ing blood glucose levels in diabetics and nondiabetics.... These properties, shared by ibuprofen, aspirin, and sodium salicylate, are not shared by indomethacin." Such a theory also fits well with several of the other known risk factors-for instance, diabetes. The fact that a full 44% of cataract patients have an abnormal glucose tolerance curve also suggests that high circulating glucose levels may be important in the development of cataracts. This means that the NSAIDs may accomplish their protective effects by a direct lowering of blood glucose, and thus prevention of glycosylation of lens proteins. The authors then raise a larger question: "If the aspirin-like analgesics can protect against cataract by a modest lowering of plasma glucose, what other damaging effects do they diminish?" Apparent protection of diabetic retinopathy is now the subject of clinical trials in the United States. The next step .in the research on the preventive effects of NSAIDs is to get some handle on the levels of doses that are sufficient to produce these dal anti-inflammatory drugs that the effects. To that end, van Heyningen effect reached real significance. With and Harding are starting another those who took steroids excluded, the case-control study at Oxford. ® relative risk for cataracts after NSAIDs was 0.43. The researchers then tackled the question of what mechanism lay behind the observed effect. One hypothesis that's been kicking around assumes that acetylation of proteins in the lens prevents the opacification of cataract. But this notion doesn't jibe with other facts. For one thing, there are no acetyl groups in many of the NSAIDs that exhibit a protective effect. Alternatively, it's easy to suspect that prostaglandins might somehow be involved. But again, the facts don't fit. Acetaminophen, which is only a weak inhibitor of prostaglandins, appears to be a potent protector, whereas indomethacin, a powerful inhibitor of prostaglandin synthesis, provides no protection at all . Instead, the authors believe that the cataract-preventing action of NSAIDs entails their effect on glucose metabolism. They point out, "Aspirin-like analgesics lower fast-
Aspirin. Other NSAIDs Protect Against Cataracts ince no one knows what actually causes cataracts, the search has necessarily shifted to an investigation of risk factors. The list, as compiled so far, is an odd one-including diarrhea, diabetes, glaucoma, renal failure, and high plasma levels of glucose and urea. But one finding keeps popping up in many studies: somehow, long-term use of aspirin seemed to have a pronounced protective effect on formation of cataracts.
To investigate this phenomenon more precisely, Ruth van Heyningen and John Hardin g of Oxford University (Lancet, May 17, 1986, p. 1112) compared 300 patients (aged 50-79 years) hospitalized for cataract response , with 609 case-matched control subjects. All subjects were interviewed about their medical history, including use of regular medication (any drugs taken for at least four months), and smoking and drinking habits. The usual pattern of risk factors turned up when the data were analyzed. Comparisons of patients and controls revealed diabetes, glaucoma, and consumption of steroid drugs, in addition to renal failure (though the numbers of cases in both groups were small). The preventive effect of aspirin had been observed before, but those studieshad met with severe criticism. van Heyningen and Harding found a slight protective effect with aspirinone that failed to reach statistical significance. It was only when the data on aspirin were pooled with data on acetaminophen and other nonsteroi-
Ame rican Pharmacy, Vol. NS26 , No.8, August 1986/601
Even in Hypertensives, Is Unpredictable -
follow them closely to find out whether those who were sensitive to salt in the original study go on to develop hypertension. He's also writ-
esponses to a loading dose of sodium show an amazingly broad pattern of distribution, new research has found, among both normotensive and hypertensive individuals. At a meeting of the American Heart Association Council on High Blood Pressure in Cleveland, Myron Weinberger reported on his findings using a standardized salt-loading technique. First, the baseline blood pressure of each patient is recorded; then, 2 I of normal saline is administered IV over four hours. At the end ofthe infusion period, blood pressure is recorded once again, and a plasma sample is taken. On the next day, each subject is given three 40-mg doses of furosemide and _a low-salt diet 00 mEq sodium). The next morning, blood pressure readings and plasma samples are taken once more. Response to salt loading is then calculated by comparing blood pressure immediately after salt infusion with pressure after salt and volume depletion. A change of pressure that was 10 mm Hg or more was said to indicate salt sensitivity, while an alteration of 5 mm Hg or then was designated as salt resistance. Weinberger did his test in 378 normotensives and 198 individuals with essential hypertension. Both groups showed responses that fell on a bellshaped curve. In general, though, hypertensives did seem to be more sensitive to salt than their normote nsive counterpa.rts----one-halfof the subjects met Weinberger's criterion for sensitivity to sodium. But there was another substantial group of hypertensives (one-third of the study population) who were sodium resistant . Among the normotensives, more than half were. resistant to sodium challenge. In fact, many of those with normal pressure actually showed decreases in blood pressure after the sodium load was administered . Conversely, one-quarter of the normot ens ives were found to be sensitive to sodium.
In general, t hough, hypertensives did seem to be more sensitive to.salt than their normotensive counterfJartsone-half the subjects met Weinberger's criterion sensitivity t o sodium. But t here was anot her substantial: group of hypertensives (one-third of the study population) who were sodium resist ant . Based on such heterogeneous results, Weinberger concludes, ''All patients with hypertension aren't alike. Physicians shouldn't reflexively treat them all in the same way." . Weinberger says that the next question is, "Can sodium sensitivity predict who's likely to develop hypertension or who's likely to respond to diuretic therapy?" Weinberger plans now to study sodium-sensitive individuals to see if he can uncover the physiologic basis of their reaction to salt. Then, there will be other investigations of his normotensive volunteers; he'll
ing up a study protocol to test whether an intervention that includes a low-salt diet will help in preventing the onset of hypertension in sodium-sensitive hypertensives. Although Weinberger says that his salt-loading test "is a simple, practical way to identify people who are sodium sensitive," there is an even simpler alternative---a onedose diuretic trial. This method may allow clinicians to dist inguish between patients likely to benefit from volume reduction therapy from those who will be best treate d by other kinds of hypertension me dications. ®
New Intranasal Hormone Treatment for Endometriosis n analog of gonadotropin-releasing hormone (GnRH), nafarelin, shows promise for the remission of a most troubling condition' endometriosis. In eight women with intractable endometriosis, nafarelin produced definite improvement in tests at the University of California, San Francisco. Given as a nasal 'spray, the drug stopped hormonal stimulation of the endometrium and caused existing implants to virtually disappear. By the third month of therapy, symptoms in all eight women had markedly decreased. Surgical
American Pharmacy, Vol. NS26, No.8, August 1986/602
examination afte r eight months revealed only small endomet rial implants. After the treatment ended, all patients began menstruat ing; several were able to have painles s sexual int ercourse for the first time in years. Hot flashes were the major side effect of nafarelin therapy, but researchers are confident that adjustments in dosage will be able to solve this problem. The long-term effects of treatment with this drug are still unknown , but researchers speculate that endometriosis will return in some of the patients in time. ®