Gabica Mechanism of Action

Pharmacology: Pharmacodynamics: Pregabalin reduces neuronal calcium currents by binding to the alpha-2-delta subunit of voltage gated calcium channels in CNS tissues and this particular mechanism may be responsible for effects in neuropathic pain, anxiety and other pain syndromes. 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.
Pharmacokinetics: Absorption and Distribution: Following oral administration of pregabalin capsules under fasting conditions, peak plasma concentrations occur within 1 hour following both single and multiple dose administration. Pregabalin oral bioavailability is ≥90% and is independent of dose. Following single (25 to 300 mg) and multiple-dose (75 to 900 mg/day) administration, maximum plasma concentrations (C_max), and area under the plasma concentration-time curve (AUC) values increase linearly. Following repeated administration, steady state is achieved within 24 to 48 hours. The rate of pregabalin absorption is decreased when given with food resulting in a decrease in C_max by approximately 25%-30% and a delay in t_max to approximately 2.5 hours. However, administration of pregabalin with food has no clinically significant effect on the extent of pregabalin absorption.
Pregabalin does not bind to plasma proteins. The apparent volume of distribution of pregabalin following oral administration is approximately 0.56 L/kg.
Metabolism and Elimination: Pregabalin undergoes negligible metabolism in humans. About 98% of the dose is excreted in the urine as unchanged drug. The N-methylated derivative of pregabalin, found in urine, accounted for 0.9% of the dose. Pregabalin mean elimination half-life is 6.3 hours and is eliminated from the systemic circulation primarily by renal excretion as unchanged drug. Pregabalin is removed by hemodialysis.
Special Populations: Renal Insufficiency: Pregabalin plasma clearance and renal clearance are directly proportional to creatinine clearance. Pregabalin clearance is reduced in patients with impaired renal function. Dose adjustments are required in patients with renal impairment (CL_CR ≤60 mL/min). Pregabalin is effectively removed by hemodialysis (following a 4-hour hemodialysis treatment plasma pregabalin concentrations are reduced by approximately 50%). Dose adjustments are required for patients on hemodialysis.
Elderly (Over 65 years of age): Pregabalin clearance tends to decrease with increasing age. This decrease in pregabalin oral clearance is consistent with decreases in creatinine clearance associated with increasing age. Reduction of pregabalin dose may be required in patients who have age related compromised renal function.