Drugs for Angina and Heart Failure Treatment (Module 4, Section 2) PDF

 for the Treatment of Angina and Drugs Heart Failure...

 for the Treatment of Angina and Drugs Heart Failure Introduction > - characterized to Coronary Artery of Disease /reduced blood flow to tissue) by arteries and Ischemia of the heart narrowing a coronary - most from Ischemia (Chest pain/discomfort) common condition resulting is angina pectoris > - advanced disease lead to heart failure coronary artery can Angina Pectoris (chest pain) (auldup of fate usually due atherosclerosis of the coronary sholesterol and other and > - to arteries , substances in walls on artery > causes narrowinga nindering flow > - which O > delivered to heart from diminished blood flow d O the heart and thus supplying > - pain arises , , > - to a On of heart must fora 4 pain , requirement supply must the 4 "t's" heart) associated angina pectors (they all the O demand of > - with : · Exercise · Excitement Eating · · Exposure to cold Types of Angina Pectoris > - O> requirements of heart 4 When there is an 4 in HR force of contraction arterial pressure or volume of , , blood pumpal > - during all precipitated exercise ① Typical angina ↳ chest pain with EXERTION ↳ often due to CORONARY atherosclerotic a Obstruction such as plaque ② Variant angina ↳ Chest pain DURING REST L due to thought to be coronary vasospasm without obstruction , such as temporary sudden of of the arteries (CONSTRICTION , narrowing one coronary Classes of brugs That Treat Angina · Organic nitrates Includes ↳ isosorbide dinitrate short-acting nitroglycerin and long lasting · B blockers - proprando is the prototypical drug · Calcium Channel Antagonists > - rasodilator > - nedipine is prototypical drug Organic Nitrates : Nitroglycerin > - they relax the smooth muscle of blood vessels and exert their therapeutic effect via I mechanisms : 1. Relaxation of large capacitance veins , leading to rasodilation Iresulte Lo in d in venous blood returning to the heart causing ↓ Co h eart , carryblo and BP > - because there is I so , there is d O2 requirement of heart Dialation of 2. large Coronary arteries carry blood causes blood to be diverted to areas of heartwf I blood flow , IO into heart supply mechanism of action : the In body nitroglycerin oxide (NO) > - is converted to nitric ↳ normally enzyme nitric oxide synthase (Nos) catellyzes the conversion of citulline and No r arginine into ↳ then NO passes from endothelial calls into smooth muscle ↳ here No and steps , leads activates enzyme guanyly) cyclase , through many to vasodilation ↳ GTN this initiates by enering blood vessels and moving into smooth muscle cells where it is converted to No , adverse effects of organic nitrates hypotension , tachycardia (thr throbbing headache flushing and : , , dizziness  Sublingual Nitroglycerin effects (under intere sublingual tounge oral administration > - given by opposed are more when as to because GTN down G1 is rapidly broken in tract , d amount that can be absorbed peah level achieved 5 drug after 20-30 > - in plasma within minutes , but action terminated min Transdermal GTN and Tolerance sublingual is appropriate for episodes of but has limited value preventing > - acute angina , In episode of it would need to be administered 30 minute angina as every GTN patch designed administer transdermally (through or skin) > - a was to GTN across effect (v24hrs) however develops provides long lasting > - a tokranc over , a 24 ur period When taken sublingually several time day there is · a , , no developement of tolerance · but it does occur to transdermal GTN after several hours > so - the patch is applied to skin for 12 hours , then removed for period Covernight 12 hour to allow to to GTN patient to recoury sensitivity Therapeutic Uses of GTN · Termination of an individual attack ↳ sublingual admin /fast , sudden termination of pain) o Prevention of individual attack ↳ sublingual GTN ↑ exertion tolerated by a patient ↳ so patient take GTN a can sublingual prior to exercise that from would normally produce angina , preventing angina developing > - protective effect would last 30 min · Chronic prophylaxis (isoorbide dinitrate If ↳ a patient has numerus attacks/day , a long-acting organic nitrate may be prescribed w/ aim of ↓ # of arginal attacks Isosorbide 2-3 times/day > - dinitrate will # when given orally of arginal attacke ↳ Transdermal GTN is alternative  > - Antianginal brugs : B blockers ex. propranolol precipitated by facture that I SNS activity such as stress and exercise > - angina is , ↳I sus activity = ↑ HR 4 myocardial contractility leading to ↑CO and & myocardial On requirement resulting pain in argina of > - B blockers In activation of sus , and can thus be used for long term prophylaxis of typical angina (pain w/ exertion) but are often avoided in variant angina Calcium Channel Antianginal brus : Blocking brugsCa' d blocking drugs of extracellular site inside calcium channel amount reaching > - to vascular smooth muscle leading : , - relaxation of arterioles - decreased resistance of arteriole - reduced workload on heart * to them coronary arteries are more sensitive force of myocardial they also black calcium channels In cardial muscl , reducing contraction > - , and reducing the workload oxygen demand on the heart calcium channel blockers 13 blockers for long term prophylaxis of variant angina > - are chosen over adverse effects hypotension flushing ankle swelling headache = , , , ex. Nifedipine Development of Heart Failure most Coronary artery disease > - common cause = other conditions also hypertension > - such as contribute > - edema is often present (congestive heart failure) failurepressive -heart ventricles caracterized by de diseethat both voveone or a symptoms > - : · shortness of breath Fatigue - · Tachycardia (4HR) Cardiomegaly (enlarged · heart Compensation for Heart Failure > - the body compensates by : 1. ↑ activation of SNS , 4 HR and force of contraction z. activation of the RAS (4 BP) Mechanisms of Heart Failure > - prolonged activation of B, receptors in heart due to SNS activation ↑ amount of caspases (protean enzyme wh role ideath n and inflammation ↑ (dialation other slow structural both angiotensin 11 leads to cardiovascular + change in > - remodeling the heart and bloodvessels) > - a both cause I Cardiac sell death , resulting in cardiac cells to do the work of the heart , i stress on the heart 4 > - heart compensat by musch mas to maintain cardiac output ↳ initially beneficial but in long run , contributes to worsening #heart Failure Goals of Heart Failure Treatment 1. Reduce symptoms + slow progression of heart failure 2 Manage acute episodes of decompensated failure. Non-pharmalogical Treatment of Heart Failure 1) Behavioural modifications ↑ - physical activity - a dietary control (sult restriction armne ↳ from e -health bloodresetaken 2) leg coronary artery by pase) transplantation ( Surgery (coronary revascularization , or cardiac  > - Pharmacological Treatment can consist of : of Heart Failure o diuretics /P salt and water expelled I BP CO and workload of heart E in urive primary , , nt o rasodilators (ex calcium · channel blocksa · Inhibitors of RAS (d rase constriction ↓ BP) 2ndline o , positive inotropic agents lie cardia. glycode - digitals on L Positive Inotropic Agents : Cardiac Glycosidee Sie. digoxin mechanism of action : 1) digoxin binds to the enzyme Sodium-potassion-ATPase (inhibiting extrusion of sodium from cardial cells 2) result in 4 intracellular cone of sodium , d the extrusion of calcium via the sodium-calcium exchanger 314 Ca't myocardial contractility due to ↑ main tissue in heart Therapeutic Uses of Digoxin (2nd line !) Patients with heart failure and atrial fibrillation Cirregular heart rhyth ( · ↳ only 50 % of patients with normal heart rhythm will have relief of heart failure from digoxin > - but better resulte are seen in patients who also have atrial fibrillation · Treatment of disordered electrical cardial rhythms (arrhythmias digoxin electrical properties of the heart > - causes changes in ↳ it decrease the # of electrical impulses from atria lo ventricle passing ↳ it the rate of of the ventricles disorder the atria slows beating in rhythe arising in Adverse Effects of Digoxin > - digoxin has narrow TI of just 2 , so blood levels must be monitored digoxin also accumulates the > - in body ↳ because of these two factors , 2S of taking digoxin a % patients show some siges of toxicity -early sign 61 symptoms (diarnea =  adverse effects disorder cardiac rhythms /arrhythmial : though it can treat this ! ↳ even · disturbances of vision · neurological effecte /headache , fatique , muscle weakness , confusion Drug-Drug Interactionspotassium of Digoxin of digoxin (4 activity change in Intracellular will affect the activity · because and potassium compete for the ↳ digoxin same spot on the sodium-potassion - Atpase > - occurs wh directio num · Antibiotics /erythromycin) erythromycinIntract w heget flord ↳ that function to break don is