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RPCC Pharmacy Forum: December 2016

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RPCC Pharmacy Forum: December 2016 December 2016 RPCC Pharmacy Forum Issue 19 Flubromazolam - Deadly Designer Benzodiazepine Brent Durrett, Pharm. D. Candidate, 2017 Special Interest Articles: Flubromazolam is a triazole analog of as binding to the benzodiazepine receptor flubromazepam and is a very high affinity, site on the gamma amino butyric acid in-vitro benzodiazepine related (GABA)-A receptor. By binding to the • Flubromazolam compound. It contains a fluorine, a GABA-A receptor, the benzodiazepine is bromine, and a methylated triazole able to change the shape of the receptor’s • PPIs and Dementia substituent on its core benzodiazepine chloride channel. This change causes the structure. Flubromazolam is a novel cell to hyperpolarize and causes the • Ultra-Long Acting Pill designer drug that is a synthetic version inhibitory effect, which decreases the of the benzodiazepine class. Many excitability of the brain’s neurons. designer drugs are former research drugs or drugs that were previously approved in The most common effect seen when other countries. Flubromazolam is a taking flubromazolam is heavy sedation. former research drug that did not make it Flubromazolam is a strong hypnotic with to clinical trials. It is still being sold as a moderate anxiolytic and amnesic effects. research chemical but has found its way Did you know? According to Erowid Experience Vaults, into the recreational drug marketplace. several drug users report that Twenty-five years flubromazolam would knock them out for Designer drugs are often many times most of the day, even on some of the ago, Eli Lilly’s Prozac stronger than the original substance due lowest doses of 0.25mg. This is due to the (fluoxetine) became to its creation for abuse. Flubromazolam drug’s potency as well as a seemingly is one of the newer drugs that made its long half-life. The half-life is theorized to the first selective debut in 2014. The original designer drug, be around 18 hours long due to how long flubromazepam, was first synthesized in it takes people to come out of their serotonin reuptake the 1960s, but was forgotten until it sedated sleep. inhibitor (SSRI) to be resurfaced in 2012. Flubromazolam is known as CAS 612526-40-6 in the Flubromazolam is very dangerous, released to the research chemical world. especially if taken in combination with market, where it other hypnotics, barbiturates, and alcohol. Flubromazolam has not been widely The signs and symptoms of a possible quickly advanced in studied due to its lack of use in humans overdose include shallow respiration, popularity for the and animals. Exact pharmacology is clammy hands, dilated pupils, rapid pulse, speculation at this point. Due to its coma, and in the worst cases, death. treatment of benzodiazepine-like structure, it is seen depression. Soon, the References 1. Wohlfarth A, Vikingsson S, Roman M, et al. Looking at flubromazolam metabolism from four different angles: Metabolite profiling in human liver drug was bringing in microsomes, human hepatocytes, mice and authentic human urine samples with liquid chromatography high-resolution mass spectrometry. Forensic Science more than a billion International. November 2016. doi:10.1016/j.forsciint.2016.10.021. 2. Mandrioli R, Mercolini L, Raggi M. Benzodiazepine metabolism: An analytical dollars in earnings- at perspective. Current drug metabolism. 2008;9(8):827–44. https://www.ncbi.nlm.nih.gov/pubmed/18855614. Accessed November 18, 2016. a time when the 3. Griffin CE, Kaye AM, Bueno FR. Benzodiazepine pharmacology and central nervous System–Mediated effects. 2013;13(2). average American’s https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684331/. Accessed November 18, 2016. income was $25,000. 4. New and Designer Drugs. Project Know: Understanding Addiction. http://www.projectknow.com/research/new-and-designer-drugs/. Accessed Laura Read RPh, CSPI November 18, 2016. 5. Zirtonic. Erowid experience vaults: Flubromazolam - you’ve got 20 minutes - [email protected] 107192. Erowid. https://erowid.org/experiences/exp.php?ID=107192. Accessed November 19, 2016. 6. Drugs of abuse 2015 edition: A DEA resource guide, Drug Enforcement Agency, (2015). https://www.dea.gov/pr/multimedia- library/publications/drug_of_abuse.pdf#page=55. Accessed November 19, 2016. Page 2 of 3 Page 2 of 3 Proton Pump Inhibitors and the Development of Dementia Page 2 of 3 Lindsay England, Pharm. D. Candidate, 2017 Proton pump inhibitors (PPIs) account lysosomes that induce the degradation for one of the most commonly of β-amyloid in the microglia by prescribed drug classes. In 2015, two acidification. The acidification process PPIs were considered to be among the is pH-dependent and is also mediated top 100 drugs in the United States – by proton pumps therefore if the esomeprazole (Nexium®) and proton pumps are inhibited by PPIs, dexlansoprazole (Dexilant®) were then the clearance of β-amyloid is prescribed a combined 19.9 million diminished while accumulation furthers times which totaled over $6.5 billion in until severe cognitive impairment. sales. Other PPIs include omeprazole (Prilosec®), lansoprazole (Prevacid®), Lastly, the third mechanism that can “Current literature pantoprazole (Protonix®), and potentially increase the risk of ® concludes that the rabeprazole (Aciphex ). These drugs dementia is a vitamin B12 deficiency. It avoidance of PPIs are approved by the U.S. Food and is theorized that PPIs may inhibit may contribute to the Drug Administration (FDA) for the secretin of intrinsic factor which prevention of treatment of duodenal ulcer disease, promotes neurologic damage due to erosive esophagitis, and impaired DNA synthesis. According to dementia, however, gastroesophageal reflux disease a study published in August of 2016, only statistical (GERD). Even though PPIs are the clinical significance of a B12 evidence associates frequently used for gastrointestinal deficiency caused by acid suppression the two.” disturbances, researchers now believe is inconclusive and longer prospective they have the potential to cause studies are needed. cognitive decline. Although the underlying mechanism to According to a which PPIs can cause dementia is yet pharmacoepidemiological analyses to be determined, it can be speculated published in February of 2016 in JAMA that acid suppression works Neurology, researchers have come up throughout the body instead of just the with several proposed mechanisms parietal cells within the stomach. that could increase the risk of a Increased β-amyloid plaque, pH dementia diagnosis. The first disturbances, and the absence of mechanism presented was a mouse vitamin B12 are all potential risk factors model that showed an increase in the that may contribute to dementia – all levels of β-amyloid plaque in the brain because of a very commonly – a protein that contributes as a major prescribed and misused medication. pathological sign of dementia. More Current literature concludes that the specifically, some PPIs have been avoidance of PPIs may contribute to reported to cross the blood-brain the prevention of dementia, however, barrier and interact with the enzymes only statistical evidence associates the β- and γ-secretase which leads to the two. In order to formulate a direct accumulation of β-amyloid. cause and effect, randomized, The second mechanism involves prospective clinical trials are needed. References 1. Available at: http://www.medscape.com/viewarticle/844317. Accessed November 20, 2016. 2. Proton Pump Inhibitor. In: Micromedex 2.0. Greenwood Village (CO): Thompson Reuters. [updated 11/16/16; accessed 11/20/16]. http://www.thomsonhc.com.ezproxy.samford.edu/micromedex2/librarian/. 3. Gomm W, Von holt K, Thomé F, et al. Association of Proton Pump Inhibitors with Risk of Dementia: A Pharmacoepidemiological Claims Data Analysis. JAMA Neurol. 2016;73(4):410-6. 4. Linder L, Tamboue C, Clements JN. Drug-Induced Vitamin B12 Deficiency: A Focus on Proton Pump Inhibitors and Histamine-2 Antagonists. J Pharm Pract. 2016. Page 3 of 3 Slow-Breaking, Ultra Long- Acting Pill: Medical Breakthrough A new pill, developed by researchers researchers used a mucoadhesive at MIT, demonstrates promise in polymer called Carbopol for one side allowing for effective long-term of the pill and for the other, used delivery of drugs, with the ability to cellulose acetate to repel stomach stick to the gastrointestinal tract for contents. The repellant side was lengthy periods of time. One side of textured to imitate a lotus leaf, which the pill is designed to hold it in place, has tiny protrusions that make it while the other repels liquid and food extremely hydrophobic. Once the that could otherwise displace it. This texturing was complete, the surface type of drug delivery could oust was fluorinated and lubricated to make inconvenient regimens that require it repel practically anything it comes repeated doses, which would help to into contact with. overcome one of the major obstacles to treating and potentially eliminating The technology could improve patient diseases such as malaria. In a recent adherence in various indications and study, an ingested “ultra long-acting” slash health costs. Approximately 50% capsule was able to deliver a of patients in the developed world do controlled release of a malaria drug to not take their medicines as prescribed pigs for up to 14 days. The pill is about - a statistic that is even more the size of a vitamin and when challenging in the developing world. ingested, after five seconds in the Long-acting pills could be especially stomach, the pill opens to the shape of helpful for elderly patients or those a star. The star shape prevents the pill with mental conditions who often fail to from being passed, allowing it to follow prescription instructions. release a drug for days to weeks. At a Scientists plan to investigate potential calculated point in time, the pill then applications beyond infectious breaks down and safely passes disease, including chronic diseases through the gastrointestinal tract, such as psychiatric disease, heart thanks to the dissolution of pH- and disease, and renal disease. time-dependent linkers. In the design, References 1.
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