Existing and Future Drugs for the Treatment of the Dark Side of Addiction

Addiction is a major problem that accompanies many commonly prescribed drugs especially benzodiazepines to opioids. While these medications due have a medical use that can help many people, they are often abused for their euphoria producing properties. When they are abused, they can lead the abuser down a road to addiction. Once addicted, someone will do whatever it takes to get the drug, often ruining his or her life in the process. For this reason, treating addiction is a topic commonly researched.

 

Addiction involves 3 stages. The binge/intoxication stage when someone is actually taking the drug, the withdrawal/negative effect stage after the person comes down from their high and the preoccupation/anticipation stage where the person becomes focused on getting the drug to not only produce the high again but to relieve themselves of the negative withdrawal effects. Often, the rewarding and intoxicating portion of the addiction cycle is targeted, especially when you look at treatments like Suboxone that saturate the receptors in order to block the high of drugs. This review article, however, cites a “revisionist” view of treating addiction. They believe that by treating the stressful symptoms of withdrawal, we can diminish the “negative reinforcement” portion of addiction. Negative reinforcement is when you take a drug to alleviate the withdrawal symptoms.
I think this article makes a very good point. Withdrawal symptoms can be miserable and definitely factor into an addicts decision to continue using. If we could develop drugs that can be used in adjunct therapy with the ones currently availabkle to alleviate addiction symptoms, we could block both the highs and the lows of addiction and hopefully help more addicts defeat their addictions.

 

Koob G, & Mason B. Existing and future drugs for the treatment of the dark side of addiction. Annu Rev Pharmacol Toxicol. 2016:56(1);299-322.

 

Opioid Pharmacokinetics-Pharmacodynamics Clinical Implications in Acute Pain Management in Trauma

Pain management is a tough puzzle that faces many health care providers especially those in the emergency room. Trauma is the most common reason for someone to go to the emergency room and therefore opioids are some of the most commonly prescribed medications in the ER. But despite being so commonly used, opioids are very complex drugs that can be difficult to deal with. The first question that needs to be answered is whether or not an opioid is needed. Once this has been decided, the next question is which one. With so many opioids with almost identical mechanisms of action, how do doctors and pharmacists decide which one is the most appropriate?

 

In a review article composed by Mackenzie et al, they addressed this difficult decision by reviewing primary articles about the pharmacokinetic and pharmacodynamics profiles of morphine, hydromorphone and fentanyl. They found differences in each drug’s onset of action, their duration of action as well as the effects of titrating doses to achieve optimal pain relief. They ended up breaking down the profile of each drug and showing how they should be used to treat different types of pain. Fentanyl for a quick onset of acute pain, morphine for long term constant pain management, and hydromorphone for pain similar to morphine but best used without a loading dose.

 

This study showed that by investigating opioids Pk and Pd profiles, we can learn more about which situations call for which opioids. By knowing these facts, prescribers will be able to better customize a patients’ regimen to suit his or her needs. Should we be more interested in the pharmacokinetics of drugs? What about non-opioids?

 

Mackenzie M, Zed P, & Ensom M. Opioid pharmacokinetics-pharmacodynamics: clinical implications in acute pain management in trauma. Ann Pharmacother, 2016;50(3):209-218.

 

Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: systematic review and meta-analyses

According to the new guidelines for treatment of hypertension, it is recommended to initiate pharmacological treatment in diabetic patients when their blood pressure goes above 140/90. This recommendation is one of many that come from JNC 8, a trusted guideline by pharmacists and doctors all over the world. One issue with the JNC treatment guidelines, however, is that while they give extensive and thorough recommendations about the initiation of antihypertensive therapy, they offer little to no recommendations about when antihypertensives should be continued or stopped after a goal blood pressure has been reached.

 

In this review article that looked at 49 randomized controlled trials, it was determined that further treatment of diabetes patients with anti-hypertensives after they were below goal blood pressure actually increased risk of cardiovascular death as well as correlated to an increase towards all types of mortality. This surprised me because it seems counterintuitive that antihypertensive medications could ever increase the possibility of a cardiovascular death, even in a patient with healthy blood pressure.

 

I think this article may shed some light on the “if it ain’t broke don’t fix it” attitude of many doctors towards maintenance medications. Many doctors will keep their patients on anti-hypertensives or statins even if the patient’s blood pressure or lipid levels are at goal. This attitude, as shown by this review article, could have some negative effects on patient outcomes. What do you think? Should patients be discontinued on medications when they reach their goals? Or is this review finding specific to patients with both hypertension and diabetes?

 

Brunström M. & Carlberg, B. Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: Systematic review and meta-analyses. Bmj 2016;352:I717.

Is Trimethoprim-Sulfamethoxazole a Valid Alternative in the Management of Infections in Children in the Era of Community-Acquired Methicillin-Resistant Staphylococcus aureus? A Comprehensive Systematic Review

One of the growing problems in he practice of pharmacy is the increasing emergence of strains of bacteria immune to the antibiotics that are currently on the market. Through over-prescribing, non-adherence, and other contributing factors, the need for new antibiotics is as high as it was when penicillin was first discovered. But as we all know, a drug doesn’t hit the market immediately. It can be over 10 years to before a drug is approved so what are we supposed to do in that time? Let the bacteria beat our current antibiotics? Or is there something more we can do to combat antibiotic resistance.

 

Rosanova et. al reviewed the literature to determine if trimethoprim-sulfamethoxazole had been proven to effectively treat Methicillin-Resistant Staphylococcus aureus (MRSA) in children. According to the first consult page on MRSA on clinicalkey, the outpatient treatment of MRSA includes drugs like clindamycin and linezolid for both pediatrics and adults. It also mentions trimethoprim-sulfamethoxazole as a treatment but only in adults. The review done by Rosanova et al found just 4 primary articles that studied trimethoprim-sulfamethoxazole in a randomized controlled study in children and the results were inconclusive.

 

While the findings of this article may not be significant, the fact that it was even written is. This article proves that while we work to discover newer and more effective antibiotics, we must also reevaluate the ones we currently use and find other possible uses for them.

 

Rosanova, M. T., Pompa, L. C., Perez, G., Sberna, N., Serrano-Aguilar, P., & Lede, R. (2016). Is Trimethoprim-Sulfamethoxazole a Valid Alternative in the Management of Infections in Children in the Era of Community-Acquired Methicillin-Resistant Staphylococcus aureus? A Comprehensive Systematic Review. Journal of Pharmacy Technology, 32(2), 81-87. Retrieved February 22, 2016.

 

A classic drug could become our cheapest and safest new cancer drug.

When you think of drugs used to treat cancer, you often think of drugs that are expensive that attack not only the cancer cells but also your own cells. They often cause severe side effects and aren’t always effective. There is a class of very common and relatively inexpensive drugs, however, that are showing promise in their ability to treat tumor cells.

 

Bisphosphonates are a very common class of drug that are often prescribed to treat osteoporosis. They work by inhibiting osteoclasts that break down bone into minerals to be used by the body. Another property of bisphosphonates that is being investigated is their effect on tumor cells. They have shown evidence to work against tumor cells in five different ways. They can trigger tumor cells to undergo apoptosis, inhibit tumor cell adhesion, and prevent tumor angiogenesis or blood vessel development. In addition to these direct effects on tumor cells, bisphosphonates can help the body better defend against the tumor cells by inhibiting macrophages produced by the tumor as well as activating a certain class of cytotoxic T-cells. Lastly, bisphosphonates exhibit a synergistic relationship with a number of anti-tumor drugs, providing an opportunity for them to be added to cancer patients’ existing medication regimens.

 

These properties of bisphosphonates are exciting and worth devoting more time and money into researching them. A cheap, and safe drug that can be used to treat cancer could be a potential breakthrough in the complex and expensive field of oncology. With more research, we could very well see bisphosphonates as a part of every cancer patient’s medication regimen.

 

Acker, H. H., Anguille, S., Willemen, Y., Smits, E. L., & Tendeloo, V. F. (2016). Bisphosphonates for cancer treatment: Mechanisms of action and lessons from clinical trials. Pharmacology & Therapeutics, 158, 24-40.

 

 

New study on effects of mirtazapine on tumor necrosis factor-α and serum BDNF could change the way we treat depression.

In a study conducted by Gupta et.al at Guru Teg Bahadur Hospital, New Delhi, they found that mirtazapine could work as a treatment for patients with clinically diagnosed severe depression. According to the drug label for mirtazapine found on Dailymed, it is indicated to treat major depressive disorder as defined by DSM III. Based on DSM IV, episodes of depression can be categorized as mild moderate and severe. According to this paper, mirtazapine has only been proven to be effective in moderate to severe depression, so they intended to test its effect strictly with patients who had severe depression.

 

This study looked at 30 severely depressed patients who were receiving services from the outpatient psychiatric clinic at Guru Teg Bahadur Hospital. They were each given 30 mg of mirtazapine per day and monitored for up to 12 weeks. Their levels of tumor necrosis factor-α and serum BDNF were also monitored, as there are new hypotheses that link high and low amounts respectively of these compounds to depression. The results of the study showed that mirtazapine not only significantly reduced patients’ depression, but also significantly increased mean levels of serum BDNF and significantly decreased mean levels of tumor necrosis factor-α.

 

While this study is exciting and could raise questions about whether the current monoamine theory of depression should be reconsidered, it also has some flaws. For starters, there was a small sample size of just thirty participants. Additionally, the mirtazapine wasn’t tested against a placebo or a positive control such as fluoxetine to determine if it was more or less effective. While the results point in a positive direction, there is still a lot of research to be done to determine if mirtazapine should be considered a first line therapy in the treatment of severe depression.

Link to Article

References

 

Gupta R, Gupta K, Tripathi A, K, Bhatia M, S, Gupta L, K, Effect of Mirtazapine Treatment on Serum Levels of Brain-Derived Neurotrophic Factor and Tumor Necrosis Factor-α in Patients of Major Depressive Disorder with Severe Depression. Pharmacology 2016;97:184-188

 

Remeron (mirtazapine) indications and usage. Hatfield, Hertfordshire: Mylan; 2007 May.

 

American Psychiatric Association. (2000). Diagnostic and statistical manual of mental disorders (4th ed., text rev.).