Differential Impact of Selective Serotonin Reuptake Inhibitors on Platelet Response to Clopidogrel: A Randomized, Double-Blind, Crossover Trial

SSRIs and other antidepressant medications constitute one of the most commonly prescribed drug classes that pharmacists will see in the community setting. When taken alone, any one of these medications can be a good treatment option for patients experiencing depression; however, these drugs can cause a patient who is taking multiple drugs  to experience significant interactions with his/her other medications. For this reason, it is crucial to know how the effects of other medications can be altered through this therapy.  This study analyzed the effects of two SSRIs (citalopram and fluvoxamine) on the blood thinning medication clopidogrel. These medications all work on the same CYP enzyme (CYP2C19)  and have opposing effects. Researches tested these medications on healthy individuals and found that fluvoxamine was the only drug that caused significant inhibition of clopidogrel action.

I think this is important to note because these medications are commonly utilized by patients and thus there is a high likelihood that they may be taken together. As pharmacists, we should be able to provide adequate care in response to possible drug-drug interactions. To do this, we have to be able to recognize when there could potentially be a problem in medication therapy. By taking the proper precautions when these situations arise, pharmacists will be more likely to help patients avoid adverse medical events associated to drug therapy methods.

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.

 

Pharmacokinetics of oral and intravenous melatonin in healthy volunteers

Lars Andersen and colleagues created a study to examine the pharmacokinetics of melatonin administered orally, and intravenously.  This was a cohort crossover study in which volunteers were given either 10 mg melatonin orally or 10 mg of intravenous melatonin on two occasions.  Twelve male volunteers with an average age of 27 years old and an average BMI of 23.2 kg/m2.

Some pharmacokinetic parameters were measured for both oral and intravenous routes including half-life, area under curve (AUC), and volume of distribution for intravenous.  The half-life for the oral route was found to be 53.7 minutes, and 39.4 minutes for the intravenous method.  The AUC for the oral melatonin 281,538.3 pg*mL-1*min, and the intravenous melatonin was found to have an AUC 14,179,767.6 pg*mL-1*min.  The volume of distribution was found to be 1.2 L/kg.

The study concluded that the oral melatonin had a very low bioavailability of about 3%.  They commented how other studies they found ranged from 9-33% availability.  The one similarity between the studies they reviewed and this study was that there was high variability between patients.  The low availability was due to the extensive first pass effect from the liver.  The intravenous melatonin was found to be have first order elimination kinetics.  The parameters found with the intravenous study fell within the limits that were predicted based on previous studies.

Studies like this one are very important to help optimize a medications effects.  When examining pharmacokinetic effects do you think that it is important to include both sexes in the volunteer pool?  How does the variable bioavailability affect the results of each patient that takes oral melatonin?

BMC Pharmacol Toxicol. 2016;17:8.