ANTIHYPERTENSIVE THERAPY MAY HELP YOUNG DIABETICS WITH NEPHROPATHY

The effects on glomerular filtration rate (GFR) and albuminuria of early aggressive therapy for elevated arterial BPwere assessed prospectively in 12 young insulin-dependent diabetics with diabetic nephropathy. The antihypertensiveagents used were metoprolol, hydralazine and frusemide (furosemide) or a thiazide. Patients were investigated for acontrol period of 23-41 months prior to antihypertensive therapy and for a 30-48 month treatment period.One patient was inadequately treated and another was not treated due to quite low BP which remained constant forthe 56-month observation period. During the control period arterial BP and urinary albumin excretion progressivelyincreased but during treatment significant and stable decreases occurred: in 10 of the II patients who were treated,arterial BP decreased from 144/97 to 128/84mm Hg and in 9 of these, urinary albumin excretion decreased from 977to 433 JLg/min. During treatment, the rate of decline in GFR in 9 of the 10 patients who were effectively treated, fellfrom 0.91 (prior to treatment) to 0.39 ml/min/month. There was a marked reduction in GFR soon after beginningantihypertensive therapy in 4 patients. It appears that arterial BP and diabetic nephropathy have a complexrelationship, with nephropathy increasing BP, and BP hastening the progress of nephropathy. The results of this studysuggest that ' ... early and effective antihypertensive treatment reduces albuminuria and the decline in kidney functionin young male and female insulin-dependent diabetic patients with diabetic nephropathy.'Parving. H-H. et al.: Lancet I: 1175 (28 May 1983)

hours after guanfacine treatment than after placebo. There was no significant change in BP variability with guan­facine compared with placebo.Clement. D.L. et al.: British Journal of Clinical Pharmacology 15 (Suppl. 4): 471S (1983)

Guaofacine does not appear to cause marked sedation ...Nine healthy normotensive males received oral azepexole 5mg or placebo, at least 7 days apart, in a single-blindstudy. BP, heart rate and sedation (using a visual analogue scale) were measured at intervals of up to 24 hours.Plasma noradrenaline (norepinephrine) was measured 2 and 6 hours after dosing. Six hypertensive inpatients re­ceived oral guanfacine 3mg (4 patients) or 4mg (2 patients). BP, heart rate, sedation and plasma noradrenaline weremeasured at intervals for 36 hours and after 7 more daily doses. Guanfacine was continued in titrated doses for 8­10 weeks after which placebo was substituted.Azepexole caused a reduction in BP between I and 6 hours after dosing, but it was not significantly reduced vsplacebo at 8 and 24 hours. There were no orthostatic effects. Plasma noradrenaline was reduced 2 hours afterazepexole vs placebo but there was no difference at 6 hours. Drowsiness increased significantly between I and 4hours post-administration.All guanfacine patients showed a fall in BP, significant between 4 and 30 hours after dosing vs pretreatment values.There were no orthostatic effects. After guanfacine treatment for 8-10 weeks, placebo substitution resulted in BPgradually returning to pretreatment values over a period of 3-4 days. Sedation increased (although not markedly)after initial doses of guanfacine and was not significant on subsequent days of treatment. Plasma noradrenaline wasdecreased with guanfacine therapy and increased progressively on its withdrawal. Four days after withdrawal stand­ing plasma noradrenaline was significantly elevated.Thus, , ... a-adrenoceptor stimulation in the brain appears to be responsible for both the sedative and antihyper­tensive effects of c10nidine and the non-imidazoline agents, guanfacine and azepexole. While the acute effects of thesetwo agents are similar, the duration of hypotensive action of guanfacine is longer'.Reid. J.L. et al.: British Journal of Clinical Pharmacology 15 (Suppl. 4) 463S (1983)

... and might be beneficial for patients with GH-secreting pituitary tumoursGuanfacine and methyldopa exert their effects, at least in part, via central monoaminergic pathways and thereforetheir prolonged use might be expected to alter plasma levels of anterior pituitary hormones.Of 8 patients given methyldopa 750 mg/day for 3-8 months, 5 had increased plasma prolactin (PRL) levels.Loss of libido and/or impotence was reported for 3 male patients who were then treated with bromocriptine 7.5mg/day in addition to methyldopa. The combination therapy normalised PRL levels and sexual performance, andreduced BP further.Guanfacine has previously been demonstrated to be a strong stimulator of growth hormone (GH) secretion, followingacute administration. The reactions of 6 patients with GH-secreting pituitary tumours to the acute administrationof oral guanfacine 2mg were investigated. However, the elevated basal plasma GH levels in 5 of the 6 patientsshowed a significant decrease in the interval 90-240 min postadministration, while BP was not changed.Thus' ... a clinical trial of chronic treatment of hypertensive acromegalic patients with guanfacine appears justifiedto investigate effects on GH secretion and on blood pressure.'Lambel1s. S.W.J.: British Journal of Clinical Pharmacology 15 (Suppl. 4) 525S (1983)

10 INPHAAMA 11 June 1983 0156-2703/83/0611-0010/0$01.00/0 "ADIS Press