CASE 21 Michelle Legaspi

65 y/o male retired teacher sought consult because of occasional chest heaviness non-radiating occuring during a moderate physical exertion (e.g. climbing up the stairs, or carrying a heavy object), or after an emotional outburst. He noticed that this was often relieved by rest or relaxation with duration 5-10 minutes. He also claims to have a positive family history of heart disease

Angina Pectoris Pain in the chest Characteristic: heaviness Relieved by rest Male: years old Usually due to atherosclerotic heart disease Classic Angina or “angina of effort” Impaired oxygen delivery as a result of abnormalities of the coronary arteries

vital signs patient history physical exam ECG ST depression during treadmill test Laboratory Examinations

Plan of Management Pharmacologic a.Beta blockers b.Nitrates c.Calcium channels blockers Non-Pharmacologic a. Stop smoking b. Decrease alcohol consumption c. Stress management d. Decrease fat and cholesterol in diet e. Lose weight f. Decease salt intake

Pharmacokinetics Nitrates –First past effect (liver-nitrate reductase) –Bioavailability: low 10-20% –Route: Sublingual: avoids the 1 st past effect Oral: longer duration of action Buccal Spray IV Transdermal Ointment –Metabolites 2 dinitroglycerin: significant vasodilator efficacy; most therapeutic effect of oral route 2 mononitro –Excretion: kidney in the form of glucuronide derivative

Pharmocodynamics Dilates all the smooth muscles, biliary systems, ureters and bronchioles Relaxing action is most active in the blood vessels Anti-angina effect is due to a reduction on peripheral arterial resistance and thus decrease in after load Dilate veins: reduce venous return Results in decrease in left ventricular volume makes the heart move efficiently Decrease in both the preload and afterload as a result of respective dilation of venous capacitance and arteriolar resistance vessel

Side effects Throbbing headache Flushing of the face Dizziness especially in the beginning of treatment Postural hypotension due to the pooling of blood in the dependent portions of the body

Contraindication Renal ischemia Acute myocardial infarction Patients receiving other anti-hypertensive agents

Beta Adrenergic Blocking Drugs Beneficial –Hemodynamic effect Decrease heart rate, blood pressure, contractility Decrease myocardial oxygen requirements at rest and during exercise Increase in diastolic perfusion time Reduce heart rate and blood pressure Reduce myocardial oxygen consumption

Side effects Increase end-diastolic volume Increase in ejection time Increase myocardial oxygen associated with increased diastolic volume Can be balanced by the use of nitrates

Contraindication Congestive heart failure –decrease in cardiac output; heart compensate by increasing heart rate Asthma –block beta 1 and beta 2 receptor Complete heart block –heart rate is slow DM –inhibit insulin and stimulate glucagon

Calcium channel blockers Pharmacokinetics –Inhibits calcium transport, excitation-contraction and cardiac work are depressed. –Peripheral vasodilation which further reduces cardiac work load Pharmacodynamics –Relaxes and reduces the tone of all smooth muscles –Relaxing action is marked on vascular smooth muscle –Arterioles are much more affected than veins –Lower blood pressure and reduce afterload without appreciable effect on the preload

Side effects Nausea and vomiting Dizziness Flushing Tachycardia: due to hypotension

Contraindication Cardiogenic shock Recent myocardial infarction Heart failure Atrio-ventricular block

Combination therapy Nitrate and Beta blockers –beta blockers block reflex tachycardia Calcium channel blockers and beta blockers – exertional angina that is not controlled Calcium channel blocker and nitrates –severe vasopastic or exertional angina w/ CHF and sick sinus syndrome Calcium channel blocker, Beta blockers and Nitrate –exertional angia not controlled by administration of two types of anti-anginal agent

Nitrates –Short acting Nitroglycerin, sublingual Isosorbide dinitrate, sublingual Amyl nitrite, inhalant –Long acting Nitroglycerin, oral sustained-action Nitroglycerin, 2% ointment, transdermal Nitroglycerin, slow-release, buccal Nitroglycerin, slow-release patch, transdermal Isosorbide dinitrate, sublingual Isosorbide dinitrate, oral Isosorbide dinitrate, chewable oral Isosobide monoitrate oral

Beta Adrenergic Blocking Drugs –Popranolol absorbed well in the GIT, t1/2 = 3-5 hours –Nadolol Calcium Channel Blockers –Nifedipine –Verafamil –Diltiazem