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Cardiovascular Medications

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Presentation on theme: "Cardiovascular Medications"— Presentation transcript:

1 Cardiovascular Medications
February 2002

2 Introduction Pharmacology versus Therapeutics Diseases HTN CAD AMI CHF
Arrhythmias Thromboembolic

3 Goals and Objectives To provide general information about cardiovascular medications Learn pharmacologic properties including mechanism of action, adverse effects, and clinical use of the following medications: Diuretics ACE inhibitors ARBs Beta blockers CCBs Vasodilators Nitrates Digoxin

4 Hypertension BP=CO X SVR CO Venous return SVR
Myocardial contractility, heart rate, venous return Venous return Total blood volume Kidney Percentage of blood volume circulating centrally Venous tone SVR Arteriolar smooth muscle tone

5 Hypertension Kidney Sympathetic nervous system
Production of renin Regulation of blood volume Sympathetic nervous system Regulation of cardiac output and peripheral resistance Renin-angiotensin-aldosterone Vasoconstriction (angiotensin II) Increased cardiac output secondary to sodium retention (aldosterone)

6 Hypertension Medications
Diuretics Reduce blood volume Inhibitors of angiotensin Reduce SVR and blood volume Sympatholytic agents Reduce SVR and CO Direct vasodilators Reduce SVR

7 Diuretics General mechanism of action Specific mechanisms
Decrease blood volume Long-term effects from decreased PVR Specific mechanisms Effect transport proteins of tubular cells Prevent water reabsorption Inhibit enzymes Interfere with hormone receptors

8 Diuretics

9 Carbonic Anhydrase Inhibitors
Acetazolamide, methazolamide CA leads to reabsorption of bicarbonate Inhibition leads to a sodium bicarbonate diuresis and reduction in bicarbonate stores Not used for hypertension Glaucoma, urinary alkalination (uric acid elimination, ASA), acute altitude sickness

10 Osmotic Mannitol, glycerin
Large, non absorbed molecule passing through highly water permeable proximal tubule and descending limb of Loop decreases reabsorption of water Not used for hypertension Reduce intraocular, intracranial pressure

11 Loop Furosemide, bumetanide, ethacrynic acid, torsemide
Inhibition of Na/K/Cl transport in the ascending limb of the Loop of Henle, increases excretion of Na and water. CV uses primarily in CHF, also edema, renal failure

12 Thiazide Hydrochlorothiazide, chlorthalidone, indapamide, metolazone
Inhibits NaCl cotransporter in epithelial cells of distal convoluted tubule

13 Potassium Sparing Spironolactone – competitive antagonist binds to aldosterone receptors, increases Na excretion Amiloride, triamterene – acts on the collecting tubule to inhibit sodium transport through ion channels

14 Diuretics

15 Clinical Uses Hypertension CHF Edema
Thiazide, thiazide with potassium sparing CHF Loop Spironolactone Edema

16 Adverse Effects Thiazide Loop Hypokalemic metabolic alkalosis
Hyperuricemia Impaired carbohydrate tolerance Hyperlipidemia Hyponatremia Loop Ototoxicity Hypomagnesemia

17 Adverse Effects Potassium Sparing Hyperkalemia
Hyperchloremic metabolic acidosis Gynecomastia Acute renal failure Kidney stones

18 Diuretic Mechanisms Effect transport proteins of tubular cells
Loop, thiazide, amiloride, triamterene Prevent water reabsorption Osmotic Inhibit enzymes Acetazolamide Interfere with hormone receptors Spironolactone

19 ACE Inhibitors Generic Brand Benazepril Lotensin Captopril Capoten
Enalapril Vasotec Fosinopril Monopril Lisinopril Prinivil Moexipril Univasc Perindopril Aceon Quinapril Accupril Ramipril Altace Trandolapril Mavik ACE Inhibitors

20 Angiotensin Receptor Blockers
Generic Brand Candesartan Atacand Irbesartan Avapro Losartan Cozaar Telmisartin Micardis Valsartan Diovan

21 Renin 1 Converting Enzyme 1 2 2 Angiotensinogen Kininogen
Kalikrein Increased prostaglandin synthesis Angiotensin I Bradykinin 1 Converting Enzyme 1 Angiotensin II Inactive 2 2 Vasoconstriction Aldosterone secretion Vasodilation Increased sodium and water retention Decreased peripheral vascular resistance Increased peripheral vascular resistance Increased blood pressure Decreased blood pressure

22 Clinical Uses HTN CHF Diabetic Nephropathy Post-MI

23 Adverse Effects Hypotension Acute renal failure Hyperkalemia Dry cough
Angioedema CI in 2nd and 3rd trimester

24 Beta Blockers Competitively antagonize the effects of catecholamines at B-adrenergic receptors. Decrease heart rate, stroke volume and cardiac output Initial increase in peripheral resistance from blockade of B-receptors in vessels that promote vasodilation, leaving unopposed alpha vasoconstriction

25 Beta Blockers Cardioselective ISA MSA Mixed First pass Renal Half life

26 Beta Blockers Clinical Uses Adverse Effects

27 Calcium Channel Blockers
Inhibition of calcium influx into arterial smooth muscle cells Nifedipine and other dihydropiridine agents are more selective as vasodilators, with less cardiac depressant effects than diltiazem and verapamil

28 CCB Smooth muscle – long lasting relaxation
Cardiac muscle – reduction in contractility throught the heart and decrease in sinus node pacemaker rate and AV node conduction velocity

29 CCB Dihydropyridine Miscellaneous Amlodipine Felodipine Isradipine
Nicardipine Nimodipine Nisoldipine Nitrendipine Miscellaneous Bepridil Diltiazem Verapamil

30 CCB Clinical Uses Adverse Effects

31 Central Alpha2-Receptor Agonists
Clonidine, guanabenz, guanfacine, and methyldopa Decrease sympathetic outflow from the vasomotor center in the brain and increase in vagal tone. Peripheral activity plays a lesser role Stimulation of presynaptic a2-receptors decreases sympathetic tone

32 Central Alpha2-Receptor Agonists
Effects Decreased heart rate Decreased peripheral resistance Decreased renin activity Blunted baroreceptor reflexes

33 Central Alpha2-Receptor Agonists
Sedation and dry mouth Depression Rebound hypertension

34 Methyldopa Catecholamine type molecule
Stimulates central inhibitory alpha-adrenergic receptors Decreases peripheral vascular resistance, decreases systolic and diastolic BP, decreases heart rate

35 Methyldopa Sodium and fluid accumulation lead to tolerance of hypotensive effect, therefore diuretic use is needed Rare hepatitis and hemolytic anemia Coombs' positive (20%) Coombs' positive HA (1%)

36 Clonidine Reduces sympathetic outflow from the brain secondary to direct stimulation of alpha-receptors in the medulla Increased vagal tone leads to decreases in peripheral vascular resistance and heart rate Baroreceptors are blunted, leading to orthostatic hypotension and tachycardia

37 Clonidine Weekly patch for improved compliance and fewer side effects
Disadvantages – cost, skin irritation, 2-3 day delay of effect

38 Clonidine Uses Hypertensive urgency Adjunctive pain therapy
Withdrawal – alcohol, BZD, nicotine, opiate Adjunct to prolong anesthesia Migraine prophylaxis Menopausal symptoms Anxiety-related disorders

39 Alpha1 Blockers Prazosin, terazosin, doxazosin
Selective alpha-1 blockade decreases total peripheral resistance and venous return. Inhibition of alpha-1 receptors in the periphery prevents vasoconstriction from adrenergic stimulation, allowing vasodilation without affecting heart rate or cardiac index.

40 Alpha1 Blockers Benign Prostatic Hypertrophy
Prevent stimulation of alpha-1 receptors and subsequent smooth muscle contraction in the bladder neck and prostatic urethra Significantly increase urinary flow rates and decrease outflow obstruction and irritation symptoms

41 Alpha1 Blockers CNS side effects – lassitude, vivid dreams, depression
First dose phenomenon – dizziness, faintness, palpitations, syncope ALLHAT

42 Vasodilators Hydralazine, minoxidil
Relax arteriolar smooth muscle by increasing the intracellular concentration of cyclic GMP Decrease peripheral vascular resistance Activate baroreceptor reflexes, increasing sympathetic outflow Activate RAA system

43 Vasodilator Hypotensive effect diminishes over time without concomitant use of a diuretic and sympathetic inhibitor. Angina can be exacerbated if vasodilators are used without sympathetic inhibitor (B blocker)

44 Vasodilator Hydralazine – lupus-like syndrome, dermatitis, drug fever, peripheral neuropathy, hepatitis, vascular headache Minoxidil – greater compensatory effects (HR, CO, renin, sodium retention), hypertrichosis

45 Vasodilators Nitroprusside IV used for hypertensive emergency
Decreases PVR without increasing CO, unless there is left ventricular failure Continuous IV infusion, effect is immediate and lasts 2-5 minutes Thiocyanate levels should be measured if infusion lasts longer than 72 hours

46 Vasodilators Diazoxide
Direct acting arteriolar vasodilator decreases PVR, increases cardiac output, and maintains or increases renal plasma flow IV use for HTN emergency SE – nausea, vomiting, tachycardia, hyperglycemia Use with diuretic

47 Cardiac Glycosides - Digoxin
Positive inotropic effect Inhibits active transmembrane transport of sodium and potassium Binds to membrane-bound sodium-potassium ATPase enzyme, disabling the pump Increase of intracellular sodium activates sodium-calcium pump, increasing intracellular calcium

48 Digoxin Increased calcium improves myocardial contractility
Indirect effect of vagal stimulation on SA and AB nodes, decreases sinus rate

49 Digoxin Loading dose 10 mcg/kg IV or PO 75% oral bioavailability
Oral maintenance dose to 0.5 mg Renal function, baseline cardiac function, size, age affect dosing Monitor drug levels

50 Digoxin Used in heart failure with supraventricular tachyarrhythmias
Early in therapy to control ventricular response Used in HF with NSR No survival benefit Reduces symptoms and improves quality of life

51 Digoxin Adverse effects GI- N/V, abdominal pain, anorexia
CNS- headache, hallucination, delirium, Vision changes Gynecomastia Arrhythmias Hypokalemia Hypercalcemia Hypomagnesemia

52 Nitrates Used in ischemic heart disease
Reduces myocardial oxygen demand secondary to venodilation and arterial dilation, causing a reduction in wall stress from reduced ventricular volume and pressure Direct dilation of coronary arteries

53 Nitrates Mechanism Smooth muscle relaxation
Nitric oxide stimulates guanylyl cyclase which increases cGMP leading to relaxation Preload and afterload are reduced Cardiac output and blood pressure are reduced Oxygen requirement is reduced

54 Nitrates Pharmacokinetics Large first-pass effect
Short half lives (except isosorbide mononitrate) Large interindividual variations in blood concentrations

55 Nitrates Short, intermediate, long Acute attack v. prophylaxis
IV, sublingual, PO, transdermal Half life 1-5 minutes Isosorbide dinitrate is well absorbed and has half-life of 5 hours

56 Nitrates Tolerance Adverse effects – postural hypotension, headaches, flushing, nausea

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