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Opinions on Practice Management

Steven R. Feldman, MD, PhD

The Three Pillars of Drug Therapy: Pharmacokinetics, Pharmacodynamics and…“Pharmacomore”?

Steven R. Feldman, MD, PhD

Wednesday, December 08, 2010

Pharmacology has traditionally been concerned with pharmacokinetics and pharmacodynamics. Pharmacokinetics is what the body does with the drug, whereas pharmacodynamics is what the drug does to the body. Of course, understanding the pharmacokinetics and pharmacodynamics of dermatologic treatments is critically important. The third pillar of dermatologic drug therapy is patients' adherence behavior - whether and how well patients take their medications.

I'm not sure we have a good word for this yet. Pharmionics has been suggested (similar to avionics to describe all the things that go into flying planes) but doesn't seem to be catching on.1,2  Pharmacobehavior has no ring to it. The Greek for "behavior", symperifora, seems to create a most unwieldy pharmacosymperifora - that won't catch on. "Pharmacomore" (far-mah-ko-mo-ray) - "more" from the Latin word for "behavior" - may be a better word to describe the vast role that behavior plays in the effects of drug therapy.

"Pharmacomore" - Factors Contributing to a Poor Outcome

The effectiveness of drug treatment depends, firstly, on patients procuring the recommended medication(s). We probably take for granted that patients obtain the prescribed treatment, but research demonstrates that it is very common for patients not to collect their treatment. A study of Danish pharmacy records revealed that about 10% of acne prescriptions, 30% of atopic dermatitis prescriptions and a whopping 50% of psoriasis prescriptions were never filled.3 This isn't just a problem in Denmark. A US study found low rates of prescription filling for psoriasis medications, even when the cost of treatment was not prohibitive.4

Once a prescription is filled, it is unlikely that the patient will use the medication as directed. Numerous studies have revealed poor use of medication in both clinical trials and clinical practice.5-10 The reasons why adherence is poor are many and varied; frustration with medication efficacy, inconvenience and fear of side effects are among the most common.11,12

In a wonderful article, Vrijens et al. describe the various ways in which patients don't use their medication as directed, coming up with useful nomenclature for the different components of poor adherence (Figure 1).13 First, the patient may or may not start on treatment. This phase is termed "Acceptance". At the end comes "Discontinuation", often occurring well before the time that patients are supposed to stop. (As an aside, the commonly used term "tachyphylaxis", used to describe the tendency of medications to stop working in dermatologic practice, may be a synonym for early discontinuation.14)

 

 

 

Figure 1. The components of adherence behavior.

Between these two phases comes the period of "Persistence". During persistence, patients may or may not use their medication appropriately, defined by the "Quality of Execution", which in turn encompasses intermittent missed doses, prolonged drug holidays, and compensatory overuse. Some patients miss doses unpredictably, whereas others miss doses on a regular schedule (perhaps they find Monday a busy day). Drug holidays are also common. Patients may go on holiday and forget their medication, or they might miss several days of treatment in a row because they didn't order a refill in a timely way. Often, patients will make up for a missed dose by taking twice as much the next day.

Conclusions

"Pharmacomore" comprises a rich, varied, and critically important aspect of dermatologic drug treatment, as important or even more important than pharmacokinetics and pharmacodynamics. With the growing understanding of patients' adherence behavior, I believe a new field of pharmacologic research will soon develop - research into physician behaviors that change patients' use of their medication. I don't think that we should blame patients for poor use of medications; we probably have a lot more control over what patients do than we think we do.15 Future studies are likely to provide us with the tools to enhance treatment outcomes by improving the ways in which our patients use their medicines.

References

  1. Urquhart J. Pharmionics: research on what patients do with prescription drugs.Pharmacoepidemiol Drug Saf 2004;13:587-590.
  2. Lee IA, Maibach HI. Pharmionics in dermatology: a review of topical medication adherence.Am J Clin Dermatol 2006;7:231-236.
  3. Storm A, Andersen SE, Benfeldt E, Serup J. One in 3 prescriptions are never redeemed: primary nonadherence in an outpatient clinic. J Am Acad Dermatol 2008;59:27-33.
  4. Bhosle MJ, Feldman SR, Camacho FT, et al. Medication adherence and health care costs associated with biologics in Medicaid-enrolled patients with psoriasis. J Dermatolog Treat2006;17:294-301.
  5. Storm A, Benfeldt E, Andersen SE, Serup J. A prospective study of patient adherence to topical treatments: 95% of patients underdose. J Am Acad Dermatol 2008;59:975-980. 
  6. Armstrong AW, Watson AJ, Makredes M, et al. Text-message reminders to improve sunscreen use: a randomized, controlled trial using electronic monitoring. Arch Dermatol2009;145:1230-1236.
  7. Krejci-Manwaring J, Tusa MG, Carroll C, et al. Stealth monitoring of adherence to topical medication: adherence is very poor in children with atopic dermatitis. J Am Acad Dermatol2007;56:211-216.
  8. Carroll CL, Feldman SR, Camacho FT, Manuel JC, Balkrishnan R. Adherence to topical therapy decreases during the course of an 8-week psoriasis clinical trial: commonly used methods of measuring adherence to topical therapy overestimate actual use. J Am Acad Dermatol2004;51:212-216. 
  9. Krejci-Manwaring J, McCarty MA, Camacho F, et al. Adherence with topical treatment is poor compared with adherence with oral agents: implications for effective clinical use of topical agents. J Am Acad Dermatol 2006;54(Suppl):S235-S236.
  10. Yentzer B, Hick J, Williams L, et al. Adherence to a topical regimen of 5-fluorouracil, 0.5%, cream for the treatment of actinic keratoses. Arch Dermatol 2009;145:203-205.
  11. Brown KK, Rehmus WE, Kimball AB. Determining the relative importance of patient motivations for nonadherence to topical corticosteroid therapy in psoriasis. J Am Acad Dermatol2006;55:607-613.
  12. Feldman SR, Horn EJ, Balkrishnan R, et al; International Psoriasis Council. Psoriasis: improving adherence to topical therapy. J Am Acad Dermatol 2008;59:1009-1016.
  13. Vrijens B, Vincze G, Kristanto P, Urquhart J, Burnier M. Adherence to prescribed antihypertensive drug treatments: longitudinal study of electronically compiled dosing histories. BMJ 2008;336:1114-1117.
  14. Feldman SR. Tachyphylaxis to topical corticosteroids: the more you use them, the less they work? Clin Dermatol 2006;24:229-230.
  15. Feldman SR: Practical ways to improve patients' treatment outcomes. Winston-Salem, NC, USA: Medical Quality Enhancement Corporation, 2009.

 

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