Anticonvulsants (also commonly known as antiepileptic drugs or as antiseizure drugs ) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder and personality threshold disorder, as many seem to act as mood stabilizers, and for the treatment of neuropathic pain. Anticonvulsants suppress rapid firing of neurons during an attack. Anticonvulsants also prevent the spread of spasms in the brain.
Conventional antiepileptic drugs can block sodium channels or increase? -aminobutyric acid (GABA) function. Some antiepileptic drugs have multiple or uncertain mechanisms of action. In addition to the voltage-gated sodium channels and GABA system components, their targets include GABA receptors A , GAT-1 GABA transporters, and GABA transaminases. Additional targets include voltage-gated calcium channels, SV2A, and? 2? By blocking sodium or calcium channels, antiepileptic drugs reduce the release of exitatoric glutamate, whose release is thought to be elevated in epilepsy, but also in GABA. This may be a side effect or even the actual mechanism of action for some antiepileptic drugs, because GABA itself can, directly or indirectly, act proponively. Another target of antiepileptic drugs is the alpha receptor peroxisome-activated alpha. The 5th best-selling drug class in the US in 2007.
Some anticonvulsants have demonstrated antiepileptogenic effects on epilepsy models. That is, they also prevent the development of epilepsy or can stop or reverse the development of epilepsy. However, no drug has been demonstrated in human trials to prevent epileptogenesis (development of epilepsy in risky individuals, such as after head injury).
Video Anticonvulsant
Terminology
Anticonvulsants are more aptly called antiepileptic drugs (abbreviated as "AEDs"), and are often referred to as antiseizure drugs because they provide symptomatic treatment only and have not been proven to alter the course of epilepsy.
Maps Anticonvulsant
Approval
The usual method of obtaining approval for drugs is to show it is effective when compared to placebo, or that it is more effective than existing drugs. In monotherapy (where only one drug is taken) it is considered unethical by most to have a trial with a placebo on a new drug with uncertain efficacy. This is because untreated epilepsy leaves the patient at significant risk of death. Therefore, almost all new epilepsy drugs were initially approved only as adjunctive therapy. Patients whose epilepsy is currently not controlled by their drug (ie, refractory to treatment) were selected to see if drug supplementation with new drugs leads to increased seizure control. Any reduction in seizure frequency compared with placebo. The lack of superiority over existing treatments, combined with the lack of placebo-controlled trials, means that some modern drugs have been approved by the FDA as early monotherapy. On the contrary, Europe only needs equality with existing care, and has agreed more. Despite the lack of FDA approval, the American Academy of Neurology and the American Epilepsy Society still recommend some of these new drugs as early monotherapy.
Drugs
In the following list, the dates in parentheses are the earliest approved use of the drug.
Aldehydes
- Paraldehyde (1882). One of the earliest anticonvulsants. It is still used to treat epileptic status, especially where there is no resuscitation facility.
Alliclic aromatic alcohol
- Stiripentol (2001 - limited availability). Indicated for the treatment of Dravet syndrome.
Barbiturates
Barbiturates are drugs that act as central nervous system (CNS) depressants, and based on this they produce a broad spectrum of effects, from mild sedation to anesthesia. The following are classified as anticonvulsants:
- Phenobarbital (1912). See also related primidone medications.
- Methylphenobarbital (1935). Known as mephobarbital in the US. No longer marketed in the UK
- Barbexaclone (1982). Only available in some European countries.
Phenobarbital was the major anticonvulsant from 1912 until the development of phenytoin in 1938. Currently, phenobarbital is rarely used to treat epilepsy in new patients because there are other less effective effective drugs. Phenobarbital sodium injections may be used to stop acute seizures or epilepticus status, but benzodiazepines such as lorazepam, diazepam or midazolam are usually tried first. Other Barbiturates have only an anticonvulsant effect on anesthetic doses.
Benzodiazepines
Benzodiazepines are a class of drugs with hypnotics, anxiolytic, anticonvulsive, amnestic and muscle relaxation. Benzodiazepines act as central nervous system depressants. The relative strength of each of these properties in each given benzodiazepine varies greatly and affects the prescribed indication. Long-term use can cause problems due to the development of tolerance to anticonvulsant effects and dependence. Of the many drugs in this class, only a few are used to treat epilepsy:
- Clobazam (1979). Mainly used in the short term around menstruation in women with catamenial epilepsy.
- Clonazepam (1974).
- Clorazepate (1972).
The following benzodiazepines are used to treat epileptic status:
- Diazepam (1963). May be administered rectally by a trained nanny.
- Midazolam (N/A). More and more is used as an alternative to diazepam. This water-soluble drug is sprayed to the side of the mouth but not swallowed. It is rapidly absorbed by the buccal mucosa.
- Lorazepam (1972). Given by injection in the hospital.
Nitrazepam, temazepam, and especially nimetazepam are strong anticonvulsant agents, but their use is rarely due to increased incidence of adverse effects and strong sedative and motor properties.
Bromides
- Potassium bromide (1857). The earliest effective treatment for epilepsy. There will be no better medicine until phenobarbital in 1912. It is still used as an anticonvulsant for dogs and cats.
Carbamate
- Felbamate (1993). This effective anticonvulsant drug has a very limited use because of the rare but life-threatening side effects.
Carboxamides
The following are carboxamides:
- Carbamazepine (1963). Popular anticonvulsant drugs are available in generic formulations.
- Oxcarbazepine (1990). Carbamazepine derivatives that have similar properties but are more tolerable and are also generally available.
- Eslicarbazepine acetate (2009)
Fatty Acids
The following are fatty acids:
- valproat - valproic acid, sodium valproate, and sodium divalproex (1967).
- Vigabatrin (1989).
- Progabide
- Tiagabine (1996).
Vigabatrin dan progabide juga merupakan analog dari GABA.
Turunan fruktosa
- Topiramate (1995).
GABA analog
- Gabapentin (1993).
- Pregabalin (2004).
Hydantoins
Berikut ini adalah hydantoins:
- Ethotoin (1957).
- Phenytoin (1938).
- Mephenytoin
- Fosphenytoin (1996).
Oxazolidinediones
Berikut ini adalah oksazolidinedion:
- Paramethadione
- Trimethadione (1946).
- Ethadione
Propionat
- Beclamide
Pyrimidinediones
- Primidone (1952).
Pyrrolidines
- Brivaracetam
- Etiracetam
- Levetiracetam (1999).
- Seletracetam
Succinimides
Berikut Ini Adalah succinimides:
- Ethosuximide (1955).
- Phensuximide
- Mesuximide
Sulfonamides
- Acetazolamide (1953).
- Sultiame
- Methazolamide
- Zonisamide (2000).
Triazines
- Lamotrigine (1990).
Ureas
- Pheneturide
- Phenacemide
Valproylamides
- Valpromide
- Valnoctamide
Lainnya
- Perampanel
- Stiripentol
- Pyridoxine (1939)
Anticonvulsant non-farmasi
Occasionally, the ketogenic diet or vagus nerve stimulation is described as "anticonvulsant" therapy as well. But they do not work as well as anticonvulsants
Maintenance guidelines
According to guidelines by the American Academy of Neurology and the American Epilepsy Society, particularly based on a large article review in 2004, patients with newly diagnosed epilepsy who require treatment may begin in standard anticonvulsants such as carbamazepine, phenytoin, valproic acid/valproate semisodium, phenobarbital, or newer anticonvulsants of gabapentin, lamotrigine, oxcarbazepine or topiramate. The anticonvulsant choice depends on the characteristics of each patient. Both newer and older drugs are generally equally effective in new-onset epilepsy. New drugs tend to have fewer side effects. For partial seizures or newly diagnosed mixtures, there is evidence to use gabapentin, lamotrigine, oxcarbazepine or topiramate as monotherapy. Lamotrigine may be included in the option for children with undiagnosed seizures newly diagnosed.
History
The first anticonvulsant was bromide, proposed in 1857 by the English gynecologist Charles Locock who used it to treat women with "hysterical epilepsy" (perhaps catamenial epilepsy ). Bromide is effective against epilepsy, and also causes impotence, which is not associated with anti-epileptic effects. Bromide also suffers from the way it affects behavior, introducing the idea of ​​'epilepsy personality' which is actually the result of treatment. Phenobarbital was first used in 1912 for both sedative and antiepileptic properties. In the 1930s, the development of animal models in epilepsy research led to the development of phenytoin by Tracy Putnam and H. Houston Merritt, who had distinct advantages in treating epileptic seizures with poor sedation. In the 1970s, the initiative of the National Institutes of Health, the Antikonvulsan Screening Program, led by J. Kiffin Penry, serves as a mechanism to attract the interests and abilities of pharmaceutical companies in the development of new anticonvulsant drugs.
Marketing approval history
The following table lists anticonvulsants along with approved marketing dates in the US, UK and France. Data for English and French is incomplete. In recent years, the European Medicines Agency has approved drugs throughout the European Union. Some drugs are no longer marketed.
Pregnancy
During pregnancy, some anticonvulsant metabolism is affected. There may be an increase in clearance and decrease resulting in lamotrigine, phenytoin, and carbamazepine concentrations at lower levels, and possibly lower levetiracetam levels and active oxcarbazepine metabolites, monohydroxy derivatives. Therefore, these drugs should be monitored when used in pregnancy.
Many commonly used drugs, such as valproate, phenytoin, carbamazepine, phenobarbitol, gabapentin have been reported to cause an increased risk of birth defects. Among anticonvulsants, levetiracetam and lamotrigine appear to carry the lowest risk of causing birth defects. The risk of untreated epilepsy is believed to be greater than the risk of side effects caused by these drugs, which require continuous antiepileptic treatment.
Valproic acid, and its derivatives such as sodium valproate and divalproex sodium, cause cognitive deficits in children, with increased doses leading to decreased intelligence. On the other hand, conflicting evidence for carbamazepine concerns an increased risk of congenital physical anomaly or neurodevelopmental disorders by intrauterine exposure. Similarly, children exposed to lamotrigine or phenytoin in the womb do not seem to differ in their skills compared to those exposed to carbamazepine.
There is insufficient evidence to determine whether newborns of women with epilepsy who are taking anticonvulsants have an increased risk of hemorrhagic disease in newborns.
Regarding breastfeeding, some anticonvulsants may pass to breast milk in significant amounts clinically, including primidone and levetiracetam. On the other hand, valproate, phenobarbital, phenytoin, and carbamazepine may not be transferred to breast milk in clinically significant amounts.
In animal models, some anticonvulsant drugs have been shown to induce neuronal apoptosis in the developing brain.
References
Further reading
- New fluorothiazole derivatives anti-epilepsy activity replaced by Devid Chutia, RGUHS
External links
- eMedicine: Antiepileptic drugs: overview
- NINDS: Antikonvulsan Scanning Program
- Use of anticonvulsants in Bronchial Asthma Pharmacotherapy
- MDNG: Anticonvulsant and Bone Health
- The Miami Children's Brain Institute - Antikonvulsan
- Drug Reference for FDA Approved Epilepsy Drugs
- Epilepsy Action: List of UK Anti-Epilepsy Drugs
Source of the article : Wikipedia
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