Development of Pregabalin

(Image of Pregabalin Medication Label)

Pregabalin, also known as Lyrica, was first introduced by Pfizer Inc. in 2004 as treatment for neuropathic pain with associated diabetic peripheral neuropathy. In the year to follow, Pregabalin was then FDA approved as treatment for partial epileptic seizures. Later, in 2007, Pregabalin was declared the first approved medication to treat fibromyalgia. However, Pregabalin is regulated under the Controlled Substances Act and is classified as a Schedule V drug by the Drug Enforcement Agency (DEA). 

Generic Name:		Pregabalin
Trade Name:	Lyrica
Chemical Name:	(S)-3-(aminomethyl)-5-methylhexanoic acid
Classification:	Anticonvulsant; Antiepileptic; Antiseizure
Company	Pfizer Inc.
Year Introduced	2004

Four Therapeutic Uses

Epilepsy, Diabetic Peripheral Neuropathy, Postherapetic Neuralgia, and Fibromyalgia.

Epilepsy 

Over excitability of brain neurons leading to seizures. Other symptoms include convulsions and moments of unconsciousness as well as memory, cognitive learning, and mood complications (Lehne 2013, 227).

Diabetic Peripheral Neuropathy

Diabetic Peripheral Neuropathy can be present in people with diabetes mellitus type I or II. The result is damaged micro blood vessels causing loss of sensation as well as numb, tingling pain in extremities such as legs, feet (Lehne 2013, 301).

Postherapetic Neuralgia

Chronic pain due to damaged nerve fibers as a result of shingles. Destroyed nerve fibers are unable to properly transmit signals from skin to brain leading to pain, sensitivity to touch, numbness, and itching (Mayo Clinic 2012).

Fibromyalgia

Fibromyalgia Syndrome (FMS) involves pain in the muscle, bones, and joints due to improper processing regarding the perception of pain. In other words, pain signals are inadequately processed leading to a significantly low pain threshold (Lehne 2013, 1361).

Pharmacodynamics of Pregabalin

Calcium Channel Binding

Pregabalin takes affect once it binds to the calcium channels that exist on presynaptic nerve terminals. Once bound, pregabalin has the ability to inhibit the flow of calcium ions, or calcium influx, therefore preventing the release of other neurotransmitters that are known to cause the over-excitability of the nerves. A decreased release of neurotransmitters such as norepinephrine, glutamate, and substance P., allow the symptoms of nerve pain to be temporarily relieved or controlled.

It is important to understand that Pregabalin (Lyrica) does not provide a cure or overall treatment, yet the effect is to temporarily inhibit or decrease the production of neurotransmitters that predispose pain.

(Model of Pharmacodynamic of Pregabalin. Left: Hyperexcited Neuron without Pregabalin. Right. Hyperectited Neuron with Pregabalin.)

Pharmacokinetics of Pregabalin

Absorption

Pregabalin is an orally administered drug with a peak plasma level (maximum level of obtained drug) in approximately 1.5 hours when fasting. Seeing as the route is oral, food consumption before taking can lower the rate of absorption. However, the bioavailability of Pregabalin, or extent of drug that reaches the circulatory system, exists at greater than or equal to 90% (Lehne 2013, 242). As a result, taking Pregabalin with or without food has no impact on the total absorption.

Distribution

Involving the distribution of Pregabalin, animal clinical studies have concluded the blood-brain barrier as well as placenta barrier allow the drug to cross. Yet no trials or clinical studies regarding the distribution of Pregabalin have been conducted on human beings. Also discovered was the inability for plasma proteins to bind with Pregabalin (Lehne 2013, 242). 

Metabolism

Metabolism remains negligible in regards to human studies with Pregabalin. However, 98% of the radioactivity present in the urine has been noted as Pregabalin unchanged (Lehne 2013, 242).

Elimination

Pregabalin is eliminated via renal excretion with a half-life of about 6.3 hours (Lehne 2013, 242).

Adverse Effects of Pregabalin

Adverse Effects

Frequently reported adverse or negative effects included:

• Dizziness (29%)
• Somnolence/drowsiness (22%)
• Blurred Vision (6%)
• Weight Gain (8%)
• Difficulty Thinking (6%)
• Headache (5%)
• Peripheral Edema (6%)
• Dry Mouth (4%)

Post-marketing declared risks for:

• Hypersensitivity
• Angioedema (swelling of face, tongue, lips, gums, throat, and larynx)

(Lehne 2013, 242)

Drug Interactions

Pregabalin depressant effects are further stimulated or intensified with combined with opioids, alcohol, benzodiazepines, and other CNS depressants such as barbiturates.

Nursing Implications & Discontinuing Use

Nursing Implementations

On top of frequent assessment for adverse reactions, other nursing implementations need to be incorporated as well. Monitoring for edema (hypersensitivity reactions), myaglia, weight gain, and muscle breakdown as well as baseline serum creatinine and creatinine kinase levels.

Discontinuing Pregabalin Use

Sudden discontinuation may lead to withdrawal symptoms such as nausea, headaches, diarrhea, suicidal thoughts and insomnia. Therefore, it is recommended to discontinue using Pregabalin at a slow rate over the course of a week or more.