Drugs for Angina and Myocardial Infarction I. Ischemic heart Disease (IHD) a.

Complication that occurs secondary to coronary artery disease (atherosclerosis) b. 2 primary forms of IHD i. Angina Pectoris- chronic condition characterized by episodic chest discomfort that occurs during transient coronary ischemia 1. Typical angina- oxygen demand increases due to exercise or stress but the oxygen supply is limited due to atherosclerosis a. Stable angina- attacks ha e similar characteristics and occur under same circumstances b. !nstable angina- attacks increase in fre"uency and se erity (often preclude #$) %. &ariant angina (aka 'rinzmetal angina) a. Due to acute coronary vasospasm and often occurs during rest or sleep. #ay be considered a form of unstable angina ii. Myocardial infarction acute and complete occlusion of coronary artery caused by thrombosis Angina a. !haracteristics of angina i. 'ain secondary to ischemia because of decrease nutrients( increase metabolic )astes( *% depri ation ii. Can be sudden( se ere( substernal and radiating to the left shoulder- confused )ith heart burn iii. Can be induced by exercise( emotions( eating or cold temperature b. "ationale of treatment of angina i. +estore balance bet)een myocardial *% supply and demand 1. $ncrease *% supply- increase perfusion( dilate essels( and keep entricles in diastole longer. Coronary arteries fill during diastole )hen semi-lunar al es close a. ,etermined by coronary blood flo)( regional blood flo) and *% extraction b. &asodilators (nitrates and CC-s) used to increase total coronary flo) c. -eta blockers can impro e distribution of coronary flo) by reducing intra entricular pressure %. ,ecrease myocardial *% demand- amount of energy re"uired to support the )ork of the heart a. ,etermined by heart rate( cardiac contractility and myocardial )all tension b. -eta blockers and CC-s decrease .+( decrease -'( and decrease contractility

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c. #asodilators reduce )all tension ia their effects on entricular olume and pressurei. #enous decrease cardiac filling( preload( enous pressure ii. Arterial- decrease arterial pressure and afterload /. Typical angina s. ariant angina a. Typical- asodilators and beta blockers )ork to decrease *% demand ia mechanism outlined abo e i. *% demand )ith regular supply b. &ariant- asodilators increase *% supply by relaxing coronary smooth muscle and restoring normal coronary flo). -eta blockers 0*T effecti e because they can1t counteract asospasm i. Chest pain at rest because of ischemia Pharmacological $reatment of Angina 0o *% demand but supply is decreasing and leads to ischemia a. %rganic &itrites and nitrates i. #*2- release of nitric oxide- diffusion into ascular smooth muscle cells- formation of cyclic 3#'- enous dilation- enous pooling- decrease preload( decrease entricular diastolic olume and decrease entricular pressure- decrease myocardial )all tension and decrease myocardial %2 demand ii. 2t higher doses4 arterial dilation- decrease '&+ and left entricular e5ection pressure (afterload) 1. +elease of nitric oxide re"uires sulfhydryl groups but e entually the sulfhydryl become depleted and patient becomes tolerant iii. $ndications4 angina( #$( C.6 i . Contraindications4 concurrent use 'ith #iagra( )evitra( etc7 angle closure glaucoma( head trauma or cerebral hemorrhage( se ere anemia and se ere hypotension (S-' 89:) . 2,+s4 .;2( dizziness( )eakness( postural hypotension( rash( tolerance( and anxiety. <ith o erdose- reflex tachycardia and arrhythmias i. ,,$4 ',= > inhibitors (&iagra and others)- se ere hypotension and death ha e occurred7 $sosorbide is C?'/2@ substrate ii. #onitoring parameters- blood pressure( heart rate iii. 6ormulations 1. 2myl 0itrate ($0.) (A) a. +apid onset and brief ,*2 b. !sed for acute angina attacks and cyanide poisonings %. 0itroglycerin ($&( '*( SB( buccal( topical( transdermal) (C)

a. SB form (0itro"uik( 0itrostat) and buccal form (0itrogard)- deteriorates in sunlight( bottle only good for /: days i. Soluble in lipids and li"uid. 3ood bioa ailability b. *intment form (0itro--id %C or 0itrol %C)absorbed through skin o er se eral hours i. *nly used in hospital ii. :.>-1 inch /x a day to chest c. 'atch form (0itro,ur( 0itrek)- a ailable in se eral doses d. '* form (0itro-time =+)- must be administered D, or -$, only to minimize tolerance i. 0itrate free inter al to a oid tolerance e. $& form- contains propylene glycol( need special tubing /. $sosorbide ('*( SB) (C)- maintenance therapy for outpatient a. ,initrate form ($sordil)- a ailable '* or SB( gi e T$, b. #ononitrate form ($smo is -$,7 $mdur is D,) a ailable '* only. Bonger acting metabolite of dinitrite form. EF hours apart b. !alcium !hannel *loc+ers, 'regnancy category C i. #*2- bind to calcium ion channels in smooth muscle and cardiac tissue- smooth muscle relaxation and suppression of cardiac acti ity- increase *% supply and;or decrease myocardial *% demand ii. $ndications- .T0( angina (especially useful for ariant angina)7 arrhythmias (dilitiazem and erapimil) iii. Contraindications- ary amongst agents i . 2,+s- nausea( constipation( fatigue( headache( flushing( dizziness( hypotension( bradycardia( reflex tachycardia( edema. $mmediate release forms of nifedipine and other short acting CC-s ha e increased risk of #$( C.6( and death due to coronary heart disease . ,,$- see .T0 handout i. #onitoring parameters- -'- .+( =G3 ()ith certain agents) 1. 0on-dihydropyredenes ii. Specific drugs used 1. 2mlodipine (0or asc) %. 0ifedipine ('rocardia) /. 0icardipine (Cardene) @. &erapimil (Calan( $soptin) >. ,ilitiazem (Cardizem( Tiazac) H. -epridil (&ascor)- indicated for angina )ith asospasm c. *eta *loc+ers, I*B*BJ drugs (pregnancy category C;,

i. #*24 decrease .+( decrease -'( and decrease contractilitymyocardial *% demand ii. $ndications- .T0( C.6( typical angina( #$( certain arrhythmias( migraine (certain agents). 0*T used for ariant ;'rinzmetal angina or acute angina attacks 1. 'rophylactically for exercise induced pain. 're ent reflex tachycardia from other agents like CC- nondihydropyredenes iii. Contraindications- sinus bradycardia( heart block( cardiogenic shock. 0on-selecti e agents are contraindicated in C*',( asthma( ,# i . 2,+s- fatigue( insomnia( dizziness( bradycardia( C.6( edema( hypotension( mental depression( hypercholesterolemia( sexual dysfunction . ,,$s- erapimil (greatest potential for decrease contractility and decrease C*( other CC-s safer to combine)( see .T0 handout for other ,,$s i. #onitoring parameters- -'( .+ ii. Specific drugs used4 -eta 1 specific and non-$S2 preferred 1. propanolol ($nderal) %. 0adolol (Corgard) /. #etoprolol (Bopressor)- -eta 1 specific @. 2tenolol (Tenormin- -eta 1 specific d. Antiplatelet Drugs i. 2spirin1. #*2- inhibits synthesis of prostacyclin and thrombo-ane A2- pre ent platelet aggregation- decrease thrombosis %. $ndications- se eral. 6or angina- primarily used to pre ent #$ in patients )ith unstable angina ii. *ther agents 1. Clopidogrel ('la ix)- in place of aspirin %. <arfarin (Coumadin) e. %ther management of angina i. #odification of cardiac risk factors 1. Stop smoking %. Control lipid le els /. Control ,#( .T0 @. <eight reduction >. =xercise H. 'roper diet ii. 3oals of treatment 1. +elie e acute symptoms %. 're ent ischemic attacks /. +educe risk of #$ and other cardio ascular problems iii. Type and se erity of angina

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1. *ccasional episode- SB 0T3 to reli e symptoms %. 'redictable episodes upon exertion- SB 0T3 or SB $sosorbide prophylactic ally /. 6re"uent episodes re"uiring regular SB 0T3- long tern prophylactic therapy )ith nitrate( -- or CC@. 2ngioplasties tents or bypass may be necessary. 3lycoprotein %-/2 inhibitor i . Consideration of concomitant disease states 1. 2sthma- CC- and nitrate most preferred( beta blocker least preferred %. heart failure- 0itrate most preferred( beta blocker( and non,.' CC- least preferred /. .T0- beta blocker and CC- most preferred( CC- least preferred @. '!,- beta blocker and nitrate most preferred( CC- least preferred . *ther factors to consider 1. -eta blockers only anti-angina drugs sho)n to reduce incidence of entricular arrhythmias that cause sudden death in patients )ith #$. Cardioprotecti e effect so many consider them drug of choice for angina unless other )ise contraindicated %. 'atients )ith unstable angina )ith high risk of #$ should recei e aspirin /. CC-s less preferred than beta blockers for unstable angina because ,.' cause reflex tachycardia and erapimil and dilitiazem reduce contractility @. 6or ariant angina- beta blockers 0*T effecti e( use CCexcept for bepridil and nicardipine Pharmacological Management of Acute MI a. 3oals of therapy i. Bimit infarct size ii. +eperfuse obstructed coronary arteries iii. +educe morbidity and mortality i . 're ent post-#$ complications b. 2spirin i. 2ntiplatelet agent ii. ,ose4 1H%-/%>mg ST2T( then K1-/%>mg D, iii. !se for all #$ patients unless contraindicated. Start 2S2'( continue indefinitely i . +educes morbidity and mortality associated )ith #$ c. $& 0itroclycerin i. +ecommended for the first %@-@K hours in patients )ith acute #$ ii. 0T3 alle iates ischemic myocardial pain d. 2nalgesics

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i. $ntra enous morphine- %-@ mg e ery > minutes( )ith some patients re"uiring as much as %>-/:mg before pain relief is ade"uate. +elie e anxiety ii. 'ain control also includes-oxygen to reperfuse -eta -lockers i. +ecommended to start $& dose 2S2' and continue post #$ )ith '* doses unless contraindicated ii. +eduction in morbidity and mortality- immediate beta blocker therapy appears to reduce (1) the magnitude of infarction and incidence of associated complications in sub5ects not recei ing concomitant thrombolytic therapy and (%) the rate of reinfarction in patients recei ing thrombolytic therapy 2C= inhibitors i. +ecommended for all post #$ patients )ith substantial left entricular dysfunction and;or clinical C.6 Calcium Channel -lockers i. Contro ersial in #$- does not affect morbidity and mortality ii. #ay be gi en to patients intolerant to beta blockers iii. ,ilitiazem- may be useful in patients )ith non-D )a e #$ )ithout B& dysfunction 2nticoagulants i. !nfractionated heparin ii. Bo) molecular )eight heparins- =noxaparin and ,alteparin are appro ed for non-D )a e #$ Thrombolytics;6ibrinolytics i. 6ibrinolytics are the preferred therapeutic approach to achie ing rapid thrombolysis. 2ll of the thrombolytic (fibrinolytic) agents currently a ailable and under in estigation are plasminogen acti ators ii. Thrombolytic therapy pro ides a sur i al benefit for patients )ith acute #$( based on large( )ell-controlled clinical trials iii. See tables on page K