Right Medication, Right Dose, Right Time

Alvin B. Lin, MD, FAAFP
Dr. Lin is an associate professor of family and community medicine at University of Nevada School of Medicine and an adjunct professor of family medicine and geriatrics at Touro University Nevada College of Medicine. He also serves as an advisory medical director for Infinity Hospice Care and as medical director of Lions HealthFirst Foundation. Dr. Lin maintains a small private practice in Las Vegas, NV. The posts represent the views of Dr. Lin, and in no way are to be construed as representative of the above listed organizations. Dr. Lin blogs about current medical literature and news at


One of the 1st year residents approached me earlier this week to discuss a patient. Apparently this elderly patient was complaining of some joint pain not amenable to acetaminophen and ibuprofen. Therefore, the resident wanted to escalate the patient's pain control rapidly up the WHO pain ladder. I suggested that, before stepping up to opioid relief, s/he should confirm treatment failure. By that, I wanted to be sure that the patient had really failed acetaminophen, eg 3 g daily, and ibuprofen, eg 2400 mg daily. The resident wasn't exactly thrilled at having to go back in and get further details but agreed to do so. S/he returned sheepishly stating that the patient had only been taking acetaminophen 325 mg daily along with ibuprofen 200 mg daily. This was clearly not a case of treatment failure but rather failure to treat adequately.

To me, this is analogous to putting cheap gas (yes, I know the good stuff is expensive - in fact, it was over $4.65/gallon at Costco in Southern California over the Easter holiday weekend) in a Ferrari 458 Italia and then complaining that something was wrong with the car because it wasn't driving properly. Putting diesel into this sports car wouldn't have helped either. While the former is akin to giving the wrong dose, the latter is more like giving the wrong medication altogether. But what about timing? After all, is there really any need to go to another the gas station after you've driven 5 miles from the previous one? Seems like a waste of time to me.

But that's the whole point of my story. For medications to work, we have to prescribe the right drug (gasoline vs diesel vs electrical charge) in the right dose (87 octane vs 91 octane) at the right time (somewhere around three-quarter empty or when the low fuel signal first lights up seems right to me) using the right administration route for the right person. Likewise, while many observational studies have demonstrated the benefit of fish consumption and omega 3 fatty acids in cardiovascular disease in both 1o & 2o prevention, the cause and effect data are still quite murky, and interpretation is open to debate.

So you can imagine my surprise when a meta-analysis was published earlier this week in the Archives of Internal Medicine suggesting that there really isn't enough evidence to suggest that omega 3 fatty acids prevent recurrent heart disease. The authors arrived at their conclusion after culling through 1007 articles to find 14 randomized, double-blind, placebo-controlled trials involving 20,485 participants followed, in some studies, for over 2 years. Remember that observational studies can only prove correlation while it takes a randomized controlled trial to prove cause and effect. So how can we explain the discrepancies?

The editorialists noted that perhaps we need to consume real fish to gain the desired benefits since fish would surely suppress the desire to consume less healthy protein options. So in this case, we have all three tenets to consider: are omega 3 fatty acids really good for us, even equivalent to "real fish"?; how much omega 3 fatty acids (EPA + DHA) do we need?; and are they only effective in 1o prevention (before clinical manifestation)?