Clinical Briefs

By Louis Kuritzky, MD

Erythromycin and the Risk of Sudden Death

Agents which alter cardiac repolarization have been associated with torsades de pointes. Although erythromycin (ERY) is a generally safe and efficacious medication, it does have the potential to prolong cardiac repolarization, especially when drug levels are elevated. Because ERY is metabolized through the CYP-450 3A system, substances which block CYP3A (such as antifungal agents, diltiazem, and verapamil) can have a potent effect upon raising ERY levels, resulting in at least a doubling of ERY plasma levels when coadministered.

To evaluate whether coadministration of ERY with CYP3A blockers is associated with any meaningful risk of cardiac adversities, data from a Tennessee Medicaid cohort (n = 1,249,943 person-years of follow-up) was examined to identify persons who had received ERY, CYP3A inhibitors, or both. As a control, persons who had not received antibiotics, as well as a comparator control of persons who had received amoxicillin (which has no measurable effect upon cardiac repolarization), was included.

Persons who had used ERY had twice as high a death rate from cardiac causes than persons who had not used antibiotics. Amoxicillin was not associated with an increase in cardiac deaths. Although ERY in the absence of a CPY450 3A inhibitor was not associated with an increase in sudden death, concomitant administration was associated with a greater than 5-fold increase.

Coadministration of ERY with CYP3A inhibitors is associated with a meaningful increase in risk of adverse cardiac events, and should be avoided. YP3A inhibitors which fall into this risk category include (but are not limited to) ketoconazole, itraconazole, fluconazole, diltiazem, verapamil, troleandomycin, nefazodone, and protease inhibitors.

Ray W, et al. N Engl J Med. 2004;351: 1089-1096.

Acute Hyperglycemia, Mood, and Cognitive Performance in People with Type 2 Diabetes

Hyperglycemia in diabetes is associated with increased incidence of neuropathy, nephropathy, and retinopathy. Data about the effects of hyperglycemia upon cognitive function have been conflicting, however. To test whether hyperglycemia impacts cognitive function in type 2 diabetics, a study was performed by maintaining glucose levels using the glucose clamp method over brief, monitored time intervals.

Study subjects underwent cognitive testing after a sustained period of blood glucose levels maintained at either 81 mg/dL or 297 mg/dL. Testing modalities included complex visual scanning, motor performance, speed of coding, reaction time, auditory verbal learning (intermediate and delayed), visual memory, attention, digit span, and letter/number sequencing. The University of Wales Institute of Science and Technology mood checklist was also administered.

Although not all metrics registered significant impairment during hyperglycemia, complex visual scanning, coding performance, and reaction time were significantly decremented. Digit Span and Letter/number sequencing were also impaired. For mood, decreased happiness and alertness were found, as well as an increased sense of agitation during periods of sustained hyperglycemia.

Because this study evaluated persons during a very brief window of observation (80 minute intervals), it is impossible to ascertain the long-term effect of hyperglycemia upon cognitive and mood function. Nonetheless, these data support energetically seeking euglycemia in an effort to maintain best cognitive function and mood.

Sommerfield AJ, et al. Diabetes Care. 2004;27(10):2335-2340.

Psychosocial Risk Factors and Risk of Acute MI

Studies in North America, Europe, and Japan have provided some support for the concept that emotional stress is a risk factor for coronary heart disease (CHD), but there is scanty information about other populations. In addition to limited information, defining what actually constitutes stress, and how to measure it, has been elusive.

This study of 12,461 cases of acute MI in 52 countries included an assessment of psychological stress by means of questions about stress at home and at work. Stress was defined as "feeling irritable, filled with anxiety, or having sleeping difficulties as a result of conditions at work or at home." Patients were also asked to quantify their stress by indicating whether it was present never, some periods, several periods, or permanently.

All measurements of stress were more prevalent in persons who had suffered an acute MI. Confounders to the association included the fact that those who reported more stress also had a higher BMI and a greater incidence of smoking. According to this analysis, stress accounts for as much as 33% of the population attributable risk for MI, and hence may have been somewhat neglected as a an important modifiable risk factor.

Rosengren A, et al. Lancet. 2004;364: 953-962.

Dr. Kuritzky, Clinical Assistant Professor, University of Florida, Gainesville, is Associate Editor of Internal Medicine Alert.