Anticonvulsants are drugs used to treat epileptic seizures. Sometimes these pharmacological agents are referred to as antiepileptic drugs or anti-seizure drugs. Whichever nomenclature we decide to use, one thing is certain – that this drug class has an immensely important therapeutic role.
Some drugs, though defined as anticonvulsant drugs, are also used to treat other conditions. Drugs such as gabapentin or pregabalin are, for example, commonly used to treat neuropathic pain. The central mechanism behind this drug class is quite simple – to reduce the intense neural firing that comes with a seizure.
Below, we go through many of the most essential facts about antiepileptic drugs. We focus on therapeutic indications, mechanisms, important side effects and clinically significant drug interactions. The below list is by no means intended to be exhaustive. It does, though, offer a framework onto which you can build your knowledge further.
- Barbiturates were originally the most commonly used antiepileptic drugs. They work as CNS depressants, enhancing the effects of GABA. Examples include:
– Phenobarbital: a drug first marketed in 1912. It is still used to treat most seizure types, except absence seizures.
– Primidone: one of the active metabolites of primidone is phenobarbital. Not widely used, if at all in many developed countries.
- Benzodiazepines dominated treatment of epileptic seizures from their introduction to the market in the 1960s. Long-term use of benzodiazepines are associated with dependence and tolerance (Cl + am = Clam):
Other benzodiazepines – such as diazepam, midazolam and lorazepam – are used to treat status epilepticus.
- Ethosuximide is used to treat absence seizures; seizures that are sometimes referred to as petit mal seizures. Absence seizures are characterised by a brief loss of consciousness. Ethosuximide is sometimes used alongside valproic acid for this indication. Ethosuximide works in part by blocking T-type calcium channels.
- Phenytoin is used to prevent partial seizures and tonic-clonic seizures, but not absence seizures. More common side effects with phenytoin include:
– Loss of appetite
– Increased hair growth
– Gingival hyperplasia
– Purple glove syndrome
Phenytoin works by blocking voltage-dependent sodium channels. Fosphenytoin is a water-soluble prodrug – a means to deliver phenytoin to the patient in a safer IV capacity.
- ‘Purple glove syndrome’ refers to swollen, discolored and painful extremities; a rare condition associated with large IV doses of phenytoin. In some cases of PGS, amputation is required.
- Lamotrigine is associated with an increased risk of skin rash which may, in some cases, lead to the potentially fatal Stevens-Johnson syndrome or toxic epidermal necrolysis. Patients should be monitored for skin rash during treatment. Lamotrigine works by blocking sodium channels and enhancing effect of GABA.
- Lennox-Gastaut syndrome refers to childhood-onset epilepsy (usually presenting between years 2 and 6) – characterised by multiple types of seizure, abnormal EEG patterns and intellectual impairment. Drugs used to treat LGS include:
– Vaproates – valproic acid, sodium valproate
– Benzodiazepines – clobazam, clonazepam
- Levetiracetam is used to treat the following seizure types:
– Partial onset
The most common side effects of levetiracetam are CNS related: somnolence, agitation, lethargy, dizziness, mood swings. Some patients experience coordination problems, anxiety and depression.
- GABA analogs – such as gabapentin and pregabalin – are frequently used to control seizures.
– Gabapentin is primarily used to treat focal seizures and mixed seizures. It’s also indicated to treat neuropathic pain, hot flashes and restless legs syndrome.
– Pregabalin is often used alongside other medicines to control partial epilepsy.
- Topiramate is a fructose derivative. It is used to treat epilepsy in both children and adults, particularly in cases of Lennox-Gastaut syndrome. It is also used alongside phentermine as a weight loss treatment. Drug interactions with topiramate include:
– Topiramate inhibits carbonic anhydrase; this means when used alongside other carbonic anhydrate inhibitors, such as acetazolamide, it increases the risk of kidney stones.
– Carbamazepine, another anticonvulsant, increases the elimination of topiramate from the body.
– Topiramate reduces the effectiveness of digoxin, estrogens and oral contraceptives.
- Fatty acids are important antiepileptic agents. Examples include:
– Valproates: valproic acid, sodium valproate
Valproic acid has a broad-spectrum of anticonvulsant activity – from tonic-clonic and absence seizures to myoclonic seizures and partial seizures. It comes with a risk of hepatotoxicity, pancreatitis and fetal abnormalities.
Vigabatrin works by inhibiting the breakdown of GABA.
Tiagabine is used to treat partial seizures in patients 12 years and older; a drug classified as a GABA-reuptake inhibitor (GRI).
- Carboxamides are another important class of antiepileptic drugs:
– Carbamazepine: effective for a wide range of seizures except absence seizures and myoclonic seizures. Bone marrow suppression remains a serious potential side effect. It works as a sodium channel blocker.
– Oxcarbazepine: used alone or in combination with other drugs in the treatment of partial seizures. It too works as a sodium channel blocker.
– Eslicarbazepine acetate: used alone or in combination with other drugs in the treatment of partial-onset seizures.
- The primary sulphonamide drug used to treat epilepsy is zonisamide; a drug used to treat partial seizures, generalized seizures and combined seizures. Zonisamide is believed to work by blocking sodium and T-type calcium channels.
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