Block 4 Pharmacology Final Exam

Block 4 Pharmacology Final Exam How venodilator treatment reduces preload/end-diastolic volume - by decreasing venous return How arterial dilator treatment reduces afterload/end-systolic volume - by decreasing arterial/aortic pressure Description of O2 supply of heart - ATP synth by aerobic metab w/ interm O2 supply (not continuous bl supp b/c BVs supp myocard constr during systole) - extr up to 70% O2 from blood Pathophysiology of IHD - 1). Stable angina = chron disr bl supp to myocard tiss by asymp athero plaque 2). Stable ischemia/angina = stab fixed athero plaque 3). Unstable ischemia/angina = plaque disr+plt aggreg but not yet thrombus formation 4). NSTEMI = thrombus form but not compl occlusive 5). STEMI = compl occl thromb Angina Pectoris Description & Types - press-like discomf/pain from myocard isch/underl athero --> O2 dem>O2 supp - IHD = angina+MI - Typ ang = O2 dem incr (ie. exerc/stress) but cor bl fl+O2 supp lim by athero - Stab ang = sim angina attacks each time - Unstab ang = ang attacks worse each time by rup plaque; MI forerunner - Variant/Prinzmetal's ang = ac cor vasosp w/ pain @ rest --> TREAT w/ CCBs/BBs Drug Classes used for Stable Angina Treatment - - Nitrites & Nitrates - CCBs - BBs - Drugs modifying myocard metab General Pharmacology of Drugs for Stable Angina Treatment - - Incr O2 supp by: incr reg fl distrib by nitrates, CCBs, BBs & incr cor bl fl by nitrates, CCBs - Decr O2 dem by: decr HR+contractility by BBs, CCBs & decr wall tens (pre+afterload) by nitrates, CCBs Examples & Use of Nitrites in Stable Angina Treatment - Amyl nitrite for ac ang by inhal Examples & Use of Nitrates in Stable Angina Treatment - incl nitroglycerin, isosorbide dinitrate, isosorbide mononitrate - Use = prev+treat ang attacks by pref relax ven sm musc (venodil) - IV nitro also for MI-assoc ac HF MOA & Effects of Nitrites & Nitrates in Stable Angina Treatment - - MOA = biotransf prod NO activ guanylyl cyl --> cGMP -->sm musc relax --> vasodil (pref in veins) - Effects = pref dil ven sm musc to red preload --> decr vent wall tens --> decr O2 dem; cor art dil --> incr cor bl fl+distrib to subendoc --> incr O2 supp Block 4 Pharmacology Final Exam Onset & Duration of Action of Nitroglycerin, Isosorbide dinitrate, Isosorbide mononitrate - - SL Nitro = onset 2 mins, dur 25 mins - PO sust-rel Nitro = onset 35 mins, dur 4-8 hrs - TD Nitro = onset 30 mins, dur 8-14 hrs **useful for prev nocturnal angina** - SL IsoD = onset 5 mins, dur 1 hr - PO slow-rel IsoD = onset 30 mins, dur 8 hrs - PO ext-rel IsoM = onset 30 mins, dur 12 hrs Therapeutic Uses & AEs of Nitrates - - Uses = prev+treat ang attacks - AEs = excess vasodil --> HA, hypoTN, dizz; refl tachy by sympa stim --> incr O2 dem so BB w/ nitrate to prev tachy; Tolerance by mitoch aldehyde dehydrog inactiv biotransf nitro --> interrupt ther for 8-10hr/day to restore resp DIs for Nitrates - w/ Sildenafil (Viagra) for ED --> serious hypoTN Types of Ca Channels in Smooth Muscle Cells & Cardiomyocytes - - Sm musc cells = L+T-type --> vasocon - Cardiomyocytes = L-type only --> card contractility, SA automaticity, AV cond vel Examples & Potency of Dihydropyridine CCBs - - Amlodipine - Felodipine - Isradipine - Nicardipine - Nifedipine - Nimodipine - Nisoldipine potent vasodils w/ min/no effect on heart, MOSTLY @ BVs for stab/var angina treatment **incr O2 supp** Examples & Potency of Phenylalkylamine & Benzothiazepine CCBs - - Verapamil (phenylalkylamine) & Diltiazem (benzothiazepine) act @ both heart & BVs --> decr SA node autom, decr AV node cond vel, decr card contractility for stab/var angina treatment **incr O2 supp+decr O2 dem** **SUPERIOR for IHD treatment** Other uses for CCBs aside from Angina Treatment - - HTN - Verap+Dilt for arrhyth - Nimodipine for SAH Block 4 Pharmacology Final Exam AEs, DIs, CIs for CCBs - - AEs = fatigue, HA, dizz, flush, periph ed by vasodil/hypoTN; gingiv hyperpl; Dihydropyr --> refl tachy/arrhyth by pot vasodil; Verap, Dilt, Bepridil --> arrhyth - DIs = Verap+Dilt red digoxin clear --> risk dig tox - CIs = Verap+Dilt CI in ac HF pts b/c -inotropic effects Nitrates+BBs combo for angina - - exertional/stab ang treatment - BB prev refl tachy & +inotrop effects nitrates CCBs+Nitrates combo for angina - additive effs w/ CCBs red afterl, nitr red prel --> decr O2 dem; both dil cor arts to incr O2 supp CCBs+BBs+Nitrates combo for angina - for exert ang not contr by Nitrates+BBs/CCBs+Nitrates but incr SEs - CCBs to red afterl & nitrates to red prel --> decr O2 dem - CCBs+nitr dil cor arts --> incr O2 supp - BBs red HR+contractility --> decr O2 dem MOA of BBs in Angina Treatment - 1). - inotr eff by decr contractility & - chronotr eff by decr HR --> decr O2 dem 2). maybe incr bl fl to isch area --> incr O2 supp Therapeutic Uses of BBs in Angina & MI Treatment - - beta-1 sel Atenolol+Metoprolol & nonsel Nadolol+Propranolol for stab ang treatment - unstab ang treatment by red recur isch episodes+progr to ac MI - ac MI by red SCD due to ac vent arrhyth - NOT for var ang b/c NOT effective in vasodil (USE CCB instead) Other Therapeutic Uses of BBs aside from Angina Treatment - - HTN - Card arrhyth - CHF AEs of BBs for Angina Treatment - - worsen ac HF by -inotr effs but LOW dose for chron HF to red myocard remod - nonsel B2 block --> bronchocon (USE B1-sel) MOA of Ranolazine for Angina Treatment - modif myocard by inhib FA oxid & inhib Na+influx+cardiomyo Ca overl --> red diast relax failure, incr gluc oxid+incr efficient O2 util by heart Uses & AEs of Ranolazine for Angina Treatment - - Uses = improv exerc cap, red ang attack freq, red nitro use; 2nd LINE for chron stab ang - AEs = nausea, constip, dizz, **QT prolong** Stable Angina Treatment Algorithm - 1). Stab IHD --> guideline-dir med ther+lifestyle modifs for CV risk red Block 4 Pharmacology Final Exam 2). Ang sx --> SL nitro for immed rel (+/- BB) 3). If SL nitro+BB inadeq relief --> ADD CCB OR long-acting nitrate 4). If SL nitro+BB+CCB/LA nitrate inadeq relief --> ADD Ranolazine Guideline-directed medical therapy for Lipid Management in Stable IHD - daily phys activ, wt mgmt, smoking cess, avoid smoke expos - diet ther for all pts incl sat fat red - mod/high dose statin - bile ac seqs/niacin/both for statin-intol pts Guideline-directed medical therapy for BP Management in Stable IHD - antiHTN if BP >/=140/90+lifestyle modifs (incl ACEIs +/or BBs, thiaz diurs, CCBs) to achieve BP<140/90 Guideline-directed medical therapy for Diabetes Management in Stable IHD - short-dur DM & long life expec has HgbA1c goal </=7% **NO Rosiglitazone for SIHD pts** Guideline-directed medical therapy for Antiplatelet Therapy in Stable IHD - - Aspirin 75- 162mg daily unless CI - maybe Asp75-162+Clopidogrel 75 mg if high-risk pts w/ SIHD **Dipyridamole NOT REC for SIHD pts b/c vasodil having DIs w/ angina meds** Guideline-directed medical therapy for Psychological Treatment in Stable IHD - consider depression screening/refer/treat when indic Guideline-directed medical therapy for BB Treatment in Stable IHD - start+cont 3 yrs all pts w/ nl LV func after MI/ACS - all pts w/ LV sys dysf EF 40% w/ HF/prior MI unless CI **Carvedilol/Metoprolol/Bisoprolol** Guideline-directed medical therapy for ACEIs/ARBs in Stable IHD - - ACEIs all pts w/ SIHD+HTN/DM/LVEF</=40% w/ HF/CKD unless CI - ARBs for HTN/DM/LV syst dysf/CKD for ACEI-intol pts Guideline-directed medical therapy for Influenza Vaccination in Stable IHD - annual infl vacc rec Guideline-directed medical therapy for Relief of Sx in Stable IHD - - SL nitro/nitro spray for immed ang relief - BBs = INITIAL ther for sx relief - CCBs/LA nitrates if BBs CI/unacc SEs; LA nondihyrop CCB (Verap/Dilt) instead of BB reasonable - Ranolazine as BB subs if BB treatment w/ unacc SEs/ineff/CI - Ranolazine+BB combo if initial BB treatment not successful Block 4 Pharmacology Final Exam Treatment of occasional angina episode - SL nitro for ac sx relief Treatment of angina episodes occurring predictably w/ exertion - SL nitro/IsoD as proph before exert Treatment of angina if severity requires regular SL nitro - long-term proph consid w/ angiog to eval for angiopl/bypass graft but no decr mort w/ PCI Treatment of stable angina requiring long-term treatment - BB/LA nitrate/CCB as initial therapy Treatment of unstable angina - Aspirin/antithromb to prev plt aggreg+thromb for