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FEBRUARY 10,2110 MEDPHARM DRUGS FOR ISCHEMIC HEART DISEASE VIGNETTE A 47 yr old man reports a 6 month Hx of chest pressure while playing handball.He describes substernal tightness and left arm numbness only while exerting.The total cholesterol and LDL are elevated. The exercise test is positive.How should the patient’s case be managed? Typical Progression of Coronary Atherosclerosis Abrams, J. N Engl J Med 2005;352:2524-2533 Symptoms of Angina Abrams J. N Engl J Med 2005;352:2524-2533 Classification and Severity of Angina Abrams J. N Engl J Med 2005;352:2524-2533 Lalplace Equation • Wall stress = Pr/w where: P = pressure r = radius w = wall thickness EFFECTS OF NITROGLYCERIN Marked venodilation with sublingual use Decreased ventricular preload Decreased ventricular size Decreased end-diastolic pressure NET EFFECT: Decreased oxygen demand Slight arteriolar dilation with higher doses Regulation of the Relaxation of Vascular Smooth Muscle by Nitric Oxide NITROGLYCERIN Griffiths, M. J.D. et al. N Engl J Med 2005;353:2683-2695 NITROGLYCERIN USES: Angina pectoris-prophylaxis and treatment Heart failure SIDE EFFECTS: Tolerance Headache Syncope Interaction with sildenafil(Viagra &others) NITROGLYCERIN Direct relaxation of all vascular smooth muscle Venous relaxation with oral or topical use Arteriolar and venous relaxation with IV use ISOSORBIDE DINITRATE ACTION Venous relaxation – Long acting USES Oral Angina pectoris – prophylaxis Heart failure-when ACE inhibitors/ARBs contraindicated ADR Headache, Nitrate tolerance Interaction wiih sildenafil Regulation of the Relaxation of Vascular Smooth Muscle by Nitric Oxide NITROGLYCERIN Griffiths, M. J.D. et al. N Engl J Med 2005;353:2683-2695 BETA- ADRENERGIC BLOCKERS Equally Effective for: Hypertension Angina Arrhythmias BETA BLOCKERS METOPROLOL PROPRANOLOL BETA-BLOCKERS for ANGINA • • Limit heart rate Decrease myocardial contractility • Decrease oxygen demand BETA BOCKERS – ADVERSE EFFECTS CNS Bad dreams Depression Cardiovascular Aggravation of severe CHF Aggravation of occlusive arterial disease Slow A-V conduction Pulmonary Bronchospasm in Asthmatics Drug interactions With drugs that impair A-V conduction (digoxin and some calcium channel blockers) CALCIUM CHANNEL ANTAGONISTS FOR ANGINA PECTORIS Verapamil Diltiazem Nifedipine Others CALCIUM CHANNEL BLOCKERS ON THE HEART PHARMACODYNAMICS OF CALCIUM CHANNEL BLOCKERS EFFECT VERAPAMIL DILTIAZEM NIFEDIPINE/AMLODOPINE VASODILATION MODERATE MODERATED MARKED DECREASED CONTRACTILITY MILD NONE NONE OF REFLEX INCREASE MILD NONE DECREASED A-V MILD CONDUCTION CALCIUM CHANNEL ANTAGONISTS MECHANISM OF ACTION IN ANGINA PECTORIS Decreased in myocardial oxygen demand Decrease in afterload Decrease in cardiac contractility ( V & D)* Increase in myocardial oxygen supply Increase in coronary blood flow * Verapamil & Diltiazem CALCIUM CHANNEL ANTAGONISTS ADVERSE EFFECTS Hypotension Headache Constipation Heart failure AV Block Peripheral edema ANTIANGINAL DRUGS COMPARATIVE PHARMACOLOGIC EFFECTS Nitrates Calcium Channel Blockers Beta Blockers Increase in O2 Supply o + o Decrease in O2 Demand + + + ANTIANGINAL DRUGS COMPARATIVE ADVERSE EFFECTS Nitrates Calcium Channel Blockers Beta Blockers AV Block + + LV Dysfunction + -/+ Bronchoconstriction +
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