BNF for Children 2011-2012

BNFC 2011–2012 2.5.5 Drugs affecting the renin-angiotensin system 101Hypertension ACE inhibitors may be considered forhypertension when thiazides and beta-blockers are contra-indicated,not tolerated, or fail to control bloodpressure; they may be considered for hypertension inchildren with type 1 diabetes with nephropathy (see alsosection 6.1.5). ACE inhibitors can reduce blood pressurevery rapidly in some patients particularly in thosereceiving diuretic therapy (see Cautions, below); thefirst dose should preferably be given at bedtime.Diabetic nephropathy For comment on the role ofACE inhibitors in the management of diabetic nephropathy,see section 6.1.5.Renal effects Renal function and electrolytes shouldbe checked before starting ACE inhibitors (or increasingthe dose) and monitored during treatment (more frequentlyif features mentioned below are present).Hyperkalaemia and other side-effects of ACE inhibitorsare more common in children with impaired renal functionand the dose may need to be reduced (see RenalImpairment, below).Concomitant treatment with NSAIDs increases the riskof renal damage, and potassium-sparing diuretics (orpotassium-containing salt substitutes) increase the riskof hyperkalaemia.In children with severe bilateral renal artery stenosis (orsevere stenosis of the artery supplying a single functioningkidney), ACE inhibitors reduce or abolish glomerularfiltration and are likely to cause severe and progressiverenal failure. They are therefore contra-indicated inchildren known to have these forms of critical renovasculardisease.ACE inhibitor treatment is unlikely to have an adverseeffect on overall renal function in children with severeunilateral renal artery stenosis and a normal contralateralkidney, but glomerular filtration is likely to bereduced (or even abolished) in the affected kidney andthe long-term consequences are unknown.ACE inhibitors are therefore best avoided in those withknown or suspected renovascular disease, unless theblood pressure cannot be controlled by other drugs. Ifthey are used in these circumstances renal functionneeds to be monitored.ACE inhibitors should also be used with particularcaution in children who may have undiagnosed andclinically silent renovascular disease. ACE inhibitorsare useful for the management of hypertension andproteinuria in children with nephritis. They are thoughtto have a beneficial effect by reducing intra-glomerularhypertension and protecting the glomerular capillariesand membrane.Cautions ACE inhibitors need to be initiated with carein children receiving diuretics (important: see ConcomitantDiuretics, below); first doses can cause hypotensionespecially in children taking high doses of diuretics,on a low-sodium diet, on dialysis, dehydrated, orwith heart failure (see above). Discontinue if markedelevation of hepatic enzymes or jaundice (risk of hepaticnecrosis). Renal function should be monitored beforeand during treatment. For use in pre-existing renovasculardisease, see Renal Effects above. The risk ofagranulocytosis is possibly increased in collagen vasculardisease (blood counts recommended). ACE inhibitorsshould be used with care in children with severeor symptomatic aortic stenosis (risk of hypotension) andin hypertrophic cardiomyopathy. They should be usedwith care (or avoided) in those with a history of idiopathicor hereditary angioedema. Children with primaryaldosteronism and Afro-Caribbean children mayrespond less well to ACE inhibitors. Interactions:Appendix 1 (ACE inhibitors).Anaphylactoid reactions To prevent anaphylactoidreactions, ACE inhibitors should be avoided duringdialysis with high-flux polyacrylonitrile membranesand during low-density lipoprotein apheresis withdextran sulphate; they should also be withheld beforedesensitisation with wasp or bee venom.Concomitant diuretics ACE inhibitors can cause a veryrapid fall in blood pressure in volume-depleted children;treatment should therefore be initiated with very lowdoses. In some children the diuretic dose may need tobe reduced or the diuretic discontinued at least 24 hoursbeforehand (may not be possible in heart failure—risk ofpulmonary oedema). If high-dose diuretic therapy cannotbe stopped, close observation is recommended afteradministration of the first dose of ACE inhibitor, for atleast 2 hours or until the blood pressure has stabilised.Contra-indications ACE inhibitors are contra-indicatedin children with hypersensitivity to ACE inhibitors(including angioedema) and in bilateral renovasculardisease (see also above).Renal impairment See Renal Effects above; start withlow dose and adjust according to response.Pregnancy ACE inhibitors should be avoided inpregnancy unless essential—they may adversely affectfetal and neonatal blood pressure control and renalfunction; skull defects and oligohydramnios have alsobeen reported.Side-effects ACE inhibitors can cause profound hypotension(see Cautions), renal impairment (see RenalEffects above), and a persistent dry cough. They canalso cause angioedema (onset may be delayed; higherincidence reported in Afro-Caribbean patients), rash(which may be associated with pruritus and urticaria),pancreatitis, and upper respiratory-tract symptoms suchas sinusitis, rhinitis, and sore throat. Gastro-intestinaleffects reported with ACE inhibitors include nausea,vomiting, dyspepsia, diarrhoea, constipation, and abdominalpain. Altered liver function tests, cholestatic jaundice,hepatitis, fulminant hepatic necrosis, and hepaticfailure have been reported—discontinue if marked elevationof hepatic enzymes or jaundice. Hyperkalaemia,hypoglycaemia and blood disorders including thrombocytopenia,leucopenia, neutropenia, and haemolyticanaemia have also been reported. Other reportedside-effects include headache, dizziness, fatigue,malaise, taste disturbance, paraesthesia, bronchospasm,fever, serositis, vasculitis, myalgia, arthralgia, positiveantinuclear antibody, raised erythrocyte sedimentationrate, eosinophilia, leucocytosis, and photosensitivity.Neonates The neonatal response to treatment withACE inhibitors is very variable, and some neonatesdevelop profound hypotension with even small doses;a test-dose should be used initially and increased cautiously.Adverse effects such as apnoea, seizures, renalfailure, and severe unpredictable hypotension are verycommon in the first month of life and it is therefore2 Cardiovascular system