Ghana: Neuropathic Pain Treatment – Pregabalin VRS Gabapentin

Neuropathic pain seems common today, especially with the rise in diabetes and strokes. Neuropathic pain is caused by damage or injury to the nerves that transfer information between the brain and the spinal cord from the skin, muscles, and other parts of the body. The pain is usually described as a burning sensation and the affected areas are often tender to the touch. Neuropathic pain can result from disorders of the peripheral nervous system or the central nervous system (CNS). Neuropathic pain may be associated with abnormal sensations or pain from normally nonpainful stimuli. It can have continuous and/or episodic components. These look like stab wounds or electric shocks. Common qualities include burning or coldness, tingling sensations, numbness and itching.

I saw an article about neuropathic pain in the Pharmacy Times on September 22, 2015 titled “How Gabapentin Differs From Pregabalin” in the Management of Neuropathic Pain. About 25% of people with diabetes suffer from painful diabetic neuropathy. Additionally, about 25% of people with herpes zoster infection will develop persistent neuropathic pain. More than 85% of patients with neuropathic pain caused by peripheral neuropathy will require drug therapy.

Pregabalin and gabapentin are often considered first-line treatments for various neuropathic pain syndromes, usually regardless of cause. The Pharmacy Times article compares the pharmacokinetics (PK) and pharmacodynamics (PD) of pregabalin with gabapentin and conversion regimens.

Pregabalin and gabapentin are antiepileptic drugs structurally similar to gamma-aminobutyric acid (GABA), although neither agent has activity in GABA neural systems. The effectiveness of pregabalin and gabapentin in neuropathic pain is related to their ability to bind to voltage-gated calcium channels in the CNS, in particular alpha-2-delta protein. This binding decreases the release of neurotransmitters in the CNS due to the reduced influx of calcium through the gated channels.

Gabapentin is indicated as an adjunctive treatment for partial onset seizures and postherpetic neuralgia. Pregabalin is indicated for the same uses as gabapentin, in addition to the management of fibromyalgia and neuropathic pain associated with diabetes, particularly diabetic neuropathy. The overall pharmacokinetic profiles of pregabalin and gabapentin are similar, but there are significant differences. Both drugs are structurally similar to the amino acid leucine and both can undergo facilitated transport across cell membranes via system L-amino acid transporters. Pregabalin has a better additional absorption system as it is almost completely absorbed unlike Gabapentin. Moreover, the absorption of gabapentin is limited to the small intestine while pregabalin is absorbed throughout the small intestine and extends to the ascending colon.

Gabapentin is more slowly and variably absorbed with peak plasma concentrations approximately 3 hours after administration. Pregabalin is rapidly absorbed, with the maximum absorption rate being 3 times that of gabapentin. It reaches peak blood levels within an hour of ingestion.

Gabapentin absorption is saturable, leading to a nonlinear pharmacokinetic profile. Increases in drug exposure are not linearly related to increases in administered doses. Pregabalin is not saturable and the drug has a linear pharmacokinetic profile.

The bioavailability of generic gabapentin in tablet and capsule formulations equivalent to the Neurontin brand is approximately 80% at lower doses such as 100mg every 8 hours, but only 27% bioavailable at doses of 1600mg every 8 hours. Pregabalin has a bioavailability greater than 90% over a dosage range of 75 mg to 900 mg per day in divided doses. Food increases gabapentin absorption, but pregabalin absorption is not affected by food.

The distribution of the two drugs is similar – neither is bound to any significant extent to plasma proteins, decreasing the likelihood of drug interactions due to protein binding. Neither is equally affected by cytochrome (CYP) drug-drug interactions, as neither is metabolized by CYP enzymes. Both undergo metabolism to a negligible extent (

Pregabalin and gabapentin are well tolerated. Dizziness and drowsiness are the most common side effects of both drugs (more than 20% seen with gabapentin). Cases of confusion and peripheral edema have been reported with gabapentin. The side effects of both drugs are dose-dependent and reversible if the drug is stopped. Abrupt discontinuation of gabapentin is not recommended due to withdrawal symptoms such as anxiety, insomnia, nausea, pain, and sweating.

Pregabalin is a more potent analgesic in neuropathic pain than gabapentin. The analgesic effect of pregabalin is about 6 times greater than that of gabapentin. This is taken into account when switching from gabapentin to pregabalin.

Overall, although pregabalin and gabapentin have similar pharmacokinetic and pharmacodynamic profiles, there are significant differences – pregabalin has more predictable pharmacokinetics, shows stronger binding affinity to its target receptor, increased potency, a steeper dose-response curve in neuropathic pain that does not cap overdose levels. Pregabalin has fewer side effects and may be more effective for neuropathic pain than gabapentin. The conversion ratio of gabapentin to pregabalin is approximately 6:1.

In situations where one must resort to complementary or alternative medicine, cocoa rich in flavanols is a very good option due to its anti-inflammatory and anti-nociceptive effects.

FROM DR. EDWARD O.AMPORFUL

CHIEF PHARMACIST

COCOA CLINIC

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