MEDPHARM DRUGS FOR ISCHEMIC HEART DISEASE FEBRUARY 10,2110

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?

Abrams, J. N Engl J Med 2005;352: Typical Progression of Coronary Atherosclerosis

Abrams J. N Engl J Med 2005;352: Symptoms of Angina

Abrams J. N Engl J Med 2005;352: Classification and Severity of Angina

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

Griffiths, M. J.D. et al. N Engl J Med 2005;353: Regulation of the Relaxation of Vascular Smooth Muscle by Nitric Oxide 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

Griffiths, M. J.D. et al. N Engl J Med 2005;353: Regulation of the Relaxation of Vascular Smooth Muscle by Nitric Oxide NITROGLYCERIN

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 Cardiovascular Bad dreams Aggravation of severe CHF Depression 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 VerapamilOthers Diltiazem Nifedipine

CALCIUM CHANNEL BLOCKERS ON THE HEART

PHARMACODYNAMICS OF CALCIUM CHANNEL BLOCKERS EFFECTVERAPAMILDILTIAZEMNIFEDIPINE/AM- LODOPINE VASODILATIONMODERATEMODERATEDMARKED DECREASED CONTRACTILITY MILDNONENONE OF REFLEX INCREASE DECREASED A-V CONDUCTION MILD NONE

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 HypotensionHeart failure HeadacheAV Block ConstipationPeripheral edema

ANTIANGINAL DRUGS COMPARATIVE PHARMACOLOGIC EFFECTS NitratesCalciumBeta Channel Blockers Blockers Increase in O 2 o + o Supply Decrease in O Demand

ANTIANGINAL DRUGS COMPARATIVE ADVERSE EFFECTS NitratesCalcium Beta Channel Blockers Blockers AV Block  ++ LV Dysfunction  +-/+ Bronchoconstriction   +