Gabapentin/Pregabalin

Slang Terms:

Mikey Franks PHPR 486 Fall 2022

G abapentin-specific denoted with (G); Pregabalin-specific denoted with (P)

• Gabbies (G)

• Johnnies(G)

• Budweisers(P)

• Buds(P)

History/Background:

Gabapentin was approved by the FDA in 1993. It was originally used as a muscle relaxer and an anti-spasmodic. It was later found to have significant anti-convulsive properties. Because the mechanism of action of gabapentin was not initially understood, it was believed to have a low addiction potential.

Pregabalin was approved by the FDA in 2004 for neuropathic pain associated with various conditions. Pregabalin is one of the top 30 most prescribed medications.

Both drugs are notable for their many off-label uses. Both are used for recreational drug withdrawal has lead to an increase in abuse. Those addicted to recreational drugs have found the effects, in high enough doses, to be similar to drugs such as cocaine.

Pharmacology/Drug Effects:

Gabapentin and pregabalin are structurally similar to gamma-aminiobutyric acid (GABA), however, they have not been found to interact with any GABA receptors. Both have a high affinity to voltagegated calcium channels, specifically in the alpha-2-delta-1 subunit. Upon binding, they inhibit the release of excitatory neurotransmitters including: norepinephrine, dopamine, serotonin, glutamate, substance P, and calcitonin gene-related peptide receptors.

By inhibiting these excitatory neurotransmitters, these two drugs effectively reduce anxiety, seizures, restless leg syndrome, pain associated with neuralgia, and withdrawal (alcohol and cocaine).

Pharmacokinetics:

Bioavailability

• 60%-27%; inversely proportional to dose (G)

• >90% (P)

Time to Peak

• 2-4 hours; 8 hours for extended release (G)

• 8 hours for extended release with food (P)

Half-life Elimination:

• 5-7 hours; increased with renal impairment(G)

• 6.3 hours (P)

Absorption

Variable; absorbed by proximal small bowel by L-amino transport system. Pregabalin absorption is a saturable process. The higher the concentration of drug saturating transporters, the less bioavailable it becomes.

Interactions/Toxicology:

Bioavailability is reduced if either is taken on an empty stomach. Administer with food. There have not been any reports of serious overdoses of gabapentin or pregabalin. Overdose could lead to mild sedation, confusion, apathy, and rarely seizures. Gastric lavage and single-dose charcoal activated charcoal are common treatments for overdose.

Common side effects include bradycardia, hypotension, diarrhea, nausea, vomiting, dizziness, drowsiness, lethargy, slurred speech, tremor

Gabapentin/pregabalin withdrawal symptoms include anxiety, difficulty sleeping, nausea, pain, and sweating.

Worsened withdrawal and rebound symptoms occur if either are not gradually discontinued

Laws:

Gabapentin is not controlled everywhere in the US except Kentucky.

Pregabalin is classified as a Schedule V drug

Rising abuse has called into question the previous classifications of both gabapentin and pregabalin

Professional Opinion:

While Pregabalin is classified as a controlled substance, I believe that Gabapentin should become classified as well. The urgency of monitoring for abuse increases sharply as a substance becomes controlled. This is especially important as both, when abused, can increase suicidal thoughts in patients. Although the lethal overdose potential of both has been determined as low, the risk of severe harm when unregulated is very high.

References:

Avoid use with:

• Other CNS depressants

• Alcohol

• Cocaine

• Antisiezure drugs

• Sedatives

Monitoring/Drug Screens:

When patient is taking either, it is important to monitor the following:

• Efficacy (pain intensity/seizure frequency)

• Degree of sedation

• Mental alertness

• Suicidal thoughts

• Respiratory depression (Respiratory impairment)

• Assess for history of drug abuse

Screening:

• Blood: 5-7 hours

• Urine: three days

• Hair follicle: 90 days

• Saliva: Undetectable

Abuse Potential:

Studies have shown that patients with a history of opioid use and psychiatric disorders are at a higher risk of abusing gabapentinoids.

An increasing number of fatalities has been observed in people who abuse gabapentinoids with other psychoactive substances simultaneously.

Pregabalin is more commonly misused than gabapentin

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2. Hoeg N, Parisi T, Bhatt A. Gabapentin Addiction And Abuse. Addiction Center. Published July 17, 2022. Accessed October 5, 2022. https://www.addictioncenter.com/drugs/gabapentin/#:~:text=The%20drug’s%20known%20street%20names,changes%20in%20a%20user’s%20behavior

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7. Schifano F. Misuse and abuse of pregabalin and gabapentin: cause for concern? CNS Drugs 2014 Jun;28(6):491-6 doi: 10.1007/s40263-014-0164-4 PMID: 24760436.

8. Rietjens SJ, Sikma MA, Hunault CC, Lange DW, Hondebrink L. Pregabalin poisoning: Evaluation of dose-toxicity relationship. British Journal of Clinical Pharmacology 2021;88(3):1288-1297. doi:10.1111/bcp.15073

9. Erowid Gabapentin (Neurontin) Vault : Law. Erowid.org. Published 2017. Accessed October 6, 2022. https://www.erowid.org/pharms/gabapentin/gabapentin_law.shtml

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