• Clinical science

Anticonvulsant drugs

Abstract

Anticonvulsant drugs are classified as either classic or newer anticonvulsants. Newer anticonvulsants are usually better tolerated and have a broader therapeutic range than classic anticonvulsant drugs. The choice of drug is guided by the type of seizure, as not all substances are equally effective in the treatment of all forms of epilepsy. First-line treatment for focal seizures includes e.g., lamotrigine or levetiracetam, while valproate is used for generalized epilepsy. All anticonvulsants have dose-dependent side effects on the central nervous system such as somnolence and nausea, but some agents have more specific side effects (e.g., gingival hyperplasia caused by phenytoin).

Besides their importance in anti-epileptic therapy, anticonvulsants are also used for pain management (e.g., carbamazepine or gabapentin as coanalgesics) or as mood stabilizers in bipolar disorders (valproate).

Overview

Agent Indication Mechanism of action Side effects

Classic anticonvulsants

Valproate

  • Inhibits GABA transaminaseGABA → decreased neuronal excitability
  • Inactivates Na+ channels

Carbamazepine

  • Inactives Na+ channels

Ethosuximide

  • Inhibition of voltage-gated calcium channels (T-type) in neurons of the thalamus

Phenytoin

  • Inactivation of Na+ channels
  • Zero-order elimination (i.e., constant rate of drug eliminated)
Benzodiazepine
  • Indirect GABAA agonistGABA action
Newer anticonvulsants

Lamotrigine

  • Exanthema, exfoliative dermatitis, Stevens-Johnson syndrome (slow dose increase necessary to prevent skin and mucous membrane reactions)
  • Rarely hepatotoxic or nephrotoxic
  • Blurry vision
  • Gastrointestinal symptoms
Phenobarbital
  • GABAA agonistGABA action
  • Sedation
  • Tolerance and dependence
  • Cardiorespiratory depression
  • Induces cytochrome P-450
Levetiracetam
  • Somnolence, nausea
  • Psychiatric symptoms (e.g., changes in personality)
Gabapentin
  • Second-line treatment for focal seizures
  • Polyneuropathy
  • Post-herpetic neuralgia
  • Inhibition of voltage-gated calcium channels (T-type and L-type) in neurons of the thalamus
Pregabalin (tentative FDA approval)
Vigabatrin
  • Inhibits GABA transaminaseGABA
  • Irreversible vision loss

Topiramate

  • Blocks voltage-gated Na+
    channels
  • GABA
Tiagabine
  • Focal seizures, with or without impairment of consciousness
  • Gastrointestinal upset: nausea, vomiting, diarrhea
  • Insomnia
  • Drowsiness
  • Weight changes

References:[1][2685;400-413]

Effects

Each anticonvulsant drugs inhibits neural activity (↓ neural excitation, ↑ neural inhibition) and increases the seizure threshold by interacting with specific receptors and ion channels.

References:[1]

Guidelines & therapy recommendations

  • Monotherapy should always be the first-line treatment → increase dosage before initiating combination therapy
  • Combination therapy: drugs from different classes and/or with different pharmacologic modes of action for refractory seizures
  • For more detailed approaches to seizure treatment and epilepsy, see treatment of epileptic seizures.

References:[1][2]

Special patient groups

Pregnancy and breastfeeding

  • Classic anticonvulsants (especially carbamazepine and sodium valproate!) should be avoided if possible → teratogenic effects
  • Newer anticonvulsants: lack of medical data and trials during pregnancy
  • Choice of treatment depends on type of seizure and which substance enables optimal control of treatment.
  • Approach
    • Optimize seizure control prior to conception.
    • Avoid multiple therapies.
    • Administer the drug at the lowest dose which controls seizures.
    • Monitor plasma drug levels regularly.

References:[1]

  • 1. Le T, Bhushan V, Sochat M, Chavda Y. First Aid for the USMLE Step 1 2017. McGraw-Hill Education; 2017.
  • 2. Schmidt D, Schachter SC. Drug treatment of epilepsy in adults. BMJ. 2014; 348(feb28 2): pp. g254–g254. doi: 10.1136/bmj.g254.
  • Herold G. Internal Medicine. Cologne, Germany: Herold G; 2014.
  • Karow T, Lang-Roth R. Allgemeine und Spezielle Pharmakologie und Toxikologie. Dr. med. Thomas Karow (2012 und 2013); 2010.
  • Lüllmann H, Mohr K, Wehling M. Pharmakologie und Toxikologie. Thieme Verlag (2002); 2003.
  • Karow T, Lang-Roth R. Pharmakologie und Toxikologie. ; 2012.
  • Katzung B,Trevor A. Basic and Clinical Pharmacology. McGraw-Hill Education; 2014.
last updated 11/20/2018
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