantage) have been allocated under each category, depending on current knowledge and clinical experience. The sum of the individual scores determines the awarding of "stars." In addition, the positive and negative features of each AED, when used as monotherapy, are highlighted. A range of established and new AEDs has been examined using the "monostars" method, including phenobarbital, phenytoin, carbamazepine, sodium valproate, lamotrigine, gabapentin, oxcarbazepine, and vigabatrin. Scores can be adjusted as new information comes to light. Other agents can be added when suitable monotherapy data become available. This analysis supports the contention that choice of treatment in newly diagnosed epilepsy should take into consideration the patient's age, sex, general health, coexisting disabilities, concomitant medication, and life style. Seizure type, syndrome, and the AED's pharmacology, efficacy, and safety profile should also be considered. Because dosing is often modest, cost should rarely be the overriding factor in choosing a drug for a patient with newly diagnosed epilepsy in the developed world. With these criteria, some of the newer AEDs have potentially more to offer the patient as monotherapy than do the established agents.
Topics: Acetates; Amines; Anticonvulsants; Carbamazepine; Cyclohexanecarboxylic Acids; Drug Administration Schedule; Epilepsy; Gabapentin; Humans; Lamotrigine; Oxcarbazepine; Phenobarbital; Phenytoin; Practice Guidelines as Topic; Practice Patterns, Physicians'; Triazines; Valproic Acid; Vigabatrin; gamma-Aminobutyric Acid
PubMed: 10530678
DOI: 10.1111/j.1528-1157.1999.tb00928.x -
British Medical Journal Jun 1972
Review
Topics: Anorexia Nervosa; Blood Cell Count; Carbamazepine; Female; Humans; Male; Middle Aged; Nausea; Phenytoin; Trigeminal Neuralgia; Vertigo; Vomiting
PubMed: 4555842
DOI: No ID Found -
The Western Journal of Medicine Apr 1998
Topics: Adolescent; Adult; Age Factors; Anticonvulsants; Child; Humans; Infusions, Intravenous; Lorazepam; Phenobarbital; Phenytoin; Status Epilepticus; United States
PubMed: 9584666
DOI: No ID Found -
The Journal of Toxicological Sciences 2021Harmine is a β-carboline alkaloid that displays antidepressant, antitumor and other pharmacological effects. However, the strong toxic effects limit its clinical...
BACKGROUND
Harmine is a β-carboline alkaloid that displays antidepressant, antitumor and other pharmacological effects. However, the strong toxic effects limit its clinical application, and should be first considered.
PURPOSE
To evaluate the in vivo toxicity of harmine and explore intervention strategies against its toxicity.
METHODS
The in vivo toxicity of harmine was assessed from the symptoms, biochemical indices, and cardiovascular effects in mice. The intervention experiments were performed by using anesthetics, central drugs, and peripheral anticholinergics.
RESULTS
The acute toxicity of harmine is significantly dose-dependent and the median lethal dose is 26.9 mg/kg in vivo. The typical symptoms include convulsion, tremor, jumping, restlessness, ataxia, opisthotonos, and death; it also changes cardiovascular function. The anesthetics improved the survival rate and abolished the symptoms after harmine poisoning. Two central inhibitors, benzhexol and phenytoin sodium, uniformly improved the survival rates of mice poisoned with harmine. The peripheral anticholinergics didn't show any effects.
CONCLUSION
Harmine exposure leads to central neurological symptoms, cardiovascular effects and even death through direct inhibition of the central AChE activity, where the death primarily comes from central neurological symptoms and is cooperated by the secondary cardiovascular collapse. Central inhibition prevents the acute toxicity of harmine, and especially rapid gaseous anesthetics such as isoflurane, might have potential application in the treatment of harmine poisoning.
Topics: Acetylcholinesterase; Anesthetics; Animals; Cardiovascular Diseases; Central Nervous System Diseases; Cholinergic Antagonists; Dose-Response Relationship, Drug; Harmine; Isoflurane; Lethal Dose 50; Male; Mice, Inbred ICR; Phenytoin; Trihexyphenidyl; Mice
PubMed: 34078836
DOI: 10.2131/jts.46.289 -
British Journal of Clinical Pharmacology Jul 2010The clearance of many drugs is reduced in the elderly, but the data regarding phenytoin are conflicting. Most studies have estimated phenytoin metabolic clearance using... (Comparative Study)
Comparative Study
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
The clearance of many drugs is reduced in the elderly, but the data regarding phenytoin are conflicting. Most studies have estimated phenytoin metabolic clearance using total drug concentrations (bound plus unbound), which may be confounded by protein binding effects. Free phenytoin concentrations are independent of protein binding and should more accurately reflect true metabolic clearance changes in elderly patients.
WHAT THIS STUDY ADDS
The two studies reported in this paper suggest a trend towards reduced free phenytoin 'apparent clearance' in the elderly, although statistically significant results were not found. Other published studies have largely found similar trends, suggesting an age effect.
AIMS
To test the hypothesis that the 'apparent clearance' of free phenytoin is reduced in elderly patients.
METHODS
Two separate studies were conducted comparing free phenytoin 'apparent clearance' in elderly vs. younger adults. The first study was a retrospective analysis of free phenytoin concentrations measured at Christchurch Hospital from 1997 to 2006. In the second study free phenytoin concentrations were measured prospectively in ambulatory subjects who were taking phenytoin regularly.
RESULTS
In the retrospective study (n= 29), free phenytoin 'apparent clearance' was 0.27 +/- 0.04 l kg(-1) day(-1) (95% CI 0.19, 0.34) in the elderly cohort vs. 0.37 +/- 0.06 l kg(-1) day(-1) (95% CI 0.22, 0.52) in younger adults, but the difference was not statistically significant. In the prospective study, free phenytoin 'apparent clearance' showed a non-significant trend to being reduced in the elderly patients (0.12 +/- 0.02 l kg(-1) day(-1), 95% CI 0.07, 0.17) compared with the younger cohort (0.18 +/- 0.07 l kg(-1) day(-1), 95% CI 0.09, 0.26) in those not taking interacting drugs (n= 21).
CONCLUSIONS
This research does not prove the hypothesis that the 'apparent clearance' of free phenytoin is reduced in the elderly. However, the trends found in these two studies are supported by trends in the same direction in other published studies, suggesting an age effect.
Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Drug Interactions; Female; Humans; Male; Metabolic Clearance Rate; Middle Aged; Phenytoin; Retrospective Studies; Young Adult
PubMed: 20642556
DOI: 10.1111/j.1365-2125.2010.03673.x -
Journal of Veterinary Internal Medicine 2004Five adult horses with ventricular extra systoles (VES) and 2 with ventricular tachycardia (VT) refractory to treatment with rest, anti-inflammatory drugs, lidocaine, or...
Five adult horses with ventricular extra systoles (VES) and 2 with ventricular tachycardia (VT) refractory to treatment with rest, anti-inflammatory drugs, lidocaine, or procainamide were treated with phenytoin sodium p.o. q12h. The starting dosage of phenytoin was 20 or 22 mg/kg body weight (BW) q12h, and the maintenance dosage varied from 8 to 17 mg/kg BW q12h. The mean +/- standard deviation therapeutic blood concentration of total phenytoin was 8.8 +/- 2.1 mg/L, and the mean concentration of free phenytoin of 2.5 +/- 0.5 mg/L was relatively constant at a range of 24 to 29% of the total phenytoin concentration. In all horses, both VES and VT were abolished after treatment with phenytoin. On the basis of the results of this clinical study, the authors propose an initial dose of 20 mg/kg BW q12h for the first 3 or 4 dosages, followed by a maintenance dose of 10 to 15 mg/kg BW q12h. Phenytoin plasma concentrations should be monitored during therapy. High plasma concentrations were associated with adverse effects such as recumbency and excitement. In this study, which included a limited number of diverse patients, phenytoin sodium appeared to be an inexpensive and effective treatment for persistent VES or VT in cases where conventional treatment had failed.
Topics: Animals; Anti-Arrhythmia Agents; Drug Administration Schedule; Electrocardiography; Female; Horse Diseases; Horses; Male; Phenytoin; Tachycardia, Ventricular; Treatment Outcome
PubMed: 15188823
DOI: 10.1892/0891-6640(2004)18<350:psaatf>2.0.co;2 -
Revista Da Escola de Enfermagem Da U S P Feb 2014Phenytoin is an anticonvulsant that has been used in wound healing. The objectives of this study were to describe how the scientific production presents the use... (Review)
Review
Phenytoin is an anticonvulsant that has been used in wound healing. The objectives of this study were to describe how the scientific production presents the use ofphenytoinas a healing agent and to discuss its applicability in wounds. A literature review and hierarchy analysis of evidence-based practices was performed. Eighteen articles were analyzed that tested the intervention in wounds such as leprosy ulcers, leg ulcers, diabetic foot ulcers, pressure ulcers, trophic ulcers, war wounds, burns, preparation of recipient graft area, radiodermatitis and post-extraction of melanocytic nevi. Systemic use ofphenytoinin the treatment of fistulas and the hypothesis of topical use in the treatment of vitiligo were found. In conclusion, topical use ofphenytoinis scientifically evidenced. However robust research is needed that supports a protocol for the use ofphenytoinas another option of a healing agent in clinical practice.
Topics: Humans; Phenytoin; Publishing; Wound Healing
PubMed: 24676123
DOI: 10.1590/s0080-623420140000100021 -
Arquivos de Neuro-psiquiatria Jan 2021Data on prescribing patterns of antiepileptic drugs (AEDs) to older adult inpatients are limited.
BACKGROUND
Data on prescribing patterns of antiepileptic drugs (AEDs) to older adult inpatients are limited.
OBJECTIVE
To assess changes in prescribing patterns of AEDs to older adult inpatients with late-onset epilepsy between 2009-2010 and 2015-2019, and to interpret any unexpected patterns over the 2015-2019 period.
METHODS
Patients aged ≥60 years with late-onset epilepsy from a tertiary center were selected. Demographic data, seizure characteristics and etiology, comorbidities, and comedications were analyzed, in addition to prescription regimens of inpatients taking AEDs to treat epilepsy. AED regimens were categorized into two groups: group 1 included appropriate AEDs (carbamazepine, oxcarbazepine, valproic acid, gabapentin, clobazam, lamotrigine, levetiracetam, topiramate, and lacosamide); and group 2 comprised suboptimal AEDs (phenytoin and phenobarbital). Multivariate logistic regression analysis was performed to identify risk factors for prescription of suboptimal AEDs.
RESULTS
134 patients were included in the study (mean age: 77.2±9.6 years). A significant reduction in the prescription of suboptimal AEDs (from 73.3 to 51.5%; p<0.001) was found; however, phenytoin remained the most commonly prescribed AED to older adult inpatients. We also found an increase in the prescription of lamotrigine (from 5.5 to 33.6%) and levetiracetam (from 0 to 29.1%) over time. Convulsive status epilepticus (SE) and acute symptomatic seizures associated with remote and progressive etiologies were risk factors for the prescription of suboptimal AEDs.
CONCLUSIONS
Phenytoin was the main suboptimal AED prescribed in our population, and convulsive SE and acute symptomatic seizures associated with some etiologies were independent risk factors for phenytoin prescription. These results suggest ongoing commitment to reducing the prescription of suboptimal AEDs, particularly phenytoin in Brazilian emergence rooms.
Topics: Aged; Aged, 80 and over; Anticonvulsants; Brazil; Humans; Inpatients; Levetiracetam; Phenytoin
PubMed: 33656108
DOI: 10.1590/0004-282X-anp-2020-0012 -
Journal of Neurology, Neurosurgery, and... Jul 1985One hundred and eighty one patients with previously untreated epilepsy were randomised to sodium valproate, phenytoin or carbamazepine as monotherapy and followed up for... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
One hundred and eighty one patients with previously untreated epilepsy were randomised to sodium valproate, phenytoin or carbamazepine as monotherapy and followed up for a median period which ranged from 14 to 24 months. All three drugs were highly effective in the control of generalised seizures but less effective for partial seizures. Excellent or good control was achieved with therapeutic levels of sodium valproate and carbamazepine, but with subtherapeutic levels of phenytoin.
Topics: Adolescent; Adult; Aged; Carbamazepine; Child; Child, Preschool; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Therapy, Combination; Electroencephalography; Epilepsies, Partial; Evoked Potentials; Female; Humans; Kinetics; Male; Middle Aged; Phenytoin; Prospective Studies; Valproic Acid
PubMed: 3928820
DOI: 10.1136/jnnp.48.7.639 -
Lamotrigine and phenytoin, but not amiodarone, impair peripheral chemoreceptor responses to hypoxia.Journal of Applied Physiology... Dec 2006Amiodarone, lamotrigine, and phenytoin, common antiarrhythmic and antiepileptic drugs, inhibit a persistent sodium current in neurons (I(NaP)). Previous results from our... (Comparative Study)
Comparative Study
Amiodarone, lamotrigine, and phenytoin, common antiarrhythmic and antiepileptic drugs, inhibit a persistent sodium current in neurons (I(NaP)). Previous results from our laboratory suggested that I(NaP) is critical for functionality of peripheral chemoreceptors. In this study, we determined the effects of therapeutic levels of amiodarone, lamotrigine, and phenytoin on peripheral chemoreceptor and ventilatory responses to hypoxia. Action potentials (APs) of single chemoreceptor afferents were recorded using suction electrodes advanced into the petrosal ganglion of an in vitro rat peripheral chemoreceptor complex. AP frequency (at Po(2) approximately 150 Torr and Po(2) approximately 90 Torr), conduction time, duration, and amplitude were measured before and during perfusion with therapeutic dosages of the drug or vehicle. Hypoxia-induced catecholamine secretion within the carotid body was measured using amperometry. With the use of whole body plethysmography, respiration was measured in unanesthesized rats while breathing room air, 12% O(2), and 5% CO(2), before and after intraperitoneal administration of amiodarone, lamotrigine, phenytoin, or vehicle. Lamotrigine (10 microM) and phenytoin (5 microM), but not amiodarone (5 microM), decreased chemoreceptor AP frequency without affecting other AP parameters or magnitude of catecholamine secretion. Similarly, lamotrigine (5 mg/kg) and phenytoin (10 mg/kg) blunted the hypoxic but not the hypercapnic ventilatory response. In contrast, amiodarone (2.5 mg/kg) did not alter the ventilatory response to hypoxia or hypercapnia. We conclude that lamotrigine and phenytoin at therapeutic levels impair peripheral chemoreceptor function and ventilatory response to acute hypoxia. These are consistent with I(NaP) serving an important function in AP generation and may be clinically important in the care of patients using these drugs.
Topics: Action Potentials; Amiodarone; Animals; Anticonvulsants; Chemoreceptor Cells; Female; Hypercapnia; Hypoxia; Lamotrigine; Male; Phenytoin; Rats; Rats, Sprague-Dawley; Respiratory Mechanics; Triazines; Vasodilator Agents
PubMed: 16902058
DOI: 10.1152/japplphysiol.00633.2006