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Wednesday, March 19, 2014

Valproic Acid Linked with Reduced Risk of Developing Head and Neck Cancer

Sodium valproate is a common mood stabilizer
Sodium valproate is a common mood stabilizer (Photo credit: Wikipedia)
I was surprised to read this press release this morning concerning valproic acid, an antiepileptic, mood stabilizing medication that has also been used traditionally in the management of neuropathic pain.

I am interesting in seeing the doses most commonly encountered and the relevant toxicities. As PCF-4 (PalliativeDrugs.org) notes, no single mode of action accounts for its anti-seizure activity. It is a:
  • sodium and T-type calcium channel blocker
  • an NMDA receptor-channel blocker (?helpful in hyperalgesia)
  • alters GABA (distinctively selective for midbrain), dopamine and serotonin transmission
T-type calcium channels have been implicated in thalamic burst firing (absence seizures), neuropathic pain and possibly in regulating pain excitation thresholds in a 'T-rich' subset of peripheral nociceptors. 

Beneficial effects have been reports in cancer-related neuropathic pain in Europe and Australia, but mixed results in other pain scenarios. Onset of action can often be within 24 hours for neuropathic pain.

But I digress - on to the news of the day:


Excerpt of Press Release via Wiley:

"A new study indicates that a commonly used mood stabilizing drug may help prevent head and neck cancer. The study is published early online in CANCER, a peer-reviewed journal of the American Cancer Society.

Valproic acid (VPA) is currently prescribed as an anti-seizure medication and mood stabilizer, but it is also being studied as an anticancer agent because it inhibits histone acetyl transferases, which help control gene expression by changing DNA structure.

Johann Christoph Brandes MD, PhD, of the Atlanta Veterans Affairs Medical Center and Emory University in Atlanta, led a team that assessed the anticancer effects of VPA in a study of 439,628 veterans, of whom 26,911 were taking the medication for bipolar disorder, post-traumatic stress disorder, migraines, and seizures.

Veterans who took VPA for at least one year had a 34 percent lower risk of developing head and neck cancer compared with those who did not take the medication. Higher doses and longer duration of VPA use seemed to provide additional benefits. No significant differences were observed for lung, bladder, colon, and prostate cancer incidences.

“A 34 percent risk reduction for the development of head and neck cancer with VPA use could result in the prevention of up to approximately 16,000 new cases and 3,000 to 4,000 annual deaths in the US alone,” said Dr. Brandes. “Head and neck cancer is an important global health crisis, and low cost and low toxicity prevention strategies like VPA use have a high potential impact on pain, suffering, costs, and mortality associated with this disease.”

Article: “Long-term use of valproic acid in United States Veterans associates with reduced risk of smoking related head-and neck cancer.” Hyunseok Kang, Theresa Gillespie, Michael Goodman, Seth Brodie, Mina Brandes, Maria Ribeiro, Suresh Ramalingam, Dong Shin, Fadlo Khuri, and Johann Christoph Brandes. CANCER; Published Online: March 24, 2014 (DOI: 10.1002/cncr.28479).
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Pharmacy History

"The earliest known compilation of medicinal substances was ARIANA the Sushruta Samhita, an Indian Ayurvedic treatise attributed to Sushruta in the 6th century BC. However, the earliest text as preserved dates to the 3rd or 4th century AD.
Many Sumerian (late 6th millennium BC - early 2nd millennium BC) cuneiform clay tablets record prescriptions for medicine.[3]

Ancient Egyptian pharmacological knowledge was recorded in various papyri such as the Ebers Papyrus of 1550 BC, and the Edwin Smith Papyrus of the 16th century BC.

The earliest known Chinese manual on materia medica is the Shennong Bencao Jing (The Divine Farmer's Herb-Root Classic), dating back to the 1st century AD. It was compiled during the Han dynasty and was attributed to the mythical Shennong. Earlier literature included lists of prescriptions for specific ailments, exemplified by a manuscript "Recipes for 52 Ailments", found in the Mawangdui tomb, sealed in 168 BC. Further details on Chinese pharmacy can be found in the Pharmacy in China article."

From Wikipedia: http://en.wikipedia.org/wiki/Pharmacy#History_of_pharmacy

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