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  • June 1, 2017
  • 12:59 AM

D10 in the Treatment of Prehospital Hypoglycemia: A 24 Month Observational Cohort Study

by Rogue Medic in Rogue Medic

Why treat hypoglycemia with 10% dextrose (D10), rather than the more expensive, potentially more harmful, and less available traditional treatment of 50% dextrose (D50)? Why not? The only benefit of 50% dextrose appears to be that it is what people are used to using, but aren't we used to starting IVs (IntraVenous lines) and running fluids through the IVs? ... Read more »

  • March 31, 2017
  • 08:00 AM

Friday Fellow: Mexican Giant Horsetail

by Piter Boll in Earthling Nature

by Piter Kehoma Boll If you are walking through the forest of Central America, you may end up finding something that at first you could think is a group of bamboos, plants growing as a cylindrical segmented stem that can … Continue reading →... Read more »

  • March 3, 2017
  • 06:14 AM

Rare Disease Day – Findacure Scientific Conference: Drug Repurposing for Rare Diseases

by Joana Guedes in BHD Research Blog

This year’s Findacure Scientific Conference took place in London on Rare Disease Day and was again focused on Drug Repurposing for Rare Diseases. The conference brought together over 100 representatives from patient groups, researchers and members of the healthcare industry to discuss the importance and the latest developments in drug repurposing for rare diseases.... Read more »

  • January 28, 2017
  • 09:42 AM

Distortions of Reality

by The Neurocritic in The Neurocritic

President Trump this week repeated an assertion he made shortly after his election: that millions of ballots cast illegally by undocumented immigrants cost him the popular vote. If true, this would suggest the wholesale corruption of American democracy.

Not to worry: As far as anyone knows, the president’s assertion is akin to saying that millions of unicorns also voted illegally.

- In a

... Read more »

Preller, K., Herdener, M., Pokorny, T., Planzer, A., Kraehenmann, R., Stämpfli, P., Liechti, M., Seifritz, E., & Vollenweider, F. (2017) The Fabric of Meaning and Subjective Effects in LSD-Induced States Depend on Serotonin 2A Receptor Activation. Current Biology. DOI: 10.1016/j.cub.2016.12.030  

Wacker, D., Wang, S., McCorvy, J., Betz, R., Venkatakrishnan, A., Levit, A., Lansu, K., Schools, Z., Che, T., Nichols, D.... (2017) Crystal Structure of an LSD-Bound Human Serotonin Receptor. Cell, 168(3), 377-2147483647. DOI: 10.1016/j.cell.2016.12.033  

  • January 20, 2017
  • 06:19 AM

RCC: Updates on Guidelines for Adjuvant Therapy and new drug combination

by Joana Guedes in BHD Research Blog

The European Association of Urology (EAU) Renal Cell Carcinoma (RCC) guidelines panel has recently updated its recommendation on adjuvant therapy with sunitinib in non-metastatic RCC after surgical tumour removal (Bex et al., 2016). These clinical guidelines provide urologists with evidence-based information and recommendations for the management of RCC and the panel includes urological surgeons, oncologists, pathologists, radiologists and patient advocates. Based on the conflicting results of two available clinical studies (ASSURE and S-TRAC), the panel rated the quality of the evidence of the trials, the harm-to-benefit ratio, the patient preferences and the costs. As a result, the EAU panel, including representatives from a patient advocate group (International Kidney Cancer Coalition) voted and reached a consensus recommendation that adjuvant therapy with sunitinib for patients with high-risk RCC after nephrectomy should not be given.... Read more »

  • November 15, 2016
  • 12:38 PM

Celebrex Boosts Antidepressant Response

by William Yates, M.D. in Brain Posts

I ran into an interesting article at ScienceDaily providing data on a small sample size study of the anti-inflammatory drug celecoxib (Celebrex) in depression.Access the ScienceDaily report on this study by clicking HERE.This study focused on subjects with bipolar depression. All subjects were in a depressed phase and received the antidepressant drug escitalopram (Lexapro).Although only 55 subjects participated in this study, the results were significant and large. Adding Celebrex to escitalopram increased depression remission rates from 10% to 63%. I have summarized the data from the article in this attached graph.Additionally, the study team found a more rapid response to antidepressant drug therapy when Celebrex was added.I have been involved in use of anti-inflammatory agents in the treatment of bipolar depression. Dr. Jonathan Savitz and our colleagues at the Laureate Institute of Brain Research and the University of Kansas examined aspirin and minocycline in a clinical trial that has not yet been published.I have included the methods manuscript for our study that can be accessed by clicking the the link provided below.Neuroinflammation may be a contributing factor in a variety of brain disorders including depression. Better understanding of the role and treatment of inflammation may improve depression outcomes.Follow me on Twitter WRY999Figure in this post is an original figure from data abstracted from the research report.Savitz, J., Preskorn, S., Teague, T., Drevets, D., Yates, W., & Drevets, W. (2012). Minocycline and aspirin in the treatment of bipolar depression: a protocol for a proof-of-concept, randomised, double-blind, placebo-controlled, 2×2 clinical trial BMJ Open, 2 (1) DOI: 10.1136/bmjopen-2011-000643... Read more »

  • November 4, 2016
  • 06:00 AM

Friday Fellow: Silvergreen Moss

by Piter Boll in Earthling Nature

by Piter Kehoma Boll Found throughout most of the world, you probably have encountered this fellow many times in your life, but did not pay any attention. After all, it is just a moss! Scientifically known as Bryum argenteum and popularly … Continue reading →... Read more »

  • September 23, 2016
  • 08:00 AM

Friday Fellow: Rosy Crust

by Piter Boll in Earthling Nature

by Piter Kehoma Boll If you are walking through a forest in Europe you may find the bark of some trees covered by a thin rosy or orange crust. Commonly known as rosy crust, its scientific name is Peniophora incarnata. As … Continue reading →... Read more »

Suay, I., Arenal, F,, Asensio, F. J., Basilio, A., Cabello, M. A., Díez, M. T., García, J. B., González del Val, A., Gorrochategui, J., Hernández, P.... (2000) Screening of basidiomycetes for antimicrobial activities. Antonie van Leeuwenhoek, 78(2), 129-140. DOI: 10.1023/A:1026552024021  

  • September 12, 2016
  • 01:36 PM

Opioid Abuse: Treatment Guidelines

by William Yates, M.D. in Brain Posts

Molecular model of the drug buprenorphineThe U.S. Surgeon General recently sent a letter to all physicians about the danger of prescription opioids, particularly when used in combination with benzodiazepines (i.e. Valium, Xanax).  This combination greatly increases the risk of overdose death.Clinicians can successfully assist those with opioid use disorders. Marc Schuckit, M.D. recently published a nice summary review of entitled "Treatment of Opioid-Use Disorder" in the New England Journal of Medicine (see citation below).The review contains some nice tables including tables related to:Diagnostic criteria of opioid use disorderAn opiate withdrawal rating scaleOpioid free treatment aids in management of opioid withdrawalOpioid agonist aids in management of opioid withdrawalOpioid agonist use in long-term maintenanceOpioid withdrawal is generally non-life threatening, but extremely uncomfortable and a strong motivator for return to opioid use.Use of opioid agonists such as buprenorphine (pictured in molecular model above) is the best tolerated and least uncomfortable pathway to treatment of opioid withdrawal. However, it is restricted to prescription by a small group of physicians who have completed a special training program.This means many opioid users end up with less tolerated and more uncomfortable withdrawal episodes treated with drugs such as clonidine, diazepam or even over-the-counter drugs such as Imodium.The review notes that with high relapse rates, supervised opioid maintenance with prescribed opioids such as methadone or buprenorphine often are required for long-term abstinence. One barrier to using these types of interventions is availability and cost. Buprenorphine can be expensive and requires regular monitoring in a physicians office.With high costs and lack of access to supervised opioid management, opioid users commonly return to street heroin or prescription opioid pills (licit or illicit). Readers with more interest in this topic can access the free full-text manuscript by clicking on the DOI link in the citation below.Follow me on Twitter @WRY999Model of buprenorphine is from a Wikipedia Creative Commons File attributed to:Crystallographic data from J. Mazurek, M. Hoffmann, A. Fernandez Casares, P. D. Cox and M. D. Minardi (June 2014). "Buprenorphine". Acta Cryst. E70, o635. DOI:10.1107/S1600536814009672Schuckit, M. (2016). Treatment of Opioid-Use Disorders New England Journal of Medicine, 375 (4), 357-368 DOI: 10.1056/NEJMra1604339... Read more »

Schuckit, M. (2016) Treatment of Opioid-Use Disorders. New England Journal of Medicine, 375(4), 357-368. DOI: 10.1056/NEJMra1604339  

  • September 9, 2016
  • 01:10 PM

Statin Therapy: Rethinking Benefits and Risks

by William Yates, M.D. in Brain Posts

A recent 30-page manuscript provides an exhaustive review of the evidence for the efficacy and safety of statin therapy.The authors of this excellent review provide some context for the relative value of statins.The note that putting 10000 individuals with a history of a vascular event on a statin drug for 5 years would prevent 1,000 subsequent events. This is an example of secondary prevention--preventing another adverse outcome in those already experiencing an adverse event.But the statin drugs also appear very powerful in primary prevention-preventing a first event in those at high risk for vascular disease. They estimate putting 10,000 individuals at high risk for vascular events on statins would result in prevention of 500 vascular events over five years.This review provides an up-to-date review of the safety of statins and generally supports the therapy as very low risk.One proposed adverse event of statin therapy is concern about memory and cognition. However, the authors note that well-designed studies of statin therapy in older individuals find no evidence of adverse cognitive effects compared to placebo.They argue that:"..given the weight of evidence against adverse effects of statin therapy on memory or other adverse effects of cognition, it would now be appropriate for regulatory authorities to consider removal from the lists of potential adverse effects on the drug labels so that patients are not inappropriately deterred from using statin therapy." (emphasis mine).The authors go on to emphasize the potential adverse public health consequences of misleading claims regarding the safety of the statin drug class.This excellent review is likely to lead to further discussion about extending the indications for statin use in the general population.Readers with more interest in this topic can access the full free-text manuscript by clicking on the link in the citation below.Follow me on Twitter by clicking HERE.Photo of osprey in flight is from my photography files.Collins R, Reith C, Emberson J et al.  (2016). Interpretation of the evidence for the efficacy and safety of statin therapy Lancet : Read more »

Collins, Rory, Reith, Christina, & Emberson, Jonathan. (2016) Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet. info:/

  • August 30, 2016
  • 12:59 PM

Dyslexia Improvement in Medication Trial

by William Yates, M.D. in Brain Posts

Dyslexia or developmental reading disorder is a common learning disorder affecting about 5% of the school age population.Treatment of dyslexia is difficult and typically is focused on special education classes and reading exercises.Medication treatment for dyslexia is nearly unheard of as no FDA-approved drug is available for the condition.However, a recent randomized clinical drug trial found evidence to support the potential use of atomoxetine for dyslexia.Atomoxetine is a drug approved for attention deficit hyperactivity disorder but it has not received much attention in dyslexia or other learning disorders.Dr. Sally Shaywitz of Yale University along with colleagues recently published results of their clinical trial of atomoxetine in dyslexia with the following key design and results:Study population: Children and adolescents between 10-16 years of age with a DSM-IV-TR diagnosis of dyslexia alone (N=58) or dyslexia and ADDH (N=124).Medication intervention: atomoxetine 1.0 to 1.4 mg/kg/day or placeboOutcome measures: Woodcock Johnson III, Comprehensive Test of Phonological Processing, Gray Oral Reading Test and Test of Word Reading EfficacyResults: Atomoxetine improved reading scores in both the dyslexia alone and dyslexia and ADHD groups compared to placeboThe authors note in the discussion that their study suggests the potential for atomoxetine as an adjunct to traditional behavioral and academic interventions in the treatment of dyslexia.This study will need replication. It might also prompt further study of other stimulant medications such as methylphenidate in dyslexic populations.Readers with more interest in this trial can access the free full-text manuscript by clicking on the PMID link in the citation below.Follow me on Twitter @WRY999Photo collage of hummingbirds is from my personal files.Shaywitz S, Shaywitz B, Wietecha L, Wigal S, McBurnett K, Williams D, Kronenberger WG, & Hooper SR (2016). Effect of Atomoxetine Treatment on Reading and Phonological Skills in Children with Dyslexia or Attention-Deficit/Hyperactivity Disorder and Comorbid Dyslexia in a Randomized, Placebo-Controlled Trial. Journal of child and adolescent psychopharmacology PMID: 27410907... Read more »

  • August 19, 2016
  • 08:00 AM

Friday Fellow: Asian Pigeonwing

by Piter Boll in Earthling Nature

by Piter Kehoma Boll Today’s Friday Fellow is a creeping (but not creepy) plant with nice deep blue flowers shaped like a human female genitalia. Yeah, you read that right. Its scientific name is Clitoria ternatea, the genus name being a … Continue reading →... Read more »

  • August 17, 2016
  • 02:30 PM

The PROCAMIO Trial – IV Procainamide vs IV Amiodarone for the Acute Treatment of Stable Wide Complex Tachycardia

by Rogue Medic in Rogue Medic

This is a very interesting trial that may surprise the many outspoken amiodarone advocates, but it should not surprise anyone who pays attention to research.

ALPS showed that we should stop giving amiodarone for unwitnessed shockable cardiac arrest. The lead researcher is still trying to spin amiodarone for witnessed shockable cardiac arrest, even though the results do not show improvement in the one outcome that matters – leaving the hospital with a brain that still works.[1],[2],[3]... Read more »

Kudenchuk PJ, Brown SP, Daya M, Rea T, Nichol G, Morrison LJ, Leroux B, Vaillancourt C, Wittwer L, Callaway CW.... (2016) Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest. The New England journal of medicine, 374(18), 1711-22. PMID: 27043165  

Marill KA, deSouza IS, Nishijima DK, Senecal EL, Setnik GS, Stair TO, Ruskin JN, & Ellinor PT. (2010) Amiodarone or procainamide for the termination of sustained stable ventricular tachycardia: an historical multicenter comparison. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, 17(3), 297-306. PMID: 20370763  

Marill KA, deSouza IS, Nishijima DK, Stair TO, Setnik GS, & Ruskin JN. (2006) Amiodarone is poorly effective for the acute termination of ventricular tachycardia. Annals of emergency medicine, 47(3), 217-24. PMID: 16492484  

Kułakowski P, Karczmarewicz S, Karpiński G, Soszyńska M, & Ceremuzyński L. (2000) Effects of intravenous amiodarone on ventricular refractoriness, intraventricular conduction, and ventricular tachycardia induction. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, 2(3), 207-15. PMID: 11227590  

Bonny A, De Sisti A, Márquez MF, Megbemado R, Hidden-Lucet F, & Fontaine G. (2012) Low doses of intravenous epinephrine for refractory sustained monomorphic ventricular tachycardia. World journal of cardiology, 4(10), 296-301. PMID: 23110246  

Kowey PR. (1988) The calamity of cardioversion of conscious patients. The American journal of cardiology, 61(13), 1106-7. PMID: 3364364  

  • August 11, 2016
  • 09:30 PM

Acupuncture vs intravenous morphine in the management of acute pain in the ED

by Rogue Medic in Rogue Medic

Should we have people providing "fake" acupuncture in the Emergency Department?

If so, how should we do this?

Since it is not the acupuncture, but the patient's reaction to the "ceremony of the placebo" that appears to be providing the pain relief, how many different ways might we vary the "treatment" to improve the placebo effect?... Read more »

Grissa, M., Baccouche, H., Boubaker, H., Beltaief, K., Bzeouich, N., Fredj, N., Msolli, M., Boukef, R., Bouida, W., & Nouira, S. (2016) Acupuncture vs intravenous morphine in the management of acute pain in the ED. The American Journal of Emergency Medicine. DOI: 10.1016/j.ajem.2016.07.028  

Espay, A., Norris, M., Eliassen, J., Dwivedi, A., Smith, M., Banks, C., Allendorfer, J., Lang, A., Fleck, D., Linke, M.... (2015) Placebo effect of medication cost in Parkinson disease: A randomized double-blind study. Neurology, 84(8), 794-802. DOI: 10.1212/WNL.0000000000001282  

Ee, C., Xue, C., Chondros, P., Myers, S., French, S., Teede, H., & Pirotta, M. (2016) Acupuncture for Menopausal Hot Flashes. Annals of Internal Medicine, 164(3), 146. DOI: 10.7326/M15-1380  

Cherkin, D., Sherman, K., Avins, A., Erro, J., Ichikawa, L., Barlow, W., Delaney, K., Hawkes, R., Hamilton, L., Pressman, A.... (2009) A Randomized Trial Comparing Acupuncture, Simulated Acupuncture, and Usual Care for Chronic Low Back Pain. Archives of Internal Medicine, 169(9), 858. DOI: 10.1001/archinternmed.2009.65  

Goldman, R., Stason, W., Park, S., Kim, R., Schnyer, R., Davis, R., Legedza, A., & Kaptchuk, T. (2008) Acupuncture for Treatment of Persistent Arm Pain Due to Repetitive Use. The Clinical Journal of Pain, 24(3), 211-218. DOI: 10.1097/AJP.0b013e31815ec20f  

  • August 5, 2016
  • 08:00 AM

Friday Fellow: Beggar’s tick

by Piter Boll in Earthling Nature

by Piter Kehoma Boll What if the cure for cancer has been living in your garden all this time and you have been trying to get rid of it because it is an annoying weed? I cannot assure you that … Continue reading →... Read more »

Chiang, L., Chang, J., Chen, C., Ng, L., & Lin, C. (2003) Anti-Herpes Simplex Virus Activity of Bidens pilosa and Houttuynia cordata. The American Journal of Chinese Medicine, 31(03), 355-362. DOI: 10.1142/S0192415X03001090  

Kviecinski, M., Felipe, K., Schoenfelder, T., de Lemos Wiese, L., Rossi, M., Gonçalez, E., Felicio, J., Filho, D., & Pedrosa, R. (2008) Study of the antitumor potential of Bidens pilosa (Asteraceae) used in Brazilian folk medicine. Journal of Ethnopharmacology, 117(1), 69-75. DOI: 10.1016/j.jep.2008.01.017  

  • July 22, 2016
  • 10:01 AM

Update on clinical trials and treatments for RCC

by Joana Guedes in BHD Research Blog

Renal cell carcinoma (RCC) is the most common type of kidney cancer and although the majority of cases are sporadic approximately 3% of cases are caused by genetic conditions such as BHD, VHL, HLRCC and TSC (Randall et al., 2014). These inherited forms of RCC have provided great insights into sporadic cancer genetics. BHD patients can develop multiple kidney tumours. In most cases these tumours are small local RCCs that can be surgically removed. However, these treatments are not without risk, and sometimes complete nephrectomies are carried out which leave patients with severely reduced kidney function and at risk of recurrence. The development of selective drug treatments that target only cancer cells can therefore improve disease outcome and increase patient quality of life. Even though significant advances have been made in the treatment of kidney cancer, there is a need for effective and more tolerable treatments, both for single agent and combination use. This blog summarises recent results from clinical trials assessing new treatments.... Read more »

  • July 14, 2016
  • 02:27 PM

Weird stuff found in recreational drugs: Cocaine edition

by Rosin Cerate in Rosin Cerate

This is the fifth and final post in a series on strange substances accidentally or intentionally added to street drugs. When you're done here, check out the posts on alcohol, meth, opioids, and pot/LSD.If a drug is being sold illegally, chances are its sellers have added crap to it in order to make more money. Cocaine is no exception to this deception. Substances added to nose candy because they resemble the drug but otherwise don't mimic or influence its effects include talc powder, flour, cornstarch, inositol and other sugar alcohols, various salts, boric acid, and microcrystalline cellulose. Snorting any of talc, starch, or cellulose into your lungs can result in an inflammation that disrupts your ability to breathe normally.A decidedly artsy photo of talc powder between two brushes (Source)There are also a bunch of drugs known to be mixed in with cocaine to dupe a buyer into believing they're purchasing a higher quality product. Caffeine is used in this capacity because it's cheap and is a stimulant (it perks you up) like cocaine, albeit a way less intense one. Several relatives of cocaine, including procaine, lidocaine, and benzocaine, are used as local anesthetics to do things like numb your mouth at the dentist before the drilling commences. Cocaine also causes mouth numbness, so adding these other drugs to it can trick customers into thinking they're getting a higher quality product.One of the stranger yet very common additions to cocaine is a drug called levamisole. It's good at killing parasitic worms and also appears to be able to influence the immune system in useful ways. Unfortunately, it also has a tendency to ruin bone marrow and cause a serious dip in the number of white blood cells being made there (agranulocytosis), which is a fantastic way to catch a life-threatening infection. Snorting cocaine contaminated with levamisole can also damage blood vessels in the arms and legs via vasculitis. The role of levamisole as a cocaine adulterant is a bit of a mystery. It's apparently transformed into aminorex, an amphetamine-like drug, when given to racehorses, suggesting it can enhance the effects of cocaine. There's also some evidence that levamisole can act on receptors in the brain to enhance how good cocaine makes you feel. Alternatively, it may simply be added because it's cheap, resembles cocaine, and is often easy to acquire since it's sold as a veterinary medication.Our tour of drug additions to cocaine ends with diltiazem. This drug acts to block the movement of calcium through channels in the outer membranes of heart cells, permitting it to be used to help control an erratic heartbeat (arrhythmia) and other heart issues. It's been suggested that some distributors decided to add diltiazem to their cocaine in order to negate the negative effects it can have on the heart, which happen to include arrhythmias. Even so, there isn't any evidence diltiazem can provide a protective effect. If anything, it might actually make things worse.ReferencesBrunt TM, Rigter S, Hoek J, Vogels N, van Dijk P, Niesink RJ. 2009. An analysis of cocaine powder in the Netherlands: Content and health hazards due to adulterants. Addiction 104(5):798-805.Cole C, Jones L, McVeigh J, Kicman A, Syed Q, Bellis M. 2011. Adulterants in illicit drugs: A review of empirical evidence. Drug Testing and Analysis 3(2):89-96.Tallarida CS, Tallarida RJ, Rawls SM. 2015. Levamisole enhances the rewarding and locomotor-activating effects of cocaine in rats. Drug and Alcohol Dependence 149:145-150. [Full text]... Read more »

  • July 12, 2016
  • 12:36 PM

Dextromethorphan for Alzheimer's Disease Agitation

by William Yates, M.D. in Brain Posts

In my last post I summarized a review of the pharmacology of the drug dextromethorphan.This drug is receiving significant attention for disorders in neuroscience medicine. A phase 2 clinical trial of dextromethorphan-quinidine (DM-Q) was published last fall in JAMA.Here are the key design and results from this study:Subjects: 220 subjects with a diagnosis of probable Alzheimer's disease with clinically significant agitation.Randomization Design: This was a five week trial of 3:4 randomization to received DM-Q or placebo. Placebo subjects were re-randomized and enrolled in a 1:1 DM-Q versus placebo trialDrug Dose Design: DM-Q 20mg-10mg daily for one week, then 20-10 twice daily for two weeks then 30mg-10mg twice daily for remainder of study.Outcome: The primary outcome score was the agitation/aggression subscale score from the Neuropsychiatric Inventory. Active drug assignment reduced this score more than placebo (7.1 to 3.8 versus 7.0 to 5.3).Adverse effects: Serious adverse effects were more common in active drug groups 7.9% versus 4.7% and included higher rates for falls, diarrhea and urinary tract infections. The authors note in the discussion that the higher rate of falls may have been due to an imbalance of fall risk at randomization.This is an important study of a novel treatment approach to agitation in the elderly with Alzheimer's disease. Current drug treatment approaches are limited and linked to significant side effects.Phase 3 studies of this drug combination are recruiting at the present time.Follow the author on Twitter WRY999Readers can access the free full-text manuscript by clicking on the PMID link below.Figure of dextromethorphan comes from a Wikipedia Creative Commons file authored by Benjah-bmm27.Cummings JL, Lyketsos CG, Peskind ER, Porsteinsson AP, Mintzer JE, Scharre DW, De La Gandara JE, Agronin M, Davis CS, Nguyen U, Shin P, Tariot PN, & Siffert J (2015). Effect of Dextromethorphan-Quinidine on Agitation in Patients With Alzheimer Disease Dementia: A Randomized Clinical Trial. JAMA, 314 (12), 1242-54 PMID: 26393847... Read more »

Cummings JL, Lyketsos CG, Peskind ER, Porsteinsson AP, Mintzer JE, Scharre DW, De La Gandara JE, Agronin M, Davis CS, Nguyen U.... (2015) Effect of Dextromethorphan-Quinidine on Agitation in Patients With Alzheimer Disease Dementia: A Randomized Clinical Trial. JAMA, 314(12), 1242-54. PMID: 26393847  

  • July 11, 2016
  • 12:41 PM

When Laughing Isn't Funny

by William Yates, M.D. in Brain Posts

Inappropriate uncontrollable laughing or crying is common in many neuroscience medicine disorders including after traumatic brain injury or stroke. It can be socially embarrassing and restrict opportunities for social interaction.This loss of control over emotional responses is known by the term pseudobulbar affect or PBA. Until recently, few therapeutic options were available to treat this condition. Now a relatively new drug Nuedexta uses a combination of dextromethorphan and quinide to treat pseudobulbar affect. This drug combination has received FDA approval in the U.S.A recent review article summarized what is known about the pharmacology of the drug dextromethorphan (DM). DM is found in over-the-counter cough medications, for example Robitussin DM.The DM mechanism of action is felt to be due to the blocking of the NMDA receptor (N-methyl-D-aspartate). This results in a inhibition of the excitotoxic neurotransmitter glutamate. The effect of DM on neurotransmitter function is non-specific and effects on other neurotransmitter systems include:Inhibition of serotonin reuptakeInhibition of norepinephrine uptakeAntagonism of the nicotinic acetylcholine receptorsAgonism of sigma1-R geneQuinidine inhibits CYP2D6 the cytochrome P450 liver enzyme involved in liver enzyme metabolism of DM. This results in much higher and prolonged blood levels of dextromethorphan.The potential therapeutic targets for DM mentioned in the review include the following:Pseudobulbar affectEpilepsyPainPeripheral neuropathyTBIStrokeAlzheimer’s disease (agitation)I will take a look at some of the specific research studies in these additional targets over the next week or two.Follow the author on Twitter WRY999Figure of Advertising Card showing phases of laughter is from Wikipedia Creative Commons.By not known, printed by Young's, The Hatter - eBay store Web page: CP, Traynelis SF, Siffert J, Pope LE, & Matsumoto RR (2016). Pharmacology of dextromethorphan: Relevance to dextromethorphan/quinidine (Nuedexta®) clinical use. Pharmacology & therapeutics PMID: ... Read more »

  • June 15, 2016
  • 11:18 AM

Weird stuff found in recreational drugs: Meth edition

by Rosin Cerate in Rosin Cerate

As Breaking Bad has taught us, the clandestine manufacture of methamphetamine is a very dangerous undertaking. It involves the use of many harmful substances, which depending on the synthesis method include highly corrosive acids and bases, cancer-causing benzene, brain-damaging mercury and lead, jaw-wrecking phosphorus, and blood-breaking sodium cyanide. Blending these various substances together can produce noxious fumes, making gas masks and chemical suits a necessity if you want to avoid getting seriously hurt.Meth cooks, at least those involved in small scale operations, tend not to be trained chemists. If they don't follow the correct recipe, either because they lack the necessary knowledge or skill, or they just don't care, the aforementioned harmful substances can end up in the final product. Lead is a particularly dangerous meth contaminant. A batch of meth responsible for an outbreak of acute lead poisoning in Oregon in 1988 was found to contain >60 percent lead by weight, which is insane! If meth is synthesized using crushed tablets of pseudoephedrine, granules from the tablets can make their way into the veins of intravenous users, causing skin irritation and the increased likelihood of nasty bacterial infections. Meth can also be contaminated with organic compounds closely related to something called alpha-benzyl-N-methylphenethylamine, which when tested in mice proved to be more potent inducers of seizures compared to meth.In addition to the nasty stuff inadvertently introduced into a batch of meth during its manufacture, an interesting collection of substances are used to dilute meth prior to selling it (got to maximize those profits). These cutting agents are known to include sugars such as lactose and mannitol (cheap way to add bulk), methylsulfonylmethane (physically resembles meth, improving the perceived quality of the drug), mild stimulants such as caffeine and ephedrine (mimic the effects of meth), and sidewalk chalk (used to provide a splash of colour). ReferencesBurton BT. 1991. Heavy metal and organic contaminants associated with illicit methamphetamine production. NIDA Research Monograph 115:47-59. [Full text]Cole C, Jones L, McVeigh J, Kicman A, Syed Q, Bellis M. 2011. Adulterants in illicit drugs: A review of empirical evidence. Drug Testing and Analysis 3(2):89-96. [First page]Poulsen EJ, Mannis MJ, Chang SD. 1996. Keratitis in methamphetamine abusers. Cornea 15(5):477-482.Strathdee SA et al. 2008. The color of meth: Is it related to adverse health outcomes? An exploratory study in Tijuana, Mexico. American Journal on Addictions 17(2):111-115. [Full text]... Read more »

Cole C, Jones L, McVeigh J, Kicman A, Syed Q, & Bellis M. (2011) Adulterants in illicit drugs: A review of empirical evidence. Drug Testing and Analysis, 3(2), 89-96. PMID: 21322119  

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