BNF for Children 2011-2012

BNFC 2011–2012 2.6.2 Calcium-channel blockers 105Contra-indications hypersensitivity to nitrates; hypotensiveconditions and hypovolaemia; hypertrophiccardiomyopathy; aortic stenosis; cardiac tamponade;constrictive pericarditis; mitral stenosis; toxic pulmonaryoedema; head trauma; cerebral haemorrhage;cerebrovascular disease; marked anaemiaHepatic impairment caution in severe impairmentRenal impairment manufacturers advise use withcaution in severe impairmentPregnancy not known to be harmfulBreast-feeding no information available—manufacturersadvise use only if potential benefit outweighsriskSide-effects postural hypotension, tachycardia (butparadoxical bradycardia also reported); throbbingheadache, dizziness; less commonly nausea, vomiting,heartburn, flushing, syncope, temporary hypoxaemia,rash, application-site reactions with transdermalpatches; very rarely angle-closure glaucomaInjection Specific side-effects following injection (particularlyif given too rapidly) include severe hypotension, diaphoresis,apprehension, restlessness, muscle twitching, retrosternaldiscomfort, palpitation, abdominal pain; prolongedadministration has been associated with methaemoglobinaemiaLicensed use not licensed for use in childrenIndication and doseHypertension during and after cardiac surgery,heart failure after cardiac surgery, coronaryvasoconstriction in myocardial ischaemia,vasoconstriction in shock. By continuous intravenous infusionNeonate 0.2–0.5 micrograms/kg/minute, doseadjusted according to response; usual dose 1–3 micrograms/kg/minute; max. 10 micrograms/kg/minuteChild 1 month–18 years initially 0.2–0.5 micrograms/kg/minute,dose adjusted according toresponse, usual dose 1–3 micrograms/kg/minute;max. 10 micrograms/kg/minute (do not exceed200 micrograms/minute)Administration for continuous intravenous infusion,dilute to max. concentration of 400 micrograms/mL(but concentration of 1 mg/mL has been used via acentral venous catheter) with Glucose 5% or SodiumChloride 0.9%.Glass or polyethylene apparatus is preferable; loss ofpotency will occur if PVC is used.Neonatal intensive care, dilute 3 mg/kg body-weightto a final volume of 50 mL with infusion fluid; anintravenous infusion rate of 1 mL/hour provides adose of 1 microgram/kg/minuteGlyceryl Trinitrate (Non-proprietary) AInjection, glyceryl trinitrate 1 mg/mL. To be dilutedbefore use or given undiluted with syringe pump. Netprice 50-mL vial = £15.90Injection, glyceryl trinitrate 5 mg/mL. To be dilutedbefore use. Net price 5-mL amp = £6.49; 10-mL amp =£12.98Excipients may include ethanol, propylene glycolNitrocine c (UCB Pharma) AInjection, glyceryl trinitrate 1 mg/mL. To be dilutedbefore use or given undiluted with syringe pump. Netprice 10-mL amp = £5.88; 50-mL bottle = £13.77Excipients include propylene glycolNitronal c (Merck Serono) AInjection, glyceryl trinitrate 1 mg/mL. To be dilutedbefore use or given undiluted with syringe pump. Netprice 5-mL vial = £1.80; 50-mL vial = £14.762.6.2 Calcium-channel blockersCalcium-channel blockers (less correctly called ‘calcium-antagonists’)interfere with the inward displacementof calcium ions through the slow channels ofactive cell membranes. They influence the myocardialcells, the cells within the specialised conducting systemof the heart, and the cells of vascular smooth muscle.Thus, myocardial contractility may be reduced, theformation and propagation of electrical impulses withinthe heart may be depressed, and coronary or systemicvascular tone may be diminished.Calcium-channel blockers differ in their predilection forthe various possible sites of action and, therefore, theirtherapeutic effects are disparate, with much greatervariation than those of beta-blockers. There are importantdifferences between verapamil, diltiazem, and thedihydropyridine calcium-channel blockers (amlodipine,nicardipine, nifedipine, and nimodipine). Verapamil anddiltiazem should usually be avoided in heart failurebecause they may further depress cardiac function andcause clinically significant deterioration.Verapamil is used for the treatment of hypertension(section 2.5) and arrhythmias (section 2.3.2). However,it is no longer first-line treatment for arrhythmias inchildren because it has been associated with fatal collapseespecially in infants under 1 year; adenosine isnow recommended for first-line use.Verapamil is a highly negatively inotropic calcium channel-blockerand it reduces cardiac output, slows theheart rate, and may impair atrioventricular conduction.It may precipitate heart failure, exacerbate conductiondisorders, and cause hypotension at high doses andshould not be used with beta-blockers (see p. 109).Constipation is the most common side-effect.Nifedipine relaxes vascular smooth muscle and dilatescoronary and peripheral arteries. It has more influenceon vessels and less on the myocardium than does verapamil,and unlike verapamil has no anti-arrhythmic activity.It rarely precipitates heart failure because any negativeinotropic effect is offset by a reduction in leftventricular work. Short-acting formulations of nifedipineare not recommended for long-term management ofhypertension; their use may be associated with largevariations in blood pressure and reflex tachycardia.However, they may be used if a modified-release preparationdelivering the appropriate dose is not availableor if a child is unable to swallow (a liquid preparationmay be prepared using capsules). Nifedipine may alsobe used for the management of angina due to coronaryartery disease in Kawasaki disease or progeria and in themanagement of Raynaud’s syndrome.Nicardipine has similar effects to those of nifedipineand may produce less reduction of myocardial contractility;it is used to treat hypertensive crisis.Amlodipine also resembles nifedipine and nicardipinein its effects and does not reduce myocardial contractilityor produce clinical deterioration in heart failure. Ithas a longer duration of action and can be given oncedaily. Nifedipine and amlodipine are used for the treat-2 Cardiovascular system