Pregabalin is an anticonvulsant drug used for neuropathic pain, epilepsy and generalized anxiety disorder. Although as per the FDA Label the mechanism of action has not been definitively defined, there is evidence that pregabalin achieves antihyperalgesic activity by binding to the α2δ subunit of the voltage-dependent calcium channels Pregabalin is a medication used to treat epilepsy, neuropathic pain, fibromyalgia, restless leg syndrome, and generalized anxiety disorder. Its use in epilepsy is as an add-on therapy for partial seizures .When used before surgery, it improves pain but results in greater sedation and visual disturbances. It is taken by mouth. Pregabalin is useful when added to other treatments, when those other treatments are not controlling partial epilepsy. Its use alone is less effective than some other seizure medications. The European Federation of Neurological Societies recommends pregabalin as a first line agent for the treatment of pain associated with diabetic neuropathy, post-herpetic neuralgia, and central neuropathic pain. Pregabalin is modestly effective and is safe for treatment of generalized anxiety disorder. It appears to have anxiolytic effects similar to benzodiazepines with less risk of dependence
Side effect:
Common side effects include headache, dizziness, sleepiness, confusion, trouble with memory, poor coordination, dry mouth, problem with vision, and weight gain. Serious side effects may include angioedema, drug misuse, and an increased suicide risk. When pregabalin is taken at high doses over a long period of time, addiction may occur, but if taken at usual doses the risk is low. Pregabalin is a gabapentinoid and acts by inhibiting certain calcium channels.
Exposure to pregabalin is associated with weight gain, sleepiness and fatigue, dizziness, leg swelling, disturbed vision, loss of coordination, and euphoria. It has an adverse effect profile similar to other central nervous system depressants.
Withdrawal symptoms:
Following abrupt or rapid discontinuation of pregabalin, some people reported symptoms suggestive of physical dependence. The FDA determined that the substance dependence profile of pregabalin, as measured by a patient physical withdrawal checklist, was quantitatively less than benzodiazepines. Even people who have discontinued short term and or long term use of pregabalin have experienced withdrawal symptoms, including insomnia, headache, nausea, anxiety, diarrhea, flu like symptoms, nervousness, major depression, pain, convulsions, hyperhidrosis and dizziness..
Pharmacokinetic:
Pregabalin is absorbed from the intestines by an active transport process mediated via the large neutral amino acid transporter. The oral bioavailability of pregabalin is greater than or equal to 90% across and beyond its entire clinical dose range (75 to 900 mg/day). Pregabalin is not metabolized and is almost entirely unchanged in the urine it is not bound to plasma proteins and has virtually no drug-drug interaction. Likewise, other drugs do not affect the pharmacokinetic of pregabalin. The half-life pregabalin range from about 4.5 hours to 7 hours, thus requiring more than one per day dosing most patients. Food does not significantly influence the oral bioavailability of pregabalin. Pregabalin is rapidly absorbed when administered on an empty stomach, with a Tmax (time to peak levels) of generally less than or equal to 1 hour at doses of 300 mg or less. However, food has been found to substantially delay the absorption of pregabalin and to significantly reduce peak levels without affecting the bioavailability of the drug; Tmax values for pregabalin of 0.6 hours in a fasted state and 3.2 hours in a fed state. Pregabalin crosses the blood–brain barrier and enters the central nervous system. However, due to its low lipophilicity. Pregabalin requires active transport across the blood–brain barrier. The LAT1 is highly expressed at the blood–brain barrier and transports pregabalin across into the brain. In humans, the volume of distribution of an orally administered dose of pregabalin is approximately 0.56 L/kg.[3] Pregabalin is not significantly bound to plasma proteins .
Pregabalin is eliminated renally in the urine, mainly in its unchanged form. It has a relatively short elimination half-life, with a reported value of 6.3 hours. Because of its short elimination half-life, pregabalin is administered 2 to 3 times per day to maintain therapeutic levels. The renal clearance of pregabalin is 73 mL/minute
Dose:
Pregabalin is given orally with or without food. The recommended dose of pregabalin is 75-600 mg daily usually in two or three divided administration. Alcohol and drugs that cause sedation may increase the sedative effects of pregabalin. When discontinuing pregabalin, taper gradually over a minimum of 1 week
Pregnancy and breastfeeding:
Pregabalin has been shown to cross the placenta in rats and is present in the milk of lactating rats. Use during pregnancy or breastfeeding is of unclear safety. Breastfeeding while using pregabalin is not recommended.