Elimination half-life is 16±3 hours and can decrease to 4–9 hours when combined with enzyme inducers. Chemistry
Valproic acid is a branched short-chain fatty acid and the 2-n-propyl derivative of valeric acid. History
Valproic acid was first synthesized in 1882 by Beverly S. Burton as an analogue of valeric acid, found naturally in valerian. Valproic acid is a carboxylic acid, a clear liquid at room temperature. For many decades, its only use was in laboratories as a "metabolically inert" solvent for organic compounds. In 1962, the French researcher Pierre Eymard serendipitously discovered the anticonvulsant properties of valproic acid while using it as a vehicle for a number of other compounds that were being screened for antiseizure activity. He found it prevented pentylenetetrazol-induced convulsions in laboratory rats. It was approved as an antiepileptic drug in 1967 in France and has become the most widely prescribed antiepileptic drug worldwide. Valproic acid has also been used for migraine prophylaxis and bipolar disorder. Society and culture
Valproate is available as a generic medication. Approval status
Off-label uses
In 2012, pharmaceutical company Abbott paid $1.6 billion in fines to US federal and state governments for illegal promotion of off-label uses for Depakote, including the sedation of elderly nursing home residents.Some studies have suggested that valproate may reopen the critical period for learning absolute pitch and possibly other skills such as language. Formulations
Valproate exists in two main molecular variants: sodium valproate and valproic acid without sodium (often implied by simply valproate). A mixture between these two is termed semisodium valproate.
Similarly, it is the preferred type of beta blocker for treatment of patients with CPVT, as it has been shown to be more efficacious than selective beta blockers, like atenolol or bisoprolol.Nadolol has the advantage of once daily dosing and thus improved patient compliance. For patients with decreased kidney function, nadolol may be dosed less often. It has also been found to be useful (off-label) for several neurological disorders such as the prevention of migraine attacks, attention deficit/hyperactivity disorder(ADHD) and its use has been explored as a treatment for essential tremor and Parkinsons disease but neither is well established. Side effects
The most common side effects include dizziness and fatigue. Contraindications
Nadolol and other beta blockers should be used with cautions in people with heart failure and its use should not be abruptly stopped. It is contraindicated for people with asthma, a slow heart rate and certain severe heart problems. Mechanism of action
Nadolol is a non-selective beta blocker; that is, it non-selectively blocks both beta-1 and beta-2 receptors. It has a preference for beta-1 receptors, which are predominantly located in the heart, thereby inhibiting the effects of catecholamines and causing a decrease in heart rate and blood pressure. Its inhibition of beta-2 receptors, which are mainly located in the bronchial smooth muscle of the airways, leads to airway constriction similar to that seen in asthma. Inhibition of beta-1 receptors in the juxtaglomerular apparatus of the kidney inhibits the renin–angiotensin system, causing a decrease in vasoconstriction and a decrease in water retention.