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By Louis Kuritzky, MD
St John’s Wort and Drug Interactions
The cytochrome p450 system is responsible for the metabolism of the majority of currently prescribed medications. The 2 most common P450 pathways involved in drug metabolism are CYP 3A4 and 2D6, which together are responsible for metabolizing almost three quarters of currently available medications. Any agent that either blocks or enhances either of these enzyme pathways can potentially induce medication toxicity (through drug accumulation) or reduce drug efficacy (through more rapid metabolic disposal).
St. John’s Wort (SJW) is a popular over-the-counter agent used for depression, the active ingredient of which is felt to be hypericum. Case reports have suggested that SJW might affect drugs as diverse as cyclosporine, indinavir, tricyclic antidepressants, simvastatin, and even oral contraceptives. For instance, it has been suggested that the enhanced activation of the CYP3A4 system by SJW might lead to increased metabolism of ethinyl estradiol in oral contraceptives, leading to unplanned pregnancy.
Markowitz and associates studied pharmacokinetics of substances metabolized by the 3A4 and 2D6 CYP systems when coadministered with SJW. A 2-fold increase in 3A4 activity was seen, but no effect upon 2D6 was found. Since many drugs are metabolized by the CYP 3A4 system, clinicians must recognize which patients are taking SJW to minimize adverse effects upon medication pharmacokinetics.
Markowitz JS, et al. JAMA. 2003;290:1500-1504.
Serum Potassium and Stroke Risk Among Hypertensive Adults
Observational data indicate that persons who consume greater levels of dietary potassium have both lowered blood pressure and reduced risk of stroke. This protective effect of dietary potassium intake is seen in both hypertensive and normotensive persons, though it is more pronounced in men than women. In some hypertension trials, serum potassium levels have shown an inverse relationship with stroke, but of course many of these subjects received diuretic therapy with an anticipatable decline in serum potassium, and these findings have not been consistent among all populations.
Using data from the Group Health Cooperative observational study (a Washington state-based HMO), Smith and colleagues evaluated the relationship between hypokalemia and subsequent ischemic (n = 593) or hemorrhagic stroke (n = 125) in this population of hypertensive adults compared to controls (n = 2397). Potassium status was defined by traditional levels of hypokalemia (potassium < 3.5) measured in the year prior to stroke.
Hypokalemia was associated with substantial increases in risk of stroke, both for ischemic (odds ratio, 2.04) and hemorrhagic (odds ratio, 3.29) stroke. Since no gradient of stroke risk through the normal range of potassium was discerned, the likelihood that it is indeed the hypokalemia that is etiologically related to stroke risk is further strengthened. Use or non-use of diuretics did not affect the relationship between hypokalemia and stroke. The mecha-nism by which hypokalemia might aggravate stroke risk is uncertain.
Smith NL, et al. Am J Hypertens. 2003;16:806-813.
Skin Cancer Prevention and Detection Practices Among Siblings of Patients with Melanoma
More than one-half million Americans have invasive malignant melanoma (MEL), and the incidence of this disorder has risen an alarming 15-fold since World War II. Family members (first degree) of persons with MEL have as much as a 2-8-fold increased risk of developing MEL.
Recommendations by such agencies as the United States Preventive Services Task Force and the National Institute of Health include the suggestion that family members of patients with MEL should be provided skin cancer screening, risk education, and reduction of ultraviolet radiation exposure. When surveillance for MEL is carried out amongs family members, the stage at which MEL is discovered is earlier than that of the index case. Whether such recommendations are adequately used has not been studied.
Geller and associates contacted 585 siblings of 278 persons diagnosed with MEL within the previous 2 months. Although most of the siblings (62%) had examined their skin in the past year, only slightly more than half used sunscreen with at least SPF 15, and only 27% had received a skin cancer examination by a dermatologist. The message to family members of MEL victims about positive steps to maintain their own cutaneous health requires greater advocacy.
Geller AC, et al. J Am Acad Dermatol. 2003;49:631-638.
Dr. Kuritzky, Clinical Assistant Professor, University of Florida, Gainesville, is Associate Editor of Internal Medicine Alert.