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Your Pharmacy is Most Likely an Alternative, Complimentary, Off Label, Patient Centred One
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Most Pharmacists rely on the foundation that their “evidence-based” mantra is being followed. A simple Google search shows us that:

“Alternative medicine is any practice that is put forward as having the healing effects of medicine, but does not originate from evidence gathered using the scientific method, is not part of biomedicine, or is contradicted by scientific evidence or established science.”

Just in case you were wondering, Google defines biomedicine as “a branch of medical science that applies biological and other natural-science principles to clinical practice. The branch especially applies to biology and physiology”.

This last one is important as we shall see, because it opens the window for recommendations to be made even in the absence of placebo controlled randomized trials (but yet remain outside of the realm of alternative medicine). It allows biochemistry and physiology and biology to guide recommendations to patients, even though direct studies on humans measuring an effect compared to placebo are lacking. For example, if you are thirsty, drink water or you will eventually die. There really are no such studies to prove this but we believe it anyway. Fair enough. Let’s agree on this for a minute or two as we look at our “go to” recommendations we do every day in the pharmacy.

In 2012 the International Journal of Pharmacy Practice published a research paper that looked into the effect of evidence-based training on Pharmacists everyday recommendations. It found that Pharmacists did not routinely utilize evidence-based resources when making decisions about OTC medicines and some felt uncomfortable discussing the evidence-base for OTC products with patients. (1)

In fact most pharmacists go by three things when making OTC recommendations, what they were taught in school (since most OTC ingredients don’t really change all that much from year to year or decade to decade), what they learn through continuing education and what they see works in their patients over time (also known as clinical experience). This is why I gave up recommending OTC teeth whitening products.   I do however recommend specialized toothpastes for sensitive teeth even though I have never read one independent RCT on either subject – because I routinely hear results from many customers. (2)(3)

These are simple recommendations that on the surface seemed to be a great idea. Not that the success of OTC teeth whitening grew into an urban myth to me but it really didn’t seem right to recommend something I had no scientific proof to back me up and make a profit on it plus lacked the positive feedback from my customers. Perhaps that is alternative therapy?

It’s part of every retail pharmacist’s day, stepping out from behind the dispensary counter and making recommendations that draws from the vast pool of for the most part, unchanging static list of ingredients in the front store. I draw a fair share of comments that claim some recommendations I make are “alternative” or “complimentary”, sometimes referred to as CAM therapies. The definition of this term seems to change with whomever makes up the argument. Some arguments against CAM are certainly legitimate, and some include categories that show some effectiveness but are not mainstream. Some involve treatment, cure or prevention of Health Canada Schedule A disorders, which include many conditions that we try to help daily – we just can’t advertise the products as such. They include obesity, hypertension, diabetes, acute anxiety and others. Either way, there are some regular recommendations made by Pharmacists daily that said Pharmacist assumes is proven to work based on mainstream suggestions, but are you making recommendations based on the same science that backs up the prescriptions you hand out daily. Furthermore, if these therapies do not meet these same evidence based standards, are they automatically shuffled into the CAM category or is there another category they might be moved into? Perhaps urban myths make mainstream otc pharmaceutical suggestions.   Lets look at what the current literature says about common therapies. Are there any studies at all that back up what you are suggesting to your customer as fact? If there are studies, do they have the power to the same? If not, what is your rationale for making these recommendations and at what point do we call the recommendations as alternative or not evidence based. In fact, pharmacists do not always rely on the definition of evidence based in making an OTC recommendation.

Cough Therapy

Turning to the Cochrane Data Base, there are a few reviews for common OTC cough medications. In reviewing 29 trials involving 4835 people (adults and children – studies were current up to March 2014), the Cochrane Library stated “ We found no good evidence for or against the effectiveness of OTC medications in acute cough”.  In a 2006 statement, the American College of Chest Physicians stated that its recommendation for cough due to cold was to treat with an antihistamine/decongestant combination. (4)(5) Also, the findings of using codeine or antihistamines for cough showed neither was superior to placebo. A study in the Archives of Pediatrics and Adolescent Medicine found that in Parent reported cough response to buckwheat honey, a DM cough syrup flavored with honey and a placebo, the honey alone treatment was superior to the DM syrup or the placebo in children. (6)(7) Popular cough syrups that use pine needle oil and Canadian Balsam in a capsicum tincture are popular in all pharmacies but lacking evidence.

 

Narcotics for pain

Marketing by drug companies has been quite successful in the widespread use of narcotics today. In fact when various types of pain are treated with opioids, NSAIDS, and acetaminophen, narcotics’ recommendations often fall at the bottom. Dental pain, while often treated with narcotics, has been shown by the Cochrane Database to be treated more effectively with combination ibuprofen and acetaminophen and back pain has also been shown to have more favorable outcomes when treated with non-opioid medications. (8) Historically pharmacists police OTC meds, sometimes blind while trying to keep patients restricted to a days supply. This is now going to be easier with the dawn of the Drug Information System (DIS) in Nova Scotia, giving more real time data than the triplicate prescription monitoring system. Logging in OTC codeine products allows pharmacists to see in real time the profile of the patient at other pharmacies that are also on the system.

It is becoming more and more clear that opioids are to be the exception rather than the rule when it comes to most pain relief. Terminal conditions involving pain are a clear indication for opioids. The numbers needed to treat are typically higher in the opioids compared to the non-opioid medications and in acute pain to chronic pain conditions the opioids are not preferred unless absolutely necessary. Jumping to OTC codeine has not proven to be the answer with most patients based on science.

 

Antacids

Next to cough and cold, and analgesics, acid suppressing agents are a main staple in a pharmacist’s OTC toolbox. Three main categories are antacids, H2-blockers and PPI’s, all available OTC. Most pharmacists may be under the impression that when these are given, they help neutralize acid in the stomach in their own way and relieve reflux symptoms, and that’s that. It turns out these three medications have differing effects that must be kept in mind to help the patient. Antacids have a role in neutralizing acid in the esophagus transiently but do not significantly affect the pH in the stomach. As a result it has been found that in cases of chronic heartburn, repeated administration of antacids commonly result in erosive esophagitis. For this reason it is important to recommend them only in cases of GERD that is temporary or intermittent in nature and to realize that ulcer healing will be minimal. With the H2 blockers, there is a tolerance that can develop rather quickly with these medications that unfortunately is not dose dependent and there is also a secondary analgesic effect on the tissue of the esophagus. (9)

The key in OTC recommendations is recognizing the strengths and the limitations of each of these medications. Simply giving an antacid for a patient with “heartburn” without knowing the exact details of frequency goes against the indication for that suggestion. Monographs for these medications state a six week course and should not be used long-term for acid suppressing agents. It is important to not continue to give antacids too frequently in order to prevent further damage to the esophagus. In fact there is no evidence to support long-term treatment with H2 blockers or PPI’s.

 

Head Lice

While it was something pharmacists had suspected for years, it has now been shown in clinical trials that the effectiveness of the pediculicide known as permethrin has dropped from 99% in 1996 to 25% in 2009. In 2010 this effectiveness was estimated to be 18% as opposed to 46% for isopropyl myristate, which is now a popular alternative for head lice. This is a case of staying on top of current literature.   (10)   Although something may have been proven to work before, it may not have the same effectiveness now and is continued to be used assuming older data is still appropriate.

 

Chronic Constipation

One of the most commonly recommended laxatives for both occasional and chronic constipation as well as narcotic induced constipation is senna. There are no well designed randomized placebo controlled trials for senna and for the most part I think most pharmacists are unaware of this and go by clinical results in making this recommendation. Also no known studies comparing stand alone efficacy of docusate over placebo exist. Fiber, fluids and exercise show surprisingly little results unless the patient is deficient in any of them. (11)

One of the common arguments against alternative therapy is not so much a lack of studies, but a lack of what is considered quality studies by the one against alternative therapies. Sometimes it is what the majority of us do that removes something from alternative. While there are no lack of studies on nicotine replacement therapy OTC in smoking cessation there are many limitations to many of the studies (12). This is a common argument against treatments that are considered alternative.   At some point however we need to treat somehow and we see clinical results, based on science (RCT or biology) and we use this to guide our recommendations safely.

 

Having said all this, the point is from our experience most over the counter meds really do work for their intended uses. If we required iron clad prescription drug quality studies to flip through on all of our front shop recommendations, we may very well cut the front store medicine section in half, not to mention the prescription medications that are prescribed off label. Certainly a lot of the cosmetic anti-aging and skin cream products would fall away. We also must remember that although we counsel based on past results with patients, we still make recommendations based on our education. Being against alternative medicine, whatever your own definition, may mean supplements, nutraceuticals, hormone therapy or herbal products to you. Maybe you consider selling vitamins as alternative. Some bad examples of irresponsible alternative therapy have painted all therapies with the same brush, and some reported side effects and hospitalizations of patients using alternative therapies fail to mention hospitalizations of patients on conventional medicine. As pharmacists, we value what is considered modern medicine but it’s not all that is out there that works. We must be considered the drug expert in all therapies, whether they are proven and safe to completely unproven and unsafe and everything in between in order to make an informed recommendation. Perhaps “evidence based” is a point we try to achieve but never completely reach until we change our definition of what it is. Based on how we defined alternative medication at the start of this article, perhaps alternative therapies are not as uncommon in pharmacies as is claimed by those that are against them.

 

 

 

 

References

 

1) Lezley-Anne Hanna and Carmel Hughes; The influence of evidence-based medicine training on decision-making in relation to over-the-counter medicines: a qualitative study; International Journal of Pharmacy Practice Volume 20, Issue 6, pages 358–366, December 2012

2) Demarco FF, Meireles SS, Masotti AS. Over-the-counter whitening agents: a concise review. Braz Oral Res. 2009;23 Suppl 1:64-70

3) Ilze Maldupa, Anda Brinkmane, Inga Rendeniece, Anna Mihailova ;Evidence based toothpaste classification, according to certain characteristics of their chemical composition ; Stomatologija, Baltic Dental and Maxillofacial Journal, 14:12-22, 2012

4) Smith SM, Schroeder K, Fahey T. Over-the-counter (OTC) medications for acute cough in children and adults in community settings. Cochrane Database of Systematic Reviews 2014, Issue 11. Art. No.: CD001831.

5) Smith SM, Schroeder K, Fahey T. Over-the-counter medications for acute cough in children and adults in ambulatory settings. Cochrane Database Syst Rev. 2008;(1)

6) Paul IM, Beiler J, McMonagle A, Shaffer ML, Duda L, Berlin CM Jr Effect of honey, dextromethorphan, and no treatment on nocturnal cough and sleep quality for coughing children and their parents Arch Pediatr Adolesc Med. 2007 Dec;161(12):1140-6.

7) An De Sutter. There is no good evidence for the effectiveness of commonly used over-the-counter medicine to alleviate acute cough ; Evid Based Med 2015;20:98 doi:10.1136/ebmed-2014-110156 Systematic review

8) Dr Donald Treater M.D. Evidence for the Efficacy of Pain Medications. National Safety Council (NSC.org)

9) McRorie, J. W., Gibb, R. D. and Miner, P. B. (2014), Evidence-based treatment of frequent heartburn: The benefits and limitations of over-the-counter medications. American Assoc Nurse Prac, 26: 330–339

10) Sanofi-Pasteur , Evidence Based Management of Head Lice 2014

* (Sanofi-Pasteur is a manufacturer of ivermectin lotion)

11) Lawrence Leung, MBBChir, FRACGP, FRCGP, Taylor Riutta, MD, Jyoti Kotecha, MPA, MRSC, and Walter Rosser MD, MRCGP, FCFP Chronic Constipation: An Evidence-Based Review . Journal of the American board of family medicine July-August 2011 Vol. 24 No. 4 pp 436-451

12) Nicotine Replacement Therapy for Smoking Cessation or Reduction: A Review of the Clinical Evidence [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2014 Jan 16. SUMMARY OF EVIDENCE.

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Why the Pharmacy OTC Section Will Be a Growing Target for Evidence Based Medicine Trolls
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The front store of the pharmacy has traditionally been where the pharmacist and patient relationship grows to a level beyond where it would be with just prescription counseling alone. It affords to pharmacists a selection of products that empowers the lay public to take some sort control of their health in almost any way they choose. With certain selective issues (or perhaps a wider selection in their minds), they can bypass the waiting room of the physician, the poking and prodding, the embarrassing questions, the waiting at the pharmacy counter – all gone with just a wave of the hand from the OTC aisle to the pharmacist peering down to you from his or her stoop in the dispensary.

The general public questions this type of medical treatment very little, partially because of the level of trust that is consistently demonstrated towards pharmacists, or perhaps because most of what is available to choose from in this realm has been virtually unchanged in its ingredient list for decades. In fact I am willing to bet that if I were to walk through the aisles of my neighborhood pharmacy on the day I was born nearly 50 years ago, aside from a few struggles with brand names and a few recognized products that have been discontinued, the ingredient list on most items in the entire store would be much the same as my store today. This brings with it a level of trust in these products by the public, sometimes a false sense.

Back then many of these products were put there in the front store without a whole lot of randomized placebo controlled double blinded/crossover trials (RCT’s) that brought most of the prescription medications to market and back 50 years ago there was little debate as to their effectiveness. The pharmacist recommended it and you took it and it worked. That was that. The path that each product took to land on the shelves of your pharmacy each has a story and history of their own.

There is a growing concern that pharmacists are now selecting items for patients that have little backing scientifically. For example, one of these families of products, known as homeopathic, is one of them. Back 50 years ago you may have even spotted one of these in your neighborhood pharmacy. Now before I go any further I’ll end your guessing of my views of homeopathy: I don’t think it really does much of anything for anybody. For those of you still reading, because you’re in agreement of that last statement, just hold on a second. If we are slamming this mode of treatment because we feel the studies don’t back it or because there is nothing in the actual dosage form, that is fair enough. The supplement aisle is another category that brings about much criticism, and for the record, I have a different belief in this category (just not fanatical in like everyone should have all of them). But as “evidence based” practitioners, in all fairness we need to apply this to the entire store.

Applying our strong standard of evidence to everything else, we look with our magnifying glass at all other products: cough medicines, constipation relief, lice remedies, pain relief selections, antacids and reflux relief meds, skin creams, acne relief, teeth whitening (ok maybe not available in the 60’s), hemorrhoid relief, bug spray, lozenges, lip balm, and lots more. Can you quote or summarize the randomized controlled history for these categories? Perhaps can you find evidence against what you are recommending that product for? Acetaminophen for lower back pain? Cough syrup for someone with a common cold. You can check out a fuller explanation of these categories here .

So getting back to our original claim slammed against us: Why do we sell these items that obviously have some doubt as to their effectiveness? As a pharmacist I am always striving to supply what people want to use for their health as long as it does not harm their health in taking it. Secondly it should be effective. The order of these two is important. My community wanted organic food so that’s what I got in to sell at the pharmacy. Removed 12 feet of magazines and replaced it with organic, gluten free, non gmo. Does it harm them? No. Is it effective for what they are taking it for? Maybe. Maybe not. But it does not harm them.

When Cold FX was going through it’s court case on the claims it was making I voluntarily removed it from my shelves. When the case ruled in their favor I brought it back – much to the delight of my customers who had been asking for it for weeks and months. Is it safe – yes, and is it effective – who the hec knows. I push vaccines, but I also sell Muco Coccinum and stress that you cannot rely on that to prevent the flu or much of anything else. I sell probiotics but screen those with suppressed immune system who cannot safely take them. I ensure that it is used safely first and if it is effective for their gut health, immune health, skin health or mental health then so be it. I try to guide them with the studies I have available to me but first and foremost it must be used safely. That means the product won’t interact with their medication or medical condition or result in them omitting proper established treatment for their condition especially should it be serious or life threatening. No one should be curing cancer or treating their heart disease in this part of the store, but if they have a drug induced lowering of vitamin B12 then I’m their guy. If they are looking to prevent a cold they feel might be coming on with Zinc tablets then great (something I take).

The point of all this is most if not all of new drug research is targeted towards bringing new prescription medication to market, not OTC drugs. While it’s true that some prescription medication may trickle down to OTC status (and thankfully this should have RCT’s to back them up, which is great) not much groundbreaking in the OTC field happens for the most part. Recently I have seen a new product come out for varicose veins and one for vaginal dryness, but for the most part we are stuck with what we have out there, and it’s not an area where we test existing products on new indications, nor do we really go testing a lot of the current indications for existing products that they are sold for (perhaps with a few exceptions). Unfortunately the vitamin/supplement and herbal market is always pushing the boundaries of what science thinks will happen if you take pill A and what an RCT says. What this means is going forward we will be left with an aging pool of products, a number of which have questionable efficacy for the indication they are being sold for and a growing list of products that have the same backup. This pool may have some new additions here and there but the old standards stay around.

Complaining about a select group of these items such as homeopathy is noble, but is kind of two faced when we don’t slam other pharmacists that sell all the other products that have similar lack of actual evidence to back them up. Particularly when the pharmacist is following the law. Being a pharmacist is not being a doctor. We can now prescribe for minor ailments in my area, but the pharmacists today didn’t invent this front store they have available to them. A pharmacist’s recommendation may not always be the same as a doctor’s recommendation, or the same as another’s recommendation, but it should be as safe.

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Going forward with the opioid crisis as a health practitioner.

If you’re a prescriber or pharmacist, you owe it to yourself to check out the Atlantic Mentorship Network’s Prescribing Course – Safe Opioid Prescribing for Chronic Non-Cancer Pain. I had the pleasure of attending this course this weekend in Halifax, Nova Scotia. Although I had been trying to get to this amazing course for quite some time, my schedule finally permitted me to get there this year. In fact it was such an incredible learning experience I felt I should share it with you. As a disclaimer: I am a pharmacist, I have presented for the Mentorship program before, I have no financial interest in the program although I am involved with the planning of the program’s Fall Conference in Inverness Cape Breton this year. Other than that I’m just a fan of the Network.

Chaired by Dr. Peter MacDougall and Dr. John Fraser, this day-long event goes through pearls on what best practices are to deal with the average person with pain. This is not end of life pain or cancer pain, where boundaries are much wider. It is the tough world of dealing with pain at a time that threatens the potential of addiction more than we were aware of at any other time. It threatens safety of prescriber, patient, and the public. Even Dr. MacDougall claimed what many of us were told years back when dealing with narcotics: that we used to think that as long as there was still pain, the chance of addiction was extremely rare. The Nova Scotia College of Physicians and Surgeons are quite active now in reducing the narcotic load in our patients, as are the other provinces in Canada as the wave of overdoses washes eastward. They have adopted the CDC guidelines for treating this type of pain, which includes more of an emphasis on non-narcotic and non-drug.

As someone who feels the burn of the “online” world of alternative treatments and skeptics’ treatment of them, believe me it was refreshing to be in an entire room full of 40 legitimate practitioners embrace whatever works for their patients. I have commented on this phenomenon before and it was evident here again. Terms like physiotherapy, chiropractic, massage, TENS, acupuncture, qigong, yoga and other terms used side by side are embraced by physicians as treatments that have clinical results that they may or may not have success with. I have been working as a pharmacist for almost 24 years and the most important clinical pearls I picked up were:

-If someone claims to be travelling away and needs their Narcotics early ask them when, how are they getting there and where are they staying. This allows you to call contacts (landline) while the patient is sitting in front of you in the office and gives an opportunity to ask (demand) to see plane/bus/train tickets.

– There are many Addiction Risk Assessment tools that really don’t have any evidence to back them up but they can be clinically effective tools in seeing who might be at the highest risk for addiction in the future and who may require special attention going forward with their therapy.

– Although many patients in our patient records claim to be allergic to morphine, this “allergy” may actually be a normal pruritis side effect from the morphine and not an allergy at all.

-An increased request for more narcotic dosing may occur after a previous increase in dose for many reasons. It may be from hyperalgesia from the narcotic causing more pain. It may be from the increased activity that the pain relief allowed – which causes more pain. The concepts of pseudoaddiction, tolerance, pseudotolerance, opioid withdrawal, failed opioid trial and chemical coping are all important factors to consider.

-One way to realize if an aberrant behavior more serious or less serious is to ask yourself,   “I would never think to do that” or “I wouldn’t even know how to do that”. If the answer is “yes”, then it is most likely a more serious behavior.

– Safety of the prescriber is paramount

– UDT or Urine drug testing (preferably onsite) and a patient contract should be a standard practice for your opioid patients. It should be kept in mind that not only is UDT an important piece to the overall puzzle, its limitations should be kept in mind.

– “It is the information and not the story” that should be considered with abberant behavior. Why you ran out early is less important than the fact that you ran out early.

– Evidence on opioid rotation is primarily anecdotal but it can be an important method to reduce narcotic load after a failed opioid trial.

– As much as the goal of no narcotics beyond 3 months for this pain is ideal, we will always see these medications given. The goal of “no pain” is not a concept we entertain, and function should always come before pain relief. PRN doses of narcotics on top of long acting narcotics only focuses on the pain relief and not the function. Long acting narcotics are perfectly ok for initiation of narcotics rather than the tried and tested method of “start with short acting meds then convert to long acting”. Patients will not feel the same on these two types of meds and it might be counter productive to have the patient switch to long acting and not feel as well as the short acting med made them feel.

– Determining the goals of the patient and the expectations of treatment are important.

If you can’t make it to this annual event (now in its 18th presentation), you should get to a similar program in your area. This one gets definite kudos from me. Well done!

 

Graham MacKenzie Ph.C.

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How Open Minded Your Physician is May Determine Your Pain Relief

When I graduated from Pharmacy school in 1993, topically applied preparations for pain relief were limited to lidocaine and capsaicin, or so I was told up to that point. I was also taught that narcotics were safe not only for short term pain relief but also for long term pain that was non palliative and non cancer related and that addiction was rare in cases where total pain relief had not been reached yet. Medication is a constantly evolving and changing world. 23 years has passed and all of this has changed in a drastic manner.

It’s difficult to know exactly how it all started, but many in the medical community like to lay blame on the shoulders of a company called Purdue that had its beginnings in New York City as a relatively small pharmaceutical firm in the early 1950’s when it was purchased by two psychiatrist brothers, Mortimer and Raymond Sackler. The success of OxyContin from this company generated billions of dollars in revenue and made the Sacklers one of the wealthiest families in the country. Unfortunately, we began to see a trend happening where claims of this company and the aggressive and inappropriate marketing practices resulted in the alarming abuse and trafficking of this medication over decades of use. The company had to pay 635 million dollars after executives plead guilty.

You’d think that would have been the end of it. However the Mundipharma associated foreign corporations are agressively marketing this same medication worldwide with no plans to scale back. They also are running training programs to physicians in these countries urging them to overcome “opiophobia” and to just go ahead and write for these painkillers. They also have campaigns urging patients to take what their doctors prescribe to them.

The issue now is we have created an entire continent of addicts who would not normally have been there without these recommendations. For example, Jane Doe gets in a car accident. She has undeniable pain from this and it is not handled with NSAIDS. She is given a narcotic based on the recommendations from companies like Purdue who claim their studies show this is a safe medication to prescribe in this patient. In a little while Jane needs a higher dose of the medication and after not too long, despite her repeated denials, is addicted to painkillers. She then is unable to get a continuous supply of the drug from her doctor who now recognizes the problem. She starts to purchase the medication off the street. Her addiction becomes stronger as her supply and quality of the medication becomes more and more questionable. She then finds herself injecting to keep up with her addiction. In the last number of years, she has lost her job, her husband, her children, her home, car, money, friends, and everything she owns is in a small bag that she uses as a pillow because she lives on the streets with a sole purpose of seeking her next supply of fentanyl.

Is this scenario typical of everyone on narcotics? Of course not. If you walked down Vancouver’s downtown Eastside and asked random passersby what their story is, you might hear this one. Canada has recognized this in a west – east manner this year. Canada’s largest mental-health/addictions hospital, the Centre for Addiction and Mental Health in Toronto called on Ottawa in November to remove these high dose opioids from the market and to launch a review of prescription painkillers across Canada.

In fact, in the last 4 years, the number of opioid prescriptions dispensed per 1000 population has decreased in the United States whereas in Canada the number has more or less remained the same over that time frame. The provinces in Canada have been steadily spending more and more each year on opioid addiction. Not surprisingly, BC has lead this spending. PEI and NB are 2nd and 3rd behind them surprisingly. NS is near the bottom of the list. Towards the end of the year, Nova Scotia’s chief medical officer, Dr. Robert Strang, made a statement where he wanted the provinces’ physicians to ween patients back from current prescribed levels of narcotics exceeding the 90 mg per day of morphine and to keep to max of 50 mg if possible. He also wants long-term fentanyl patients backed off this drug in an effort to fit in with upcoming guidelines. The Nova Scotia College of Physicians and Surgeons is endorsing the CDC guidelines for prescribing opioids.

Lately in the news on the west coast we had a story in the news of 13 overdose deaths in one day making emergency kits a necessity. Nova Scotia Pharmacists are now able to dispense rescue kits of naloxone for overdose and these kits are becoming more available as the awareness of the antidote and education spreads.

The CDC promotes the prescreening of patients to avoid addiction. Overdose concerns are more prevalent with those over 65 years of age, history of overdose, substance abuse disorder (including alcohol), history of depression, renal or hepatic impairment and sleep-disordered breathing. Any patient may be considered at risk for overdose if they combine opioids with benzodiazepines, on a longterm formulation or especially just starting this medication, on an opioid for longer than 3 months, or on more than 100 morphine mg equivalents. Addiction is more prevalent with this level of morphine equivalents as well as being on the opioid longer than 3 months.

Nova Scotia’s Dr. Mary Lynch has gone on the record as not being in favour with these strict guidelines and claims that there are many of her patients where there simply is no alternative drug for them. Many physicians are unclear as to what they are supposed to use to control the pain of their patients.

Unfortunately later this year we heard of a list of Doctors flagged by Ontario’s Ministry of health because they were prescribing the equivalent opioid dose of 150 Tylenol 3’s daily for some patients. 86 physicians were the target of this probe.

The recommendations include such non pharmacologic modalities as cognitive-behavioral therapy, exercise therapy, complimentary medicine (like yoga, meditation and acupuncture). Nonopioid analgesics recommended include acetaminophen, NSAIDS, Cox-2 inhibitors, anticonvulsants like gabapentin or pregabalin, and antidepressants like tricyclics and serotonin and norepinephrine reuptake inhibitors. Other therapies involve epidural injection and biofeedback.

With such a sense of urgency and recommendations of treatments not normally seen by physicians in general medicine, one would expect that physicians would be open to topical pain relief. In speaking to physicians I have found a friendly acceptance but a definite hesitance in writing for these compounds. These compounds are new to them and contain such familiar oral ingredients as ketamine, ketoprofen, clonidine, gabapentin, and lidocaine. They may also use lorazepam, carbamazepine, baclofen, cyclobenzaprine, dextromethorphan, and others. A recent article written by myself and a local palliative care doctor covers these ingredients.  Check it out here.

This is a tremendous opportunity to reduce opioid use and improve pain relief. As I have seen from physicians that have tried this and seen it working in their patients, confidence comes with numbers and experience. The lack of side effects, interactions and lowered dose is something they like. Contact a compounding pharmacy and ask them more.

 

Graham MacKenzie

Owner/Compounding Pharmacist

Stone’s Pharmasave

Baddeck, N.S.

www.stonesphamasave.com

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The Continuum of Evidence Based Medicine
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image002Should Pharmacists be blasted for selling what some call alternative therapies or products that are not “evidence based”? These criticisms can blindside unsuspecting Pharmacists trying to do what they can for their patients regardless of the fact that they are making a profit from it or not. What makes it more difficult is the way in which these criticisms are delivered, especially when delivered in an offensive type of online statement like most opinions are delivered today. It makes one grow thick skin if they wish to continue. As a pharmacist myself, I can reflect on the strong personal feelings we have towards our patients, especially in small community pharmacies. Not that many other health care professionals don’t have this deep feeling of ownership in their patient’s heath, it’s just that as pharmacists, the frequency we see these people is just so much higher, either in person or on the phone. We are one of the most if not the most accessible in their health care team and we answer a lot of questions from them, gladly.

Not only are we seeing these people regularly for health related concerns, but we also see them in passing when they need milk or a greeting card. In short, they feel and we feel like we see them more than some of our own family members sometimes. Couple this with the utter vastness of concerns this patient has and relies on us for.

Quite often these questions fall within the 80% of questions we hear every day. Prescription medications, interactions, side effects, screening what should go on to the doctor and what doesn’t need to, and OTC issues like supplements, cough and cold, pain relief, skin ailments, self treatable infections of all kinds, preventative measures, weight loss advice, and many more. During Med Review interviews, we uncover medical issues not being addressed fully or at all. There are medical issues that are treated in ways that the patient would prefer were treated a different way, either due to current side effects, potential side effects, interactions, or for the simple reason that they just want to be on fewer medications.

Now some may consider this an environment that sets up a scenario for a trap of giving the patient something that hasn’t been proven with studies of thousands and thousands of test subjects in randomized controlled trials. There has been no drug rep with glossy handouts showing graphs and impressive relative change overshadowing a less impressive absolute change in results. Perhaps the pharmacist has no idea of any studies that might exist for anything at their OTC disposal, no numbers needed to treat are at their fingertips (however unimpressive even Rx values for NNT are).

The truth is, a lot of these OTC treatments, even though we are taught them in Pharmacy school as recommended treatments, don’t have all that much in the way of studies to prove they work as I pointed out in a previous blog . This starts the slippery slope of evidence based to non evidence based medicine. This is a continuum rather than a conscious switch. As pharmacists who see the direct results of these recommendations daily, we begin to realize what the term “evidence based” means. It includes the evidence they see every day. Some refer only to large centre, many subject, randomized controlled trials for their definition of this term. Of course this is the basis of our scientific and medical knowledge and has extended lifespan many years. These people however may also recommend some things in what is known as off label use of some medications where the evidence is less plentiful. This is outlined in a recent blog: https://stonespharmasave.com/blog/?p=796 . The statistical method is a gift that helps us weed out chance encounters from truth (https://stonespharmasave.com/blog/?s=statistics ) . Anecdotal evidence can be notoriously prone to incorrect conclusions as it sidesteps statistics in its conclusions. Sometimes we just don’t have these studies available to us and must rely on smaller studies or a physiological basis for a recommendation.

I see this with topical pain compounding all the time. Repeated successful results with a scientific basis and numerous small studies and numerous anecdotal reports drive more recommendations and more feedback. This spreads to physicians that may be skeptical on how these products work. With one patient with a favourable results they become more comfortable in writing again. If a patient tries a prescription medication and it doesn’t work is the Doctor a quack?  Of course not.  Evidence based becomes what you see before you in your little world, regardless of what online bullies think, as long as your first priority is to keep the patient safe.

 

Graham MacKenzie Ph.C.

Stone’s Pharmasave

Baddeck N.S.

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Copy of letter from the Canadian League Against Epilepsy

 

For Information Only, For Those on Frisium/clobazam.  Re: SHORTAGE SITUATION.  Letter posted online June 4, 2016

 

Canadian League Against Epilepsy I Ligue canadienne contre l’épilepsie

Clobazam Shortage?Suggestions for Management of Pediatric & Adult Patients with Epilepsy

June 4, 2016

There are shortages of clobazam, generic and brand name (Frisium). The situation has worsened during the past month reaching a crisis level.

Health Canada arranged a teleconference on June 3, 2016 to discuss the clobazam supply situation. Canadian League Against Epilepsy members participated in this meeting to convey the serious implications of a widespread clobazam shortage for patients with epilepsy.

Improvements in the clobazam supply are expected by late June to early July. Apotex Inc., the major supplier of clobazam in Canada, will be returning to regular supply levels. Several batches of Apo-Clobazam are expected to be released to wholesalers during the last two weeks of June.

Also, there should be additional Frisium (brand name clobazam) in the coming weeks from Lundbeck LLC.

There may continue to be some serious supply problems during the next three to four weeks. It is hoped that efforts will be made to identify sources of clobazam in the drug supply chain in order to protect patients.

Clobazam is a Level 1 Critical Drug for patients with epilepsy, according to the Canadian Pharmacists Association classification.

Prescribers asked to switch a patient from clobazam to an alternate drug, due to the shortage, should first request that the patient’s pharmacist double check all supply avenues to obtain either the same formulation or an interchangeable form (generic or brand) of clobazam. In addition to regular wholesalers, pharmacists can explore if supply is available from other wholesalers, other pharmacies or directly from one of the manufacturers.

All supply avenues should be exhausted before a patient who has been stabilized on clobazam is switched to an alternate drug. A decision must be made more quickly if the patient has minimal supply remaining to prevent interruption in therapy.

Clobazam is a 1,5-benzodiazepine with a long duration of action and has been marketed as an antiseizure drug in Canada for nearly 20 years. This medication is commonly used to treat epilepsy.

Interruption or sudden discontinuation of antiseizure drug therapy can cause a loss of seizure control, or worsening of a patient’s condition, with significant short- and long-term implications for patient safety, independence and quality of life. Breakthrough seizures can have potentially fatal consequences.ii

There are additional concerns related to this particular drug shortage. Sudden discontinuation of clobazam can cause benzodiazepine withdrawal syndrome.iii Abrupt discontinuation of clobazam may exacerbate seizures and cause other benzodiazepine withdrawal symptoms.iv Abrupt withdrawal of clobazam can also put patients at risk of life-threatening status epilepticus.v

Suggestions for Patient Management During the Clobazam Shortage

Patients who require de novo treatment?In patients who require de novo treatment with an antiseizure medication during the clobazam shortage, physicians should consider whether an alternative medication could be used at least initially.

Patients currently taking clobazam?If all supply avenues have been exhausted and there is no clobazam available, an alternate medication should be substituted until clobazam can be resupplied to the patient.

The following rationale for the selection of clonazepam as an alternative medication to clobazam during a drug shortage is from a document written by J.C. Martin del Campo, MD, FRCP and Jorge G. Burneo, MD, MSPH in 2013vi:

From the benzodiazepine group, only two other drugs have been found useful for the chronic management of seizure disorders: nitrazepam and clonazepam.

While there is no published evidence of efficacy under the circumstances, the most reasonable substitute for clobazam is clonazepam.

It is not known if this will be efficacious in all patients or if the recommended equivalent will result in a decompensation of the seizure disorder, but it is reasonable to surmise that it may prevent the development of a withdrawal state resulting in status epilepticus. Any given dosage will need to be carefully monitored by the prescribing physician and adjustments made where necessary.

While making these recommendations, it is hoped that the health authorities and pharmaceutical companies will protect the public by urgently implementing a strategic plan that will prevent such shortages from occurring. It is imperative to be reminded of the potentially fatal consequences of breakthrough seizures.vii

Reproduced with permission from del Campo and Burneo.

Recommendations for Therapeutic Substitution of Clonazepam for Clobazam

Clonazepam (brand name Rivotril) is a 1,4-benzodiazepine. This medication is available as an oral tablet in 0.25 mg, 0.5 mg, 1 mg and 2 mg formulations.

ClonazePAM and cloBAZam have similar lipophilicity and protein binding therefore likely very similar CNS penetration.

Clonazepam is more potent than clobazam. It is at least 10X more potent than clobazam if not ?20X, therefore, 1 mg of clonazePAM may be similar in potency to 10 mg of cloBAZam but could be as potent as 20 mg of cloBAZam.viii

Following conversion to clonazepam, some dose titration may be required to achieve the desired therapeutic effect. Clinical judgement is necessary to determine the optimum dose for each patient.

Patients should be carefully monitored for changes in seizure frequency, as well as the emergence of any adverse effects (excessive sedation, ataxia, increased difficulty handling secretions, worsening liver function) following the switch. ClonazePAM causes more sedation than equipotent doses of cloBAZam and tolerance may be more likely to develop to its antiseizure activity.

The excipients and non-medicinal ingredients between formulations may be different so caution should be exercised in patients with known hypersensitivity to excipient. These, along with any differences in adverse event profiles, can be verified in the appropriate Product Monographs and labels. The Product Monographs are available from the Health Canada Drug Product Database.ix

ADULTS? Initiate at 0.5 mg clonazePAM for every 10 mg clobazam (1:20)x; in 3-5 days, in the absence of adverse effects, increase to 1 mg clonazePAM for every 10 mg clobazam if required, to a maximum of 3 mg clonazepam/day.

Consider initiating clonazepam with a simultaneous gradual tapering of cloBAZam by 5-10 mg/week if supply allows.

PEDIATRICS?Initiate at 0.5 mg clonazePAM for every 10 mg clobazam (1:20); direct substitution can be made, tapering of clobazam is not mandatory. Dose titration, up or down, should be based on patient response.

Dose increases in pediatric patients, if required, are typically 0.25-0.5 mg/day every 5-7 days to a maximum of 0.1 mg/kg/day (or 0.2mg/kg/day for patients on enzyme-inducing drugs)xi

SENIORS, PATIENTS WITH LIVER DISEASE OR PATIENTS ON MEDICATIONS THAT INHIBIT P450-3A4 Initiate clonazepam at lower dosages in the elderly, in patients with liver disease, or in patients who are currently on medications which inhibit cytochrome P450-3A4.

 

Drug Metabolism and Pharmacokinetics

CloBAZam and clonazePAM are primarily metabolized by CYP 3A4. CloBAZam’s active metabolite, N- desmethylclobazam, is primarily metabolized by CYP 2C19. When substituting clonazePAM for cloBAZam, a thorough drug interaction assessment should be done taking these metabolic paths into consideration.

Information and Support for Practitioners and Patients

Should practitioners have reservations or concerns about the clinical management of their patients with epilepsy during this shortage, they should consult their nearest neurologist with epilepsy expertise or comprehensive epilepsy centre.

Patients and caregivers can contact their local Canadian Epilepsy Alliance agency for information and support by calling 1-866-EPILEPSY (1-866-374-5377).

i “Level 1 Critical Drug: Drug therapy for disease is essential and cannot be interrupted for even one dose or one day.” From: Canadian Pharmacists Association (2010), Drug Shortages: A Guide for Assessment and Patient Management www.pharmacists.ca/cpha-ca/assets/File/cpha-on-the-issues/DrugShortagesGuide.pdf?ii Steinhoff, B.J., et al. (2009) Substitution of anticonvulsant drugs. Ther Clin Risk Manag., 5, 449–457. www.ncbi.nlm.nih.gov/pmc/articles/PMC2701486/pdf/tcrm-5-449.pdf

iii Frisium Product Monograph (2015) iv ibid

vii Steinhoff, B.J., et al. (2009) Substitution of anticonvulsant drugs. Ther Clin Risk Manag., 5, 449–457.?viii Sankar, R. et al. (2014) Clinical considerations in transitioning patients with epilepsy from clonazepam to clobazam: a case series. J. Med. Case Rep., 8: 429. www.ncbi.nlm.nih.gov/pmc/articles/PMC4302143/pdf/13256_2014_Article_3028.pdf?ix Product monographs are available for download from the Health Canada Drug Product Database: www.hc-sc.gc.ca/dhp-mps/prodpharma/databasdon/index-eng.php?x Benzodiazepine equivalence table http://www.benzo.org.uk/bzequiv.htm (accessed May 16, 2016)?xi Farrell, K. and Michoulas, A. (2008) Benzodiazepines. In J.M. Pellock et al. (Ed), Pediatric Epilepsy: Diagnosis and therapy, 3rd Edition. Demos Medical Publishing, New York, page 559.?xii Brodie, M.J., et al. (2016) Clobazam and clonazepam use in epilepsy: Results from a UK database incident user cohort study. Epilepsy Research 123, 68-74.?xiii ibid?xiv Comparison of benzodiazepines http://www.vhpharmsci.com/vhformulary/tools/benzodiazepines- comparison.htm (accessed May 18, 2016)

Drug Benzodiazepine Group Active Metabolite Half-life of parent (hrs) Half life of active metabolite (hrs)
cloBAZam 1,5-benzodiazepine N-desmethylclobazam 30xii 80xiii
clonazePAM 1,4-benzodiazepine   18-39xiv

v Engel, J. (2013). Seizures and Epilepsy, 2nd Edition. Oxford University Press, New York, page 557.?vi Del Campo, M. and Burneo, J. (2013). Therapeutic alternative to clobazam: Medical recommendation for adults with epilepsy. Retrieved from Epilepsy Ontario website: epilepsyontario.org/wp- content/uploads/2014/01/Clobazam_Therapeutic-alternative-for-adults_Jan2013.pdf

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Off label use of medications – cherry picking at its best
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IMG_2313[2]I had a conversation with our local palliative care and pain clinic doctor the other day. As a disclaimer, this physician is open to treating patients with the safety of the patient first in mind and he also has what I refer to as an “open mind” when it comes to doing whatever we can to alleviate pain and suffering. A lot of the time it involves using medications and therapies that most physicians would prescribe. It also involves therapies that are safe and effective but are shunned by other physicians either because of lack of knowledge or experience with them or because they claim it is an off label use or one that lacks either a firm recommendation from a governing body or has not been recommended at a recent conference they attended.

Off label prescription writing is certainly not a stranger to my daily dispensing of drugs. Some reviews put this practice as high as 10% of prescriptions written in Canada. A May 2012 MacLean’s article discusses this as a major issue and a huge gamble for the physicians writing these prescriptions. As a pharmacists, I can assure you that this practice is the norm and for the most part doesn’t land people in the hospital any more often than officially approved writing of any other prescription medication such as NSAIDS, narcotics, blood pressure or heart meds, or antibiotics, to name a few. There are hundreds of examples of off label uses of drugs now being written for. A few common ones listed by the Lexicomp Facts and Comparisons Off Label are:

 

ASA for high risk coronary artery disease

Clonidine for hot flashes

Erythromycin for acne vulgaris

Folic acid for neural tube defects

Gabapentin for diabetic neuropathy

Nifedipine topical for anal fissures

Trazodone for insomnia in the elderly

Amitriptyline (oral or topical) for neuropathic pain

Childhood and adolescent uses of many medications

 

Note the use of the amitriptyline topically. Topical compounds are notoriously listed here although there are studies showing they work for various types of pain when used correctly at the right strength. Granted many of these studies are small but many are well designed and like I always say, nothing beats the experience of the first patient a physician tries and sees the topical preparation working and the lack of side effects compared to oral medications is an added bonus.

Most consider topical pain therapy to be limited to capsaicin, lidocaine and camphor menthol combinations.  There is an entire universe out there of other ingredients used in these preparations. And for those who like a few references here you go.

Dubinsky RM, Kabbani H, El-Chami Z, Boutwell C, Ali H; Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter: treatment of postherpetic neuralgia: an evidence-based report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2004;63(6):959-965.[PubMed 15452284]

Ho KY, Huh BK, White WD, Yeh CC, Miller EJ. Topical amitriptyline versus lidocaine in the treatment of neuropathic pain. Clin J Pain. 2008;24(1):51-55.[PubMed 18180637]

Lynch ME, Clark AJ, Sawynok J, Sullivan MJ. Topical 2% amitriptyline and 1% ketamine in neuropathic pain syndromes: a randomized, double-blind, placebo-controlled trial. Anesthesiology. 2005;103(1):140-146.[PubMed 15983466]

Lockhart E. Topical combination of amitriptyline and ketamine for post herpetic neuralgia. Poster presented at: American Pain Society Annual Meeting; May 6-9, 2004; Vancouver, BC. http://www.ampainsoc.org/db2/abstract/view?poster_id=2185#893. Accessed November 4, 2008.

 

-Lexicomp

 

Now a common complaint is that I supply studies that cherry pick what I am trying to prove, although I assume that whomever is asking has plenty of studies to favour something against my side. The point is, when you know something works, and it’s safe, you tend to care more about potential patients and less about converting non believers. Topical pain relief is just one of those “alternative” therapies. Many would consider off label use to be alternative therapy by definition. If alternative therapy is something that wanders past a monograph or official indication, then many practice alternative medicine. If that therapy is “recommended” by a medical group then for most it becomes accepted therapy and therefore not alternative. Although this may make them more comfortable with prescribing choices, alternative therapy’s definition is one that changes based on the one defining it.

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What’s worth more? A favorable statistical p value or clinical results?
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testpostWith the recent talk of p-values and their value in scientific journals it brings to light an important interpretive tool in efficacy of therapies, clinical experience.  P value is the chance of getting a positive response in a scientific study when there is no real effect after all, also known as a false positive.  The smaller this number, the better the certainty that what you are observing is truly an effect of what you are studying.  This number often is given as p .05 meaning that only 5% of the time would you see this happen by chance, the rest of the time it is a true effect of what you are studying.  Put another way, you can say that you are rejecting the “no effect” assumption, and come to the conclusion that drug A has effect B on the body and claim that your results are statistically significant.

This has been the backbone of science forever to determine if what you are seeing is not a fluke.  On closer examination though this value may not be as strong as we first thought.  Don’t get me wrong, it is an awesome way to reduce bias in a study and the best we have to weed this out as long as we don’t play around with this p value after our calculations are done.  What if we applied this 5% theory to a supplement that was being tested for a certain condition.  If we wanted to try 100 supplements for a given condition and only one of these supplements actually did something to improve the condition, we would find 5 supplements that appeared to help (false positives) and one extra that actually did, the one effective supplement in the bunch.  Of the six supplements you came away with thinking worked for the condition, really only one worked.  This means that out of those six conclusions that claim to help the problem, only 1 in truth really does.  You are incorrect 83% of the time in your determination of effective products even though you successfully eliminated 94 ineffective products!  Imagine, a randomized, placebo controlled trial with a p value of 0.05 with this kind of result.

Retractions of published papers also appear to be on the rise and after being involved myself this past year in a scientific study, there really is a lot of pressure felt by the authors to get published in a scientific journal.  It’s almost like a final approval by the cool kids in class and seems to psychologically give a stamp of approval on your work not only to the authors that did the study, but by the public and scientific community that will read or hear about the study.  If you aren’t published, there is almost a sense of failure felt towards the whole project, regardless of how astounding the results are.

This brings us to the world of the front line where these products are actually handed out to the public, the Pharmacy.  Many times I see products written on prescription that work exactly the way they are supposed to but sometimes they fail miserably.   Regardless of how many studies were done on a drug, if a patient paid $100 for it and it didn’t work, they really don’t care how many studies were done or what the p value was; they are out $100 and they now need to fork over more money for another product.  This doesn’t mean the studies that brought this to market were bad, it’s just that they were some of the outliers in the results that didn’t respond to the drug.

When you deal with supplements you often are labeled and dare I say it with  “alternative therapy”, you are always searching for these studies.  They are often small studies but you still look for them.  The same is true for pain compounding.  It is not difficult to be labeled a quack or a charlatan when you try to help someone that doesn’t seem to fit into the regular modern medicine model or wants to try another way first.   Nothing replaces clinical experience in determination of a product’s net worth and if studies are done correctly your results should mimic the studies you originally read.  Keep in mind that this may mean a 70% success rate as determined by the studies.   It is only when you see something work before your own eye(s) that makes you comfortable suggesting it more.  Those products that showed promise in studies and it doesn’t pan out with your patients, these products fall away rather quickly.  When you deal with people that are paying out of pocket for something, you know it is working when they come back for more to spend more money on.  I have had physicians steer away from a product because of one or two bad experiences with it with their own patients.  As always, patient safety is key with any product.  Will this therapy harm this patient based on their existing meds, allergies or medical condition?   Will it cause a dangerous delay in treatment with another more proven product?  These are important questions to as when a patient looks for an alternative medication.

Clinical experience with pain compounding creams has completely change the thinking of a lot of physicians I deal with at the pharmacy level.  Many of these doctors haven’t read even one of the studies I have on the response rate of this type of therapy but when they took a leap of faith with just one patient, then another and another, they realized the value of a therapy they were not taught in school.  When I get in my car and turn the key, a lot goes on to start the car and keep it running.  I haven’t read any studies on car engines but I do it because it seemed to work for others and it works for me for the most part as well.

False positives and subjective results can happen this way as well, but when a patient that was previously addicted to hydromorphone prefers a pain cream or an addition of omega-3 with their pain medication, it helps to alleviate thoughts that they are pretending the pain went away.   As one palliative care physician said to me, “If the placebo effect is 30% on drug X, I’ll take that kind of response rate”.  When there are doubts as to the effectiveness of a well-designed trial, clinical experience acts as an effective filter to refine one’s beliefs.

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Sugar: Necessary or Poison?

Guest post from Roni Davisimage1

” From an obese couch potato to a fit and healthy champion figure athlete, fitness writer, personal trainer, and nutrition & wellness specialist, Roni Davis has made it her life’s mission to teach other women how good their bodies are designed to look and feel, how strong they are and how to love the skin they’re in.”

By now you’d have to have been living under a rock to not have heard the phrase “empty calories” in relation to sugar, but is sugar really just empty calories or is it something far worse? Dr. Robert Lustig, Professor of Pediatric Endocrinology at the University of California, San Francisco School of Medicine, best-selling author and the leading expert in childhood obesity will tell you it’s a poison that’s slowly killing us and based on everything I have studied, I happen to agree wholeheartedly. Continue reading

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So you’re against the flu shot?

It’s a pharmacist’s job to promote the flu vaccine, not twist a patient’s arm into taking it.

photo credit: One Way Stock via photopin cc

photo credit: One Way Stock via photopin cc

How many times in the run of a day does a pharmacist make recommendations on medications to a patient, nurse, physician, parent, caregiver, or pet owner? Often we finish the quick interview of medical issues, current medications, allergies, and what have they already tried with a go-to personal recommendation based on a certain intuition called, clinical judgement. Quite often, we do not get any type of follow-up or feedback on how that recommendation went.

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