Tag: GABA

Take Gabapentin as an Anticonvulsant

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 borderline personality disorder, since many seem to act as mood stabilizers, and for the treatment of neuropathic pain.

Anticonvulsants suppress the rapid and excessive firing of neurons during seizures. Anticonvulsants also prevent the spread of the seizure within the brain. Some investigators have observed that anticonvulsants themselves may cause reduced IQ in children.   However these adverse effects must be balanced against the significant risk epileptic seizures pose to children and the distinct possibility of death and devastating neurological sequelaesecondary to seizures.

Anticonvulsants are more accurately called antiepileptic drugs (abbreviated “AEDs”), and are often referred to as antiseizure drugs because they provide symptomatic treatment only and have not been demonstrated to alter the course of epilepsy.

Gabapentin (Neurontin) has been approved as adjunctive therapy in adults with partial seizures with or without secondary generalization . Begin with 300 mg daily; increase to 900 to 1,800 mg daily given every 6 to 8 hours.  Side Effects maybe: Somnolence, fatigue, ataxia, dizziness, gastrointestinal upset, dyspnea.

A gamma-aminobutyric acid (GABA) analog, gabapentin does not interact with GABA receptors. Its mechanism of action is unknown.

Gabapentin is well absorbed orally, circulates mostly unbound in the plasma and is excreted unchanged in the kidneys without appreciable metabolism in the body. Oral bioavailability is approximately 60 percent and is not affected by food. The half-life is five to seven hours and is related to the creatinine clearance. Therefore, excretion is decreased in patients with renal impairment and decreased cardiac function, and in elderly patients. Gabapentin can be removed from the system through hemodialysis.

In clinical studies,  gabapentin was found to be effective in adults with refractory partial seizures and was also effective in preventing the progression of partial seizures to generalized tonic-clonic seizures.

Because gabapentin has no known pharmacokinetic interactions with any other antiepileptic drugs, it is useful in patients taking other antiepileptic medication.

 

Gabapentin Pharmacology

Gabapentin is structurally related to GABA. However, it does not bind to GABAA or GABAB receptors, and it does not appear to influence synthesis or uptake of GABA.

Gabapentin is a medication that belongs to the class of drugs known as anticonvulsants or antiepileptics. It is primarily used to treat seizures and neuropathic pain, but it is also used off-label for various other conditions such as anxiety, insomnia, and restless leg syndrome.

Gabapentin works by binding to a specific type of voltage-gated calcium channel (the alpha-2-delta subunit) in the brain and spinal cord. This reduces the release of various neurotransmitters, including glutamate, substance P, and noradrenaline, which are involved in pain perception and seizures.

Gabapentin is rapidly absorbed after oral administration, and its bioavailability is not affected by food. The peak plasma concentration is reached within 2-3 hours after administration. Gabapentin is not metabolized in the liver and is primarily eliminated by renal excretion.

The half-life of gabapentin is approximately 5-7 hours, and it is typically administered three times a day to maintain therapeutic levels in the blood. The dosage of gabapentin may need to be adjusted in patients with renal impairment, and it should be used with caution in patients with a history of substance abuse or suicidal ideation.

Overall, gabapentin is a well-tolerated medication, but common side effects may include dizziness, drowsiness, fatigue, and ataxia. Gabapentin may also increase the risk of suicidal thoughts or behaviors, particularly in younger patients. Therefore, close monitoring is recommended during treatment with gabapentin.

High affinity gabapentin binding sites have been located throughout the brain; these sites correspond to the presence of voltage-gated calcium channels specifically possessing the alpha-2-delta-1 subunit.

Gabapentin 800mg
Gabapentin 800mg

This channel appears to be located presynaptically, and may modulate the release of excitatory neurotransmitters which participate in epileptogenesis and nociception.

Absorption

Variable, from proximal small bowel by L-amino transport system; saturable process; dose-dependent

Vd: 58 ± 6 L; CSF concentrations are ~20% of plasma concentrations

Metabolism

Not metabolized

Excretion

Proportional to renal function; urine (as unchanged drug)

Clearance: Apparent oral clearance is directly proportional to CrCl: Clearance in infants is highly variable; oral clearance (per kg) in children <5 years of age is higher than in children ≥5 years of age

Time to Peak

Immediate release: Infants 1 month to Children 12 years: 2 to 3 hours; Adults: 2 to 4 hours; Extended release: 8 hours

Half-Life Elimination

Infants 1 month to Children 12 years: 4.7 hours

Adults, normal: 5 to 7 hours; increased half-life with decreased renal function; anuric adult patients: 132 hours; adults during hemodialysis: 3.8 hours

Protein Binding

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Why Is Lyrica a Controlled Substance?

Lyrica is a controlled substance that falls under schedule V classification. Some patients develop a dependence, requiring help to stop using it.

Lyrica is a controlled substance that belongs to a class of medications rated as having the lowest potential for abuse. Lyrica isn’t a narcotic, but it does produce similar effects.

People with a history of alcohol or drug abuse are at a greater risk of abusing Lyrica. Additionally, researchers have received reports of physical and/or psychological dependence.

Every year, thousands of people abuse prescription medications at least once, according to statistics from the National Institute on Drug Abuse. Understanding how your medications work and taking them according to your doctor’s instructions are two critical steps in minimizing the risk of abusing Lyrica.

Why Is Lyrica a Controlled Substance?

Lyrica is a Schedule V drug, which places it among those with the lowest potential for abuse. For this reason, research on the prevalence of Lyrica addiction has been minimal.

Studies do show that Lyrica produces psychoactive effects, such as euphoria, that are similar to those produced by other controlled substances. Reports have surfaced of patients abusing the medication. Research also suggests that although Lyrica is considered a controlled substance, it could serve as a viable substitute for medications that put patients at higher risk of abuse and addiction, including benzodiazepines and opioids.

What Is in Lyrica That Makes It a Controlled Substance?

So, what’s in Lyrica that makes it a controlled substance? This prescription medication, known as pregabalin in its generic form, isn’t a narcotic.

It’s a gamma-amino-butyric acid (GABA) analog that’s roughly three to four times more potent than its predecessor, gabapentin, according to research published by the U.S. National Library of Medicine. It works by powerfully binding to components of the nervous system to soothe damaged or overactive nerves.

Side effects like dizziness and sleepiness could increase if you take Lyrica with alcohol or narcotic medications.

Although more research on Lyrica withdrawal is needed to fully understand the risks, patients who stop taking it without tapering the dosage over time could experience various withdrawal symptoms.