1 The pharmacokinetics of enalaprilat were studied after administration of single and multiple doses of enalapril maleate to people with normal and impaired renal function. 2 Renal impairment was associated with higher serum concentrations of enalaprilat, longer times to peak concentrations, slower decline of serum concentrations and with reduced urinary elimination. Urinary elimination of enalaprilat was closely related to renal function.3 In patients with severe renal impairment (GFR values below 30 ml min7l 1.73 m-2) significantly smaller doses of enalapril maleate will be required than in patients with normal or less severely impaired renal function.

SUMMARY Baroreflex function was assessed in elderly hypertensive patients and compared with that observed in young hypertensives and young normotensives. Mean arterial pressure was reduced by 20% using intravenous nitroprusside infusion in 10 elderly hypertensive patients (older than 65 years and diastolic pressures over 95 mm Hg), in 10 young hypertensives (under 60 years and diastolic pressures over 95 mm Hg), and in seven young normotensive subjects (under 60 years and diastolic pressures under 95 mm Hg). Elderly subjects demonstrated greater sensitivity (p < 0.005) and greater variability of response (p < 0.025) to nitroprusside than either young group. There was no significant difference between the slight heart rate increases observed in the supine position in the three groups. However, in the erect position, heart rate increases were significantly less in the elderly hypertensive group than in the young hypertensive group (p < 0.01) or the young normotensive group (p < 0.005). Furthermore, the slope of the regression line relating change in blood pressure with change in R-R interval was less for the elderly patients than for the young hypertensives (p < 0.05) or the young normotensives (p < 0.025). We conclude that the heart rate component of the baroreflex is impaired in elderly hypertensives, and anticipate that the clinical response to antihypertensive drugs will be altered. (Hypertension 5: 763-766, 1983) KEY WORDS * nitroprusside * heart rate • aging A GING is associated with alteration in many physiological systems that can respond to drugs. 1 Previous workers have shown altered response in the cardiovascular system to various pharmacological agents.2 " 3 Baroreflex activity, which is important in cardiovascular homeostasis, has been shown to decline with increasing arterial pressure 67 and with increasing age up to 66 years. 8 However, no information is available in older hypertensive patients. Since impaired baroreflex function in such patients would have important therapeutic implications, we assessed some aspects of the baroreflex by studying blood pressure and heart rate response to nitroprusside in a group of such patients, and comparing the results with those observed in young hypertensives and young normotensives. Methods and MaterialsThree groups of patients were studied -elderly hypertensives, young hypertensives, and young normotensives. The elderly hypertensives were all older than 65 years, with ages ranging from 66 to 80 years. Diastolic pressures were greater than 95 mm Hg in each case. The supine mean arterial pressure (diastolic pressure + Vi pulse pressure) ranged from 115 to 154 mm Hg, and the erect mean arterial pressure ranged from 113 to 160 mm Hg. The mean baseline supine heart rate was 74.9 ± 2.9 beats min~' and the mean erect heart rate was 77.3 ± 2.9 beats min." 1 . The young hypertensives were under 60 years of age -ranging from 32 to 56 years. Their diastolic pressures were greater than 95 mm Hg, with supine mean arterial pressures ranging from 114 to 135 mm Hg and ...

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2 Gordon-Taylor G, Walls EW. Sir Charles Bell: his life and times. London: E and S Livingstone, 1958. 3 Spillane JD. The doctrine of the nerves. Chapters in the history of neurology. Oxford: Oxford University Press, 1981 :220. 4 Bell C. Letters of Sir Charles Bell selected from his correspondence with his brother, George3Joseph Bell. London: Murray, 1870. s Anonymous. Lancet gallery of medical portraits: Sir Charles Bell. Lancet 1833;ii :756-61. 6 Bell C. Engravings of the arteries illustrating the second volume of the anatomy of the human body and serving as an introduction to the surgery of the arteries. 3rd ed. London: Longmans, 1810. 7Bell C. A system of dissections. 1st ed. Edinburgh: Mundell and Son, 1798. 8 Bell C. A series of engravings explaining the course of the nerves, plate II. London: Longman, 1803. 9 Anonymous. Hunterian Oration of the Royal College of Surgeons, 1843. Lancet 1842-3;i:765-70. 1 Corner ER. Unpublished watercolor sketches of Sir Charles Bell, with observations on his artistic qualities. Johns Hopkins Hosp Bull 1914;25: 185-9. 15 Bell C. Essays on the anatomy of the expression in painting. 1st ed. London: Murray, 1806. (Later entitled Essays on the anatomy and philosophy of the expression, 1824; and The anatomy and philosophy of expression as connected with the fine arts, 1893.) 12 Bell C. Essays on the anatomy and philosophy of expression. 2nd ed. London:

1. Although systolic blood pressure elevation is responsible for increased incidence of cardiovascular accidents in old people, the preventive benefit of lowering systolic hypertension in elderly has not been confirmed. 2. A double blind study comparing the effects of a placebo and of an active regimen (hydrochlorothiazide-triamterene with or without methyldopa) in people over 60 years with isolated systolic hypertension has been undertaken by the European Working Party on High blood pressure in the Elderly (EWPHE). 3. The actively treated group shows a lowered sitting blood pressure (-15/6 mm Hg), a mild increase of serum creatine, serum uric acid and blood glucose and a mild decrease of serum potassium after two years of treatment when compared to the spontaneous changes observed in the placebo treated group. 4. The study is continuing to evaluate if the blood pressure reduction prevents or reduces the incidence of cardiovascular accidents, although some biochemical changes were provoked by the treatment.

Inhaled steroids, delivered by metered dose aerosol and dry powder inhalers, have proved effective in reducing the need for oral steroids in patients with oral steroid-dependant asthma. This randomized, double-blind study, compared the efficacy and tolerability of nebulized fluticasone propionate (FP Nebules), 2 mg b.d. (FP 4 mg) and 0.5 mg b.d. (FP 1 mg) with placebo, on the reduction of oral steroid requirement in 301 adult patients with oral steroid-dependent asthma. Primary efficacy was assessed by the reduction in daily oral steroid dose. Secondary efficacy parameters included daily diary card peak expiratory flow (PEF), day and night-time symptoms and clinic lung function measurements. Safety was assessed by adverse event monitoring and serum cortisol levels. After 12 weeks of treatment the adjusted mean +/- SEM reduction in oral prednisolone was significantly greater in the FP 4 mg group (4.44 +/- 0.98 mg day-1) compared with FP 1 mg (2.16 +/- 1.00 mg day-1, P = 0.039) and placebo (1.20 +/- 1.02 mg day-1, P = 0.004). A higher percentage of patients discontinued the use of oral steroids with FP 4 mg (37%) compared with FP 1 mg (26%, P = 0.038) and placebo (18%, P < 0.001). Following treatment, the adjusted mean morning PEF showed a trend in favour of FP 4 mg (280 +/- 41 min-1) compared with placebo (270 +/- 51 min-1, P = 0.053) and the evening PEF was significantly higher with FP 4 mg (305 +/- 41 min-1) compared with FP 1 mg (292 +/- 41 min-1, P = 0.010). FP 4 mg resulted in a significantly higher percentage of days when the patients were free from daytime (P = 0.036) and night-time (P = 0.021) wheeze, compared with placebo. Significantly fewer patients withdrew from the FP 4 mg group compared with the other two groups (vs. FP 1 mg, P = 0.003; vs. placebo, P = 0.032). All three treatments were well tolerated and the incidence of adverse events was similar between the groups. FP Nebules at a daily dose of between 1 and 4 mg are a safe and effective means of reducing the oral steroid requirement of patients with chronic oral steroid dependent asthma.