management of ischaemic heart disease stroke 缺血性心脏病药物治疗中风课件

Pharmacological management of Ischaemic heart disease and acute myocardial infarction October 2006 Atherosclerosis The complications of atherosclerosis constitute the greatest cause of morbidity and mortality in the Western World accounting for 40% of all deaths Atherosclerosis nProgressive luminal narrowing - angina pectoris - intermittent claudication nPlaque rupture and thrombosis - acute coronary syndromes - transient ischaemic attack nAneurysm formation Aims of treatment nRelieve symptoms nSlow disease progression nReduce risk of acute event nImprove survival Management overview nPharmacological treatment nManaging risk factors nInterventional procedures Angina pectoris nMyocardial oxygen demand exceeds supply chest pain nStable angina - transient myocardial ischaemia - predictable, reproducible - relieved by rest or GTN Principles of treatment nIncrease oxygen supply or reduce oxygen demands of myocardium Reduce heart rate Reduce preload Reduce afterload Improve coronary blood flow Symptomatic treatment nNitrates nBeta blockers nCalcium channel blockers nPotassium channel activators nSelective pacemaker If current inhibitorIvabradine (Procolalan) Describing any drug nMOA and pharmacological properties nIndications nCautions/Contraindications nSide effects nImportant interactions nDose/overdose Nitrates - Mode of action nMetabolised to release Nitric oxide (NO) n cGMP nDephosphorylation of myosin light chains nIncreased intracellular calcium nMuscle relaxation Nitrates - Mode of action nVenodilation - preload nCoronary artery vasodilation - supply nModerate arteriolar dilation - afterload Pharmacological properties nGlyceryl trinitrate (GTN) short acting, first pass metabolism sublingual/intravenous/patch administration nIsosorbide dinitrate intermediate acting sublingual/intravenous/oral administration nIsosorbide mononitrate long acting oral administration Alfred Nobel Pharmacological properties nTolerance (tachyphylaxis) - reduced therapeutic effects n“Monday morning sickness” n? due to depletion of free tissue SH nLong-acting preparations /infusions/transdermal patches n“Nitrate free period” Indications nRelief of acute angina attack nProphylaxis of stable angina (prior to exercise GTN or long- acting) nLeft ventricular failure Cautions/Contraindications nHypotension nAortic stenosis nHOCM nConstrictive pericarditis Side effects nHeadache nFlushing nDizziness nPostural hypotension nTachycardia nOverdose rarely precipitates methaemoglobinaemia Important interaction nPhosphodiesterase inhibitors eg sildenafil nInhibits cGMP breakdown severe hypotension nitrates contraindicated if taken within the previous 24 hours nInfusion reduces anticoagulant effect of heparin Beta blockers Mode of action nCompetitive inhibitors of catecholamine at beta-adrenoceptor sites nInhibit sympathetic stimulation of heart and smooth muscle n HR contractility 1 nVasoconstriction bleeding disorders nAortic dissection nHistory of cerebrovascular disease nActive peptic ulceration nSevere menorrhagia nSevere hypertension nActive cavitating lung disease nAcute pancreatitis nSevere liver disease nOesophageal varices nPrevious reaction to streptokinase (Streptokinase) Relative contraindications nVenepuncture (non-compressible site) nRecent invasive procedure nExternal chest compressions nPregnancy nAbdominal aortic aneurysm nDiabetic retinopathy nAnticoagulant therapy Side effects nNausea and vomiting nBleeding nReperfusion arrhythmias nHypotension nBack pain nAllergic reactions (esp streptokinase) Unstable angina/NSTEMI n“MONA” morphine; O2; nitrate; aspirin nHeparin eg enoxaparin 1mg/kg 12 hourly nBeta-blocker atenolol 5mg over 5 mins repeated after 10-15 mins nClopidogrel nGlycoprotein IIb/IIIa inhibitors (abciximab) if undergoing P