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Drugs Affecting the Cardiovascular System

Drugs Affecting the Cardiovascular System. Heny Ekowati Pharmacy Department Faculty of Medicine and Health Sciences March 201 3. CARDIOVASCULAR DISEASE. CHF Arrhythmias Angina Hipertensi Hiperlipidemia Stroke Etc. Congestive Heart Failure. The Problem:

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Drugs Affecting the Cardiovascular System

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  1. Drugs Affectingthe Cardiovascular System HenyEkowati Pharmacy Department Faculty of Medicine and Health Sciences March 2013

  2. CARDIOVASCULAR DISEASE • CHF • Arrhythmias • Angina • Hipertensi • Hiperlipidemia • Stroke • Etc

  3. Congestive Heart Failure • The Problem: • Heart cannot pump enough blood • Causes: • Htn, arteriosclerosis, valvular disease • The Solution(s): • Vasodilator • Diuretics • Inotropes } Goal is to increase cardiac output

  4. Angiotensin II VasodilatorsHow do they work? • Mechanism 1: • ACE converts Angiotensin I to Angiotensin II • Angio II has effects as shown • ACE inhibitors decrease A II • End Results: • Decrease fluid retention, afterload • Examples: • Enalapril, Captapril Angiotensin I ACE ↑ Sympathetic Output ↑ Bradykinin Constrict Vascular Smooth Muscle ↑ Na+/H20 Retention

  5. Other Vasodilators: • Mechanism 2: • Direct smooth muscle relaxants • Nitrates • Venous dilators • Reduce preload • Eg: sodium nitropruside • Calcium channel blockers • Amlodipine, felodipene

  6. Diuretics • Bottom line: they decrease fluid volumes • Four Flavours: • Carbonic anhydrase inhibitors • Loop diuretics • Thiazide diuretics • K+-sparing

  7. Na+ Cl- K+ Diuretics:Sites of Action Carbonic Anhydrase Inhibitors Eg: Acetazolamide Thiazides Eg: Chlorothiazide Na+ Cl- HCO3- K+ - Sparing Eg: ? Na+ K+ Loop Diuretics Eg: Furosemide

  8. Inotropes • Increase force of contraction • All increase intracellular cardiac Ca++ concentration • Eg: • Digitalis (cardiac glycoside) • Dobutamine (β-adrenergic agonist) • Amrinone (PDE inhibitor)

  9. How Digitalis Works Out Na+ Na+ ATP ADP + Pi Ca++ K+ Ca++ In Digitalis

  10. Drugs for Treating Arrhythmias • The Problem: • Abnormal cardiac impulse formation/conduction • Can be atrial, supraventricular, ventricular in origin • The solution • Several different classes of drugs • All affect cardiac action potentials

  11. Cardiac Action PotentialExample of effects of Antiarrhythmics Quinidine (a Class I drug) Membrane Potential (mV) Sotalol (a Class III drug) Time (Seconds)

  12. Actions of Antiarrhythmic Drugs

  13. Antianginal Drugs What is angina? What causes it?

  14. Angina • Problem: • Blood flow to myocardium is insufficient • Causes: narrowed artery or arterial spasm • Possible Solutions: • Relax vascular smooth muscle • Reduce work of the heart

  15. Angina Drugs • Organic nitrates • Nitroglycerin • Nitrate converted to nitric oxide • Calcium Channel Blockers • Diltiazem, Nifedipine • Β-Blockers • Propranolol Ca++ Nifedipine Propranolol cGMP Nitrate NO Pi Myosin Light Chain

  16. Antihypertensive Drugs

  17. Filling Pressure Heart Rate Contractility What Determines Arterial Pressure? ~ ~ Peripheral Resistance Arterial Pressure Cardiac Output X Arteriolar Radius

  18. Hypertension High blood pressure • Normal: Systolic < 130 mm Hg Diastolic < 85 mm Hg

  19. Classification of Blood Pressure Category Systemic BP (mm Hg) Diastolic BP (mm Hg) Normal <130 <85 High normal 130-139 85-89 Hypertension Stage 1 140-159 90-99 Stage 2 160-169 100-109 Stage 3 180-209 110-119 Stage 4  210  120

  20. Classification of Blood Pressure Primary Hypertension • Specific cause unknown • 90% of the cases • Also known as essential or idiopathic hypertension Secondary Hypertension • Cause is known (such as eclampsia of pregnancy, renal artery disease, pheochromocytoma) • 10% of the cases

  21. Treatment Rationale Short-term goal of antihypertensive therapy: Reduce blood pressure • Primary (essential) hypertension • Secondary hypertension

  22. Treatment Rationale Long-term goal of antihypertensive therapy: Reduce mortality due to hypertension-induced disease • Stroke • Congestive heart failure • Coronary artery disease • Nephropathy • Peripheral artery disease • Retinopathy

  23. Pharmacology Antihypertensives

  24. Antihypertensive Classes • diuretics • beta blockers • angiotensin-converting enzyme (ACE) inhibitors • calcium channel blockers • vasodilators

  25. Blood Pressure = CO X PVR • Cardiac Output = SV x HR • PVR = Afterload

  26. cardiac factors circulating volume ACEi’s Diuretics salt aldosterone 1. Beta Blockers 2. CCB’s 3. C.A. Adrenergics heart rate contractility BP = CO x PVR Key: CCB = calcium channel blockers CA Adrenergics = central-acting adrenergics ACEi’s = angiotensin-converting enzyme inhibitors

  27. Hormones 1. vasodilators 2. ACEI’s 3. CCB’s Central Nervous System 1. CA Adrenergics BP = CO x PVR Peripheral Sympathetic Receptors alphabeta 1. alpha blockers 2. beta blockers Local Acting 1. Peripheral-Acting Adrenergics

  28. Alpha1 Blockers Stimulate alpha1 receptors -> hypertension Block alpha1 receptors -> hypotension • doxazosin (Cardura®) • prazosin (Minipress®) • terazosin (Hytrin®)

  29. Central Acting Adrenergics Stimulate alpha2 receptors inhibit alpha1 stimulation hypotension • clonidine (Catapress®) • methyldopa (Aldomet®)

  30. Peripheral Acting Adrenergics reserpine (Serpalan®) inhibits the release of NE diminishes NE stores leads to hypotension Prominent side effect of depression also diminishes seratonin

  31. Adrenergic Side Effects Common dry mouth, drowsiness, sedation & constipation orthostatic hypotension Less common headache, sleep disturbances, nausea, rash & palpitations

  32. ACE Inhibitors RAAS Angiotensin I ACE Angiotensin II 1. potent vasoconstrictor - increases BP 2. stimulates Aldosterone - Na+ & H2O reabsorbtion .

  33. Renin-Angiotensin Aldosterone System Angiotensin II = vasoconstrictor Constricts blood vessels & increases BP Increases SVR or afterload ACE-I blocks these effects decreasing SVR & afterload

  34. ACE Inhibitors Aldosterone secreted from adrenal glands cause sodium & water reabsorption Increase blood volume Increase preload ACE-I blocks this and decreases preload

  35. Angiotensin Converting Enzyme Inhibitors captopril (Capoten®) enalapril (Vasotec®) lisinopril (Prinivil® & Zestril®) quinapril (Accupril®) ramipril (Altace®) benazepril (Lotensin®) fosinopril (Monopril®)

  36. Na+ Na+ Drugs acting on therenin-angiotensin systemBrown MJ. Matching the right drug to the right patient. Heart 2001;86:113-120. arteries Angiotensinogen AI AII Renin adrenal glands Aldosterone kidneys

  37. Drugs acting on therenin-angiotensin systemBrown MJ. Matching the right drug to the right patient. Heart 2001;86:113-120. arteries Angiotensinogen AI AII Renin adrenal glands Aldosterone kidneys Na+ Na+

  38. ACE Inhibitors AIIRA Calcium Blockers Diuretics Beta-blockers Spironolactone Drugs acting on therenin-angiotensin systemBrown MJ. Matching the right drug to the right patient. Heart 2001;86:113-120. arteries Angiotensinogen AI AII Renin adrenal glands Aldosterone kidneys

  39. Calcium Channel Blockers • Used for: • Angina • Tachycardias • Hypertension

  40. CCB Site of Action diltiazem & verapamil nifedipine (and other dihydropyridines)

  41. CCB Action • diltiazem & verapamil • decrease automaticity & conduction in SA & AV nodes • decrease myocardial contractility • decreased smooth muscle tone • decreased PVR • nifedipine • decreased smooth muscle tone • decreased PVR

  42. Side Effects of CCBs • Cardiovascular • hypotension, palpitations & tachycardia • Gastrointestinal • constipation & nausea • Other • rash, flushing & peripheral edema

  43. Calcium Channel Blockers diltiazem (Cardizem®) verapamil (Calan®, Isoptin®) nifedipine (Procardia®, Adalat®)

  44. Diuretic Site of Action . Distal tubule proximal tubule Collecting duct loop of Henle

  45. Mechanism • Water follows Na+ • 20-25% of all Na+ is reabsorbed into the blood stream in the loop of Henle • 5-10% in distal tubule & 3% in collecting ducts • If it can not be absorbed it is excreted with the urine •  Blood volume =  preload !

  46. Side Effects of Diuretics • electrolyte losses [Na+ & K+ ] • fluid losses [dehydration] • myalgia • N/V/D • dizziness • hyperglycemia

  47. Diuretics Thiazides: chlorothiazide (Diuril®) & hydrochlorothiazide (HCTZ®, HydroDIURIL®) Loop Diuretics furosemide (Lasix®), bumetanide (Bumex®) Potassium Sparing Diuretics spironolactone (Aldactone®)

  48. Mechanism of Vasodilators • Directly relaxes arteriole smooth muscle • Decrease SVR = decrease afterload

  49. Side Effects of Vasodilators • hydralazine (Apresoline®) • Reflex tachycardia • sodium nitroprusside (Nipride®) • Cyanide toxicity in renal failure • CNS toxicity = agitation, hallucinations, etc.

  50. Vasodilators • diazoxide [Hyperstat®] • hydralazine [Apresoline®] • minoxidil [Loniten®] • sodium Nitroprusside [Nipride®]

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