Arthritis and hypertension are frequent comorbidities in the elderly hypertensive population. Nonsteroidal anti-inflammatory drugs are often used to relieve pain in arthritic patients but a side effect is sodium retention and consequent elevation of blood pressure (BP). The effect of dihydropyridine calcium blocking drugs is relatively independent of sodium intake, whereas the angiotensin-converting enzyme (ACE) inhibitors' effects can be blunted by a high-sodium diet. This study compared the effects of indomethacin with placebo in elderly patients with essential hypertension who had been controlled with amlodipine or enalapril. Indomethacin 50 mg twice daily or placebo was administered for 3 weeks in a double-blind crossover study to patients controlled with amlodipine or enalapril. The response was assessed by ambulatory BP measurement. Indomethacin raised BP and lowered pulse rates in patients taking enalapril but had little effect in patients receiving amlodipine. The difference caused by indomethacin between the two groups was 10.1/4.9 mm Hg increase in BP and a 5.6 beats/min fall in pulse in people taking enalapril. Addition of indomethacin to patients taking either drug caused a rise in weight and a fall in plasma renin. It is postulated that the effect is due to inhibition of prostaglandin synthesis, which causes sodium retention. In patients taking amlodipine, the fall in plasma renin ameliorates the effect of sodium retention on BP. In patients taking enalapril, plasma renin falls but this is not translated into an effect because of the blockage of converting enzyme. Thus, the full effect of sodium retention on BP is expressed. In patients treated with indomethacin, fewer patients may respond to ACE inhibitors. However, the major problem is the patient who intermittently takes indomethacin or other nonsteroidal anti-inflammatory drugs, which, if a person is treated by an ACE inhibitor causes BP to go out of control. In such patients amlodipine would appear to be a preferred choice to enalapril.

BackgroundAngiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blocking drugs (ARB) block the effect of angiotensin II by different mechanisms. It has been suggested that combined therapy may be more effective at reducing blood pressure (BP) than higher doses of either drug. MethodsTwenty-three elderly patients with systolic hypertension completed a double-blind crossover study comparing placebo, candesartan (C) 16 mg, C32 mg, lisinopril (L) 20 mg, L40 mg and C16 mg + L20 mg. Treatment periods were one month and ambulatory BP measurements were performed at the end of each period. The effects on albumin excretion in eight patients with microalbuminuria were determined. ResultsAll treatments lowered BP. The falls in systolic and diastolic BP with C16, C32, L20 and L40 were similar. Plasma renin rose to a similar extent. A plateau effect was reached with C16 and L20. Systolic BP on the combination of C16 + L20 was lower than on each monotherapy (C16, 3.8 mmHg [p=0.002]; C32, 6.4 [0.0003]; L20, 2.9 [0.05]; L40, 3.3 [0.003]). The additional fall in BP with the combination appeared to be due to recruitment of non-responders, rather than to an additive effect in most patients. All treatments reduced microalbuminuria to a similar extent. The combination was well tolerated and there was no deterioration in renal function.

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The literature indicates that the relative nephrotoxicities of the three drugs used in this investigation are gentamicin > tobramycin > or = netilmicin. Serum creatinine levels over time were used in an attempt to elucidate the situation. They varied widely in all three groups and in controls in theatre. No definite trend was shown. Measurements performed for the ICU period showed continued variation. Fluctuations were so great during the perioperative period that the levels were analysed in terms of 44 mumol/litre difference between admission and discharge, ignoring changes between these times. It is now clear that the operative procedure itself is associated with fluctuating serum creatinine levels. The use of these aminoglycosides does not measureably affect the situation adversely over the short period of treatment. The use of nomograms, based on creatinine levels, to set aminoglycoside doses during the perioperative period may therefore be misleading, because of the wide fluctuations shown.

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