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

Risk Factors of Hypertension and Why You Shouldn’t Take Your Stress with a Grain of Salt

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It would not be an understatement to say almost all cases of high blood pressure are likely to be classified under the term “primary” or “essential” hypertension. Even so, primary hypertension can be a real head scratcher as we have a very poor understanding of the etiology despite an estimated 90% of patients fitting the bill. As such, primary hypertension is often labeled as “idiopathic”, which is medical terminology for “no identifiable cause” that we are aware of at this time. We do, however, have an inkling for several risk factors which are associated with the development of hypertension. In this post, we will break them down using a mnemonic that helps tie everything together and provides a system to recall these characteristics moving forward. Can you think of what might be a good mnemonic for this cause? That is right: stress!

We’ve all experienced stress at some point in our lives. Imagine yourself in peak rush hour traffic, the time is now 7:45 AM and your final starts at 8:00 AM. You are moving 5 miles per hour bumper to bumper with at least a 40-minute estimated delay. Can you feel your heart racing? Maybe not, but the point stands that stress can exacerbate blood pressure and it is an excellent way to outline the following known risk factors:

“S” is for SODIUM
Excessive sodium consumption can increase risk for hypertension and even blunt antihypertensive medications. It is generally recommended patients limit their intake to less than 1,500 milligrams a day which can further help in reducing systolic blood pressure by ~5-6 mmHg2
“T” is for TIMESPAN
Time refers to patients greater than 65 years of age as they are more likely to acquire hypertension and are therefore at a further increased risk of cardiovascular disease1
“R” is for RAZZAMATAZZ  Did you know razzamatazz is a type of alcoholic beverage? Neither did we, but the name has a ring to it and highlights the fact that excessive alcohol consumption should be avoided! Men who lower consumption to 2 drinks a day and women who lower consumption to 1 drink a day can expect systolic blood pressure to decrease by ~4 mmHg1
“E” is for ETHNICITY
A family history of hypertension is a significant factor to keep in mind alongside the disproportionate degree of African American cases for this disease state: here is a study entitled, “Differences in Stroke Mortality Among Adults Aged 45 and Over: United States, 2010–2013” from the CDC. It details the implications of the “stroke belt” in the United States
“S” is for SUNDAES
Yes, we all love sundaes, but it would be wise to lay off the ice cream occasionally as Obesity and Diabetes Mellitus are commonly associated with hypertension. Exercise and a healthy well-balanced diet like the “Dietary Approaches to Stop Hypertension” (DASH) diet is crucial for hypertensive individuals as a 1-kilogram reduction in weight generally equals 1 mmHg reduction in blood pressure2
“S” is for SMOKING
Smoking is classified as a risk factor for hypertension alongside obstructive sleep apnea and should be avoided prior to blood pressure measurements1

As you soak in all these risk factors and suggested lifestyle changes, if there is only one thing you remember from this blog post it is the following: hypertension tends to be a disease state where adherence to therapy can be particularly troublesome. This is understandable as hypertensive patients generally feel no different but may still be expected to take several classes of medications, follow up routinely, and tolerate various adverse effects of medications that can interfere with their overall quality of life. Therefore hypertension is known as a “silent killer” and as with any disease state, a solid line of communication is vital to ensuring appropriate therapy and patient satisfaction.

Sincerely,

Jean Hanna

References

  1. Hypertension.  (n.d.).  In Micromedex.  Retrieved December 26, 2020, from https://www.micromedexsolutions.com
  2. Whelton, P. K., Carey, R. M., Aronow, W. S., Casey, D. E., Jr, Collins, K. J., Dennison Himmelfarb, C., DePalma, S. M., Gidding, S., Jamerson, K. A., Jones, D. W., MacLaughlin, E. J., Muntner, P., Ovbiagele, B., Smith, S. C., Jr, Spencer, C. C., Stafford, R. S., Taler, S. J., Thomas, R. J., Williams, K. A., Sr, Williamson, J. D., … Wright, J. T., Jr (2018). 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension (Dallas, Tex. : 1979), 71(6), 1269–1324. https://doi.org/10.1161/HYP.0000000000000066

A Brief Review on Dyslipidemia for Pharmacists

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  • General information:
    • Dyslipidemia is defined as a condition in which an individual has elevated cholesterol or lipids in an individual’s blood such as the following:
      • HDL: “Good” cholesterol
      • LDL: “Bad” cholesterol
      • Triglycerides (TGs)
    • LDL cholesterol can form plaques in vessels
    • HDL cholesterol helps remove LDL
    • TGs are formed in fat cells when calories are not burned right away
  • Symptoms:
    • Regarded as a silent disease in which patients are unaware of having it
  • Types and causes:
    • Primary dyslipidemia:
      • Inherited through genetics
    • Secondary dyslipidemia
      • Caused by lifestyle factors such as the following:
        • Obesity
        • Diabetes
        • Hypothyroidism
        • Alcoholism
  • Risk factors:
  • Review of lab values**:
 Total cholesterolHDL  LDLTGs
Desirable< 200> 40 (men) > 50 (women)  < 100< 150
Borderline200 – 239   130-159150-199
High  > 240     160-189  200-499  
Very high      > 190> 500

**All units are in mg/dL

  • Treatment options:
Class and Mechanism of ActionGeneric (Brand) NamesSide EffectsBlack Box WarningsContraindications
Statins: Inhibits the rate-limiting step for cholesterol synthesis by inhibiting HMG-CoA reductase   **first-line**Atorvastatin (Lipitor) Rosuvastatin (Crestor) Simvastatin (Zocor) Pravastatin (Pravachol) Pitavastatin (Livalo) Fluvastatin (Lescol) Lovastatin (Mevacor) Simvastatin + Ezetimibe (Vytorin)  Myalgia Arthralgia Myopathy Diarrhea Cognitive impairmentSkeletal muscle effects  

Hepatotoxicity (increased LFTs)		Pregnancy Breastfeeding  

Use with cyclosporine  

Active liver disease
Bile Acid Sequestrants: Inhibits absorption of bile acids into blood which ultimately aids in reducing LDL  Cholestyramine (Questran) Colesvelam (Welchol) Colestipol (Colestid)  Abdominal pain Cramping Flatulence Constipation Increased TGs Increased LFTs   Esophageal obstruction   Cholestyramine: Biliary obstruction  
Colesvelam: Bowel obstruction and TGs > 500
Fibrates: PPAR-α agonist; inhibits TG synthesis and decreases VLDLGemfibrozil (Lopid) Fenofibrate (Tricor)  Abdominal pain Dyspepsia Increased LFTs  
Upper respiratory tract infection (URTI)  		Risk of myopathy with concurrent statin use   Increased serum creatinine   CholelithiasisLiver disease Renal disease Gallbladder disease  

Use with repaglinide
PCSK-9 Inhibitors: Monoclonal antibodies that decrease LDLAlirocumab (Oraluent) Evolocumab (Repatha)Flu Cold URTI Injection site reaction   Urinary tract infection (UTI)    
2-Azetidinones: Inhibits absorption of cholesterol at the small intestineEzetimibe (Zetia)Myalgia Arthralgia Diarrhea URTI  Skeletal muscle effectsAvoid in patients with hepatic impairment
Fish Oils: Unknown mechanism of action    Omega-3 Acid (Lovaza) Icosapent Ethyl (Vascepa)Dyspepsia Flatulence Burping Increased LDLCaution in those with a fish/shellfish allergy 
Nicotinic acid/Vitamin B3: Decreases synthesis of VLDL, LDL, and TGs  Niacin (Niacor, Niaspan)Flushing Pruritis Nausea Vomiting Diarrhea Cough

Hyperglycemia Hyperuricemia  
Orthostatic hypotension  		Hepatotoxicity  

Rhabdomyolysis with concurrent statin use		Liver disease  

Arterial bleed  

Peptic ulcer disease
High-Intensity Statin Therapy (Lowers LDL on average by > 50%)Moderate-Intensity Statin Therapy (Lowers LDL on average by 30-49%)  
Atorvastatin 40-80 mg Rosuvastatin 20-40 mgAtorvastatin 10-20 mg
Rosuvastatin 5-10 mg
Simvastatin 20-40 mg
Pravastatin 40-80 mg
Lovastatin 40 mg
Fluvastatin 40 mg
Pitavastatin 2-4 mg  
  • Additional notes:
    • Statins
      • Patient must contact their doctor for any muscle symptoms or dark urine
      • Simvastatin, lovastatin, and fluvastatin must be taken at bedtime
      • Avoid gemfibrozil, niacin (> 1 gram), and colchicine
      • Simvastatin and lovastatin:
        • Avoid strong CYP3A4 inhibitors such as azoles, erythromycin, clarithromycin, HIV protease inhibitors, cobicistat, nefazodone, cyclosporine, grapefruit juice
    • Bile Acid Sequestrants
      • Take with food and water (colesevelam)
      • Space out with multivitamins
        • At least 4 hours of one another
      • ACC/AHA guidelines do not recommend use if TGs are > 300
    • Fibrates
      • Can increase LDL when TGs are high
      • Patient must contact their doctor for any muscle symptoms, dark urine, abdominal pain, nausea, or vomiting
    • PCSK-9 Inhibitors
      • Store in fridge
      • Prior to administration allow for syringe to warm up to room temperature for 30-45 minutes
        • Inspect for any particles and/or color changes
      • Rotate injection sites
        • Alirocumab and evolocumab: Subcutaneous injections given in the thigh, upper arm, or abdomen (except within 2 inches from belly button)
    • 2-Azetidinones (Zetia):
      • Avoid concurrent use with gemfibrozil
      • Monitor LFTs with concurrent statin or fibrate use
      • Give 2 hours before or 4 hours after bile acid sequestrants
      • Patient must contact their doctor for any muscle symptoms or dark urine
      • Concurrent use with cyclosporine may increase levels of both drugs
    • Nicotinic acid/Vitamin B3
      • Must be taken with food
      • Monitor LFTs
      • Niaspan:
        • IR: Flushing/itching
        • ER: Less flushing than IR; take at bedtime
      • Avoid spicy food and ethanol
      • Take 4-6 hours after bile sequestrant acids
  • Treatment algorithm:
Prevention type  SituationTreatment
        Primary preventionLDL > 190 mg/dLHigh-intensity statin  
Primary preventionAge 40-75LDL 70-189 mg/dLPatients with diabetesModerate-intensity statin, unless 10-year ASCVD risk > 7.5%  
Primary preventionEvaluating 10-year clinical atherosclerotic cardiovascular disease (ASCVD) score  ASCVD risk > 7.5%: high intensity statin
 
ASCVD risk > 5% but <7.5%: moderate-intensity statin  
Secondary preventionPatients with clinical ASCVD< 75 years old: high intensity statin 
> 75 years old: moderate-intensity statin  

We hope this review helped refresh your clinical knowledge on dyslipidemia!

Best of luck,

Sam Tamjidi

RxPharmacist Team

References:

  1. Micromedex Solutions. Greenwood Village, CO: Truven Health Analytics. http://micromedex.com/. Accessed October 30, 2020.

What Pharmacists Need to know about Diabetes

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As per the Centers for Disease Control and Prevention (CDC), 34.2 million people, or 1 in every 10, in the United States have diabetes. Diabetes is 7th on the list of leading causes of death while the total estimated medical costs and costs associated with lost work and wages equates to an estimated $327 billion.

Diabetes, otherwise known as increased sugar levels (hyperglycemia) may be a result of decreased insulin secretion, decreased insulin sensitivity, or both. It can present itself in one of two forms of the following:

  • Type 1
    • Autoimmune destruction of beta cells
    • Loss of insulin production
    • Must use insulin injections
  • Type 2
    • Insulin resistance
    • Decreased insulin production over time
    • Associated with obesity, physical inactivity, family history
  • Signs and symptoms of diabetes include:
Signs and Symptoms of Diabetes
  • Risk factors:
Risk Factors for Diabetes
  • General Screening Criteria:
    • All patients with BMI greater than or equal to 25 kg/m2 + 1 risk factor
    • Children/adolescents with obesity + 1 risk factor
    • 45 years old if no risk factors are present
    • Pregnant women at 24-48 weeks
PrediabetesDiabetes
->Fasting plasma glucose (FPG) 100-125 mg/dL; or
->2-hour glucose after glucose tolerance test 140-199 mg/dL; or
->A1c 5.7-6.4%  		->Symptoms + random plasma glucose > 200 mg/dL; or
->2-hour glucose after glucose tolerance test > 200 mg/dL; or
->FPG > 126 mg/dL; or
->A1c > 6.5%  
  • Glycemic targets (per ADA guidelines):
    • A1c < 7%
    • 80-130 mg/dL pre-prandial plasma glucose
    • < 180 mg/dL post-prandial plasma glucose
    • A1c should be measured quarterly if not at goal
      • Or twice yearly if at goal
      • (A1c – 2) x 30 = average blood glucose
  • Drugs that may increase blood glucose levels:
Drugs that may increase blood glucose levels
  • Non-drug treatment options:
    • Smoking cessation
    • Weight loss
      • 3500 kcal weekly reduction = 1 lb weight loss
      • Waist circumference < 35 inches for females and < 40 inches for males
    • Nutrition
      • Carbs from vegetables, fruits, grains, and dairy
      • Omega-3 fatty acids and fiber
      • Limit saturated fat, cholesterol, and sodium
      • 15 g = 1 serving of carbohydrates
    • Physical activity
      • 150 min/week, moderate intensity
      • No more than 2 consecutive days off
      • Resistance training at least 2x/week
Drug treatments (oral medications)
  • Additional notes on oral drug classes:
    • Biguanides
      • Take with food
      • Use of alcohol increases the risk of lactic acidosis
      • Discontinue before any imaging with iodinated contrast; resume after 48 hrs
    • Meglitinides
      • Take 1-30 minutes before meals
      • If skipping a meal, skip dose as well
    • Sulfonylureas
      • Take with breakfast
        • Exception: Glipizide IR 30 minutes before breakfast
      • Glyburide – avoid in elderly and patients with renal impairment
    • Thiazolidinediones
      • Take with meals
      • May take weeks to take effect
      • Additional warnings:
        • Bladder cancer (pioglitazone only)
        • Risk of macular edema
        • Fracture risk
        • Hepatic failure
        • Resumption of ovulation
    • SGLT-2 Inhibitors
      • Caution when taking with diuretics and NSAIDs (due to risk of hypotension and acute kidney injury)
      • Additional warnings:
        • Genital infections
        • Hypotension
        • Increased LDL
        • Renal insufficiency
        • Ketoacidosis
      • Monitor K+ with Canagliflozin
    • DPP-4 Inhibitors
      • Take in the morning
Drug treatments (injectable medications)

Additional notes on injectable drug classes:

  • GLP-1 Agonists:
    • Exenatide and lixisenatide are administered 60 minutes before a meal
    • All others given without regard to food
  • Amylin Analog
    • Used in treatment of both type I and II diabetes
    • Reduce mealtime insulin by 50%

  • Drug treatments (Insulin)
    • For all insulins:
      • Side effects: weight gain
      • Warnings; hypoglycemia, hypokalemia
      • Never use pens for more than one individual
      • Most are 100 units/mL concentration
      • High risk medications
    • Dosing strategies
      • Basal insulin
        • Long or intermediate acting
        • Mainly affect fasting blood glucose
      • Bolus insulin
        • Rapid or short acting
        • Two purposes:
          • Prandial (mealtime) & correction (acute elevation)
Drug treatments (Insulin medications)
  • Insulins that do not require a prescription:
    • Regular insulin, NPH, and the premixed 70/30 combination
  • Insulin dosing for Type I diabetes:
    • Rapid-acting and basal insulin preferred
    • If using NPH and regular insulin
      • 2/3 NPH, 1/3 regular
    • Initiating basal/bolus insulin:
      • Calculate total daily dose (TDD)
        • 0.6 units/kg/day using TBW
      • Step 2: Divide TDD
        • 50% basal
        • 50% bolus
      • Step 3: Divide the bolus among 3 meals
    • Based on the amount of carbohydrates in a meal, meal-time insulin can be adjusted using rule of 500 (rapid-acting insulin) or rule of 450 (regular insulin)
      • (500 or 450)/TDD = g of carbs covered by 1 unit of insulin
  • Correction factor/dose
    • Factor:
      • Determines how much blood sugar will drop for every 1 unit of insulin. Uses the rule of 1800 (rapid-acting insulin) or rule of 1500 (regular insulin)
        • (1800 or 1500)/TDD = correction factor for 1 unit of insulin
  • Dose:
    • Amount of insulin required to bring blood glucose back to normal: [(blood glucose now) – (target blood glucose)]/   correction factor = correction dose
  • General treatment algorithm for Type II Diabetes:
General treatment algorithm for Type II Diabetes
  • For A1c greater than or equal to 8.5%: Jump straight to dual treatment
  • A1C > 10%: Think insulin
  • Cardiovascular benefit:
    • GLP1 agonists: liraglutide, semaglutide, exenatide
    • SGLT2 inhibitors: empagliflozin, canagliflozin
  • Patient-specific factors
    • Drugs that minimize hypoglycemia:
      • DPP4 inhibitor, GLP1 agonist, SGLT2 or TZD
    • Drugs that promote weight loss:
      • GLP1 agonist or SGLT2 inhibitors
    • Drugs with cost concerns:
      • Sulfonylurea or TZD
  • Combinations to avoid:
    • DPP4 inhibitors + GLP1
    • Sulfonylureas + insulin
  • Insulin dosing for Type II diabetes:
    • Initiate basal insulin after patient fails to reach or maintain goal on multiple oral therapies
    • Starting dose: 0.1-0.2 units/kg/day or 10 units/day
    • Titrate by 10-15% or 2-4 units once or twice weekly until fasting blood glucose at goal
    • If patient reaches fasting blood glucose goal but their A1c is still above goal:
      • Consider the addition of rapid acting mealtime insulin or GLP-1 agonist
  • Insulin administration:
    • Abdomen is the injection site (avoid belly button)
    • May also inject in thighs, buttocks, arms
      • Be consistent with administrations
    • Prime before each dose
    • Rotate sites
  • Hypoglycemia is common with insulin products, thus important to be aware of what to look out for and how to treat it
    • Defined as a blood glucose < 70 mg/dl
    • Symptoms: sweating, pallor, irritable, hunger, lack of coordination, sleepy
      • Beta blockers mask most except hunger and sweating
    • Treatment
      • Consume 15-20 g of glucose/simple carbohydrates
      • Recheck glucose levels after 15 minutes
      • Repeat if needed
      • Eat a small meal/snack to prevent recurrence
    • Glucagon is used only if patient is unconscious
  • Diabetes in pregnancy
    • Gestational diabetes: during pregnancy
      • Risks
        • Macrosomia
        • Hypoglycemia at birth
        • Obesity and type 2 diabetes
      • Management
        • Lifestyle modifications
        • Insulin added if needed (preferred)
        • Metformin and glyburide used
      • Goals:
        • Fasting < 95 mg/dL
        • 1-hour post-meal less than or equal to 140
        • 1-hour post-meal less than or equal to 120

We hope this review helped refresh your clinical knowledge on diabetes. Next up, we will take a look at dyslipidemia.

Best of luck,

Sam Tamjidi

RxPharmacist Team

References:

  1. National Diabetes Statistics Report, 2020. Centers for Disease Control and Prevention. https://www.cdc.gov/diabetes/data/statistics-report/index.html. Accessed October 26, 2020.
  2. Micromedex Solutions. Greenwood Village, CO: Truven Health Analytics. http://micromedex.com/. Accessed October 26, 2020.

A Brief Review on Hypertension for Pharmacists

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With so many organ systems, disease states, and medications to remember, preparation for the NAPLEX may often times seem like a daunting task. While there can be a considerable amount of material to go over for each clinical module, there are certainly some things that deserve more focus than others. This brief review will cover some of the most important information you need to know about hypertension when preparing for your upcoming exam.

General information:

  • Hypertension (HTN) is asymptomatic
  • HTN increases the risk for heart attacks, strokes, and kidney failure
  • Risk factors include the following:
    • High sodium and fat diet, physical inactivity, obesity, tobacco use, excessive alcohol consumption, genetics and family history, age, sex (women more likely than men), and race (African Americans more likely than any other race)
    • Drugs can also increase blood pressure, including the following:
      • Amphetamines, cocaine, pseudoephedrine, immunosuppressants, Nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, ethanol, caffeine, serotonin and norepinephrine reuptake inhibitors (SNRIs), oral contraceptives, erythropoietin

Blood pressure categories:

 Ultimate blood pressure goal:

  • 130/80 mmHg

Treatments:

Four preferred drug classes for the following patient subgroups:

  • Non-African American: Thiazide diuretic, CCB, ACE inhibitor or ARB
  • African American: Thiazide diuretic
  • Patients with chronic kidney disease or diabetes with albuminuria ACE inhibitor or ARB
  • Initiate two drugs regimens if blood pressure is > 150/90 mmHg

Additional information:

  • ACE inhibitors, ARBs, Aliskiren
    • Do not use with Entresto
    • Do not use any combination of ACE inhibitors, ARBs, and aliskiren for treatment
  • CCBs
    • CYP3A4 substrates, avoid CYP3A4 inhibitors (eg, grapefruit)
    • Caution with ankle swelling and/or irregular heartbeat
    • Amlodipine and felodipine are the safest to use in patients with HF
  • BBs
    • No longer preferred for HTN treatment
      • Primarily used first-line for heart disease, post myocardial infarction, and HF
    • Use with caution when taking other drugs that decrease HR
    • Mask symptoms of hypoglycemia
  • Diuretics
    • Take doses in the morning or afternoon to avoid frequent urination symptoms at night
    • Provide K+ supplementation to compensate for decreased K+ levels
      • This does not remain true for K+ sparing diuretics
  • Hypertensive emergency
    • Blood pressure > 180/120 mmHg
    • Acute organ damage
    • IV medication used for treatment
      • Clevidipine, nicardipine, diltiazem, verapamil, enalaprilat, esmolol, labetalol, metoprolol tartrate, propranolol, nitroglycerin, nitroprusside, chlorothiazide
    • Goal is to decrease blood pressure by < 25% within first hour
  • Hypertensive urgency
    • Blood pressure > 180/20 mmHg
    • No organ damages
    • Oral medication for treatment
  • Pregnancy
    • Treatment with labetalol, methyldopa or nifedipine XR

Treatments (non-pharmacological):

  • Lifestyle modifications
    • DASH diet, limit salt intake (<1,500 mg/day), exercise, limit alcohol consumption, maintain proper weight (BMI between 18.5 – 24.9)

Be on the look-out for our next review, which will focus on diabetes.

Best of luck,

Sam Tamjidi

RxPharmacist Team

References: Micromedex Solutions. Greenwood Village, CO: Truven Health Analytics. http://micromedex.com/. Accessed October 12, 2020.

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