Associations of Pre-Transplant Prescription Narcotic Use With Clinical Complications After Kidney Transplantation

Prescription rates for opioid analgesics have increased dramatically in the U.S. and there have been many studies that have found a correlation between the rise in prescription narcotics and an increase in opioid-related deaths. There have also been correlations between rising narcotic use and a rise in addictions, overdoses, adverse drug events, and health care costs. Those who experience kidney failure have pain that is often multifactorial and requires management of moderate to severe pain. But, because kidney failure and dialysis can affect opioid pharmacokinetics and pharmacodynamics, those who suffer advanced renal disease could face higher risk of adverse events. Having advanced renal disease can lead to adverse drug events due to the accumulation of the drugs and their metabolites, drug interactions with concurrent medications, and also due to patient characteristics such as age.

In this article Lentine and colleagues studied the association between pre kidney transplant narcotic use and clinical complications after transplant. In their study they have created databases of linked transplant registry and pharmacy fill records by merging administrative billing claims from Medicare that capture provider-reported clinical diagnoses. Clinical complications they considered included cardiovascular, respiratory, neurological, substance abuse, accidents, and noncompliance events. They have found that high-level prescription narcotic use before kidney transplantation predicts increased risk of clinical complications after transplantation.

I find it interesting that there have not been past reported studies concerning prescribed opioids pre kidney transplant and the clinical consequences that occur after transplant. Although I found the articles look on the cardiovascular, respiratory, and neurological implications to have appropriate data for their conclusions, there may perhaps also be other variables to take in consideration for the substance abuse, accidents, and noncompliance events that they looked at. For example, the patient could already be predisposed to narcotic abuse or the patient could have household or cost issues concerning noncompliance events. Also, the article did not take a look into the possibility for patient illicit drug use nor over-the-counter medication use, which could each have a huge impact on the results that they have found. What we should take away from their results are that there needs to be further research in screening for kidney transplant patients who are more susceptible to narcotic related complications post kidney transplant.

Lentine K, Lam N, Xiao H, et al. Associations of Pre-Transplant Prescription Narcotic Use With Clinical Complications After Kidney Transplantation. Am J Nephrol. 2015; 41: 165-176.

Value of Personalized Medicine

An approach termed “personalized health care” uses predictive capabilities to create personalized health plans that would track and support health goals. Personalized health care utilizes genomic tools to quantify health risks, to find mechanisms of disease, and to develop targeted therapy. This could lead to improved risk prediction, behavior change, make lower costs, and develop public health awareness for rare diseases.

In this article, authors Snyderman, Meade, and Drake, refute challenges of personalized medicine as posed by authors Joyner and Paneth in another article. Joyner and Paneth do not believe that personalized medicine based on genomics is realistic given the general level of treatment that already exists. Synderman and colleagues understand that genomic predictive tests for common complex diseases require additional investigation, but that the identification of a patient’s health risks using advancing technologies enables a strategic practice model for health care providers.

I believe that personalized medicine via genomic testing will allow health care providers to better care for their patients. No two individuals are the same on the genomic level, so why should they be treated the exact same way when they could get different health outcomes.

Synderman R, Meade C, Drake C. “Value of Personalized Medicine” JAMA. (2016): 315(6): 613.

Joyner M, Paneth N. “Seven Questions for Personalized Medicine” JAMA. (2015): 314(10): 999-1000

Drugging Undruggable Molecular Cancer Targets

Currently, a number of cancer drug targets remain outside of the reach of pharmacological regulation and have been known as “undruggable”. These undruggable targets are just targets that the traditional approach to fighting cancer, often aimed at DNA replication, mitotic machinery, or DNA integrity, do not target. However, due to more current understandings of the factors that drive cancer’s many forms, new target classes with varying levels are being proposed.

In this article, authors Lazo and Sharlow have proposed a reclassification of the traditional cancer drug targets, as well as have highlighted some new strategies being used to reclassify them. They claim that the sequencing of the human cancer genomes have shown potentially thousands of mutations in each individual solid tumor, which could reflect many possible new cancer targets. For example, in contrast to large traditional drug targets, like growth factor receptors, small molecule targets that could lead to malignancies are only just emerging as a viable area to research. Rather than by targeting the small molecules themselves, but by more specifically using techniques such as silencing of this protein expression by antisense or microRNA mimetics is the alternative strategy being looked at.

I agree with the authors of this article in their endeavor to reclassify cancer drug targets. Having two big categories of “druggable” and “undruggable” drug targets could potentially discourage researchers from looking at that undruggable category or focus too much time and money on the druggable category. With a total reclassifcation of all of the cancer targets that have been discovered, we can narrow in on specific pathways and discover new effective therapeutics to reduce cancer morbidity and mortality.

Lazo, John S., Sharlow, Elizabeth R. “Drugging Undruggable Molecular Cancer Targets” Annu Rev Pharmacol. (2016): 56:23-40.

Adverse Effects Associated With Proton Pump Inhibitors

Proton pump inhibitors (PPIs), such as omeprazole and pantoprazole, are commonly prescribed medications used to treat indigestion and prevent gastrointestinal bleeding in patients undergoing antiplatelet therapy. PPIs act by blocking gastric proton pumps, a necessary stage in the secretion of gastric acid. There is a widely held belief that PPIs have a very few amount of adverse effects and so result in them being overprescribed by physicians.

This journal article shows several adverse effects as a result of proton pump inhibitor use. These observed adverse effects include increased risk of kidney disease, hypomagnesemia, infections, cardiovascular events, and fractures. Researchers found that the risk of developing chronic kidney disease was 50% greater and the risk of acquiring acute kidney injury was three times greater in those who use PPIs compared to those who do not. Hypomagnesemia, or abnormally low levels of magnesium in the blood, had a 40% greater risk in PPI users and can lead to other illness such as muscle weakness, convulsions, and hypotension. Bacteria may colonize much easier in the gastrointestinal tract when PPIs reduce gastric acidity. Due to this, Clostridium difficile infections showed a 74% increase and pneumonia showed a 34% higher risk of developing in patients taking PPIs. As far as adverse cardiovascular events, those on PPIs and antiplatelet drug clopidogrel have a 30% increased risk in reduction of platelet inhibition due to both drugs competitively becoming metabolized by the same liver enzymes. PPI use can also decrease bone density by reducing intestinal calcium absorption. PPIs were associated with a 26% higher risk of hip fracture, a 58% higher risk of spine fracture, and a 33% higher risk for fracture at any site.

I feel as though greater caution is required when physicians decide to prescribe PPIs. Just because they were once thought to be seemingly harmless medications does not mean that new evidence demonstrating a connection to adverse effects should not be taken seriously. Special precautions should probably be taken in consideration for those patients who are at higher risk for any of the conditions indicated in this article. Also, histamine H2 receptor antagonists should perhaps be looked at as an alternative to PPI therapy if they do not show similar adverse effects.

Schoenfeld, Adam Jacob, and Deborah Grady. “Adverse Effects Associated With Proton Pump Inhibitors.” JAMA Intern Med. 176.2 (2016): 172. Web. 15 Mar. 2016.

PD-1 Pathway Inhibitors: Immuno-Oncology Agents for Restoring Antitumor Immune Responses

The programmed cell death protein 1 (PD-1) checkpoint is a step in a pathway that prevents the activation of T-cells. Inhibitors of this pathway are designed in order to restore a patient’s antitumor immune response, which becomes suppressed during formation of tumors. Once the T-cells are activated, the immune system starts to attack tumors in the body. Immuno-oncology agents that can restore antitumor immune responses are a new class of medications that have just recently been approved for clinical use. Medications nivolumab and pembrolizumab are two such immuno-oncology agents used to inhibit the PD-1 pathway.

Researchers in this article highlight the response characteristics distinctive to immune checkpoint inhibitors as well as provide pharmacokinetic and pharmacodynamic data for pharmacists and physicians. These researchers have studied these new medications in those with advanced melanoma, metastatic non-small cell lung cancer, and advanced renal cell carcinoma. But although there are many benefits to using these drugs, there have also been many adverse events encountered in those taking this new class of medication. Along with the classic immune-mediated adverse effects expected to be seen when taking anti-cancer drugs, the PD-1 inhibitors also have potential for developing autoreactive T-cells, leading to inflammation across a range of tissues. It is for this reason that patients with a history of autoimmune diseases were excluded from these clinical trials. Despite these adverse reactions, survival rates of the patients taking these medications have increased compared to patients taking standard treatment options.

I feel that although there are many adverse events associated with this new class of cancer drug, and although these drugs were hastened to become approved by the FDA, their efficacy is greatly needed in the management of various cancers. And as demonstrated in the article, if pharmacists collaborate with physicians effectively, the majority of immune-mediated adverse effects can be managed with concurrent use of other medications to ease these symptoms without discontinuation becoming necessary.

Medina, Patrick J., and Val R. Adams. “PD-1 Pathway Inhibitors: Immuno-Oncology Agents for Restoring Antitumor Immune Responses.” Pharmacother. (2016): n. pag. Wiley Online Database. Web. 15 Feb. 2016.

Hepatitis C Drugs Top State Medicaid Expenditures According to Senate

Hepatitis C is a liver disease caused by a blood borne virus in which the severity of can range from a mild illness of a few weeks to a serious, lifelong illness. A significant number of people who are infected with the disease develop liver cirrhosis or liver cancer. It is transmitted through unsafe injection practices, inadequate sterilization procedures, and transfusion of unscreened blood. 130 to 150 million people worldwide are infected with hepatitis C and around 500,000 people die each year from the disease.

According to ranking members of the United States Senate, hepatitis C drugs have made top spots in many states’ Medicaid expenditures. Gilead Sciences’ Hepatitis C drug, Solvaldi (sofosbuvir), costs $84,000 for treatment under Medicaid programs and is ranked among the top five pharmaceutical expenditures for 33 states. In 14 of those states, Medicaid spent more on Sovaldi than any other drug. Because of the high cost of treating Solvaldi, Medicaid programs were only able to treat 2.4% of about 700,000 enrollees who are infected with hepatitis C.

I believe that there needs to be more regulation on how much manufacturers can price life-saving drugs. If Medicaid programs were to pay for the treatment of hepatitis C for all its members in the state of Washington, the cost would be three times that of its total pharmacy budget. The ridiculous price gouging of this particular drug perfectly demonstrates that the government should have more say in how much drugs should cost to prevent exploitation of this vulnerable patient population.

Rubin, R. “Hepatitis C Drugs Top State Medicaid Pharmaceutical Expenditures”. JAMA. 2016; 315(6):549. Web. 15 Feb. 2016.

“Hepatitis C.” World Health Organization. WHO, July 2015. Web. 15 Feb. 2016.