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Pharmacological management of Ischaemic heart disease and acute myocardial infarction

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.

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Pharmacological management of Ischaemic heart disease and acute myocardial infarction

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  1. Pharmacological management of Ischaemic heart disease and acute myocardial infarction October 2006

  2. Atherosclerosis The complications of atherosclerosis constitute the greatest cause of morbidity and mortality in the Western World accounting for 40% of all deaths

  3. Atherosclerosis • Progressive luminal narrowing - angina pectoris - intermittent claudication • Plaque rupture and thrombosis - acute coronary syndromes - transient ischaemic attack • Aneurysm formation

  4. Aims of treatment • Relieve symptoms • Slow disease progression • Reduce risk of acute event • Improve survival

  5. Management overview • Pharmacological treatment • Managing risk factors • Interventional procedures

  6. Angina pectoris • Myocardial oxygen demand exceeds supply  chest pain • Stable angina - transient myocardial ischaemia - predictable, reproducible - relieved by rest or GTN

  7. Principles of treatment • Increase oxygen supply or reduce oxygen demands of myocardium Reduce heart rate Reduce preload Reduce afterload Improve coronary blood flow

  8. Symptomatic treatment • Nitrates • Beta blockers • Calcium channel blockers • Potassium channel activators • Selective pacemaker If current inhibitorIvabradine (Procolalan)

  9. Describing any drug • MOA and pharmacological properties • Indications • Cautions/Contraindications • Side effects • Important interactions • Dose/overdose

  10. Nitrates - Mode of action • Metabolised to release Nitric oxide (NO) •  cGMP • Dephosphorylation of myosin light chains • Increased intracellular calcium • Muscle relaxation

  11. Nitrates - Mode of action • Venodilation -  preload • Coronary artery vasodilation -  supply • Moderate arteriolar dilation -  afterload

  12. Pharmacological properties • Glyceryl trinitrate (GTN) short acting, first pass metabolism sublingual/intravenous/patch administration • Isosorbide dinitrate intermediate acting sublingual/intravenous/oral administration • Isosorbide mononitrate long acting oral administration

  13. Alfred Nobel

  14. Pharmacological properties • Tolerance (tachyphylaxis) - reduced therapeutic effects • “Monday morning sickness” • ? due to depletion of free tissue –SH • Long-acting preparations /infusions/transdermal patches • “Nitrate free period”

  15. Indications • Relief of acute angina attack • Prophylaxis of stable angina (prior to exercise GTN or long-acting) • Left ventricular failure

  16. Cautions/Contraindications • Hypotension • Aortic stenosis • HOCM • Constrictive pericarditis

  17. Side effects • Headache • Flushing • Dizziness • Postural hypotension • Tachycardia • Overdose rarely precipitates methaemoglobinaemia

  18. Important interaction • Phosphodiesterase inhibitors eg sildenafil • Inhibits cGMP breakdown severe hypotension – nitrates contraindicated if taken within the previous 24 hours • Infusion reduces anticoagulant effect of heparin

  19. Beta blockers

  20. Mode of action • Competitive inhibitors of catecholamine at beta-adrenoceptor sites • Inhibit sympathetic stimulation of heart and smooth muscle •  HR  contractility β1 • Vasoconstriction & bronchoconstriction β2

  21. Pharmacological properties • Cardioselective – eg atenolol metoprolol • Non selective – eg propranolol • Intrinsic sympathomimetic (partial agonist) activity – eg celiprolol pindolol • Alpha-blocking activity eg carvedilol • Lipid soluble (eg propranolol) versus water soluble (eg atenolol) • Up-regulation of receptors – withdrawal syndrome

  22. Indications • Symptomatic angina • Hypertension • Acute coronary syndromes • Post myocardial infarction • Stable heart failure • Arrhythmias • Thyrotoxicosis/Benign essential tremor

  23. Cautions/Contraindications • C/I in asthma • Uncontrolled heart failure • Bradycardia • Heart block • Phaeochromocytoma without prior alpha blockade • Caution coronary spasm/COPD/PVD • Avoid abrupt withdrawal

  24. Important Interaction • Verapamil and beta blockers  precipitate heart block +- asystole • Must NOT give IV verapamil to beta blocked patients • Extreme caution combined orally

  25. Side effects • Beta-1 effects – Bradycardia, heart block, heart failure • Beta-2 effects – bronchospasm, worsening PVD, Raynaud’s phenomenon • Fatigue, depression, nightmares, impotence • May mask hypoglycaemia and worsen glycaemic control in IDDM

  26. Dose • Rational choice - long-acting cardioselective beta blocker od or bd • Anti-anginal effects are dose related • Titrate to resting heart rate 50-60 bpm

  27. Calcium antagonists

  28. Mode of action • Prevent opening of voltage-gated calcium channels • Bind to -1 subunit of cardiac and smooth muscle L-type calcium channels • Vasodilator effect on resistance vessels  afterload • Coronary artery dilation • Negative chronotropic • Negative inotropic effects

  29. Pharmacological properties • 3 classes • Phenylalkylamines eg verapamil - relatively cardioselective - -ve chronotropic and inotropic • Dihydropyridines eg nifedipine amlodipine - relatively smooth muscle selective - potent vasodilator • Benzothiazepines eg diltiazem - intermediate

  30. Indications • Symptomatic control of angina • Coronary spasm • Hypertension • Arrhythmias • Subarachnoid haemorrhage (nimodipine)

  31. Side effects • Peripheral vasodilation - flushing, headache, ankle oedema • Cardiac effects - AV block, heart failure • Constipation • Short-acting dihydropyridines a/w  mortality and MI

  32. Potassium channel activators

  33. Potassium channel activators - nicorandil • Activates K ATP channel • NO donor effects • Arterial and venodilator • S/E Flushing, dizziness, headache • Usually 3rd or 4th line agent

  34. Selective pacemaker If current inhibitor • Ivabradine (Procolalan) • reduces spontaneous beating rate of the sinus node by slowing the diastolic depolarization slope of the action potential • selective and prolonged reduction in heart rate, both at rest and during exercise • Indicated for angina where cannot give a beta blocker • Ongoing trials (Beautiful trial)

  35. Additional therapy in stable angina • Low-dose aspirin • Lipid lowering therapy • ACE inhibitors • Treat BP and diabetes • Smoking cessation • Weight reduction • Intervention

  36. Antiplatelet agents • Aspirin – inhibits cyclo-oxygenase and thromboxane A2 synthesis • Theinopyridines – clopidogrel – block binding of ADP to platelet receptor • Glycoprotein IIb/IIIa inhibitors (abciximab) – inhibit cross-bridging of platelets by fibrinogen

  37. Acute coronary syndrome • Angina at rest >20mins • New onset angina severely affecting exercise tolerance • Increasing frequency or duration or occurring with lesser exertion

  38. Acute coronary syndromes • Plaque rupture and coronary thrombosis • Unstable angina • Non-ST elevation MI (subendocardial infarction) • Acute transmural myocardial infarction

  39. Goals of treatment • Relief of ischaemic pain • Assess haemodynamic state • Anti-platelet therapy to prevent further thrombosis • Initiate reperfusion therapy with percutaneous angioplasty or thrombolysis if appropriate • Secondary prevention

  40. Initial Management • Oxygen • Aspirin 150-300mg chewed/dispersible • Nitrates GTN 0.4mg sublingual +- IV • Intravenous morphine 2.5-10mg+ antiemetic cyclizine 50mg • Decide on definitive treatment • Beta-blocker atenolol 5mg over 5 mins repeated after 10-15 mins • Clopidogrel 300mg if undergoing PCI • Glycoprotein IIb/IIIa inhibitors (abciximab) if undergoing PCI • ACE inhibitor within 24 hours • Tight glycaemic control • Optimise potassium and magnesium

  41. Definitive treatment-ST elevation Myocardial infarction Primary coronary angioplasty 90% recanalisation Door to balloon time <90mins ? up to 3hrs Ideal where cardiogenic shock and when thrombolytics contraindicated clopidogrel 300mg loading dose then 75mg od Glycoprotein IIb/IIIa inhibitors (abciximab)

  42. Definitive treatment-ST elevation Myocardial infarction Primary PCI not available Thrombolysis 50-60% recanalisation Door to needle time <30mins Effective up to 12 hours

  43. Fibrinolytic agents

  44. Mode of action • Activate plasminogen to form plasmin which degrades fibrin breaking up thrombi • Streptokinase, alteplase, reteplase, tenecteplase • Streptokinase – antibodies within 4 days • Alteplase, reteplase followed by heparin for 48 hours

  45. Indications • Acute ST elevation myocardial infarction • Acute pulmonary embolism • Acute ischaemic stroke within 3 hours

  46. Contraindications • Recent haemorrhage trauma or surgery • Recent dental extraction • Coagulation defects;bleeding disorders • Aortic dissection • History of cerebrovascular disease • Active peptic ulceration • Severe menorrhagia • Severe hypertension • Active cavitating lung disease • Acute pancreatitis • Severe liver disease • Oesophageal varices • Previous reaction to streptokinase (Streptokinase)

  47. Relative contraindications • Venepuncture (non-compressible site) • Recent invasive procedure • External chest compressions • Pregnancy • Abdominal aortic aneurysm • Diabetic retinopathy • Anticoagulant therapy

  48. Side effects • Nausea and vomiting • Bleeding • Reperfusion arrhythmias • Hypotension • Back pain • Allergic reactions (esp streptokinase)

  49. Unstable angina/NSTEMI • “MONA” – morphine; O2; nitrate; aspirin • Heparin eg enoxaparin 1mg/kg 12 hourly • Beta-blocker atenolol 5mg over 5 mins repeated after 10-15 mins • Clopidogrel • Glycoprotein IIb/IIIa inhibitors (abciximab) if undergoing PCI • ACE inhibitor if indicated • Tight glycaemic control • Optimise potassium and magnesium

  50. Reading/Website list • British national formulary BNF • www.uptodate.com • American heart association guidelines

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