Ischemic Heart Disease & Antianginal Drugs PDF

Part 3 3: Isc chemic heart h dis sease and a antia anginal drugs █ Bas sic inform mation ▌Ische emic hea...

Part 3 3: Isc chemic heart h dis sease and a antia anginal drugs █ Bas sic inform mation ▌Ische emic hea art diseas se include es: Chrronic sta able ang gina (Cl assic; exe ertional anngina): - It is due to atheromatous naarrow- ing of the coronary artery. - Pain is induced by effortt and disappearrs with rest. Acu ute corona ary syndro omes (ACS S): - Unstable e angina: It is du ue to rupture ofo atheromatous p plaque and form mation of thrombuss. The patient exxperiences s accelerattion in the frequency or severity s of chest pain, or ne ew-onset angina a pain n. - Myocardiial infarcttion: An inntraluminall thrombuss complettely occlud des the epicardial coronary artery at the site of plaque rup pture leadiing to irrev versible coagulativve necrosis s. Prin nzmetal’s angina (V Variant ang gina; angin na of rest; α-mediatted angina): The e coronary artery und dergoes se evere spas sm due to overactivitty of α1 rec ceptors. The e patient de evelops pa ain at rest. ▌Chro onic stablle angina a Definittion: retrosternal pa ain due too ischemia a of the myocardium m m as a reesult of imbalan nce betweeen heart work w emand) and (O2 de d coronary y blood flow w (O2 supp ply). 165  Clinica al picture: Centra ain is the cardinal al chest pa c syymptom:  Site e and radiiation: retrrosternal, radiating to t the left should der and thee left arm.  Chaaracter: an ny character (usuallly sense of cheest tightnesss).  Precipitated by b 3E: exertion, emo otion, eating, andd relieved by b rest andd nitrates.  Durration: usuually < 10-15 min. If longer tha an 15 mmin → susppect ACS. Diagno osis:  ECG G: - RResting 12 2-lead ECG G: this is o often normmal a and doess not exc clude isch hemic hea art d disease. - DDuring atttack: the ere is S ST segme ent d depression n and T-wa ave inversiion. - IIn myocardial infarcttion: ST ellevation an nd d deep Q-waave.  ercise ECG: reco Exe ording E ECG und der con ntrolled physical effo ort to reco ord ischem mic cha anges.  Nuc clear isoto s imaging.. ope stress  Corronary ang giography y. █ Man nagemen nt of stab ble angin na Non n-drug the erapy = life e style mo odification n:  T The same as hyperte ension (see e before). Pha armacolog gical thera apy:  Immediate treatme ent of acutte chest pain: p – Glyceryyl trinitrate ublingual or spray. e (GTN): su – Aspirin n 300 mg lo oading dosse as soonn as possib ble. It reducees the risk of progresssion to MI. – Refer the patient to hospitaal if an ACS S is suspec cted.  Long-term m therapy: 166  – Beta-blockers: the first-line agents for chronic stable (exertional) angina. – CCBs: the second-line agents for chronic stable angina – Long and intermediate acting nitrates. – pFOX inhibitors: trimetazidine – Newer antianginal drugs: ranolazine and nicorandil – Lipid lowering drugs: statins (see chapter 6). – Antiplatelet drugs: e.g. aspirin, clopidogrel (see pharmacology of blood). Surgical treatment (myocardial revascularization). Organic nitrates and nitrites Classification Dose Onset Duration Short-acting nitrates: Amyl nitrite crushable ampoules 0.3 ml inhalation 1-2 min 5-10 min Glyceryl trinitrate tablets or spray 0.5 mg SL 1-5 min 10-20 min Isosorbide dinitrate 5 mg SL 3-5 min 60 min Glyceryl trinitrate (Tridil®) 5 μg/min i.v.i. Intermediate-acting nitrates: Isosorbide dinitrate 10 mg oral 15 min 3-6 hrs 40 mg oral SR 30 min 6-10 hrs Long-acting nitrates: Isosorbide mononitrate 20 mg oral 30 min 6-8 hrs 60 mg oral SR 30 min 6-10 hrs Transdermal patches 30 min 12-18 hrs Pharmacokinetics Absorption: nitrates are rapidly absorbed from all sites of administration. Metabolism: in the liver: – If given oral → extensive first-pass metabolism (oral bioavailability