ࡱ> RTQ@ 0bjbjFF "N,,(2222222F4<F2FFFFFFFF$R:2FF22FF 2F2F522F: >J M02U,FF222220Fh@TFFFFFFFDrugs for Angina and Myocardial Infarction Ischemic heart Disease (IHD) Complication that occurs secondary to coronary artery disease (atherosclerosis) 2 primary forms of IHD Angina Pectoris- chronic condition characterized by episodic chest discomfort that occurs during transient coronary ischemia Typical angina- oxygen demand increases due to exercise or stress but the oxygen supply is limited due to atherosclerosis Stable angina- attacks have similar characteristics and occur under same circumstances Unstable angina- attacks increase in frequency and severity (often preclude MI) Variant angina (aka Prinzmetal angina) Due to acute coronary vasospasm and often occurs during rest or sleep. May be considered a form of unstable angina Myocardial infarction- acute and complete occlusion of coronary artery caused by thrombosis Angina Characteristics of angina Pain secondary to ischemia because of decrease nutrients, increase metabolic wastes, O2 deprivation Can be sudden, severe, substernal and radiating to the left shoulder- confused with heart burn Can be induced by exercise, emotions, eating or cold temperature Rationale of treatment of angina Restore balance between myocardial O2 supply and demand Increase O2 supply- increase perfusion, dilate vessels, and keep ventricles in diastole longer. Coronary arteries fill during diastole when semi-lunar valves close Determined by coronary blood flow, regional blood flow and O2 extraction Vasodilators (nitrates and CCBs) used to increase total coronary flow Beta blockers can improve distribution of coronary flow by reducing intraventricular pressure Decrease myocardial O2 demand- amount of energy required to support the work of the heart Determined by heart rate, cardiac contractility and myocardial wall tension Beta blockers and CCBs decrease HR, decrease BP, and decrease contractility Vasodilators reduce wall tension via their effects on ventricular volume and pressure- Venous- decrease cardiac filling, preload, venous pressure Arterial- decrease arterial pressure and afterload Typical angina vs. variant angina Typical- vasodilators and beta blockers work to decrease O2 demand via mechanism outlined above O2 demand with regular supply Variant- vasodilators increase O2 supply by relaxing coronary smooth muscle and restoring normal coronary flow. Beta blockers NOT effective because they cant counteract vasospasm Chest pain at rest because of ischemia Pharmacological Treatment of Angina- No O2 demand but supply is decreasing and leads to ischemia Organic Nitrites and nitrates MOA- release of nitric oxide- diffusion into vascular smooth muscle cells- formation of cyclic GMP- venous dilation- venous pooling- decrease preload, decrease ventricular diastolic volume and decrease ventricular pressure- decrease myocardial wall tension and decrease myocardial O2 demand At higher doses: arterial dilation- decrease PVR and left ventricular ejection pressure (afterload) Release of nitric oxide requires sulfhydryl groups but eventually the sulfhydryl become depleted and patient becomes tolerant Indications: angina, MI, CHF Contraindications: concurrent use with Viagra, Levitra, etc; angle closure glaucoma, head trauma or cerebral hemorrhage, severe anemia and severe hypotension (SBP <90) ADRs: H/A, dizziness, weakness, postural hypotension, rash, tolerance, and anxiety. With overdose- reflex tachycardia and arrhythmias DDI: PDE 5 inhibitors (Viagra and others)- severe hypotension and death have occurred; Isosorbide is CYP3A4 substrate Monitoring parameters- blood pressure, heart rate Formulations Amyl Nitrate (INH) (X) Rapid onset and brief DOA Used for acute angina attacks and cyanide poisonings Nitroglycerin (IV, PO, SL, buccal, topical, transdermal) (C) SL form (Nitroquik, Nitrostat) and buccal form (Nitrogard)- deteriorates in sunlight, bottle only good for 30 days Soluble in lipids and liquid. Good bioavailability Ointment form (Nitro-Bid 2% or Nitrol 2%)- absorbed through skin over several hours Only used in hospital 0.5-1 inch 3x a day to chest Patch form (NitroDur, Nitrek)- available in several doses PO form (Nitro-time ER)- must be administered QD or BID only to minimize tolerance Nitrate free interval to avoid tolerance IV form- contains propylene glycol, need special tubing Isosorbide (PO, SL) (C)- maintenance therapy for outpatient Dinitrate form (Isordil)- available PO or SL, give TID Mononitrate form (Ismo is BID; Imdur is QD) - available PO only. Longer acting metabolite of dinitrite form. >7 hours apart Calcium Channel Blockers: Pregnancy category C MOA- bind to calcium ion channels in smooth muscle and cardiac tissue- smooth muscle relaxation and suppression of cardiac activity- increase O2 supply and/or decrease myocardial O2 demand Indications- HTN, angina (especially useful for variant angina); arrhythmias (dilitiazem and verapimil) Contraindications- vary amongst agents ADRs- nausea, constipation, fatigue, headache, flushing, dizziness, hypotension, bradycardia, reflex tachycardia, edema. Immediate release forms of nifedipine and other short acting CCBs have increased risk of MI, CHF, and death due to coronary heart disease DDI- see HTN handout Monitoring parameters- BP- HR, EKG (with certain agents) Non-dihydropyredenes Specific drugs used Amlodipine (Norvasc) Nifedipine (Procardia) Nicardipine (Cardene) Verapimil (Calan, Isoptin) Dilitiazem (Cardizem, Tiazac) Bepridil (Vascor)- indicated for angina with vasospasm Beta Blockers: OLOL drugs (pregnancy category C/D MOA: decrease HR, decrease BP, and decrease contractility- myocardial O2 demand Indications- HTN, CHF, typical angina, MI, certain arrhythmias, migraine (certain agents). NOT used for variant /Prinzmetal angina or acute angina attacks Prophylactically for exercise induced pain. Prevent reflex tachycardia from other agents like CCB non-dihydropyredenes Contraindications- sinus bradycardia, heart block, cardiogenic shock. Non-selective agents are contraindicated in COPD, asthma, DM ADRs- fatigue, insomnia, dizziness, bradycardia, CHF, edema, hypotension, mental depression, hypercholesterolemia, sexual dysfunction DDIs- verapimil (greatest potential for decrease contractility and decrease CO, other CCBs safer to combine), see HTN handout for other DDIs Monitoring parameters- BP, HR Specific drugs used: Beta 1 specific and non-ISA preferred propanolol (Inderal) Nadolol (Corgard) Metoprolol (Lopressor)- Beta 1 specific Atenolol (Tenormin- Beta 1 specific Antiplatelet Drugs Aspirin- MOA- inhibits synthesis of prostacyclin and thromboxane A2- prevent platelet aggregation- decrease thrombosis Indications- several. For angina- primarily used to prevent MI in patients with unstable angina Other agents Clopidogrel (Plavix)- in place of aspirin Warfarin (Coumadin) Other management of angina Modification of cardiac risk factors Stop smoking Control lipid levels Control DM, HTN Weight reduction Exercise Proper diet Goals of treatment Relieve acute symptoms Prevent ischemic attacks Reduce risk of MI and other cardiovascular problems Type and severity of angina Occasional episode- SL NTG to relive symptoms Predictable episodes upon exertion- SL NTG or SL Isosorbide prophylactic ally Frequent episodes requiring regular SL NTG- long tern prophylactic therapy with nitrate, BB or CCB Angioplasties tents or bypass may be necessary. Glycoprotein 2B3A inhibitor Consideration of concomitant disease states Asthma- CCB and nitrate most preferred, beta blocker least preferred heart failure- Nitrate most preferred, beta blocker, and non-DHP CCB least preferred HTN- beta blocker and CCB most preferred, CCB least preferred PUD- beta blocker and nitrate most preferred, CCB least preferred Other factors to consider Beta blockers only anti-angina drugs shown to reduce incidence of ventricular arrhythmias that cause sudden death in patients with MI. Cardioprotective effect so many consider them drug of choice for angina unless other wise contraindicated Patients with unstable angina with high risk of MI should receive aspirin CCBs less preferred than beta blockers for unstable angina because DHP cause reflex tachycardia and verapimil and dilitiazem reduce contractility For variant angina- beta blockers NOT effective, use CCB except for bepridil and nicardipine Pharmacological Management of Acute MI Goals of therapy Limit infarct size Reperfuse obstructed coronary arteries Reduce morbidity and mortality Prevent post-MI complications Aspirin Antiplatelet agent Dose: 162-325mg STAT, then 81-325mg QD Use for all MI patients unless contraindicated. Start ASAP, continue indefinitely Reduces morbidity and mortality associated with MI IV Nitroclycerin Recommended for the first 24-48 hours in patients with acute MI NTG alleviates ischemic myocardial pain Analgesics Intravenous morphine- 2-4 mg every 5 minutes, with some patients requiring as much as 25-30mg before pain relief is adequate. Relieve anxiety Pain control also includes-oxygen to reperfuse Beta Blockers Recommended to start IV dose ASAP and continue post MI with PO doses unless contraindicated Reduction in morbidity and mortality- immediate beta blocker therapy appears to reduce (1) the magnitude of infarction and incidence of associated complications in subjects not receiving concomitant thrombolytic therapy and (2) the rate of reinfarction in patients receiving thrombolytic therapy ACE inhibitors Recommended for all post MI patients with substantial left ventricular dysfunction and/or clinical CHF Calcium Channel Blockers Controversial in MI- does not affect morbidity and mortality May be given to patients intolerant to beta blockers Dilitiazem- may be useful in patients with non-Q wave MI without LV dysfunction Anticoagulants Unfractionated heparin Low molecular weight heparins- Enoxaparin and Dalteparin are approved for non-Q wave MI Thrombolytics/Fibrinolytics Fibrinolytics are the preferred therapeutic approach to achieving rapid thrombolysis. 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L^`LhH. ^`hH. ^`hH. PLP^P`LhH.tm*        9XN`Cy@'#'#%#%#(@@UnknownGz Times New Roman5Symbol3& z Arial"h̒f̒f "H "H!r4''3QH)?`*Drugs for Angina and Myocardial InfarctionNicholas M. RiniNicholas M. Rini Oh+'0   <H d p |+Drugs for Angina and Myocardial InfarctionorugNicholas M. Riniandichich Normal.dot Nicholas M. Riniand2chMicrosoft Word 10.0@Ik@\I@\I "՜.+,0 hp|   H' +Drugs for Angina and Myocardial Infarction Title  !"#$%&')*+,-./123456789:;<=>?@BCDEFGHJKLMNOPSRoot Entry FRJUData (1Table0 WordDocument"NSummaryInformation(ADocumentSummaryInformation8ICompObjj  FMicrosoft Word Document MSWordDocWord.Document.89q