TREATMENT OF NEUROPATHIC PAIN- PREGABALIN VRS GABAPENTIN

Neuropathic pain seems common today especially with the increases in diabetes and stroke. Neuropathic pain is caused by damage or injury to the nerves that transfer information between the brain and spinal cord from the skin, muscles and other parts of the body. The pain is usually described as a burning sensation and affected areas are often sensitive to the touch. Neuropathic pain may 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 non-painful stimuli. It may have continuous and/or episodic components. The latter resemble stabbings or electric shocks. Common qualities include burning or coldness, ‘pins and needles’ sensations, numbness and itching.

I saw piece on neuropathic pain in the Pharmacy Times, 22 September 2015 titled “How Gabapentin Differs From Pregabalin” in the management of neuropathic pain. About 25% of persons with diabetes experience painful diabetic neuropathy. Also about 25% of persons with herpes zoster infection will develop persistent neuropathic pain. More than 85% of patients with neuropathic pain caused by peripheral neuropathy will require pharmacotherapy.

Pregabalin and Gabapentin are often considered first-line treatments for various neuropathic pain syndromes, generally irrespective 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 medications similar in structure to gamma-aminobutyric acid (GABA), though neither agent has activity in GABA’s neuronal systems. The efficacy of pregabalin and gabapentin in neuropathic pain is linked to their ability to bind to voltage-gated calcium channels in the CNS, specifically to the alpha-2-delta protein. This binding decreases neurotransmitter release in the CNS as a result of reduced calcium influx through the gated channels.

Gabapentin is indicated as adjunct therapy for partial seizures and post herpetic neuralgia. Pregabalin is indicated for the same uses as gabapentin, in addition to the management of fibromyalgia and neuropathic pain associated with diabetes, specifically diabetic neuropathy. The overall pharmacokinetic profiles of pregabalin and gabapentin are similar but there are some significant differences.Both drugs are structurally similar to the amino acid leucine and can both undergo facilitated transport across cellular membranes through system L-amino acid transporters. Pregabalinhas additional better system of absorption because it is almost completely absorbed unlike gabapentin. Furthermore absorption of gabapentin is limited to the small intestine while pregabalinis absorbed throughout the small intestine and extending to the ascending colon.

Gabapentin is more slowly and variably absorbed with peak plasma concentrations around 3 hours post-dose. Pregabalin is quickly absorbed, with the maximum rate of absorption being 3 times that of gabapentin. It reaches peak blood concentrations within an hour after ingestion.

Absorption of gabapentin is saturable, leading to a non-linear 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 brand-name Neurontin is about 80% at lower doses such as 100mg every 8 hours, but only 27% bioavailable at doses of 1600mg every 8 hours. Pregabalinhas greater than 90% bioavailability across a dosage range from 75mg to 900mg daily in divided doses.Food increases the absorption of gabapentin but the absorption of pregabalin is not affected by food.

Distribution of both drugs is similar-neither is bound by great extent to any plasma proteins, thus decreasing the likelihood of drug interactions due to protein binding. Neither is also affected by cytochrome (CYP) drug interactions, as neither is metabolized by CYP enzymes. Both undergo metabolism to a negligible extent (<1%). Renal excretion is the major method of both drugs’ elimination from the body. Agents that decrease small bowel motility can cause an increase in the absorption of gabapentin. Pregabalin is more than 90% absorbed so absorption is not affected by changes in small bowel motility.

Both pregabalin and gabapentin are well tolerated. Dizziness and somnolence are the most common side effects in both drugs (more than 20% seen in gabapentin). Confusion and peripheral oedema have been reported with gabapentin. Side effects of both drugs are dose dependent and reversible if the medication is discontinued. The abrupt discontinuation of gabapentin is not recommended because of withdrawal symptoms such as anxiety, insomnia, nausea, pain and sweating.

Pregabalin is a more potent analgesic in neuropathic pain compared with gabapentin. The analgesic effect of pregabalin is about 6 times 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, steeper dose-response curve in neuropathic pain that does not plateau overdosing levels. Pregabalin has fewer side effects and may be more efficacious for neuropathic pain than gabapentin. The ratio of conversion from gabapentin to pregabalin is about 6:1.

In situations where one has to resort to complimentary or alternative medicine, flavanol-rich cocoa is a very good option on account of its anti-inflammatory and anti-nociceptive effects.

FROM DR. EDWARD O. AMPORFUL

CHIEF PHARMACIST

COCOA CLINIC

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