Pregabalin Denk 75 mg

Indications

• Neuropathic pain
• Epilepsy (partial seizures)
• Generalized anxiety disorder

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations based on age and weight.

Adults: Refer to the BNF for specific dosing recommendations based on condition and individual patient factors.

Mechanism of action

Pregabalin binds presynaptically to the alpha2-delta subunit of voltage-gated calcium channels in the central nervous system. This binding modulates the release of excitatory neurotransmitters including glutamate, substance-P, norepinephrine, and calcitonin gene-related peptide. Additionally, it prevents the trafficking of the alpha2-delta subunit from the dorsal root ganglia to the spinal dorsal horn, contributing further to its mechanism of action. Although it is a derivative of GABA, pregabalin does not bind directly to GABA receptors or affect GABA levels in the brain.

Pharmacodynamics

Pregabalin exhibits its effects by modulating presynaptic calcium channel activity, leading to decreased neurotransmitter release and reduced neuronal excitability. It does not interact with dopamine, serotonin, opiate receptors, sodium channels, or cyclooxygenase activity, which distinguishes it from other analgesics and anticonvulsants.

Pharmacokinetics

Pregabalin is rapidly absorbed after oral administration, reaching peak plasma concentrations within 1 hour. It has a bioavailability of approximately 90% and is not significantly metabolized by the liver, with most of the drug being excreted unchanged in the urine. The elimination half-life is about 6 hours, and it is primarily eliminated via renal excretion. Dose adjustments may be necessary in patients with renal impairment.

Adverse effects

• Dizziness
• Somnolence
• Dry mouth
• Edema
• Weight gain
• Blurred vision
• Constipation

Precautions

• Use with caution in patients with a history of substance use disorder
• Monitor for worsening depression or suicidal thoughts
• Gradual withdrawal is recommended to avoid withdrawal symptoms

Pregnancy

Pregabalin should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Limited data on its safety in pregnant women.

Breast-feeding

Pregabalin is excreted in human milk. Caution should be exercised when administering to breastfeeding mothers.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Capsules
• Oral solution

Mechanism of action

Although the mechanism of action has not been fully elucidated, studies involving structurally related drugs suggest that presynaptic binding of pregabalin to voltage-gated calcium channels is key to the antiseizure and antinociceptive effects observed in animal models. By binding presynaptically to the alpha2-delta subunit of voltage-gated calcium channels in the central nervous system, pregabalin modulates the release of several excitatory neurotransmitters including glutamate, substance-P, norepinephrine, and calcitonin gene related peptide. In addition, pregabalin prevents the alpha2-delta subunit from being trafficked from the dorsal root ganglia to the spinal dorsal horn, which may also contribute to the mechanism of action. Although pregabalin is a structural derivative of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), it does not bind directly to GABA or benzodiazepine receptors. Pregabalin is an anticonvulsant that is structurally related to the inhibitory CNS neurotransmitter gamma-aminobutyric acid (GABA). Pregabalin also has demonstrated analgesic activity. Although pregabalin was developed as a structural analog of GABA, the drug does not bind directly to GABA-A, GABA-B, or benzodiazepine receptors; does not augment GABA-A responses in cultured neurons; and does not alter brain concentrations of GABA in rats or affect GABA uptake or degradation. However, in cultured neurons, prolonged application of pregabalin increases the density of GABA transporter protein and increases the rate of functional GABA transport. Pregabalin binds with high affinity to the alpha2-delta site (an auxiliary subunit of voltage-gated calcium channels) in CNS tissues. ... In vitro, pregabalin reduces the calcium-dependent release of several neurotransmitters, including glutamate, norepinephrine, and substance P, possibly by modulation of calcium channel function. Pregabalin does not block sodium channels, is not active at opiate receptors, and does not alter cyclooxygenase enzyme activity. It is inactive at serotonin and dopamine receptors and does not inhibit dopamine, serotonin, or noradrenaline reuptake. Pregabalin is a potent ligand for the alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system that exhibits potent anticonvulsant, analgesic, and anxiolytic activity in a range of animal models. ... Potent binding to the alpha-2-delta site reduces depolarization-induced calcium influx with a consequential modulation in excitatory neurotransmitter release. Pregabalin has no demonstrated effects on GABAergic mechanisms. ... For more Mechanism of Action (Complete) data for PREGABALIN (6 total), please visit the HSDB record page.

Pharmacodynamics

Although the structure of pregabalin is similar to gamma-aminobutyric acid (GABA), it does not bind to GABA receptors. Instead, it binds the alpha2-delta subunit of presynaptic voltage-gated calcium channels in the central nervous system. Pregabalin does not modulate dopamine receptors, serotonin receptors, opiate receptors, sodium channels or cyclooxygenase activity.