Coronary artery disease/ischemic heart disease

Adjuncts in the management of IHD1. manage HTN & DM2. Smoking cessation3. control obesity

Drugs aimed to lower serum cholesterolI. Bile acid sequestrants (cholestyramine, cholestipol, colesevelam) MOA: anion-exchange resins that bind bile acids within the intestines. Bile acids are synthesized from cholesterol Lowering LDL-C Taken before meals ADR: constipation, flatulence, dyspepsia (D-D): adsorption of other drugs, drugs should be taken 1 hour before or 4-6 hours after resin

II. Statins/HMG-CoA reductase (atorvastatin, fluvastatin, simvastatin) MOA: inhibits HMG-CoA reductase and reduce cholesterol production Lower LDL cholesterol levels, increase HDL, lower TG ADR: GI adverse effects, headache & dyspepsia, elevate ALT & AST (evaluate after 12 wks of therapy then annually), rhabdomyolysis or myopathy = elevated creatine kinase (CK) ADR: muscle tenderness, pain (D-D): increase risk of myopathy with cyclosporine, macrolide antibiotics, azole antifungals, niacin, fibrates & nefazodone (enzyme inhibitors)

III. Fibric acid derivatives (clofibrate) MOA: inhibit cholesterol synthesis and lower LDL-C ADR: GI effects, elevate liver function tests (D-D): increased risk of rhabdomyolysis (elevated CK) with statins

IV. Niacin MOA: lower LDL-C & TG by: Participates in tissue respiration oxidation-reduction reactions decrease hepatic LDL & VLDL production Inhibits adipose tissue lipolysis Decreased hepatic TG esterification Increase lipoprotein lipase activity ADR: GI adverse effects ADR: flushing & itchy skin (reduced with aspirin 30 mins before the dose) ADR: liver toxicity (liver function tests should be monitored)

V. Ezetimibe MOA: selectively inhibits intestinal absorption of cholesterol & related phytosterols, decrease intestinal cholesterol transport to the liver, decrease hepatic cholesterol stores, increase clearance of cholesterol from the blood reduce total cholesterol, LDL-C, TG, apolipoprotein B & increase HDL (D-D): increase risk of liver enzyme elevation with HMG Co-A reductase inhibitors

Therapeutic agentsI. Nitrates MOA: venous dilation reduce LV volume (preload) & myocardial wall tension decreasing oxygen demand MOA: reduce arteriolar resistance (reduce afterload) decreasing oxygen demand Facilitate collateral circulation Improve exercise tolerance, prolong the time of onset of angina, appearance of ST-segment depression during exercise testing SL can be used before eating, sexual activity, or known stressful event Indications: Tx of stable angina, not effective as single agent for Prinzmetal angina, IV NTG used for immediate tx of unstable angina & long-term therapeutic relief More effective when combined with -blockers ADR: increase HR (reflex tachycardia) & lower BP Preload reduction = reduction of pulmonary symptoms (e.g. shortness of breath, paroxysmal nocturnal dyspnea, orthopnea) ADR: headache (transient & disappear with continued therapy) = administer acetaminophen 15-30 mins before Nitrate tolerance (long-term use of NTG & long-acting nitrates) reversed with ACEI, diuretics & acetylcysteine by increasing the availability of sulfhydryl radicals (D-D): preferred to be combined with CCB (slow-release dihydropyridines like amlodipine, felodipine) rather than verapamil & diltiazem

II. -blockers Starting therapy for a previous MI, ACS, LV dysfunction with or without HF MOA: decrease HR & myocardial contractility = decrease BP reduce oxygen demand at rest & during exercise Indication: reduce the frequency and severity of exertional angina not controlled by nitrates (D-D): with verapamil or diltiazem = bradycardia, AV block & fatigue ADR: avoid with Prinzmetals angina because of coronary vasospasm (D-P): relative CI in asthma (D-P): masks the sign of hypoglycemia (tachycardia) among diabetics and those prone to such problems ADR: monitor heart rate (developing cardiac decompensation = fatigue, edema, shortness of breath, PND) ADR: sudden cessation can lead to withdrawal (increase HR) that may excacerbate angina attacks

III. Calcium-channel blockers MOA: prevent and reverse coronary vasospasm by inhibiting Ca influx into vascular smooth muscle & myocardial muscle increase oxygen supply MOA: decrease coronary vascular resistance increase coronary blood flow increase oxygen supply MOA: decrease systemic vascular resistance & arterial pressure & decrease inotropic effects decrease oxygen demand For stable angina that is not controlled by nitrates & -blockers (D-P): may worsen LV dysfunction Ideal for Prinzmetals angina or angina at rest Diltiazem ADR: negative inotropic effects monitor cardiac decompensation ADR: negative chronotropic bradyarrhythmias & heart block (D-D): blockers, antiarrhythmics (e.g. procainamide, quinidine) = bradycardia ADR: verapamil constipation (D-P): sick sinus syndrome, AV nodal disease, HF Nifedipine Possess greater degree of negative inotropic effects For Prinzmetal angina or refractory spasm without hypotension Short-acting, rapid-release is not ideal for IHD ADR: reflex tachycardia when used alone because of hypotension should be used with -blockers ADR: diziness, light-headedness & lower extremity edema Amlodipine, felodipine, isradipine, nicardipine, nisoldipine (2nd gen. dihydropyridines) Negative inotropic effects (D-P): heart failure

IV. Aspirin MOA: irreversibly inhibits cyclooxygenase ADR: drug allergy, GI upset (D-P): not recommended for peptic ulcer Started at 75-162 mg/day

V. Clopidogrel Alternative to patients allergic to aspirin Thienopyridine derivative MOA: inhibits ADP activation preventing platelet aggregation

VI. Ticlopidine MOA: inhibits ADP preventing platelet aggregation Thienopyridine derivative ADR: thrombotic thrombocytopenic purpura

VII. ACE inhibitors For chronic stable angina MOA: inhibits ACE decreases fluid overload (preload) and prevents vasoconstriction (afterload) decreases oxygen demand For LV ejection fraction < 40%, HTN, DM, CKD unless contraindicated

VIII. ARBs For patients intolerant to ACEI

Treatment of unstable angina/NSTEMIMorphineOxygenNitroglycerinAspirin1. Give supplemental oxygen2. Start with Nitroglycerin SL 0.4 mg every 5 mins x 3 doses3. If no relief, start IV nitroglycerin for the first 48 hours4. Aspirin 165-325 mg, chewable ASAP5. Oral -blocker should be administered within the first 24 hours if without contraindications. IV -blockers should only be used for specific indications and not as routine therapy.6. If -blockers are contraindicated, a non-dihydropyridine CCB (e.g. diltiazem, verapamil) is recommended in the absence of LV dysfunction or other contraindications.7. Oral ACEI should be started within 24 hours to patients with pulmonary congestion or LV ejection fraction < 40% in the absence of hypotension.8. Morphine is administered to STEMI, relative indication to UA/NSTEMI.9. For percutaneous intervention, clopidogrel (or + aspirin) or glycoprotein IIb/IIIa inhibitors (e.g. abciximab, eptifibatide or tirofiban) can be started

I. Morphine MOA: activates opioid receptors MOA: venous dilation venous pooling reduces preload, cardiac workload & oxygen consumption Started at 2 mg and titrate at 5-15 mins interval until pain is relieved or toxicity (e.g. respiratory depression, pinpoint pupils) becomes evident Reduces myocardial pain & anxiety ADR: orthostatic hypotension, fainting due to increase peripheral vasodilation & decreases peripheral resistance; respiratory depression ADR: vagomimetic effect bradyarrhythmia (can be reversed by atropine) ADR: nausea & vomiting ADR: constipation may produce bradycardia or overload the cardiac system due to a need of Valsalva maneuver = docusate/laxatives may be used as a prophylaxis

II. Oxygen 2-4 L/min via nasal cannula Reduce hypoxemia in MI

Treatment options in UA/NSTEMI Anticoagulants + antiplatelet can be started for UA/NSTEMI Fondaparinux is preferred on patients who are at increased risk of bleeding In PCI, GIIb/IIIa + heparin + aspirin for catheterization & PCI

Treatment of STEMI1. Initiate fibrinolytic therapy 30 mins upon arrival at the emergency room.2. Percutaneous coronary intervention should be done 90 mins upon arrival at the hospital.

I. Fibrinolytics Thrombus clot is lysed when given early after symptom onset ( 48 hours due to increased risk of heparin-induced thrombocytopenia5. Thienopyridines (clopidogrel) may be added to aspirin 6. ACEI or ARBs can be started especially in patients with LVEF< 40%7. Aldosterone antagonists (Spironolactone) can be initiated if there is no hyperkalemia or significant renal dysfunction8. Warfarin can be given to maintain INR 2.0-3.0