Last reviewed by Dr. Pooja Chauhan on September 4th, 2018.
How does Pregabalin Vs Gabapentin work in the body?
Pregabalin is a synthetic, gamma-aminobutyric acid (GABA) derivative that blocks calcium channels and functions as anti-convulsant, anti-epileptic, anxiolytic, and analgesic agent.
The exact mode of action of Pregabalin remains unclear and the proposed mechanism is based upon results involving genetically modified mice and compounds that are structurally related to the drug such as gabapentin.
The drug causes a decrease in the excitability of the neurons in the central nervous system by binding to the auxiliary subunit (α2-δ protein) of a voltage-gated calcium channel present on the neurons of the central nervous system.
Pregabalin causes a decrease of pro-nociceptive neurotransmitters (a calcium dependent process) in the spinal cord either by reduction of calcium currents or disruption of alpha2-delta containing-calcium channel trafficking. These neurotransmitters are involved in the noradrenergic and serotonergic pathways that cause modulation of pain transmission in the spinal cord.
Besides this, Pregabalin also lowers the release of several other neurotransmitters, including glutamate, noradrenaline, and substance P possibly by modulation of calcium channel function. However, the significance of this effect remains unclear. Although Pregabalin is a structural derivative of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), it does not bind directly to GABA or benzodiazepine receptors.
The sodium channels, opiate receptors, and cyclooxygenase enzymes do not play a role in the mechanism of action of Pregabalin. The drug is also inactive at serotonin and dopamine receptors and does not inhibit reuptake of the serotonin, dopamine, or noradrenaline.
The exact mechanism of action of Gabapentin is not known, however, it is speculated to exert its effect by interacting with a high-affinity binding site i.e., an auxiliary subunit of voltage-sensitive Ca2+ channels in brain membranes.
Gabapentin can cross several lipid membrane barriers through system L amino acid transporters and modulates the action of the GABA synthetic enzyme (glutamic acid decarboxylase) and the glutamate synthesizing enzyme (amino acid transaminase).
This is accompanied by an increased synthesis of neurotransmitter GABA, increased non-synaptic GABA responses from neuronal tissues and reduction in the release of several mono-amine neurotransmitters in the brain. This effect of Gabapentin is mediated by the reduction of the axon excitability in the hippocampus by its binding to presynaptic NMDA receptors.
The antihyperalgesic and antiallodynic effects of Gabapentin are mediated by the activation of the descending pain inhibitory system (noradrenergic system), resulting in the activation of spinal alpha2-adrenergic receptors. Gabapentin effects are also attributed to its binding to the adenosine A1 receptor (also causes its activation), protein kinase C, and inflammatory cytokines.
Can both Pregabalin and Gabapentin be taken together?
Yes, Pregabalin in combination with Gabapentin represent a valuable addition to the existing monotherapy with either Gabapentine or Pregabalin alone in patients with neuropathic pain and inflammatory nociception. Gabapentin and Pregabalin both are structurally similar to the neurotransmitter gamma-aminobutyric acid (GABA) and interact to calcium channels in the central nervous system.
Both the drugs are FDA-approved for treatment of postherpetic neuralgia and partial seizures. It has been observed that Pregabalin is safe and effective in patients with postherpetic neuralgia, trigeminal neuralgia, painful diabetic neuropathy and fibromyalgia. However, the drug is less effective in monotherapy in treatment of pain associated with HIV neuropathy and other neuropathic pain.
For this purpose Pregabalin is occasionally recommended in combination with other agents such as Gabapentin. Clinical studies have suggested that the combination of Pregabalin and Gabapentin are safe and effective and may offer certain advantages. Recent open-label study of neuropathic pain patients suggests that Pregabalin may provide greater analgesia and opioidsparing effects.
Safety and precautions while mixing Pregabalin and Gabapentin
Pregabalin and Gabapentin may interact with other drugs. Therefore, care should be taken when you are taking any prescription or non-prescription medicines and herbal or vitamin supplements. It is advisable that you do not start, stop or change or take any medicine unless you have discussed with your doctor or professional consult.
- Do not use the medicine if you are hypersensitive or allergic (e.g., anaphylaxis) to Pregabalin or Gabapentin, or any of the drug constituents.
- Do not share the medications with other persons having the similar kind of problems. Consult your doctor for more details.
- Gabapentin should be avoided during breast feeding as it can pass into breast milk and may harm a nursing baby. Morphine is also not recommended during breast feeding.
- Pregabalin and Gabapentin use is not recommended during driving or operating heavy machines as they may cause the patient drowsy and dizzy, and also result in decreasing their thinking and cause loss of coordination.
- Regular visits are required during administration of Pregabalin and Gabapentin as they may result in development of suicidal thoughts in some people.
- Pregabalin administration may cause harm to the foetus and should not be used during pregnancy. Gabapentin is also not recommended for use during pregnancy.
- Use of alcohol is not recommended during the administration of these medications.
- Pregabalin: Gabapentine use may result in serious blood problems or a life-threatening skin rash. It is therefore advised to consult the doctor in case of fever, unusual weakness, bleeding, or a skin rash during the use of the drugs.
- It is always recommended that analgesia should be dose–limited when used in combination due to their increased side effects. Caution should be taken before using Pregabalin in combination with Gabapentine.
- Gabapentine and Pregabalin can be taken together at the same time to treat neuropathic pain. However, the dose should be adjusted by professional healthcare, if needed.
- Do not use the medicine if you are hypersensitive or allergic (e.g., anaphylaxis or Stevens-Johnson syndrome) to Gabapentine or any other opioid drug or -aminobutyric acid (GABA) derivative or to any ingredient of the drug formulation.
- The Gabapentine and Pregabalin may interact with other drugs. Therefore, care should be taken when you are taking any prescription or non-prescription medicines and herbal or vitamin supplements. It is advisable that you do not start, stop or change or take any medicine unless you have discussed with your doctor or professional consult.
- Before taking Gabapentine-Pregabalin, tell your doctor about your medical history if you have kidney disease, liver disease, asthma, liver disease, mononucleosis (also called “mono”), a bleeding or blood clotting disorder, or any type of allergy, hay fever or hives.
- Gabapentine in combination with Pregabalin exacerbate the side effects such as drowsiness, dizziness, confusion, difficulty to focus properly, impairment in thinking, judgment, and motor coordination. These side effects are more in elderly population therefore it is recommended to avoid the activities which require alertness such as operating dangerous equipment or machinery, driving etc.
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