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UIC PCOL 425 - Knowledge objectives for Cardiovascular Pharmacology

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-1-Knowledge objectives for Cardiovascular PharmacologyAngiotensin Converting Enzyme (ACE) InhibitorsAs a result of this lecture the student will be able to:Describe the general mechanism by which peptide hormones, such as bradykinin andangiotensin, are generated and degraded.Discuss the advantages and disadvantages of developing drugs to affect critical steps in peptidehormone metabolic pathways.Recall the mechanisms by which ACE inhibitors decrease blood pressure and reducecomplications of cardiovascular disease and diabetes.Describe the side effects that limit the usefulness of these drugs.Drugs:ACE Inhibitorscaptoprillisinoprilenalapril (prodrug)enalaprilat (active form)benazeprilfosinoprilmoexipril perindoprilquinapril ramipril trandolapril.RELATED:(losartan and other "sartans"- Angiotensin receptor antagonist)(Aliskiren - renin inhibitor)CALCIUM ANTAGONISTS. Review mechanisms for regulation of intracellular calcium concentration (import,compartmentalization, sequestering, etc.)Know the major types of voltage-dependent Ca 2+ channels: L-type, long lasting, T-type,transient, and N-P-type. Ca antagonists selectively interact with L-type channels in vessels and heart.-2-As a result of vascular selectivity, Ca antagonists increase coronary perfusion that leads toimproved oxygen supply. They also decrease peripheral vessel resistance that leads to decrease inblood pressure. Together, these effects result in improved heart performance. Know the major cardiovascular pathologies treated by Ca antagonists. Know that verapamil anddiltiazem have selectivity to sino-atrial node and can be used in treatment of supraventriculardysrhytmia. New calcium antagonists have selectivity toward T-type calcium channels. They donot have negative inotropism; they do not have sympathetic activation. They can reduce heartrate, they are highly selective towards coronary vessels, they have minimal side effects. DIURETICSFocus on the following points:- Definition of diuretics and the purposes of diuretic therapy.- Please remember the table of different types of diuretics: types, examples, sites and mechanismsof action.- Several diuretics are sulfonamide derivatives.- Major clinical indications of each types of diuretics, particularly those explained by theirmechanism of action.- Side effects of each types of diuretics related to their mechanisms of action. Particularly payattention to the distortion of water and electrolyte balance.- Carbonic anhydrase inhibitors inhibit carbonate reabsorption and proton excretion.- Osmotic diuretics inhibit reabsorption of water by osmotic force. It also expand volumeof extracellular compartment and may increase heart burden.- Loop diuretics inhibit the Na+-K+-2Cl- symport in thick ascending limb of loop of Henle.-There are two types of loop diuretics (example: furosemide and ethacrynic acid).- Loop diuretics inhibit reabsorption of most ions in the tubular fluid.-The difference between loop diuretics and thiazide diuretics.-Thiazide use and mechanism of action.-Difference between potassium-sparing diuretics and other diuretics.-Different types of potassium-sparing diuretics and their use.-Drug interaction between diuretics and between diuretics and other drugs.DRUG TREATMENT OF HEART FAILURE Understand the three major therapeutic issues in CHF: Volume control, cardiac contractility,hypertrophic remodelingVolume Control (diuretics, ace inhibitors, natriuretic peptide-3-Know the key role of angiotensinWhy is control of volume and afterload one key to controlling symptoms of CHF?Cardiac ContractilityPositive Inotropic agents $ used in conjunction with diuretic agents, ACE inhibitors, vasodilators $ increase cardiac output (at constant preload and heart rate) $ increase intrinsic contractility of heart Why is enhancement of cardiac contractility one key to controlling symptoms of CHF?Cardiac glycosides$ increase cardiac contractility by direct action on cardiomyocyte $ (Na,K)-ionic pump is receptor for cardiac glycoside $ digoxin and digitoxin are commonly used glycosides $ antiarrhythmic action against supraventricular arrhythmia: slowing of A-V conduction(negative dromotropic effect) $ negative chronotropic action: due to reflex bradycardia (vagal effect) $ indications: for use in low output heart failure particularly when atrial arrhythmias arepresent $ digitalis toxicity: ventricular tachyarrhythmias; gastrointestinal upset; CNS symptomssuch as dizziness, convulsion Sympathetic agonistsDobutamine (beta1 - beta2)PDE (phosphodiesterase) inhibitorsamrinonemilrinoneVasodilatorsProven mortality Reduction:beta blockers, ACE inhibitors, spironolactoneANTIARRHYTHMIC AGENTS-4- Know the four classes of antiarrhythmic drugs. Note that side effects of overdoses of these drugsis often arrhythmia. $ Group I: Na channel blockers. Useful for treatment of ventricular tachyarrhythmia andoccasionally atrial tachyarhythmia $ Group II: Beta-adrenoceptor blockers. Useful against supraventricular tachyarrhythmias. $ Group III: Action potential prolonging agents. Used against ventricular arrythmias due toreentry circuits. Bretyllium is a 'chemical defibrillator'. $ Group IV: Calcium channel blockers. Highly effective in treatment of supraventriculartachyarrhythmias. ANTIANGINAL AGENTS These substances are for symptomatic treatment of angina. Know the three basic mechanisms of anti-anginal drugs:• Nitrates and nitrites.: Nitroglycerin and related substances restore oxygen supply-demandbalance through redistribution of coronary flow, reductions in preload, afterload, and totalperipheral resistance. • Beta- blockers reduce cardiac contractility and heart rate by antagonizing beta-effects ofendogenous catecholamines, thus resulting in diminished myocardial oxygenconsumption. • Calcium channel blockers reduce afterload and thereby decrease oxygen demand of theheart. ANTIHYPERTENSIVE DRUGS Know classification of antihypertensive drugs (AHDs) based on their mechanisms.Think about how blood pressure (BP) is maintained: BP = cardiac output (CO) x peripheral vascular resistance (PVR). Therefore, the anatomical sites ofaction for these drugs are heart, kidney, blood vessels, and part of the brain.Why diuretics have been used as first-line AHDs? How are they further divided into 3 groups basedon mechanisms of action? Know why they are useful when combined with several other AHDs. "-agonists and blockers: Know the difference between "1 and "2 adrenergic receptors. What are the sites of


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UIC PCOL 425 - Knowledge objectives for Cardiovascular Pharmacology

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