Amiloride

Hypertension frequently co-exists with diabetes, a reported prevalence of 50–70%. It is an important risk factor for the development microvascular and macrovascular complications good blood pressure control essential in management patients diabetes. Guidelines advocate use angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor antagonists initial hypertension. Diuretics typically form third-line therapy if targets are not achieved loop thiazide like diuretics, potassium sparing diuretics such as amiloride can be considered. Amiloride was first synthesised 1960s also used adjunct heart failure ascites. In contrast to other spironolactone eplerenone, acts independently aldosterone inhibiting sodium reabsorption by epithelial channels (ENaC) preventing excretion distal convoluted tubule collecting ducts. Its mechanism action shown Figure 1. administered orally reaches its peak diuretic effect at 6–10 hours. 40% protein bound has plasma half-life 6–9 does undergo metabolism liver predominantly excreted unchanged urine faeces. Drug prolonged renal impairment contraindicated eGFR <10ml/min/1.73 m2. The main adverse hyperkalaemia, serum >5.5mmol/L. hyperkalaemia increases presence impairment, co- administration ACE blockers. available several combination preparations – co-amilozide (amiloride hydrochlorothiazide), co-amilofruse furosemide), bumetanide. Spironolactone, Amiloride, Losartan, Thiazide (SALT) study1 double-blind, placebo-controlled crossover trial which investigated lowering spironolactone, amiloride, losartan bendroflumethiazide. study primarily looking see there were any differences between three included non-diuretic control. Fifty-one hypertension, low renin, elevated aldosterone:renin ratio previous response treated each drug high doses well placebo. Blood reduction 40mg (-11.5mmHg [95% CI -15.1 -7.6)]/ -3.1mmHg -5.9 -0.4]) similar that seen bendroflumethiazide 5mg (-10.5mmHg -13.3 -7.6)/ -4.0mmHg -6.3 -1.8]), 100mg (-11.6mmHg -15.4 -7.8]/ -1.3mmHg -3.8 1.2]). Prevention Treatment Algorithm-based Therapy (PATHWAY) studies trials investigating optimal treatment algorithms PATHWAY-2 335 resistant hypertension placebo 25mg spironolactone.2 An open- label runout sub-study undertaken following establish whether effective this patient population. A total 146 taking inhibitor blocker, calcium channel blocker received 10mg daily. After six weeks, reductions addition daily (systolic 20.4mmHg 18.3 22.5]) compared (18.3mmHg 16.2 20.5]). Mean increased from 4.02 4.50mmol/L (p < 0.0001).3 thiazide-like have been associated impaired glucose tolerance new-onset Thiazide-associated dysglycaemia proposed result reduced insulin sensitivity, peripheral uptake gluconeogenesis. Potassium depletion postulated underlie these effects but it so clearly understood.4 PATHWAY-3 randomised, double-blind 441 hypertensive without diabetes diuretic, substitution would prevent improve control.5 Patients randomised daily, hydrochlorothiazide plus 12.5mg Doses doubled after 12 weeks. Two-hour concentrations baseline group decreased only amiloride-hydrochlorothiazide groups. difference -0.55mmol/L (95% -0.96 -0.14; p = 0.0093) -0.42mmol/L -0.84 -0.004; 0.048) group. change home systolic -12.9mmHg -14.7 -11.2); -12.2mmHg -13.9 -10.5); -15.6mmHg -17.3 -13.8). Serum 0.63mmol/L 0.56 0.70; 0.0001) group, 0.27mmol/L -0.34 -0.2; This suggested concomitant both could negate and, importantly, neutral impact on tolerance. There some evidence ENaC activation proteinuric states, resulting enhanced retention increase pressure. hypothesised inhibitor, may therapeutic role small attempted assess efficacy type 2 proteinuria pre-hypertension (>120mmHg).6 Nine two stopped early due incidence acute kidney injury. Of nine who participated, developed injuries (6.8mmol/L 7.8mmol/L respectively). Systolic four weeks 0.5 ± 4.6mmHg, 10.2 4.4mmHg. Although experienced greater decline (10.2 7.5mmHg), changes statistically significant 0.15). Additionally, urinary creatinine ratios 15% 14% hydrochlorothiazide. antihypertensive examined open-label, non- study.7 Eighty triple (including blocker) amiloride. 24-hour 5.4mmHg 0.5mmol/L 0.001) Furthermore, albumin significantly 0.0001). Optimising reduces cardiovascular forms aspect people improves including those considered unable tolerate spironolactone. Like however, limited impairment. support reducing diabetic disease. However, superseded newer classes drugs SGLT2 outcomes disease better tolerated.