How Many Drugs is Too Many?

How Many Drugs is Too Many?

By: Caitlyn Cummings, PharmD Candidate c/o 2016 and Ruby Lee, PharmD Candidate c/o 2017

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In Dina Spector’s Business Insider article, “The World’s 2^nd-Smartest Man Reveals The ‘Brain Drugs’ That He Thinks Make Him Smarter,” the daily medications taken by Rick Rosner, said genius, are revealed.¹ There are unsubstantial descriptions for indications, no strengths or frequencies, and it is inferred that many of the over-the-counter (OTC) drugs are self-prescribed. While data is limited, it is through our professional insight that we will deconstruct his medication list in order to evaluate drug-drug interactions, potential adverse reactions, and unnecessary drug therapies; and additionally show how these ‘brain drugs’ may in fact cause him more long-term harm than good.

Polypharmacy can be defined as the use of five or more drugs by one patient. Excessive use of medications could lead to inappropriate therapies, duplicate therapies, and deadly interactions between other drugs, food, or disease states.² Additionally, the use of OTC supplements could also increase the risk of adverse reactions, since many patients mistakenly believe they are innocuous. Pharmacists and other healthcare providers are given the challenging task to keep track of a patient’s prescribed medications as well as any supplemental OTC medications the patient may take. An extreme example of polypharmacy can be seen with Rick Rosner, who takes over 40 medications each morning.

The first major interaction spotted in Rosner’s list is between his half an aspirin, SAM-e, horse Chestnut, piracctam, vitamin K, vitamin E, glucosamine, omega-3 fatty acids, curcumin and to a lesser extent coeenzyme Q₁₀, lycopene, and selenium. These drugs, with the exception of vitamin K, may increase his risk of bleeding including, but not limited to, gastrointestinal bleeding, having a hemorrhage (intracerebrally, retrobulbarly, or in the subarachnoid space), or having a hemorrhagic stroke.³

While more studies are needed to assess dietary supplements and the likelihood of these events (particularly in combination with other anticoagulant or antiplatelet drugs), there is in vitro and some in vivo evidence supporting their mechanisms of action and potential for adverse bleeding events.

Rick Rosner’s List of “Brain Drugs”1

Half an aspirin daily*

Glisodin

Fancy multivitamins from Life Extension and Vitacost

Astragalus

Curcumin*

ALA and acetyl L-carnitine

Vitamin E with Selnium and Gamma E*

Calcium

Mangosteen pomegranate noni complex

Quercetin and Bromelain

DMAE

Piracetam*

Methylene blue+

Metformin

Avodart

Sam-E* +

Fat blockers

ToCoQ10*

Vitamin D3

Lycopene*

Benfotamine

Vitamin K¨

Coffee

Aminoguanidine

Cognitex from Life Extension

Omega-3 Fish Oil Capsules*

Metoprolol

Glucosamine* and Chondroitin

RX and non-RX drugs to lower cholesterol

Fiber gummies

L-carnosine

Vitamin C

TMG (trimethylglycene)

N-acetyl cysteine

Horse Chestnut*

Phosphatidylserine

Centrophenoxine

Vinpocetine

* Increases chances of adverse bleeding events+ Increases risk of serotonin syndrome ¨ Promotes clotting

Aspirin inhibits platelet aggregation, the body’s first step in clotting after injury to the blood vessel, as do SAM-e, glucosamine, omega-3 fatty acids, vitamin E, curcumin, and lycopene. This will increase the time it takes for blood to clot and the likelihood of an adverse reaction related to bleeding.³ Glucosamine was found to increase the INR in patients on warfarin, but there is limited evidence of its effect when combined with NSAIDs.³ Studies have also shown that vitamin E may have a dose-dependent effect on the anti-coagulation cascade in patients.³ Two additional drugs that inhibit hemostasis include piracetam and horse chestnut. Piracetam is an NSAID that inhibits the formation of thromboxane A2 (pro-clotting factor) and affects blood cell deformability.⁴ Horse chestnut constricts the veins and decreases the permeability of the venous capillaries.⁵ Thus, through the interplay of various mechanisms, Rosner’s ability to clot his blood is seriously compromised.

Rosner additionally takes vitamin K, without a stated indication. Vitamin K’s only approved indication is for extreme cases of warfarin overdose by promoting liver clotting factors; it is worth noting that this is a different part of blood coagulation than the antiplatelet drugs described previously, so it does not inhibit their antiplatelet action.⁶ The effects of vitamin K on the coagulation cascade are dose-dependent due to the fact that vitamin K-dependent clotting factors (factors II, VII, IX, and X) have varying half-lives. ⁷ However, Rosner did not specify which form of vitamin K, strength, or frequency so it is unknown the extent of clotting factors formed. The bottom line is that Rosner is taking vitamin K without a clear indication and in combination with many drugs that exude opposite effects; this presents no advantage. Additionally, the combination of so many pro-bleeding supplements and their varying mechanisms in preventing clotting poses a potentially serious health threat to Rosner.

Secondly, Rick Rosner has an increased risk of serotonin syndrome by combining methylene blue and SAM-e. Serotonin syndrome is a predictable, acute-onset, and potentially fatal reaction to the use of multiple serotonergic drugs, having symptoms including hypertension, tremor, agitation, and diarrhea.⁸ Methylene blue is typically used as an injection to treat methemoglobinemia or used as a dye for diagnostic purposes,⁹ but Rosner is taking an oral dose as part of a clinical trial to reduce his risk of developing Alzheimer’s disease.¹⁰ While its use in Alzheimer’s seems promising, methylene blue also inhibits monoamine oxidase A, which in turn inhibits the breakdown of serotonin in the brain.⁹ SAM-e works by an unknown mechanism to increase serotonin in the brain as well.¹¹ Since methylene blue is only in clinical trials and data for interactions is limited, it can be theorized that Rosner has the potential for a major interaction between SAM-e and methylene blue and the combination should be avoided.

Lastly, two drugs that lack indications for Rosner include N-acetylcysteine and a fat blocker (assuming over-the-counter Orlistat). N-acetylcysteine is mainly used as an antidote for acetominophen poisoning or as an adjunct to thin the mucus in respiratory conditions.¹²  He has not listed any other pulmonary-specific drugs, making us question the use of this particular drug, especially since it causes a high incidence of vomiting.¹² Additionally, the fat blocker that Rosner takes is inappropriate because we calculated his BMI as 19.9, close to being classified as underweight.¹³ Orlistat should only be used in patients with a BMI greater than 30 or greater than 28 with additional medical conditions. It also interacts with every fat-soluble vitamin he takes, thus canceling out any effectiveness from vitamins A, D, E, or K (unless taken two hours apart).¹⁴ The danger with blocking vitamin K absorption is that he is now even more susceptible to the anti-clotting effects described previously.
The dangers of polypharmacy can be clearly seen in Rick Rosner’s case. While he claims this list of medications makes him smarter, as future pharmacists, we see a list of problems, some potentially fatal, while only scratching the surface of his medication list. As one can see, sometimes it only takes one drug to be one too many.

SOURCES:

1. Spector D. The world’s 2nd-smartest man reveals the ‘brain drugs’ that he thinks make him smarter. Business Insider. http://www.businessinsider.com/rick-rosner-iq-and-health-2014-12. Published 2 Dec. 2014. Accessed 17 Dec. 2014.
2. Cipolle RJ, Strand LM, Morley PC. Chapter 5. Drug Therapy Problems. In: Cipolle RJ, Strand LM, Morley PC. eds. Pharmaceutical Care Practice: The Patient-Centered Approach to Medication Management Services, 3e. New York, NY: McGraw-Hill; 2012. http://accesspharmacy.mhmedical.com.jerome.stjohns.edu:81/content.aspx?bookid =491&sectionid=39674905 . Accessed January 14, 2015.
3. Stranger MJ, Thompson, LA. Anticoagulant activity of select dietary supplements. Nutrition Reviews. 2012; 70 (2): 107-117. Accessed January 20, 2015.
4. Winnicka K, Tomasiak M, and Bielawska A. Piracetam – An Old Drug with Novel Properties?.Polish Pharmaceutical Society. 2005; 62 (5): 405-409. http://www.ptfarm.pl/pub/File/Acta_Poloniae/2005/5/405.pdf. Accessed December 27, 2014.
5. Horse Chestnut. In: Natural Products Database. Hudson, OH: Lexicomp. Inc. [Updated December 27, 2014; Accessed December 27, 2014]. http://online.lexi.com.jerome.stjohns.edu:81/lco/action/doc/retrieve/docid/fc_rnp 2/3750194
6. Vitamin K. In: Natural Medicines Comprehensive Database. Therapeutic Research Faculty, Stockton, CA. [Updated January 23, 2015; Accessed January 24, 2015]. http://naturaldatabase.therapeuticresearch.com/nd/Search.aspx?cs=STUDENT&s=ND&pt=100&id=983&ds=
7. Theuwissen E, Teunissen KJ. Effect of low-dose supplements of menaquinone-7 (Vit K2) on the stability of oral anticoagulant treatment: dose-response relationship in healthy volunteers. J Thromb Haemost 2013; 11: 1085-92.
8. Katzung BG. Chapter 16. Histamine, Serotonin, & the Ergot Alkaloids. In: Katzung BG, Masters SB, Trevor AJ eds, Basic & Clinical Pharmacology. 12^th ed. The McGraw-Hill Companies, Inc; 2012: 281-287.http://accessmedicine.mhmedical.com.jerome.stjohns.edu:81/content.aspx?bookid=388&sectionid=45764237&jumpsectionID=45766816&Resultclick=2. Accessed January 03, 2015
9. FDA Drug Safety Communication: Serious CNS reactions possible when methylene blue is given to patients taking certain psychiatric medications. U.S. Food and Drug Administration. Published July 26, 2011. http://www.fda.gov/Drugs/DrugSafety/ucm263190.htm
10. Medina DX, Caccamo A, Oddo S. Methylene blue reduces Aβ levels and rescues early cognitive deficit by increasing proteasome activity. Brain Pathology (Zurich, Switzerland) 2011;21(2):140-149. doi:10.1111/j.1750-3639.2010.00430.x.
11. SAMe. In: Natural Medicines Comprehensive Database. Therapeutic Research Faculty, Stockton, CA. [Updated December 27, 2014; Accessed December 27,2014]. http://naturaldatabase.therapeuticresearch.com/nd/Search
12. Acetylcysteine. In: Lexi-Drugs Online. Hudson, OH: Lexi-Comp, Inc.; [Accessed January 12, 2015]. Accessed January 12, 2015. http://online.lexi.com.jerome.stjohns.edu:81/lco/action/doc/r etrieve/docid /patchf/6281#fuses
13. Rosner, R. The World’s Second-Smartest Person Tries to Answer Your Questions- Pills and Diet. http://goo.gl/w8YDzS. Published August 7, 2014. Accessed January 12 2015.
14. Orlistat. In: Lexi-Drugs Online. Hudson, OH: Lexi-Comp, Inc.; [Accessed January 12, 2015]. http://online.lexi.com.jerome.stjohns.edu:81/lco/action/doc/retrieve/docid/patch_f/7402#f_uses