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The Compounding Conundrum of Personalized Medicine

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The Compounding Conundrum of Personalized Medicine

It is no wonder personalized medicine has been taking a rise, after all, the one size fits all approach seen in manufactured medicine cannot work for everyone. For patients with unique healthcare needs, compounding can be incredibly useful but the catch is these medications do not actually go through a traditional approval process. Why is that important? It means these medications and products have not been reviewed, studied, and evaluated by a third party regulatory entity such as the Food and Drug Administration (FDA).

Compounding is defined as the process of “combining, mixing, or altering ingredients to create medications tailored to the needs of an individual patient”1. For example, a patient with allergies to certain ingredients in a medication (such as a preservative or dye) can receive a modified compounded form instead1. Another example is a patient who may require an alternate dosage form (such as a liquid as opposed to a tablet) which is especially prominent in pediatric or geriatric populations1. You can see the interactable module below which outlines common pharmaceutical ingredients used in compounding:

Access to compounding services are invaluable for some patients; however, vigilance is critically important in this particular field of practice. In the absence of FDA review and approval, guaranteeing the safety, efficacy and quality of these medications can be tricky… so tricky you might even call it a compounding conundrum. In 2012, a Massachusetts pharmacy caused more than 750 infections and more than 60 fatalities across 20 states due to fungal contamination2. This event would lead to the Drug Quality and Security Act (DQSA) to be passed that same year and officially enacted during the following year2. A prior blog post of ours outlined the need for REMS programs and why we can’t be hasty when it comes to drug safety, the same is particularly true in this case as patients can be placed in serious harms way when appropriate measures or precautions have not been taken in compounding. 

The following links below assembled by the United States Pharmacopeial (USP) Convention are highly useful in better understanding appropraite standards for compounding and have been linked below for your convenience: 

The FDA also provides a plethora of compounding guidance and resources found here as it is trying to gain a more involved approach given the recent deaths and news from a lack of quality assurance and sterility in compounded products causing patient harm. For example, there is a federal law that specifies a 5% limit on distribution for out of state drugs compounded by pharmacies and physicians under Section 503A of the FDCA. The FDA plans not to enforce this rule until after states sign and finalize the memorandum of understanding (MOU) as ultimately it is under the state jurisdiction and regulation to oversee compounding pharmacies. 

Sincerely,

Jean Hanna

References:

  1. Compounding and the FDA: Questions and Answers. U.S. Food and Drug Administration. https://www.fda.gov/drugs/human-drug-compounding/compounding-and-fda-questions-and-answers. Published 2018. Accessed May 6, 2021.
  2. Compounding and the FDA: Questions and Answers. U.S. Food and Drug Administration. https://www.fda.gov/drugs/human-drug-compounding/compounding-and-fda-questions-and-answers. Published 2017. Accessed May 6, 2021.
  3. Ansel H, Allen L. Pharmaceutical Dosage Forms And Drug Delivery Systems. 10th ed. Philadelphia, Pa: Lippincott-Williams & Wilkins; 2014.

The Hygiene Hypothesis and Rising Rates of Asthma

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The Hygiene Hypothesis and Rising Rates of Asthma

Many years ago, I came across a tale of The Wheezing Wolf and the Three Little Pigs (you could call it a breathless spin on a timeless children’s classic). It is also a tale that manages to very creatively highlight a disease state which affects a large number of children worldwide – that’s right, asthma! It is estimated more than 22 million people (~6 million children) in the United States have some form of asthma, a chronic but reversible condition which causes inflammation and bronchoconstriction of our airways1.

Although there is no magic bullet or cure for people who suffer from asthma, we have a large variety of medications that allow for proper management which helps prevent long term airway remodeling, permanent lung damage, hospital stays and emergency room visits1. You might be wondering what causes people to acquire asthma… maybe it’s people spending a lot of time with wolves who huff and puff or maybe it just happens to be all the Hufflepuffs? Well, data is gathered meticulously to better highlight trends in asthma for this very reason. For example, one trend already identified makes clear that african american and hispanic children are generally more likely to experience mortality from asthma related causes1. Below you will find several interactable modules which outline the rise in asthma cases over the years but also the demographic aggregation of cases across the United States:

One theory that has gained traction over the years to explain the rising cases of asthma is called the hygiene hypothesis. This hypothesis suggests our post natal immune response is compromised by an ultra clean environment, causing a lack of exposure to infectious organisms and consequently leading to an “uneducated” immune system (which is more likely to predispose a child in developing conditions like asthma)3. The bacterial protein lipopolysaccharide (LPS) is an example of how our immune system can grow, learn and graduate school by “switching” on toll-like receptor 4 (TLR4), a characteristic shared by the respiratory syncytial virus (RSV) F protein commonly encountered by infants3. It is still up in the air whether RSV is helpful in the same way LPS is in regards to building a solid immune system, or whether it actually does more harm than good by potentially suppressing proliferation of T cells; however, it is an area of expanding research as we continue to ponder what effects clean houses could potentially have on the rising incidence of disorders such as asthma3. If you would like to learn more about the hygiene hypothesis and the potential implications as we navigate through the COVID-19 pandemic, this article (“The hygiene hypothesis, the COVID pandemic, and consequences for the human microbiome”) is a nice read.

As a whole, asthma attacks can vary in severity and in nature from one person to another; however, common triggers include tobacco smoke, dust mites, pollen, air pollution, mold, a man’s best friend, perfumes, harsh cleaners/disinfectants and even acid reflux2. It is important for patients who suffer from asthma to identify and avoid triggers. For example, encouraging tobacco cessation in households with smokers or using an air cleaner with a HEPA filter for people who may be allergic to their furry friends2. And lastly, if there is one thing we know from the hygiene hypothesis, it’s that people love to clean their homes. It is especially true now perhaps more than ever before and we may very well see an even steeper rate of asthma cases moving forward, even if just from COVID sequelae alone. Here is a CDC guide to properly cleaning and disinfecting homes that patients (especially those sensitive to harsh detergents or cleaners) may find useful; it’s even COVID approved. 

Sincerely,

Jean Hanna

References:

  1. Asthma Fact Sheet. (2019, May 22). Retrieved from https://www.fda.gov/consumers/minority-health-and-health-equity/asthma-fact-sheet
  2. Common Asthma Triggers. (2020, August 21). Retrieved from https://www.cdc.gov/asthma/triggers.html
  3. Asthma: The Hygiene Hypothesis. (2018, March 23). Retrieved from https://www.fda.gov/vaccines-blood-biologics/consumers-biologics/asthma-hygiene-hypothesis
board, school, dreams

Mentorship and Networking – Beyond a Job!

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Before my graduation in 2020, I was uncertain about my career and future with pharmacy being heavily saturated and the COVID-19 pandemic hit creating an ecomonic downturn. I first came across the summer internship at RxPharmacist because I recognized the opportunities that they offered including the flexibility of a remote work role, creating my own study guide, and achieving growth in medical technical writing and growing my professional network. Now as I complete the program, I am glad to share with you this incredible experience at RxPharmacist. 

My first project was to edit the CPJE guide, which aided me passing the exam on my first attempt. Besides providing feedback on my work performance, my inspiring mentor spent time discussing with me about entrepreneurship, marketing, and my career goal. There was a heavy emphasis on strategy to approach achieving my goals of attaining my dream fellowship program. For example, knowing my interest in the pharmaceutical industry, she introduced me to experts in the field and helped me on my CV, letter of intent, and practicing with mock interviews. Thanks to her unwavering support, I got accepted into my top choice fellowship program where I would practice as a clinical development fellow in oncology at Rutgers (2021-2023). Although I was already working as a full-time pharmacist, this remote job was so flexible that it allowed me to work on my own schedule. Needless to say, beyond a job, not only the internship offered a unique opportunity to expand my networks and writing skills, but it also was a good transition for me from a graduate student to a pharmacist. I’m incredibly thankful of being able to get into my top fellowship program with the unwavering support of RxPharmacist and also was able to gain the FDA ORISE fellowship as a backup opportunity should I not be able to get my top choice through their help.

Therefore, I highly recommend this internship to anyone who seeks for professional networks and experience in medical and scientific communications. The preceptors and team are highly supportive. If your willing to work hard, learn new skills, and try something new, this might be a wonderful opportunity for you.

Thi N., 2020-2021 RxPharmacist Graduate Intern

UC San Diego, Skaggs School of Pharmacy and Pharmaceutical Sciences, Class of 2020

The Fault in Our EGFRs

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The Fault in Our EGFRs

The Fault in Our Stars is a novel written by John Green. Since its release in both print and film, the moving story has managed to strangle many hearts around the world as it explores many colorful yet melancholic themes of life, cancer being among them. One example is a clever nod to Shakespeare’s Julius Caesar, specifically the following line by Caddius: “The fault, dear Brutus, is not in our stars, / But in ourselves, that we are underlings” 6. Of all the literary works I’ve read and enjoyed over the years, this line has been especially memorable. Caddius implies fate (or stars for that matter) is a negligible force, for it’s a person’s own fault alone if their life falls short of their expectations. By titling his book “The Fault in Our Stars” it is clear Green disagrees, at least as it pertains to cancer and our dear protagonists in the novel.

Although cancer can certainly be acquired through environmental means such as smoking or radiation, it can also be genetic. In fact, if we want to get a little more technical, for a select group of people their undoing could specifically be a fault in their epidermal growth factor receptor or EGFR (HER1/ErbB1) gene2. EGFR positive lung cancer is most common in people who have never/rarely smoked, have adenocarcinoma, women, young adults and people of asian or east asain heritage2. Additionally, adenocarcinoma is a subtype of non-small cell lung cancer (NSCLC) which causes nearly 80-85% of all lung cancers4. Risk of acquiring adenocarcinoma is increased for patients who smoke, inhale second hand smoke, and are exposed to radon gas, asbestos or other cancer-causing agents in their daily lives4.

Generic Naming Formula: Name = prefix + substem(s) + stem

Image adapted from: RxPharmacist CPJE Study Guide 2020

If we are dealing with an EGFR positive case of lung cancer and wish to decide on a medication, it makes sense we would attempt targeted therapy as opposed to standard chemotherapy in order to directly inhibit the EGFR receptor. Therefore, NSCLC EGFR+ patients can typically be administered EGFR inhibitors (as outlined below). I have included some other potential mutations and their therapies as a bonus below. Note they all end in -nib, as they are all tyrosine kinase inhibitors (TKI), the bolded drugs are preferred. As far as terminology, medications ending in ‘-mab’ denote monoclonal antibodies which are biologic type medications as they are usually therapeutic proteins and large structures chemically. Medications ending in ‘-nib’ are usually small molecules, think of this as a car versus an airplane which are ‘-mabs’ for size.

You should anticipate a rise in biosimilar oncology medications on the market. Overall, the Food and Drug Administration (FDA) has approved 29 biosimilar medications so far, and almost all of them have a role to play in oncology therapeutics. If you want a much deeper dive into oncology and many more disease state topics, check out our CPJE Study Guide. Additionally, here are some useful resources on cancer you can also reference:

Sincerely,

Jean Hanna

References:

  1. “What Causes Cancer?” American Cancer Society, www.cancer.org/cancer/cancer-causes.html.
  2. “EGFR Mutation and Lung Cancer: What Is It and How Is It Treated?” Lung Cancer Foundation of America, 18 Oct. 2019, lcfamerica.org/lung-cancer-info/types-lung-cancer/egfr-mutation/.
  3. “What Is Lung Cancer?: Types of Lung Cancer.” American Cancer Society, www.cancer.org/cancer/lung-cancer/about/what-is.html.
  4. Publishing, Harvard Health. “Adenocarcinoma of the Lung.” Harvard Health, www.health.harvard.edu/a_to_z/adenocarcinoma-of-the-lung.
  5. “Non-Small Cell Lung Cancer Targeted Drug Therapy: Lung Cancer Drugs.” American Cancer Society, www.cancer.org/cancer/lung-cancer/treating-non-small-cell/targeted-therapies.html.
  6. Shakespeare, W., Mowat, B. A., & Werstine, P. (2005). The tragedy of Julius Caesar. New York: Washington Square Press.

Five Varieties of Insulin and Why We Need Them

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Five Varieties of Insulin and Why We Need Them

It is estimated nearly 34.2 million people in the United States have some form of diabetes (⅕ of which are entirely unaware), and in the last 20 years the number of diagnosed adults has more than doubled in size1. The significance of this disease state is paramount from a public health perspective, especially as diabetes has been identified as the number one cause of kidney failure, lower limb amputations and microvascular complications1. You can think of diabetes as a metabolic disease which is generally broken down into four categories: type one diabetes, type two diabetes, gestational diabetes (onset during pregnancy) and prediabetes (elevated blood glucose levels that are yet to be considered entirely diagnostic of active disease)1.

The following video (“Diabetes and the body”) is an excellent visual resource for understanding diabetes and its associated consequences on the human body. Both type one and type two diabetes cause an accumulation of glucose in the bloodstream; however, it is the etiology that differentiates them. Type 1 diabetics essentially experience autoimmune destruction of their pancreatic beta cells which diminishes endogenous insulin production (usually diagnosed in younger people and makes up 5-10% of diabetics)1. In comparison, type two diabetics can produce insulin just fine but their body is unresponsive due to built up insulin resistance over time (usually diagnosed in adults and makes up 90-95% of diabetics)1.

The tricky thing about insulin is it must be injected because it is easily broken down and digested in oral form2. All patients with type one diabetes will be dependent on exogenous insulin for survival, and some type two diabetics may also require insulin for adequate control. There is a highly interesting concern in type two diabetes management surrounding a delay in insulin initiation, typically dubbed “clinical inertia”. You can read more about in the following literature review (“Clinical inertia is the enemy of therapeutic success in the management of diabetes and its complications: a narrative literature review”).

Insulins can be deadly when used inappropriately. It is important to understand and be familiar with the onset, peak and duration of insulins (as seen in the figure above) so an appropriate personalized regimen or adjustment can be made for each patient’s needs and goals. Generally, rapid and short acting insulins are intended for bolus purposes whereas intermediate and long acting insulins are intended for basal purposes. We can categorize and identify insulins in the following five categories below (note that Afrezza is inhaled as opposed to injected and can be given at the start of each meal (which may be a great option if a patient is looking for non-injectable options):

I hope this dive into insulins and their place in diabetes management has been helpful for you and your studies. As an aside, one important public health issue as it relates to insulins is actually affordability. You see, supposedly 1 in 4 diabetic patients can’t afford their insulin altogether4. The issue is complex and significant enough to have it’s own dedicated gofundme page as for many patients insulins are a non-negotiable lifeline. You can read more about the black market dedicated to the insulin trade here, but remember there are resources for patients who need them should you ever directly encounter this issue in the community. Some patients may also obtain over the counter insulin from Walmart’s ReliOn insulin program.

Sincerely,

Jean Hanna

References:

  1. What is diabetes? (2020, June 11). Retrieved from https://www.cdc.gov/diabetes/basics/diabetes.html
  2. Insulin Basics. (n.d.). Retrieved from https://www.diabetes.org/healthy-living/medication-treatments/insulin-other-injectables/insulin-basics
  3. Insulin and diabetes. (n.d.). Retrieved from https://www.diabetes.org.uk/guide-to-diabetes/managing-your-diabetes/treating-your-diabetes/insulin
  4. Fast-Acting Mealtime Insulin: Humalog® (insulin lispro injection). (n.d.). Retrieved from https://www.humalog.com/fast-acting-mealtime-insulin#about-mealtime-insulin
  5. Teare, K. (2018, December 03). One in four patients say they’ve skimped on insulin because of high cost. Retrieved from https://news.yale.edu/2018/12/03/one-four-patients-say-theyve-skimped-insulin-because-high-cost

REMS: Why We Can’t Be Hasty When It Comes to Drug Safety

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REMS: Why We Can’t Be Hasty When It Comes to Drug Safety

To be, or not to be? When it comes to drug safety, it is up to the U.S. Food and Drug Administration (FDA) to decide if a medication may be, or not be. The Risk Evaluation and Mitigation Strategy (REMS) requirement was set up by the FDA for select prescription medications which pose a high potential for serious adverse effects. As its name suggests, the REMS program is concerned with drug safety and in ensuring the benefits of a certain drug outweigh the risks1. REMS does not only oversee adverse effects alone, but seeks to “prevent, monitor and manage” any medication the FDA expects could potentially violate safe medication practices1. Although the FDA is in charge of determining whether REMS must be enforced for a medication, it is the manufacturer who is in charge of the program and submission of assessment reports for quality improvement or assurance efforts2. Below is a helpful guide provided by the FDA which can be very useful if you ever find yourself counselling a patient on a REMS classified drug. 

Image Reference: A Framework for Benefit-Risk Counseling to Patients About Drugs with a REMS

Drug safety efforts and their importance in public health can be seen as early as 1937. The antibiotic sulfonamide would result in hundreds deaths due to the toxic excipient diethylene glycol, supposedly claimed as being inert (you can read more about the incident via the June 1981 issue of the FDA Consumer magazine titled “sulfonamide disaster”)3. Later in the 1960s thalidomide was used for antiemetic effects in pregnant women, but resulted in severe teratogenic adverse effects made clear when babies were born with missing or deformed extremities3. 

Image Reference: Wikipedia Creative Commons

The difference between these two events, however, is significant from the perspective of the United States. You see, after the sulfonamide tragedy the FDA mandated the 1938 Food, Drug, and Cosmetic Act (FDCA). At this point, pharmaceutical companies were required to conduct actual studies proving a drug is safe before becoming readily available to the general public (which was exactly why sulfonamide slipped through the cracks)3. So thalidomide was never actually approved in the United States due to data suggesting deformities on animal models despite lobbying and immense political pressure against the clinical director at the time3.. As such, the unfortunate teratogenic effects seen with thalidomide were mitigated on home soil. This brief dive into history barely scratches the surface on the importance of drug safety and pharmacovigilance but is helpful in understanding what can happen if we get a little too hasty when it comes to drug safety. As such, this brings us back to REMS. You can view a list of all current REMS medications on the FDA website alongside their associated goals, materials and a comprehensive timeline of program updates for each REMS medication. Additionally, if you want to go really deep into the U.S. regulations for REMS please visit this PDF slidedeck created by the FDA. 

Sincerely,

Jean Hanna

References:

  1. Center for Drug Evaluation and Research. “Risk Evaluation and Mitigation Strategies (REMS).” U.S. Food and Drug Administration, FDA, www.fda.gov/drugs/drug-safety-and-availability/risk-evaluation-and-mitigation-strategies-rems.
  2. Center for Drug Evaluation and Research. “FAQs about REMS.” U.S. Food and Drug Administration, FDA, www.fda.gov/drugs/risk-evaluation-and-mitigation-strategies-rems/frequently-asked-questions-faqs-about-rems.
  3. Alshammari, Thamir M. “Drug Safety: The Concept, Inception and Its Importance in Patients’ Health.” Saudi Pharmaceutical Journal, vol. 24, no. 4, 9 May 2014, pp. 405–412., doi:10.1016/j.jsps.2014.04.008.
  4. “A Framework for Benefit-Risk Counseling to Patients About Drugs with a REMS.” U.S. Food and Drug Administration.

Contraceptive Options for Contraindicated Patients

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Contraceptive Options for Contraindicated Patients

In 2015-2017, it was estimated 64.9% of women in the United States between the ages of 15-49 were using some form of contraception1. The National Survey of Family Growth (NSFG) reported female sterilization (18.6%), oral contraceptive pills (12.6%), long acting reversible contraceptives (10.3%) and male condoms (8.7%) as the most popular and common options but the degree of usage for each varied largely by age1. Although some methods of contraception are far more efficacious than others, it is important to take into consideration other factors too. These include demographics, side effects, duration, reversibility and contraindications when offering contraceptive counseling, and assisting patients in deciding on the most appropriate form of birth control for their specific needs. Likewise, dual protection should always be considered to prevent risks from HIV and STIs as even highly effective methods of contraception such as Intrauterine Device (IUDs) or surgical sterilization do not protect against these infections2. 

As a whole, contraceptives can be grouped into hormonal and non-hormonal categories. See the interactive diagram which compares typical effectiveness per contraceptive method below alongside their degree of hormonal properties to get a feel for what options are available on the market and how they compare to one another.

Although there are many options to choose from, some patients may find themselves contraindicated for hormonal contraceptives, specifically estrogen. The CDC provides a helpful summary chart (U.S. Medical Eligibility Criteria for Contraceptive Use) which outlines a comprehensive medical eligibility criteria across four categories of severity for several potential conditions and sub conditions. I have put together a more condensed version of the legend below:

For women who find themselves in category 3, it would be wise to consider alternative birth control methods whereas women who find themselves in category 4 are completely contraindicated. Most commonly, this contraindication is due to hormonal therapy associated with estrogen releasing products. Patients contraindicated to hormone birth control methods can consider the following options which either circumvent hormones altogether or rely on progestin alone:

When considering the above birth control methods, it is important to tailor the best option to the patient. For example, if a patient is looking to space their children out evenly across 3 years, a Nexplanon implant might be a good option. Likewise, a patient who is no longer interested in having children may be better suited for more permanent options such as sterilization or a long term IUD. I hope our dive into contraceptives has been helpful and as always I wish you all the best of luck with your studies. 

Sincerely,

Jean Hanna

References:

  1. Products – Data Briefs – Number 327 – December 2018. (2018, December). Retrieved from https://www.cdc.gov/nchs/products/databriefs/db327.htm
  2. Contraception. (2020, August 13). Retrieved from https://www.cdc.gov/reproductivehealth/contraception/index.htm
  3. Contraception. (2020, August 13). Retrieved from https://www.cdc.gov/reproductivehealth/contraception/index.htm

Opioids and Prescribing Patterns in Pain Management

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Opioids and Prescribing Patterns in Pain Management

Imagine yourself for a moment walking through your home. You make your way across a table and then suddenly you feel a sharp insurmountable degree of pain in your foot. Is it a staple? Thumbtack? Are you dying? You can be relieved to know my story ends with you simply stepping on a LEGO, although anyone who has done so would tell you it’s no fun (just check out all these memes on the internet). Pain management is a highly fascinating and challenging area of pharmacy practice. It is typically based on subjective information which can be difficult to quantify, after all one person’s pain tolerance may be vastly different from another. Analgesics like acetaminophen (Tylenol) or non-steroidal anti-inflammatory drugs (NSAIDs) are considered relatively safe options that usually do the trick in helping to relieve pain; however, they may not be enough. The reality is many patients with moderate to severe pain will still find themselves needing additional therapy and may therefore end up being prescribed an opioid.

There are two issues that may arise at this point when we consider opioid management: under prescribing to the point that patients may remain in pain or overprescribing to the point that patients may misuse. A review of opioid pain management concluded although efforts have been made to address the opioid epidemic by monitoring prescriptions electronically or increasing education among patients/providers, there has been limited evidence of significantly improved health outcomes2. In addition, there are valid concerns that tighter regulations are causing providers to under prescribe or undertreat pain even in advanced stages of cancer2. Interestingly, there is evidence variability in opioid prescribing can be traced back to a physician’s specialty and level of training. For example, emergency medicine residents and attending physicians were found to prescribe opioids to a lesser degree as compared to non-emergency medicine providers in an acute care setting (among emergency trained providers, residents prescribed opioids to an even lesser degree than attendings!)3.

In the figure above you will find ten common non-analgesic effects and properties of opioids that may help you remember important information to go over the next time you find yourself educating a patient on what they may expect from their opioid. As a whole, the opioid epidemic is one of the most important and relevant health crises we currently have on our hands. Here is an interesting read on how Walmart is currently being sued for supposedly fueling America’s opioid crisis. Even in the case where opioid management is appropriate, you may still come across people who refuse an opioid out of fear for addiction. It makes sense when understanding the degree to which stigma surrounding substance abuse disorders remains as relevant as ever within our society and is often a cause for patients feeling ostracized or reluctant to seek help from providers4. Public health experts have since voiced concerns regarding how the current coronavirus pandemic may also further exacerbate the opioid crisis, especially as vital healthcare services have become interrupted or flipped virtually (this does not even take into account the already extensive degree of isolation patients may feel from their potential support systems at this present time)5. With this in mind, counselling patients on what they can expect from their opioid is understandably vital in making sure these medications are not only used appropriately, but also in mitigating the fear that surrounds opioids. I hope you have found this post an interesting read and the best of luck with your studies!

Sincerely,

Jean Hanna

References:

  1. Portenoy, R. K., Mehta, Z., & Ahmed, E. (2021, January 06). Prevention and management of side effects in patients receiving opioids for chronic pain. Retrieved January 30, 2021, from https://www.uptodate.com/contents/prevention-and-management-of-side-effects-in-patients-receiving-opioids-for-chronic-pain
  2. Rauenzahn, Sherri; Del Fabbro, Egidio Opioid management of pain, Current Opinion in Supportive and Palliative Care: September 2014 – Volume 8 – Issue 3 – p 273-278 doi: 10.1097/SPC.0000000000000065 
  3. Leventhal, E. L, Nathanson, L. A, & Landry, A. M. (2019). Variations in Opioid Prescribing Behavior by Physician Training. Western Journal of Emergency Medicine: Integrating Emergency Care with Population Health, 20(3). http://dx.doi.org/10.5811/westjem.2019.3.39311 Retrieved from https://escholarship.org/uc/item/6r515181
  4. NIDA. 2020, April 22. Addressing the Stigma that Surrounds Addiction. Retrieved from https://www.drugabuse.gov/about-nida/noras-blog/2020/04/addressing-stigma-surrounds-addiction on 2021, February 15
  5. Expert Perspective: The Opioid Crisis and COVID-19 … (2021, January 26). Retrieved from https://www.psychiatryadvisor.com/home/topics/addiction/opioid-related-disorder/expert-perspective-the-opioid-crisis-and-covid-19/

Renal Disorders and How Dialysis Can Help Your Kidneys ‘Let It Go’

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Renal Disorders and How Dialysis Can Help Your Kidneys ‘Let It Go’

Kidneys are a good example of the saying, “you don’t know what you’ve got ‘till it’s gone”. This is primarily because most people genuinely do not know they have reached an irreversible loss of kidney function until it is too late. You may be wondering how such a drastic decline in kidney function can silently progress under the radar, and in what ways we can help patients with renal dysfunction to still lead highly active and fulfilling lives. Well, to answer why and how renal dysfunction typically goes undetected, it is important to first understand what makes the kidneys unique to other aspects of the body.

Your vital organs are all special with their own unique abilities and superpowers. For example, the liver is the only organ in your body with the capacity to regenerate itself. The key quality to remember when it comes to kidneys is they like to both work together as a team. Now working together may not seem as much of a superpower, but it’s incredibly useful because one kidney can compensate for the impaired function of the other kidney. Even alone, a single kidney’s working nephrons can also compensate for the loss or degeneration of other nephrons within the organ itself4. In fact, the kidneys are so highly adaptable they do a stellar job of making a sinking ship look like it is sailing, but this also means trying to identify declining renal function early to prevent progression of disease can be very challenging… because a ship that is sailing does not look like it is sinking. Many patients will find themselves in this position and although we can screen for risk factors, a decline in renal function remains silent and unrecoverable.

The above figure outlines the differences between acute kidney injury (AKI) and chronic kidney disease (CKD). Since kidney damage is irreversible, prevention of AKI and CKD is paramount. For renal disorders, there is no real cure as therapy is typically supportive and dependent on the etiology1. With this in mind, you may be wondering how we can go about being more proactive towards kidney disease. Clinical surveillance is an example of an effort that serves this very cause. If we take a look at an implementation of the Nephrotoxic Injury Negated by Just-in-time Action (NINJA) project, we can see a 38% decrease in AKI exposure (estimated 633 cases avoided) and a 64% decrease in AKI (398 cases avoided) due to surveillance providing a timelier approach in identifying AKI2. Again, there is no cure for kidney disease so prevention is paramount and clinical surveillance can be an invaluable asset in this area. Likewise, although we have medications in place to treat the secondary complications and further progression of CKD, patients who do progress to end stage renal disease will find themselves dependent on dialysis in the absence of a kidney transplant1.

So, what happens to patients who officially progress to end stage renal disease and require dialysis? Well, the good news is there are some options. Patients can decide between hemodialysis (HD) or peritoneal dialysis (PD)1. HD requires several visits a week to a HD center and may cause a further decline in residual renal function as compared to PD, which may be conveniently performed at home but has a higher risk of peritonitis1. Dialysis works by helping your kidneys ‘Let It Go’. Yes, the title of this post references Frozen because that’s exactly how dialysis works: by letting all the toxins in your body go. You see, a decline in kidney function is essentially a decline in the glomerular filtration rate (GFR)1. When your kidneys are damaged, they cannot filter out all the toxins in your body as well so waste products and fluid can accumulate to a fatal degree3. Dialysis helps prevent this accumulation by allowing toxins to essentially move from the blood to the dialysate (thereby filtering the blood and acting in place of the kidneys)1. I hope our brief overview of renal dysfunction has been helpful and all the best for your studies!

Sincerely,

Jean Hanna

References

  1. DiPiro, J. T. (2020). Pharmacotherapy: A pathophysiologic approach. New York: McGraw Hill.
  2. Goldstein, S., Mottes, T., Simpson, K., Barclay, C., Muething, S., Haslam, D., & Kirkendall, E. (2016). A sustained quality improvement program reduces nephrotoxic medication-associated acute kidney injury. Kidney International, 90(1), 212-221. doi: 10.1016/j.kint.2016.03.031.
  3. Dialysis. (n.d.). Retrieved from https://www.nhs.uk/conditions/dialysis/
  4. Fattah, H., Layton, A., & Vallon, V. (2019). How Do Kidneys Adapt to a Deficit or Loss in Nephron Number? Physiology, 34(3), 189-197. doi:10.1152/physiol.00052.2018

Thyroid Disorders and What Happens When Your Glands Go to the Dark Side

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Thyroid Disorders and What Happens When Your Glands Go to the Dark Side

If you are familiar with the Star Wars franchise, you know there is a “light side” and a “dark side” of the force. These sides represent either the selfless or the selfish and essentially act to hold the galaxy together. If you consider our galactic friends and their adventures for a second, you may be able to see there is a large parallel between the galaxy and the human body. After all, the goal for all Jedi is to keep the force within balance, or in the context of the human body and for our purposes, within homeostasis. So then, what happens when your body or the galaxy is no longer in homeostasis? Well, if you go back to our simplified analogy, you’ll find it suggests some aspect within our complex body has pulled a ‘Darth Vader’ and gone to the dark side… which can predictably have devastating consequences. This Star Wars analogy is also a stellar example for the pathogenesis of cancer: a cancerous cell is in essence simply a “Darth Vader cell”, but we will dive further into cancer a couple weeks from now (so stay tuned).

The thyroid gland is situated at the base of the neck and plays an important role in metabolism and development within the human body1. The thyroid is glandular in nature (meaning it secretes hormones) and therefore can be categorized under dysfunctions of the endocrine system. Specifically, we can identify the type of dysfunction or disease by looking a little closer at where exactly regulation goes haywire. Regulation of the thyroid occurs through the hypothalamic-pituitary-thyroid (HPT) axis1. It is important to understand the HPT axis encompasses the hypothalamus, anterior pituitary and thyroid gland which also stores the thyroid hormones T3 (triiodothyronine) and T4 (thyroxine)1. An appropriate feedback loop for the HPT axis is illustrated below:

As annotated in the figure, the hypothalamus releases thyrotropin-releasing hormone (TRH) allowing for positive feedback to the pituitary gland. The pituitary gland then produces thyroid-stimulating hormone (TSH) allowing for positive feedback to thyroid gland. Lastly, the thyroid gland produces T3 and T4 allowing for negative feedback on hypothalamus and pituitary gland to decrease levels of TRH + TSH (homeostasis and balance is now upheld within the body). Notice how TRH and TSH are regulated through the negative feedback loop? In the context of a thyroid gland, an appropriate regulation of homeostasis like the example above would be referred to as “euthyroid”, meaning everything is working as it should and the force is in balance. When the force is unbalanced, we hit situations of “hypothyroidism” and “hyperthyroidism” where your glands officially go to the dark side. The good thing about thyroid dysfunction is these processes are entirely predictable if you understand what goes wrong in what part of the loop.

HYPOTHYROIDISM

In hypothyroidism, you have low levels of T3 and T41. We can predict decreased levels of both T3 and T4 leads to an increase in both TSH and TRH to ‘amp’ up the loop. However, Hashimoto’s disease is an example of an autoimmune condition where antibodies essentially destroy the thyroid gland (Hashimoto’s is typical of primary hypothyroidism)1. Destruction of the thyroid gland will cause decreased levels of both T3 and T4 leading to increased levels of TSH and TRH but because the gland is destroyed, an increase in TSH and TRH does not work, and thyroid hormones remain low. In this case, patients are typically exogenously supplemented with medications such as levothyroxine since their endogenous production is impaired.

HYPERTHYROIDISM

In hyperthyroidism, you have high levels of T3 and T41. Again, we can predict that an increase in both T3 and T4 will lead to a decrease in both TSH and TRH in an attempt to slow down the loop. However, Graves’ disease is another example of an autoimmune condition where antibodies stimulate the gland to produce more hormones (Grave’s disease is typical of primary hyperthyroidism)1. Stimulation of the thyroid gland causes increased levels of both T3 and T4 leading to decreased levels of both TSH and TRH to try and slow down hormone production. However, since the gland is being stimulated by the antibodies regardless, T3 and T4 levels remain elevated. 

Notice how in both cases of primary hyperthyroidism and primary hypothyroidism, the negative feedback loop is still trying to work, it just does not matter because there is an autoimmune issue with the gland itself. So, although the negative feedback loop is still there, the process fails due to either the destruction or dysfunction of the gland itself. In other words, if we go back to our analogy the light side is still there and trying to restore balance to the force, but it does not matter because the glands themselves have gone to the dark side. I hope our little galactic journey through primary thyroid disorders has been informative and helpful for your studies. All the best!

Sincerely,

Jean Hanna

References

  1. Kane M.P., & Bakst G (2020). Thyroid disorders. DiPiro J.T., & Yee G.C., & Posey L, & Haines S.T., & Nolin T.D., & Ellingrod V(Eds.), Pharmacotherapy: A Pathophysiologic Approach, 11e. McGraw-Hill. https://accesspharmacy.mhmedical.com/content.aspx?bookid=2577&sectionid=223397495
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