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Antiepileptic Drugs: Potassium Channel Activators01:20

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Ezocgabine or retigabine, an antiepileptic drug of remarkable efficacy, has revolutionized the management of seizures. It is a potassium channel activator, explicitly targeting the family of Q subtype potassium channels. It enhances the transmembrane potassium currents, regulating neuronal excitability. This action stabilizes the resting membrane potential, a pivotal factor in mitigating the hyperexcitability that characterizes epilepsy.
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Antiepileptic drugs, such as levetiracetam (Keppra) and brivaracetam (Briviact), have emerged as crucial tools in managing epilepsy. These medications exert their therapeutic effects by targeting the synaptic vesicle protein SV2A, a transmembrane glycoprotein primarily found in the brain.
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Antiepileptic Drugs: GABAergic Pathway Potentiators01:18

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γ-aminobutyric acid or GABA, plays a pivotal role as an inhibitory neurotransmitter in the brain. GABA pathway potentiators, also known as GABAergic drugs, are a class of pharmaceutical agents designed to enhance the functioning of the GABAergic system. These medications primarily treat epilepsy, a neurological disorder characterized by recurrent seizures.
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Glutamate is a fundamental neurotransmitter in the central nervous system, playing a vital role in neuronal communication and various cognitive processes. Glutamate stands as the principal excitatory neurotransmitter in the brain. Its presence is crucial for the communication between neurons, underpinning essential processes such as synaptic transmission, neuronal excitability, and plasticity. These functions are vital for higher-order cognitive processes, including learning and memory. The...
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Sedatives and hypnotics encompass a wide range of substances, each with its unique mechanism of action, uses, and potential adverse effects.
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Gabapentinoids: a therapeutic review.

Akshay Athavale1,2,3, Bridin Murnion1,2,3

  • 1MQ Health, Macquarie University, Sydney.

Australian Prescriber
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Summary

Gabapentinoids are prescribed for epilepsy and nerve pain but are often used off-label. Nonmedical use can lead to dependence, withdrawal, and increased poisonings, necessitating careful prescribing and deprescribing.

Keywords:
gabapentinnonmedical useoff-label prescribingpregabalin

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Area of Science:

  • Pharmacology
  • Clinical Therapeutics
  • Public Health

Background:

  • Gabapentinoids are approved for refractory focal epilepsy and neuropathic pain in Australia.
  • Off-label prescribing of gabapentinoids is prevalent, particularly for chronic nonspecific back pain and nonradicular leg pain, despite limited supporting evidence.
  • Gabapentinoids possess properties such as euphoria and sedation that may encourage nonmedical use.

Purpose of the Study:

  • To review the evidence for off-label gabapentinoid use.
  • To highlight the risks associated with nonmedical gabapentinoid use, including dependence, withdrawal, and poisoning.
  • To provide guidance on safe prescribing and deprescribing practices for gabapentinoids.

Main Methods:

  • Literature review of gabapentinoid use and adverse events.
  • Analysis of approved indications versus common clinical practice.
  • Examination of factors contributing to nonmedical use and potential harms.

Main Results:

  • Significant use of gabapentinoids outside approved indications, especially for musculoskeletal pain.
  • Increased incidence of accidental and deliberate poisonings linked to widespread nonmedical use.
  • Potential for dependence and withdrawal symptoms upon abrupt cessation; risks are elevated in patients with kidney disease.

Conclusions:

  • Clinicians must carefully consider the indication, patient factors, and harm-benefit profile when prescribing gabapentinoids.
  • Gradual dose tapering is recommended for deprescribing when continued use is uncertain.
  • Awareness of increased harm risk in vulnerable populations, such as those with renal impairment, is crucial.