Pregabalin

Detailed

Pregabalin, a structural derivative of the neurotransmitter GABA, does not directly interact with GABA receptors but instead modulates calcium channel function, leading to a reduction in the release of excitatory neurotransmitters such as glutamate, norepinephrine, and substance P. Its primary indications include:

1. Neuropathic Pain: Pregabalin is highly effective in managing neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, and spinal cord injury. The analgesic effect is achieved through the attenuation of hyperexcited neurons.
2. Epilepsy: As an adjunctive therapy, Pregabalin is used to control partial seizures in patients aged 12 years and older. Its efficacy in reducing seizure frequency is well-documented in clinical trials.
3. Generalized Anxiety Disorder (GAD): Pregabalin is also prescribed for GAD, providing anxiolytic effects through its modulation of overactive neuronal circuits.

Pregabalin is absorbed rapidly with peak plasma concentrations occurring within 1.5 hours after oral administration. The drug is excreted unchanged in the urine, and its pharmacokinetics are linear across the dosing range.

Dosage

The dosage of Pregabalin must be individualized based on the patient’s condition and response to therapy. Common dosages include:

• Neuropathic Pain: Starting dose is typically 75 mg twice daily, which may be increased to 150 mg twice daily within one week, depending on efficacy and tolerability. The maximum dose is 300 mg twice daily.
• Epilepsy: The initial dose is usually 75 mg twice daily, with potential increases up to 600 mg/day, divided into two or three doses.
• Generalized Anxiety Disorder: Starting at 75 mg twice daily, the dose can be increased to 300-450 mg/day based on therapeutic response.

Pregabalin can be taken with or without food, and dose adjustments are necessary for patients with renal impairment.

Safety and Side Effects

Pregabalin is generally well-tolerated, but patients may experience side effects, especially at higher doses. Common adverse effects include dizziness, somnolence, dry mouth, edema, blurred vision, weight gain, and difficulty concentrating. In rare cases, patients may experience more severe effects, such as hypersensitivity reactions, angioedema, and suicidal thoughts or behavior.

Caution is advised when prescribing Pregabalin to patients with a history of substance abuse, as it has potential for misuse. Additionally, abrupt discontinuation should be avoided to prevent withdrawal symptoms, and a gradual tapering is recommended. Pregabalin is contraindicated in patients with known hypersensitivity to the drug or its components.

References

1. Ben-Menachem, E. (2004). Pregabalin pharmacology and its relevance to clinical practice. Epilepsia, 45(s6), 13-18.
2. Dworkin, R. H., O’Connor, A. B., Backonja, M., Farrar, J. T., Finnerup, N. B., Jensen, T. S., … & Wallace, M. S. (2007). Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain, 132(3), 237-251.
3. Pohl, R. B., Feltner, D. E., Fieve, R. R., Pande, A. C., & Bielski, R. J. (2005). Efficacy of Pregabalin in the treatment of generalized anxiety disorder: A 4-week, multicenter, double-blind, placebo-controlled trial of Pregabalin and Alprazolam. Archives of General Psychiatry, 62(9), 1022-1030.
4. Taylor, C. P., Angelotti, T., & Fauman, E. (2007). Pharmacology and mechanism of action of Pregabalin: the calcium channel α2-δ (alpha2-delta) subunit as a target for antiepileptic drug discovery. Epilepsy Research, 73(2), 137-150.