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)

Thirty-five years since its introduction into clinical use, valproate (valproic acid) has become the most widely prescribed antiepileptic drug (AED) worldwide. Its pharmacological effects involve a variety of mechanisms, including increased gamma-aminobutyric acid (GABA)-ergic transmission, reduced release and/or effects of excitatory amino acids, blockade of voltage-gated sodium channels and modulation of dopaminergic and serotoninergic transmission. Valproate is available in different dosage forms for parenteral and oral use. All available oral formulations are almost completely bioavailable, but they differ in dissolution characteristics and absorption rates. In particular, sustained-release formulations are available that minimise fluctuations in serum drug concentrations during a dosing interval and can therefore be given once or twice daily. Valproic acid is about 90% bound to plasma proteins, and the degree of binding decreases with increasing drug concentration within the clinically occurring range. Valproic acid is extensively metabolised by microsomal glucuronide conjugation, mitochondrial beta-oxidation and cytochrome P450-dependent omega-, (omega-1)- and (omega-2)-oxidation. The elimination half-life is in the order of 9 to 18 hours, but shorter values (5 to 12 hours) are observed in patients comedicated with enzyme-inducing agents such as phenytoin, carbamazepine and barbiturates. Valproate itself is devoid of enzyme-inducing properties, but it has the potential of inhibiting drug metabolism and can increase by this mechanism the plasma concentrations of certain coadministered drugs, including phenobarbital (phenobarbitone), lamotrigine and zidovudine. Valproate is a broad spectrum AED, being effective against all seizure types. In patients with newly diagnosed partial seizures (with or without secondary generalisation) and/or primarily generalised tonic-clonic seizures, the efficacy of valproate is comparable to that of phenytoin, carbamazepine and phenobarbital, although in most comparative trials the tolerability of phenobarbital was inferior to that of the other drugs. Valproate is generally regarded as a first-choice agent for most forms of idiopathic and symptomatic generalised epilepsies. Many of these syndromes are associated with multiple seizure types, including tonic-clonic, myoclonic and absence seizures, and prescription of a broad-spectrum drug such as valproate has clear advantages in this situation. A number of reports have also suggested that intravenous valproate could be of value in the treatment of convulsive and nonconvulsive status epilepticus, but further studies are required to establish in more detail the role of the drug in this indication. The most commonly reported adverse effects of valproate include gastrointestinal disturbances, tremor and bodyweight gain. Other notable adverse effects include encephalopathy symptoms (at times associated with hyperammonaemia), platelet disorders, pancreatitis, liver toxicity (with an overall incidence of 1 in 20,000, but a frequency as high as 1 in 600 or 1 in 800 in high-risk groups such as infants below 2 years of age receiving anticonvulsant polytherapy) and teratogenicity, including a 1 to 3% risk of neural tube defects. Some studies have also suggested that menstrual disorders and certain clinical, ultrasound or endocrine manifestations of reproductive system disorders, including polycystic ovary syndrome, may be more common in women treated with valproate than in those treated with other AEDs. However, the precise relevance of the latter findings remains to be evaluated in large, prospective, randomised studies.
 ...
PMID:Pharmacological and therapeutic properties of valproate: a summary after 35 years of clinical experience. 1226 62

Epilepsy in women raises special reproductive and general health concerns. Seizure frequency and severity may change at puberty, over the menstrual cycle, with pregnancy, and at menopause. Estrogen is known to increase the risk of seizures, while progesterone has an inhibitory effect. Many antiepileptic drugs induce liver enzymes and decrease oral contraceptive efficacy. Women with epilepsy also have lower fertility rates and are more likely to have anovulatory menstrual cycles, polycystic ovaries, and sexual dysfunction. Irregular menstrual cycles, hirsutism, acne, and obesity should prompt an evaluation for reproductive dysfunction. Children who are born to women with epilepsy are at greater risk of birth defects, in part related to maternal use of antiepileptic drugs. This risk is reduced by using a single antiepileptic drug at the lowest effective dose and by providing preconceptional folic acid supplementation. Breastfeeding is generally thought to be safe for women using antiepileptic medications.
 ...
PMID:Epilepsy in women. 1240 23

Women with epilepsy have several gender-specific problems, first of all related to pregnancy and childbirth. They do, however, also meet with several other, less well-recognised specific problems. Many women have a marked change in seizure frequency in relation to their menstrual cycle, and menstrual disorders and polycystic ovaries induced by the use of antiepileptic drugs (AEDs), or by the condition itself, are more frequent in women with epilepsy. Cosmetic side effects of AEDs including weight gain, hair loss and skin problems can significantly reduce compliance in drug treatment and thus affect seizure frequency. Enzyme-inducing AEDs reduce the effectiveness of oral contraceptives and may lead to unplanned pregnancies. A higher incidence of sexual problems in women with epilepsy has also been reported. In menopause, the seizure frequency may change in parallel with the endocrine changes and some AEDs may facilitate the development of osteoporosis. Better understanding and awareness of these problems among patients and health care professionals can relieve many of the gender-specific problems in women. The goal is to tailor the treatment to the needs of the individual woman.
 ...
PMID:[Women and epilepsy]. 1282 93

A group of 105 women (54 of whom were, and had only ever been, taking valproate for at least a year, and 51 who had only ever taken either lamotrigine or carbamazepine, for at least a year) were compared with a group of 50 women who did not have epilepsy: any oral contraceptive taken at the time of testing was recorded and blood levels of follicle stimulating hormone (FSH), luteinising hormone (LH), testosterone and prolactin were estimated from days 2 to 6 of the menstrual cycle (day 1 being the first day of bleeding) and an MRI scan made of their pelvis. Women with epilepsy in general were significantly more likely to exhibit evidence on MRI scanning, of polycystic ovaries (PCO): women taking valproate but not an oral contraceptive were significantly more likely to have clinical biochemical evidence of the polycystic ovarian syndrome (PCOS) with raised LH and/or testosterone levels between days 2 and 6 of their menstrual cycle than women who did not have epilepsy: this was not so for women taking lamotrigine or carbamazepine. Since the polycystic ovary syndrome has potentially serious consequences it is suggested that, where possible, valproate is avoided in women of child bearing potential.
Seizure 2003 Sep
PMID:A study of anticonvulsant medication on ovarian function in a group of women with epilepsy who have only ever taken one anticonvulsant compared with a group of women without epilepsy. 1291 77

The prevalence of polycystic ovaries (PCO) and polycystic ovary syndrome (PCOS) in the general population is approximately 20 and 10%, respectively, and published studies suggest a similar prevalence in women with epilepsy. These data do not suggest that epilepsy is associated with a higher prevalence of the condition, and it would appear that the background prevalence of PCO and PCOS is the same as in the general population.
Seizure 2003 Sep
PMID:Polycystic ovary syndrome and epilepsy--a gynaecological perspective. 1291 86

The treatment of epilepsy extends far beyond seizure control. Many comorbidities have a significant impact on the medical management and quality of life of patients with epilepsy. In this review, we examine interactions between epilepsy and some common medical conditions. Psychiatric disorders with a high prevalence in epilepsy include mood disorders, anxiety disorders, and psychosis. Depression is common, psychosis occurs both in direct relation to seizures and interictally, and suicide rates are increased. Changes in sexual function and reduced fertility and marriage rates are described, including a discussion of polycystic ovary syndrome, which is increased in women with epilepsy. The effects of other chronic medical comorbid conditions are reviewed, including the effects of antiepileptic medications on bone health and the impact of renal insufficiency on pharmacological therapy of epilepsy.
 ...
PMID:Medical comorbidities in the treatment of epilepsy. 1452 79

Epilepsy is a condition of the central nervous system that is characterized by recurrent seizures. The goal of management is to make patients seizure free without intolerable adverse effects from treatment. Men and women differ in their physiologic makeup and therefore have different needs that must be considered when attempting to attain this goal. There are special concerns for women of child-bearing years with regard to contraception, pregnancy, and teratogenicity that should be considered during counseling and selection of appropriate treatment. There are also emerging concerns about the interaction of antiepileptic drugs and endocrine function that can affect ovarian function, induce polycystic ovary (PCO)-like syndrome, and threaten fertility. Systemic adverse effects can have a negative impact on weight, cosmetic appearance, sexual function, and bone health. Individualized treatment coupling antiepileptic drug use and the specific phase of impact of the reproductive cycle must be considered in treatment selection. Important concerns regarding long-term therapy are being raised as there are more treatment options to consider because of the plethora of new antiepileptic drugs that are available, often with more favorable pharmacokinetics and different adverse event profiles. Also, sex hormone fluctuations during maturation may exacerbate seizures at particular points during the life cycle for women, including menarche, during menses, during pregnancy, or later in the perimenopausal years, often presenting a uniquely challenging aspect to treatment. As the number of available treatment options for epilepsy increases, the optimal goal for primary care physicians is to work as a team with obstetricians, gynecologists, and neurologists in an effort to ensure the best treatment of women with epilepsy.
 ...
PMID:Updates on the treatment of epilepsy in women. 1474 36

In persons with epilepsy, both seizures and antiepileptic drugs can disturb reproductive health. For example, seizures can alter the release of hypothalamic and pituitary hormones, while some antiepileptic drugs alter concentrations of sex steroid hormones. Women with epilepsy are at increased risk for polycystic ovary syndrome and disorders of the menstrual cycle. Studies have found reduced fertility rates among men and women with epilepsy. The reasons for this reduction in fertility are likely to be both psychosocial and physiologic, and again, both epilepsy itself and antiepileptic drugs are implicated. Sexual dysfunction is common among patients with epilepsy and can have a somatic, psychological, or social basis. To provide the best care for patients with epilepsy, particularly women of reproductive age, clinicians must consider both the gender-based biology of epilepsy and the effects of antiepileptic drugs on reproductive health.
 ...
PMID:Reproductive disturbances in patients with epilepsy. 1537 96

The clinical care of women with epilepsy entails special considerations over the life span. Endogenous depression is more prevalent in persons with epilepsy than in the general population and may be unrecognized. Seizure frequency may be influenced by hormonal fluctuations, as reflected by catamenial patterns in up to 25% of women and by changes at menopause. Fertility is lower in women with epilepsy. These women should be evaluated for anovulatory cycles and particularly for polycystic ovary syndrome, with its attendant health risks. It is important to provide folate supplementation during the childbearing years and to evaluate bone health throughout life, providing calcium and vitamin D supplementation when indicated. Particular consideration is indicated before conception and during pregnancy to minimize both potential teratogenicity secondary to antiepileptic drugs (AEDs) and the risks that seizures pose to fetus and mother. At delivery, vitamin K is indicated. Some infants may need to be monitored for AED withdrawal, while others may require a perinatal team if malformations are identified in utero. Breast-feeding is possible, with sedation rarely being a problem. Recognition, evaluation, and management of these issues will minimize the negative impact of epilepsy and improve lifelong quality of life.
 ...
PMID:Recommendations for the care of women with epilepsy. 1537

We evaluated the clinical responses to add-on therapy with topiramate in eight patients with progressive myoclonic epilepsy (PME). Severe myoclonic seizures disturbing daily activities were persistent despite adequate trials of various combinations of antiepileptic drugs in all patients. After the initiation of topiramate therapy, five patients had a marked decrease in myoclonic seizure frequency, prominent improvement of daily functioning, and recovery from previous drug-related side effects such as weight gain and irregularities of menstruation due to polycystic ovary syndrome. However, we had to discontinue topiramate in three patients because of side effects. Topiramate seems to be a useful alternative agent in the treatment of PME. The antimyoclonic effect provides some independence in daily activities and decreases the side effects related to other antiepileptic drugs, which are clear benefits for this grave disease, although having a short-term effect in some patients.
 ...
PMID:Add-on therapy with topiramate in progressive myoclonic epilepsy. 1571 Mar 14


<< Previous 1 2 3 4 Next >>