Adequacy of twice daily dosing with potassium chloride and spironolactone in thiazide treated hypertensive patients.

1. The effects of 4-6 weeks treatment with placebo, potassium chloride 32 mmol 12 hourly, and spironolactone 25 mg 12 hourly upon the plasma potassium concentration-time profile were examined in hypertensive patients taking bendrofluazide 5 mg daily. 2. When compared with placebo, potassium chloride increased peak plasma potassium concentration (P less than 0.05), 12 h AUC for plasma potassium (P less than 0.1), and 12 h urine potassium excretion (P = 0.002). Spironolactone increased peak plasma potassium concentration (P less than 0.05), and 12 h AUC for plasma potassium (P less than 0.05), compared with placebo values. 3. Potassium chloride and spironolactone did not differ significantly in any respect other than 12 h urine potassium excretion. The 12 h AUC for plasma potassium was 35% larger with spironolactone than potassium chloride (not significant). 4. With both active drugs peak plasma potassium was observed 2-3 h after dosing, and efficacy tended to wane towards 12 h. However, variability of plasma potassium within the dose interval was not increased markedly, and 12 hourly dosing is probably satisfactory for both potassium chloride and spironolactone at the doses studied.

Adverse drug reactions. An overview of special considerations in the management of the elderly patient.

The incidence of adverse drug reactions increases with aging, and the elderly are more likely to suffer serious or fatal reactions. Thus, morbidity and mortality are considerable in old patients, with 15% of those in hospital suffering a reaction, and many admitted as a consequence of one. The greater propensity of older patients for adverse drug reactions largely reflects the prescription of drugs to them, although over-the-counter purchases must also play a part. The elderly take more drugs per se (which is a reflection of multiple pathology), and more drugs with a narrow therapeutic index associated with a high risk of dangerous adverse reactions and drug interactions. They also have a reduced ability to withstand any reactions due to concomitant disease, and an altered pharmacokinetic and -dynamic response which tends to increase drug effects. The recommendation must be to use fewer drugs in older patients, perhaps trying alternative medicine first in nonacute conditions. Starting doses can often be reduced in the elderly, and clinical and therapeutic monitoring of effect is mandatory. The use of diuretics, antihypertensives, anti-Parkinsonian drugs and anticoagulants emphasise these points, and is discussed in detail together with digoxin, analgesics and nonsteroidal anti-inflammatory drugs. Clear guidelines are given for the use of each of these classes of drug.

Systemic Weber-Christian disease with reversible bilateral ureteric obstruction.

It has been proposed that idiopathic retroperitoneal fibrosis may be a consequence of 'healed' retroperitoneal lesions of systemic Weber-Christian disease. However ureteric obstruction which is the hallmark of idiopathic retroperitoneal fibrosis, has not been described in systemic Weber-Christian disease. We report a patient with systemic Weber-Christian disease who, during a relapse, developed bilateral ureteric obstruction which resolved when the Weber-Christian disease remitted. The radiological appearances were consistent with a diagnosis of idiopathic retroperitoneal fibrosis, but the clinical course was slightly atypical in that the ureteric obstruction resolved completely and rapidly. Ureteric obstruction can complicate systemic Weber-Christian disease and this observation gives support to the hypothesis that idiopathic retroperitoneal fibrosis is related to systemic Weber-Christian disease.

Timolol metabolism and debrisoquine oxidation polymorphism: a population study.

1. The metabolism of orally administered timolol (T) to its ring cleavage ethanolamine (TE) and glycine (TG) products was studied in 108 unrelated hypertensive patients. 2. Statistically significant correlations between the 0-8 h urinary debrisoquine/4-hydroxy-debrisoquine ratio and the T/TE (rs = 0.74, P less than 0.001), T/TG (rs = 0.42, P less than 0.001) and T/TE + TG (rs = 0.49, P less than 0.001) ratios were found. 3. The log10 T/TE, T/TG and T/TE + TG ratios from poor metabolisers of debrisoquine (PMs) were grouped at the upper end of a unimodal distribution. 4. These results indicate that timolol metabolism is partly under monogenic control of the debrisoquine-type. 5. The mean +/- s.d. plasma timolol concentration in PMs (82 +/- 43 ng ml-1) was double that in extensive metabolisers (45 +/- 19 ng ml-1) (P = 0.011). The clinical significance of this observation remains to be established.

Is "improvement" real with percutaneous transluminal angioplasty in the management of renovascular hypertension?

58 hypertensive patients with suspected renovascular disease underwent renal arteriography, and 29 (52%) were found to have renovascular disease. Percutaneous transluminal angioplasty was technically successful in 14 (50%) of the 29. The effect on blood pressure was assessed over 20 months. Technically successful transluminal angioplasty led to cure of hypertension in 4 patients (29%) and "improvement" in 5 (36%). However, "improvement" occurred spontaneously in 8 (32%) of the 25 patients found on arteriography not to have renovascular disease and who received no intervention. This suggests that reported improvement after transluminal angioplasty may be spurious and that the true benefit of the procedure can be assessed only from the cure rate. About 50% of patients with fibromuscular renovascular disease are cured of their hypertension but only about 8% of patients with atherosclerotic renovascular disease benefit from the procedure.

Arteriovenous shunting in quadriplegia.

Arterio-venous shunting has been demonstrated in the limbs of ten subjects with traumatic quadriplegia, as shown by increased venous oxygen concentration and a Doppler sonogram pattern indicative of continuous forward flow. This phenomenon is similar to that seen in the diabetic neuropathic foot, suggesting that autonomic dysfunction is a major factor in the development of foot ulceration in the quadriplegic and in the diabetic.

Spontaneous spinal epidural haematoma with spontaneous resolution.

Spontaneous spinal epidural haematoma is of unknown aetiology, but it has been associated with hypertension. Treatment is surgical decompression but three cases of spontaneous recovery have been reported. We report the fourth such recovery in a 68 year old hypertensive woman.