1. Antihypertensive Agents

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

3. Classification of Blood Pressure CategorySystemic BP (mm Hg)Diastolic BP (mm Hg) Normal<130<85 High normal130-13985-89 Hypertension Stage 1140-15990-99 Stage 2160-169100-109 Stage 3180-209110-119 Stage 4  210  120

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

5. Blood Pressure = CO x SVR CO = Cardiac output CO = Cardiac output SVR = Systemic vascular resistance SVR = Systemic vascular resistance

6. Blood Pressure = Cardiac Output X Peripheral Resistance Cardiac Output X Peripheral Resistance Preload Contractility Heart Rate Circulating Fluid Volume RenalSodiumHandling SympatheticNervousSystem Renin Angiotensin AngiotensinAldosteroneSystem Arteriolar Venous Vasoconstriction Venous Vascular Smooth Muscle Vascular remodeling

7. V V Vasomotor center Afterload VolumeKidneys Preload Renin Ang II Aldosterone BP= CO x TPVR 1111 2222 1111 1111 Resistance arterioles Capacitance venules Total Peripheral Vascular Resistance (TPVR) Ang I Cardiac Output Heart 2222 TPVR VSMCsVascularSmoothMuscleCells

8. Antihypertensive Agents Medications used to treat hypertension Medications used to treat hypertension

9.  Therapeutic goals in hypertension To lower the high blood pressure and reduced cardiovascular morbidity and mortality by least intrusive means.  For most of the HTN patients: life-long treatment of an asymptomatic disease Antihypertensive Agents

10. Antyhepertensive Drugs New End-Points Antyhepertensive Drugs New End-Points  Effects on hard end-points  Mortality  Stroke  Heart attacks  Effects on end-organ damage  Left ventricular and vascular hypertophy  Effects on renal function  Effects on metabolic status  Blood lipids and glucose

11. Antihypertensive Agents: Categories Adrenergic agents Adrenergic agents Angiotensin-converting enzyme inhibitors Angiotensin-converting enzyme inhibitors Angiotensin II receptor blockers Angiotensin II receptor blockers Calcium channel blockers Calcium channel blockers Diuretics Diuretics Vasodilators Vasodilators

12. Antihypertensive Agents: Categories Adrenergic Agents Adrenergic Agents –Alpha1 blockers –Beta blockers (cardioselective and nonselective) –Centrally acting alpha blockers –Combined alpha-beta blockers –Peripheral-acting adrenergic agents

13. Beta Blockers ( … lol)

14. V V Vasomotor center Afterload VolumeKidneys Preload Renin Ang II Aldosterone BP= CO x TPVR 1111 2222 1111 1111 Resistance arterioles Capacitance venules TPVR Ang I Cardiac Output Heart 2222  - Blockers VSMCs ? ?

15. Beta Blockers Mechanisms and Sites of Action Negative Chronotropic & Inotropic Effects Inhibition of Renin Release _____________________________ _ - Reduction in cardiac output - Inhibition of renin release - CNS effects - Reduction in venous return and plasma volume and plasma volume - Reduction in peripheral resistance - Improvement in vascular compliance - Resetting of baroreceptor levels - Effects on prejunctional    receptors - Attenuation of pressor response to catecholamines (stress, exercise) catecholamines (stress, exercise) _____________________________ _

16.  Cardioselectivity (Beta-1 vs Beta-2 )  Intrinsic Sympathomimetic Activity (ISA; partial agonistic activity)  Affinity for alpha-1 adrenergic receptors (Labetalol, Carvedilol) Beta Blockers Beta Blockers

17.  There are 15 Beta blockers on the market in the US  Approved for hypertension (13) and for one or more of following indications:  Angina pectoris  Myocardial Infarction  Ventricular arrhythmia  Migraine prophylaxis  Heart Failure  Perioperative Hypertension Beta Blockers Beta Blockers

18. Beta Blockers ( …lol) Beta Blockers ( …lol)  Beta-1,2-Non-Selective  Propranolol [INDERAL]  Nadolol [CORGARD]  Carteolol [CARTROL] *  Timolol [BLOCADREN]  Pindolol [VISKEN] *  Sotalol [BETAPACE]  Penbutol [LEVATOL] *  Beta-1-Selective  Acebutolol [SECTRAL] *  Atenolol [TENORMIN]  Betaxolol [KERIONE]  Bisoprolol [ZEBETA]  Esmolol [BREVIBLOC]  Metoprolol [LOPRESSOR ]  Beta-1,2/Alpha 1Selective  Labetalol [TRANDATE, NORMODYNE]  Carvedilol [COREG] * - ISA X X

19.  Side Effects:  Bronchospasm  Bradicardia/heart block  Mask and prolong the symptoms of hypoglycemia  Abrupt withdrawal can precipitate MI  Cold extremities, Raynaud’s phenomenon, intermittent claudication  Decreased exercise tolerance; fatigue, depression and impotence  CNS: sleep disturbance, vivid dreams, nightmares  Effects of plasma lipids Beta Blockers Beta Blockers

20.  YES: (useful in)  Younger patients  Anxious patients  Angina pectoris  Post-MI patient Beta Blockers Beta Blockers  No: (avoid in)  Patients with COPD  IDDM  Pateints with peripheral vascular disease  Raynaud’s syndrome  2nd and 3rd degree block  Energetic patients

21. Antihypertensive Agents: Mechanism of Action Adrenergic Agents Alpha1 Blockers (peripherally acting) Block the alpha1-adrenergic receptors Block the alpha1-adrenergic receptors The SNS is not stimulated The SNS is not stimulated Result: DECREASED blood pressure Stimulation of alpha1-adrenergic receptors causes HYPERtension Stimulation of alpha1-adrenergic receptors causes HYPERtension Blocking alpha1-adrenergic receptors causes decreased blood pressure Blocking alpha1-adrenergic receptors causes decreased blood pressure

22. V V Vasomotor center Afterload VolumeKidneys Preload Renin Ang II Aldosterone BP= CO x TPVR 1111 Resistance arterioles Capacitance venules TPVR Ang I Cardiac Output Heart 2222  1 Receptors Blockers 1111 1111 1111 1111 1111

23.  1 - Receptor Blockers Inhibition of Vasoconstriction Induced by Endogenous Catecholamines at Arterioles and Veins Reduced Peripheral Resistance and Reduced Preload

24. Antihypertensive Agents: Adrenergic Agents Alpha1 Blockers doxazosin (Cardura) doxazosin (Cardura) prazosin (Minipress) prazosin (Minipress) terazosin (Hytrin) terazosin (Hytrin)

25. Antihypertensive Agents: Mechanism of Action Adrenergic Agents Central-Acting Adrenergics Stimulate alpha2-adrenergic receptors Stimulate alpha2-adrenergic receptors Sympathetic outflow from the CNS is decreased Sympathetic outflow from the CNS is decreased Result: decreased blood pressure

26. Antihypertensive Agents: Adrenergic Agents Central-Acting Adrenergics clonidine (Catapres) clonidine (Catapres) methyldopa (Aldomet) (drug of choice for hypertension in pregnancy) methyldopa (Aldomet) (drug of choice for hypertension in pregnancy)

27. V V Vasomotor center Afterload VolumeKidneys Preload Renin Ang II Aldosterone BP= CO x TPVR 1111 Resistance arterioles Capacitance venules TPVR Ang I Cardiac Output Heart 2222 Central   Agonists 1111 VSMC X X X X X

28. Diminished CNS Sympathetic Outflow Alpha-2 Agonist NE & EPI Pre-synaptic Neuron Alpha-2 Receptor Alpha-1 Receptor Beta Receptor Post-synapticEffector Activation of Pre-synaptic Alpha-2 Receptors Reduces NE & EPI Release at Synapse RostralVentrolateralMedulla Central  2 –Agonists

29. Antihypertensive Agents: Mechanism of Action Adrenergic Agents Adrenergic Neuronal Blockers (peripherally acting) Inhibit release of norepinephrine Inhibit release of norepinephrine Also deplete norepinephrine stores Also deplete norepinephrine stores SNS (peripheral adrenergic nerves) is not stimulated SNS (peripheral adrenergic nerves) is not stimulated Result: decreased blood pressure

30. Antihypertensive Agents: Adrenergic Agents Adrenergic Neuronal Blockers (peripherally acting) reserpine reserpine guanadrel (Hylorel) guanadrel (Hylorel) guanethidine (Ismelin) guanethidine (Ismelin)

31. Antihypertensive Agents: Adrenergic Agents Therapeutic Uses Alpha1 blockers (peripherally acting) Alpha1 blockers (peripherally acting) –Treatment of hypertension –Relief of symptoms of BPH –Management of of severe CHF when used with cardiac glycosides and diuretics

32. Antihypertensive Agents: Adrenergic Agents Therapeutic Uses Central-Acting Adrenergics Central-Acting Adrenergics –Treatment of hypertension, either alone or with other agents –Usually used after other agents have failed due to side effects –Also may be used for treatment of severe dysmenorrhea, menopausal flushing, glaucoma –Clonidine is useful in the management of withdrawal symptoms in opioid- or nicotine- dependent persons

33. Antihypertensive Agents: Adrenergic Agents Therapeutic Uses Adrenergic neuronal blockers (peripherally acting) Adrenergic neuronal blockers (peripherally acting) –Treatment of hypertension, either alone or with other agents –Seldom used because of frequent side effects

34. Antihypertensive Agents: Adrenergic Agents Side Effects Most common:dry mouthdrowsiness sedation constipation Other:headachessleep disturbances nausearash cardiac disturbances (palpitations) HIGH INCIDENCE OF ORTHOSTATIC HYPOTENSION

35. Antihypertensive Agents: Categories Angiotensin-Converting Enzyme Inhibitors (ACE Inhibitors) Large group of safe and effective drugs Large group of safe and effective drugs Often used as first-line agents for CHF and hypertension Often used as first-line agents for CHF and hypertension May be combined with a thiazide diuretic or calcium channel blocker May be combined with a thiazide diuretic or calcium channel blocker

36. A n g i o t e n s i n II Peripheral resistanceRenal function Cardiovascular structure Rapid Pressor Response 1. Direct vasoconstriction 2. Enhancement of peripheral noradrenergic neurotransmission 3. Increased central (CNS) sympathetic discharge 4. Release of catecholamines from adrenal medulla 1. Increases Na + reabsorption 2. Releases aldosterone from adrenal cortex 3. Altered renal hemodynamics : - renal vasoconstriction - increased noradrenergic neurotransmission in kidney - Increased renal sympathetic tone (CNS) Slow Pressor Response Cardiovascular Hypertrophy and Remodeling 1. Non-hemodynamic effects: - Increased expression of proto-oncogenes - Increased production of growth factors - Increased synthesis of extracellular matrix proteins 2. Hemodynamic effects: - Increased afterload (cardiac) - Increased wall tension (vascular)

37. V V Vasomotor center Afterload VolumeKidneys Preload Renin Ang II Aldosterone BP= CO x TPVR 1111 2222 1111 1111 Resistance arterioles Capacitance venules TPVR Ang I Cardiac Output Heart 2222 ACE I nhibitors VSMCs

38. Angiotensinogen Ang I Ang II Renin (renal) Renin Angiotensinogen Ang I mRNA AT1AT1 Ang II AT1AT1 A C E (autocrine) (paracrine) (endocrine) mRNA Reni n mRNA A C E endothelial cell tissue (VSM cells) (myocyte ) (liver) mRNA A C E mRNA Reni n Angiotensinogen Ang I ACE Ang II Local (tissue) RAS: Intrinsic; Extrinsic blood vessel

39. Bradykinin A C E Kallikrein Renin Angiotensin II Angiotensin I Angiotensinogen Angiotensin Converting Enzyme ACEIs Kininogens Inactive Peptides BK receptors AT-1 receptors ACEIs

40. 20 mmHg Afferent arteriole Bowman’s capsule Efferent arteriole Arterial pressure + Angiotensin II + + INTRAGLOMERULAR PRESSURE excess glomerular pressure hyperfiltration microalbuminuria ACEIs : Prevention of renal disease

41. Antihypertensive Agents: Mechanism of Action ACE Inhibitors RAAS: Renin Angiotensin-Aldosterone System When the enzyme angiotensin I is converted to angiotensin II, the result is potent vasoconstriction and stimulation of aldosterone When the enzyme angiotensin I is converted to angiotensin II, the result is potent vasoconstriction and stimulation of aldosterone Result of vasoconstriction: increased systemic vascular resistance and increased afterload Result of vasoconstriction: increased systemic vascular resistance and increased afterload Therefore, increased BP Therefore, increased BP

42. Antihypertensive Agents: Mechanism of Action ACE Inhibitors Aldosterone stimulates water and sodium resorption. Aldosterone stimulates water and sodium resorption. Result: increased blood volume, increased preload, and increased B Result: increased blood volume, increased preload, and increased B

43. Antihypertensive Agents: Mechanism of Action ACE Inhibitors ACE Inhibitors block the angiotensin-converting enzyme, thus preventing the formation of angiotensin II. ACE Inhibitors block the angiotensin-converting enzyme, thus preventing the formation of angiotensin II. Also prevent the breakdown of the vasodilating substance, bradykinin Also prevent the breakdown of the vasodilating substance, bradykinin Result: decreased systemic vascular resistance (afterload), vasodilation, and therefore, decreased blood pressure

44. Antihypertensive Agents ACE Inhibitors captopril (Capoten) captopril (Capoten) Short half-life, must be dosed more frequently than others Short half-life, must be dosed more frequently than others enalapril (Vasotec) enalapril (Vasotec) The only ACE inhibitor available in oral and parenteral forms The only ACE inhibitor available in oral and parenteral forms lisinopril (Prinivil and Zestril) and quinapril (Accupril) lisinopril (Prinivil and Zestril) and quinapril (Accupril) Newer agents, long half-lives, once-a-day dosing Newer agents, long half-lives, once-a-day dosing Several other agents available Several other agents available

45. Antihypertensive Agents: Therapeutic Uses ACE Inhibitors Hypertension Hypertension CHF (either alone or in combination with diuretics or other agents) CHF (either alone or in combination with diuretics or other agents) Slows progression of left ventricular hypertrophy after an MI Slows progression of left ventricular hypertrophy after an MI Renal protective effects in patients with diabetes Renal protective effects in patients with diabetes Drugs of choice in hypertensive patients with CHF

46. Antihypertensive Agents: Side Effects ACE Inhibitors FatigueDizziness FatigueDizziness HeadacheMood changes HeadacheMood changes Impaired taste Impaired taste Dry, nonproductive cough, reverses when therapy is stopped NOTE: first-dose hypotensive effect may occur!!

47. Antihypertensive Agents: Categories Angiotensin II Receptor Blockers (A II Blockers or ARBs) Newer class Newer class Well-tolerated Well-tolerated Do not cause coughing Do not cause coughing

48. Kininogens Bradykinin Inactive Peptides A C E Kallikrein Renin Endothelial Cell Plasminogen Activators Angiotensin II Angiotensin I Angiotensinogen PAI-1 + ACE Inhibitors vs AT 1 Antagonists + tPA A C E Is PAI-1 Example: Fibrinolytic System

49. V V Vasomotor center Afterload VolumeKidneys Preload Renin Ang II Aldosterone BP= CO x TPVR 1111 2222 1111 1111 Resistance arterioles Capacitance venules TPVR Ang I Cardiac Output Heart 2222 Ang II Receptor Blockers VSMCs Ang II

50. Antihypertensive Agents: Mechanism of Action Angiotensin II Receptor Blockers Allow angiotensin I to be converted to angiotensin II, but block the receptors that receive angiotensin II Allow angiotensin I to be converted to angiotensin II, but block the receptors that receive angiotensin II Block vasoconstriction and release of aldosterone Block vasoconstriction and release of aldosterone

51. Antihypertensive Agents: Angiotensin II Receptor Blockers losartan (Cozaar) losartan (Cozaar) eposartan (Teveten) eposartan (Teveten) valsartan (Diovan) valsartan (Diovan) irbesartan (Avapro) irbesartan (Avapro) candesartan (Atacand) candesartan (Atacand) telmisartan (Micardis) telmisartan (Micardis)

52. Antihypertensive Agents: Therapeutic Uses Angiotensin II Receptor Blockers Hypertension Hypertension Adjunctive agents for the treatment of CHF Adjunctive agents for the treatment of CHF May be used alone or with other agents such as diuretics May be used alone or with other agents such as diuretics

53. Antihypertensive Agents: Side Effects Angiotensin II Receptor Blockers Upper respiratory infections Upper respiratory infections Headache Headache May cause occasional dizziness, inability to sleep, diarrhea, dyspnea, heartburn, nasal congestion, back pain, fatigue May cause occasional dizziness, inability to sleep, diarrhea, dyspnea, heartburn, nasal congestion, back pain, fatigue

54. Antihypertensive Agents: Categories Calcium Channel Blockers Benzothiazepines Benzothiazepines Dihydropyridines Dihydropyridines Phenylalkylamines Phenylalkylamines

55. V V Vasomotor center Afterload VolumeKidneys Preload Renin Ang II Aldosterone BP= CO x TPVR 1111 Resistance arterioles Capacitance venules TPVR Ang I Cardiac Output Heart 2222 Calcium Channel Blockers Ca ++ L-type Ca ++ channels AV 1111

56. Antihypertensive Agents: Mechanism of Action Calcium Channel Blockers Cause smooth muscle relaxation by blocking the binding of calcium to its receptors, preventing muscle contraction Cause smooth muscle relaxation by blocking the binding of calcium to its receptors, preventing muscle contraction This causes decreased peripheral smooth muscle tone, decreased systemic vascular resistance This causes decreased peripheral smooth muscle tone, decreased systemic vascular resistance Result: decreased blood pressure Result: decreased blood pressure

57. Calcium Channel Blockers Mechanisms and Sites of Action Calcium Channel Blockers Mechanisms and Sites of Action Negative Inotropic and Chronotropic Effects Produce Vasorelaxation at Arterioles Reduced Peripheral Resistance Verap+Dilti>NifedNifed>Dilti+Verap Block transmembrane entry of calcium into arteriolar smooth muscle cells and cardiac myocytes thus inhibiting excitation- contraction L-type Ca ++ channels

58. Antihypertensive Agents Calcium Channel Blockers Benzothiazepines: Benzothiazepines: –diltiazem (Cardizem, Dilacor) Phenylalkamines: Phenylalkamines: –verapamil (Calan, Isoptin) Dihydropyridines: Dihydropyridines: –amlodipine (Norvasc), bepridil (Vascor), nicardipine (Cardene) –nifedipine (Procardia), nimodipine (Nimotop)

59. Antihypertensive Agents: Therapeutic Uses Calcium Channel Blockers Angina Angina Hypertension Hypertension Dysrhythmias Dysrhythmias Migraine headaches Migraine headaches

60. Antihypertensive Agents: Side Effects Calcium Channel Blockers Cardiovascular Cardiovascular –hypotension, palpitations, tachycardia Gastrointestinal Gastrointestinal –constipation, nausea Other Other –rash, flushing, peripheral edema, dermatitis

61. Antihypertensive Agents: Diuretics Decrease the plasma and extracellular fluid volumes Decrease the plasma and extracellular fluid volumes Results:decreased preload decreased cardiac output decreased total peripheral resistance Results:decreased preload decreased cardiac output decreased total peripheral resistance Overall effect:decreased workload of the heart, and decreased blood pressure Overall effect:decreased workload of the heart, and decreased blood pressure

62. Antihypertensive Agents: Mechanism of Action Vasodilators Directly relaxes arteriolar smooth muscle Directly relaxes arteriolar smooth muscle Result:decreased systemic vascular response, decreased afterload, and PERIPHERAL VASODILATION Result:decreased systemic vascular response, decreased afterload, and PERIPHERAL VASODILATION

63. Antihypertensive Agents Vasodilators diazoxide (Hyperstat) diazoxide (Hyperstat) hydralazine HCl (Apresoline) hydralazine HCl (Apresoline) minoxidil (Loniten, Rogaine) minoxidil (Loniten, Rogaine) sodium nitroprusside (Nipride, Nitropress) sodium nitroprusside (Nipride, Nitropress)

64. V V Vasomotor center Afterload VolumeKidneys Preload Renin Ang II Aldosterone BP= CO x TPVR 1111 Resistance arterioles Capacitance venules TPVR Ang I Cardiac Output Heart 2222 PeripheralVasodilators 1111 NO → cGMP → Ca ++ NO → cGMP → Ca ++ 2222 1111

65. Antihypertensive Agents: Therapeutic Uses Vasodilators Treatment of hypertension Treatment of hypertension May be used in combination with other agents May be used in combination with other agents Sodium nitroprusside and diazoxide IV are reserved for the management of hypertensive emergencies Sodium nitroprusside and diazoxide IV are reserved for the management of hypertensive emergencies

66. Antihypertensive Agents: Side Effects Vasodilators Hydralazine: Hydralazine: –dizziness, headache, anxiety, tachycardia, nausea and vomiting, diarrhea, anemia, dyspnea, edema, nasal congestion Sodium nitroprusside: Sodium nitroprusside: –bradycardia, hypotension, possible cyanide toxicity

67. Antihypertensive Agents: Nursing Implications Before beginning therapy, obtain a thorough health history and head-to-toe physical examination. Before beginning therapy, obtain a thorough health history and head-to-toe physical examination. Assess for contraindications to specific antihypertensive agents. Assess for contraindications to specific antihypertensive agents. Assess for conditions that require cautious use of these agents. Assess for conditions that require cautious use of these agents.

68. Antihypertensive Agents: Nursing Implications Educate patients about the importance of not missing a dose and taking the medications exactly as prescribed. Educate patients about the importance of not missing a dose and taking the medications exactly as prescribed. Patients should never double up on doses if a dose is missed; check with physician for instructions on what to do if a dose is missed. Patients should never double up on doses if a dose is missed; check with physician for instructions on what to do if a dose is missed. Monitor BP during therapy. Instruct patients to keep a journal of regular BP checks. Monitor BP during therapy. Instruct patients to keep a journal of regular BP checks.

69. Antihypertensive Agents: Nursing Implications Instruct patients that these drugs should not be stopped abruptly, as this may cause a rebound hypertensive crisis, and perhaps lead to CVA. Instruct patients that these drugs should not be stopped abruptly, as this may cause a rebound hypertensive crisis, and perhaps lead to CVA. Oral forms should be given with meals so that absorption is more gradual and effective. Oral forms should be given with meals so that absorption is more gradual and effective. Administer IV forms with extreme caution and use an IV pump. Administer IV forms with extreme caution and use an IV pump.

70. Antihypertensive Agents: Nursing Implications Remind patients that medications is only part of therapy. Encourage patients to watch their diet, stress level, weight, and alcohol intake. Remind patients that medications is only part of therapy. Encourage patients to watch their diet, stress level, weight, and alcohol intake. Patients should avoid smoking and eating foods high in sodium. Patients should avoid smoking and eating foods high in sodium. Encourage supervised exercise. Encourage supervised exercise.

71. Antihypertensive Agents: Nursing Implications Instruct patients to change positions slowly to avoid syncope from postural hypotension. Instruct patients to change positions slowly to avoid syncope from postural hypotension. Patients should report unusual shortness of breath; difficulty breathing; swelling of the feet, ankles, face, or around the eyes; weight gain or loss; chest pain; palpitations; or excessive fatigue. Patients should report unusual shortness of breath; difficulty breathing; swelling of the feet, ankles, face, or around the eyes; weight gain or loss; chest pain; palpitations; or excessive fatigue.

72. Antihypertensive Agents: Nursing Implications Men taking these agents may not be aware that impotence is an expected effect. This may influence compliance with drug therapy. Men taking these agents may not be aware that impotence is an expected effect. This may influence compliance with drug therapy. If patients are experiencing serious side effects, or believe that the dose or medication needs to be changed, they should contact their physician immediately. If patients are experiencing serious side effects, or believe that the dose or medication needs to be changed, they should contact their physician immediately.

73. Antihypertensive Agents: Nursing Implications Hot tubs, showers, or baths; hot weather; prolonged sitting or standing; physical exercise; and alcohol ingestion may aggravate low blood pressure, leading to fainting and injury. Patients should sit or lie down until symptoms subside. Hot tubs, showers, or baths; hot weather; prolonged sitting or standing; physical exercise; and alcohol ingestion may aggravate low blood pressure, leading to fainting and injury. Patients should sit or lie down until symptoms subside. Patients should not take any other medications, including OTC drugs, without first getting the approval of their physician. Patients should not take any other medications, including OTC drugs, without first getting the approval of their physician.

74. Antihypertensive Agents: Nursing Implications Monitor for side/adverse effects (dizziness, orthostatic hypotension, fatigue) and for toxic effects. Monitor for side/adverse effects (dizziness, orthostatic hypotension, fatigue) and for toxic effects. Monitor for therapeutic effects Monitor for therapeutic effects Blood pressure should be maintained at less than 140/90 mm Hg Blood pressure should be maintained at less than 140/90 mm Hg

75. Diuretic Agents

76. Drugs that accelerate the rate of urine formation. Drugs that accelerate the rate of urine formation. Result: removal of sodium and water Result: removal of sodium and water

77. V V Vasomotor center Afterload VolumeKidneys Preload Renin Ang II Aldosterone BP= CO x TPVR 1111 2222 1111 1111 Resistance arterioles Capacitance venules TPVR Ang I Cardiac Output Heart 2222 DIURETICS VSMCs

78. Sodium Where sodium goes, water follows. Where sodium goes, water follows. 20 to 25% of all sodium is reabsorbed into the bloodstream in the loop of Henle, 5 to 10% in the distal tubules, and 3% in collecting ducts. 20 to 25% of all sodium is reabsorbed into the bloodstream in the loop of Henle, 5 to 10% in the distal tubules, and 3% in collecting ducts. If it is not absorbed, it is excreted with the urine. If it is not absorbed, it is excreted with the urine.

79. Inhibition of Sodium Reabsorption Reduced Circulating Volume Reduced Preload Reduced Cardiac Output Diuretics Diuretics

80. Diuretic Agents Carbonic anhydrase inhibitors Carbonic anhydrase inhibitors Loop diuretics Loop diuretics Osmotic diuretics Osmotic diuretics Potassium-sparing diuretics Potassium-sparing diuretics Thiazide and thiazide-like diuretics Thiazide and thiazide-like diuretics

81. Carbonic Anhydrase Inhibitors (CAIs) acetazolamide (Diamox) acetazolamide (Diamox) methazolamide methazolamide dichlorphenamide dichlorphenamide

82. Carbonic Anhydrase Inhibitors: Mechanism of Action The enzyme carbonic anhydrase helps to make H+ ions available for exchange with sodium and water in the proximal tubules. The enzyme carbonic anhydrase helps to make H+ ions available for exchange with sodium and water in the proximal tubules. CAIs block the action of carbonic anhydrase, thus preventing the exchange of H+ ions with sodium and water. CAIs block the action of carbonic anhydrase, thus preventing the exchange of H+ ions with sodium and water.

83. Carbonic Anhydrase Inhibitors: Mechanism of Action Inhibition of carbonic anhydrase reduces H+ ion concentration in renal tubules. Inhibition of carbonic anhydrase reduces H+ ion concentration in renal tubules. As a result, there is increased excretion of bicarbonate, sodium, water, and potassium. As a result, there is increased excretion of bicarbonate, sodium, water, and potassium. Resorption of water is decreased and urine volume is increased. Resorption of water is decreased and urine volume is increased.

84. Carbonic Anhydrase Inhibitors: Therapeutic Uses Adjunct agents in the long-term management of open-angle glaucoma Adjunct agents in the long-term management of open-angle glaucoma Used with miotics to lower intraocular pressure before ocular surgery in certain cases Used with miotics to lower intraocular pressure before ocular surgery in certain cases Also useful in the treatment of: Also useful in the treatment of: –Glaucoma –Edema –Epilepsy –High-altitude sickness

85. Carbonic Anhydrase Inhibitors: Therapeutic Uses Acetazolamide is used in the management of edema secondary to CHF when other diuretics are not effective. Acetazolamide is used in the management of edema secondary to CHF when other diuretics are not effective. CAIs are less potent diuretics than loop diuretics or thiazides—the metabolic acidosis they induce reduces their diuretic effect in 2 to 4 days. CAIs are less potent diuretics than loop diuretics or thiazides—the metabolic acidosis they induce reduces their diuretic effect in 2 to 4 days.

86. Carbonic Anhydrase Inhibitors: Side Effects Metabolic acidosisDrowsiness AnorexiaParesthesias HematuriaUrticaria PhotosensitivityMelena

87. Loop Diuretics bumetanide (Bumex) bumetanide (Bumex) ethacrynic acid (Edecrin) ethacrynic acid (Edecrin) furosemide (Lasix) furosemide (Lasix)

88. Loop Diuretics: Mechanism of Action Act directly on the ascending limb of the loop of Henle to inhibit sodium and chloride resorption. Act directly on the ascending limb of the loop of Henle to inhibit sodium and chloride resorption. Increase renal prostaglandins, resulting in the dilation of blood vessels and reduced peripheral vascular resistance. Increase renal prostaglandins, resulting in the dilation of blood vessels and reduced peripheral vascular resistance.

89. Loop Diuretics: Drug Effects Potent diuresis and subsequent loss of fluid Potent diuresis and subsequent loss of fluid Decreased fluid volume causes: Decreased fluid volume causes: –Reduced BP –Reduced pulmonary vascular resistance –Reduced systemic vascular resistance –Reduced central venous pressure –Reduced left ventricular end-diastolic pressure Potassium depletion Potassium depletion

90. Loop Diuretics: Therapeutic Uses Edema associated with CHF or hepatic or renal disease Edema associated with CHF or hepatic or renal disease Control of hypertension Control of hypertension

91. Loop Diuretics: Side Effects Body SystemEffect CNSDizziness, headache, tinnitus, blurred vision GINausea, vomiting, diarrhea

92. Loop Diuretics: Side Effects Body SystemEffect HematologicAgranulocytosis, neutropenia, thrombocytopenia MetabolicHypokalemia, hyperglycemia, hyperuricemia

93. Osmotic Diuretics mannitol (Resectisol, Osmitrol) mannitol (Resectisol, Osmitrol)

94. Osmotic Diuretics: Mechanism of Action Work in the proximal tubule Work in the proximal tubule Nonabsorbable, producing an osmotic effect Nonabsorbable, producing an osmotic effect Pull water into the blood vessels and nephrons from the surrounding tissues Pull water into the blood vessels and nephrons from the surrounding tissues

95. Osmotic Diuretics: Drug Effects Reduced cellular edema Reduced cellular edema Increased urine production, causing diuresis Increased urine production, causing diuresis Rapid excretion of water, sodium, and other electrolytes, as well as excretion of toxic substances from the kidney Rapid excretion of water, sodium, and other electrolytes, as well as excretion of toxic substances from the kidney Reduces excessive intraocular pressure Reduces excessive intraocular pressure

96. Osmotic Diuretics: Therapeutic Uses Used in the treatment of patients in the early, oliguric phase of ARF Used in the treatment of patients in the early, oliguric phase of ARF To promote the excretion of toxic substances To promote the excretion of toxic substances Reduction of intracranial pressure Reduction of intracranial pressure Treatment of cerebral edema Treatment of cerebral edema

97. Osmotic Diuretics: Side Effects Convulsions Convulsions Thrombophlebitis Thrombophlebitis Pulmonary congestion Pulmonary congestion Also headaches, chest pains, tachycardia, blurred vision, chills, and fever

98. Potassium-Sparing Diuretics amiloride (Midamor) amiloride (Midamor) spironolactone (Aldactone) spironolactone (Aldactone) triamterene (Dyrenium) triamterene (Dyrenium)

99. V V Vasomotor center Afterload VolumeKidneys Preload Renin Ang II Aldosterone BP= CO x TPVR 1111 2222 1111 1111 Resistance arterioles Capacitance venules TPVR Ang I Cardiac Output Heart 2222 AldosteroneAntagonists VSMCs

100. Potassium-Sparing Diuretics: Mechanism of Action Work in collecting ducts and distal convoluted tubules Work in collecting ducts and distal convoluted tubules Interfere with sodium-potassium exchange Interfere with sodium-potassium exchange Competitively bind to aldosterone receptors Competitively bind to aldosterone receptors Block the resorption of sodium and water usually induced by aldosterone Block the resorption of sodium and water usually induced by aldosterone

101. Potassium-Sparing Diuretics: Drug Effects Prevent potassium from being pumped into the tubule, thus preventing its secretion Prevent potassium from being pumped into the tubule, thus preventing its secretion Competitively block the aldosterone receptors and inhibit its action Competitively block the aldosterone receptors and inhibit its action The excretion of sodium and water is promoted The excretion of sodium and water is promoted

102. Potassium-Sparing Diuretics: Therapeutic Uses spironolactone and triamterene Hyperaldosteronism Hyperaldosteronism Hypertension Hypertension Reversing the potassium loss caused by Reversing the potassium loss caused by potassium-losing drugs potassium-losing drugsamiloride Treatment of CHF Treatment of CHF

103. Potassium-Sparing Diuretics: Side Effects Body SystemEffect CNSDizziness, headache GICramps, nausea, vomiting, diarrhea OtherUrinary frequency, weakness **hyperkalemia

104. Potassium-Sparing Diuretics: Side Effects spironolactone gynecomastia, amenorrhea, irregular menses gynecomastia, amenorrhea, irregular menses

105. Thiazide and Thiazide-Like Diuretics hydrochlorothiazide (Esidrix, HydroDIURIL) hydrochlorothiazide (Esidrix, HydroDIURIL) chlorothiazide (Diuril) chlorothiazide (Diuril) trichlormethiazide (Metahydrin) trichlormethiazide (Metahydrin) Thiazide-like Thiazide-like chlorthalidone (Hygroton) chlorthalidone (Hygroton) metolazone (Mykrox, Zaroxolyn) metolazone (Mykrox, Zaroxolyn)

106. Thiazide and Thiazide-Like Diuretics: Mechanism of Action Inhibit tubular resorption of sodium and chloride ions Action primarily in the ascending loop of Henle and early distal tubule Result: water, sodium, and chloride are excreted Potassium is also excreted to a lesser extent Dilate the arterioles by direct relaxation

107. Thiazide and Thiazide-Like Diuretics: Drug Effects Lowered peripheral vascular resistance Lowered peripheral vascular resistance Depletion of sodium and water Depletion of sodium and water

108. Thiazide and Thiazide-Like Diuretics: Therapeutic Uses Hypertension (one of the most prescribed group of agents for this) Hypertension (one of the most prescribed group of agents for this) Edematous states Edematous states Idiopathic hypercalciuria Idiopathic hypercalciuria Diabetes insipidus Diabetes insipidus Adjunct agents in treatment of CHF, hepatic cirrhosis Adjunct agents in treatment of CHF, hepatic cirrhosis

109. Thiazide and Thiazide-Like Diuretics: Side Effects Body SystemEffect CNSDizziness, headache, blurred vision, paresthesias, decreased libido GIAnorexia, nausea, vomiting, diarrhea

110. Thiazide and Thiazide-Like Diuretics: Side Effects Body SystemEffect GUImpotence IntegumentaryUrticaria, photosensitivity MetabolicHypokalemia, glycosuria, hyperglycemia

111. Diuretic Agents: Nursing Implications Perform a thorough patient history and physical examination. Perform a thorough patient history and physical examination. Assess baseline fluid volume status, intake and output, serum electrolyte values, weight, and vital signs. Assess baseline fluid volume status, intake and output, serum electrolyte values, weight, and vital signs. Assess for disorders that may contraindicate the use of, or necessitate cautious use of, these agents. Assess for disorders that may contraindicate the use of, or necessitate cautious use of, these agents.

112. Diuretic Agents: Nursing Implications Instruct patients to take in the morning as much as possible to avoid interference with sleep patterns. Instruct patients to take in the morning as much as possible to avoid interference with sleep patterns. Monitor serum potassium levels during therapy. Monitor serum potassium levels during therapy. Potassium supplements are usually not recommended when potassium levels exceed 3.0 mEq/L. Potassium supplements are usually not recommended when potassium levels exceed 3.0 mEq/L.

113. Diuretic Agents: Nursing Implications Teach patients to maintain proper nutritional and fluid volume status. Teach patients to maintain proper nutritional and fluid volume status. Teach patients to eat more potassium-rich foods when taking any but the potassium-sparing agents. Teach patients to eat more potassium-rich foods when taking any but the potassium-sparing agents. Foods high in potassium include bananas, oranges, dates, raisins, plums, fresh vegetables, potatoes, meat, and fish. Foods high in potassium include bananas, oranges, dates, raisins, plums, fresh vegetables, potatoes, meat, and fish.

114. Diuretic Agents: Nursing Implications Patients taking diuretics along with a digitalis preparation should be taught to monitor for digitalis toxicity. Patients taking diuretics along with a digitalis preparation should be taught to monitor for digitalis toxicity. Diabetic patients who are taking thiazide and/or loop diuretics should be told to monitor blood glucose and watch for elevated levels. Diabetic patients who are taking thiazide and/or loop diuretics should be told to monitor blood glucose and watch for elevated levels.

115. Diuretic Agents: Nursing Implications Teach patients to change positions slowly, and to rise slowly after sitting or lying to prevent dizziness and possible fainting related to orthostatic hypotension. Teach patients to change positions slowly, and to rise slowly after sitting or lying to prevent dizziness and possible fainting related to orthostatic hypotension. Encourage patients to keep a log of their daily weight. Encourage patients to keep a log of their daily weight. Encourage patients to return for follow-up visits and lab work. Encourage patients to return for follow-up visits and lab work.

116. Diuretic Agents: Nursing Implications Patients who have been ill with nausea, vomiting, and/or diarrhea should notify their physician as fluid loss may be dangerous. Patients who have been ill with nausea, vomiting, and/or diarrhea should notify their physician as fluid loss may be dangerous. Signs and symptoms of hypokalemia include muscle weakness, constipation, irregular pulse rate, and overall feeling of lethargy. Signs and symptoms of hypokalemia include muscle weakness, constipation, irregular pulse rate, and overall feeling of lethargy.

117. Diuretic Agents: Nursing Implications Instruct patients to notify the physician immediately if they experience rapid heart rates or syncope (reflects hypotension or fluid loss). Instruct patients to notify the physician immediately if they experience rapid heart rates or syncope (reflects hypotension or fluid loss). A weight gain of 2 or more pounds a day or 5 or more pounds a week should be reported immediately. A weight gain of 2 or more pounds a day or 5 or more pounds a week should be reported immediately.

118. Diuretic Agents: Nursing Implications Monitor for adverse effects: metabolic alkalosis, drowsiness, lethargy, hypokalemia, tachycardia, hypotension, leg cramps, restlessness, decreased mental alertness metabolic alkalosis, drowsiness, lethargy, hypokalemia, tachycardia, hypotension, leg cramps, restlessness, decreased mental alertness

119. Diuretic Agents: Nursing Implications Monitor for therapeutic effects: Monitor for therapeutic effects: –Reduction in edema, fluid volume overload, CHF –Reduction of hypertension –Return to normal intraocular pressures

120. Antilipemic Agents

121. Antilipemics Drugs used to lower lipid levels Drugs used to lower lipid levels

122. Triglycerides and Cholesterol Two primary forms of lipids in the blood Two primary forms of lipids in the blood Water-insoluble fats that must be bound to apoproteins, specialized lipid-carrying proteins Water-insoluble fats that must be bound to apoproteins, specialized lipid-carrying proteins Lipoprotein is the the combination of triglyceride or cholesterol with apoprotein Lipoprotein is the the combination of triglyceride or cholesterol with apoprotein

123. Types of Lipoproteins LipidProtein Content Lipoprotein ClassificationContent MostchylomicronLeast  very-low density lipoprotein (VLDL)   Intermediate-density lipoprotein (IDL)  LeastHigh-density lipoprotein (HDL)Most

124. Instructors may want to insert EIC Image #84: Cholesterol Homeostasis

125. Coronary Heart Disease The risk of CHD in patients with cholesterol levels of 300 mg/dL is 3 to 4 times greater than that in patients with levels less than 300 mg/dL The risk of CHD in patients with cholesterol levels of 300 mg/dL is 3 to 4 times greater than that in patients with levels less than 300 mg/dL

126. Antilipemics Bile acid sequestrants Bile acid sequestrants HMG-CoA reductase inhibitors (HMGs or statins) HMG-CoA reductase inhibitors (HMGs or statins) Fibric acid derivatives Fibric acid derivatives Niacin (nicotinic acid) Niacin (nicotinic acid)

127. Antilipemics: Bile Acid Sequestrants cholestyramine (Questran) cholestyramine (Questran) colestipol hydrochloride (Colestid) colestipol hydrochloride (Colestid) Also called bile acid-binding resins and ion-exchange resins Also called bile acid-binding resins and ion-exchange resins

128. Antilipemics: Bile Acid Sequestrants Mechanism of Action Prevent resorption of bile acids from small intestine Prevent resorption of bile acids from small intestine Bile acids are necessary for absorption of cholesterol Bile acids are necessary for absorption of cholesterol

129. Antilipemics: Bile Acid Sequestrants Therapeutic Uses Type II hyperlipoproteinemia Type II hyperlipoproteinemia Relief of pruritus associated with partial biliary obstruction (cholestyramine) Relief of pruritus associated with partial biliary obstruction (cholestyramine)

130. Antilipemics: Bile Acid Sequestrants Side Effects Constipation Constipation –Heartburn, nausea, belching, bloating These adverse effects tend to disappear over time

131. Antilipemics: HMG-CoA Reductase Inhibitors (HMGs or statins) lovastatin (Mevacor) lovastatin (Mevacor) pravastatin (Pravachol) pravastatin (Pravachol) simvastatin (Zocor) simvastatin (Zocor) atorvastatin (Lipitor) atorvastatin (Lipitor) cerivastatin (Baycol) cerivastatin (Baycol) fluvastatin (Lescol) fluvastatin (Lescol) Most potent LDL reducers

132. Antilipemics: HMG-CoA Reductase Inhibitors Mechanism of Action Inhibit HMG-CoA reductase, which is used by the liver to produce cholesterol Inhibit HMG-CoA reductase, which is used by the liver to produce cholesterol Lower the rate of cholesterol production Lower the rate of cholesterol production

133. Antilipemics: HMG-CoA Reductase Inhibitors Therapeutic Uses Treatment of type IIa and IIb hyperlipidemias Treatment of type IIa and IIb hyperlipidemias –Reduce LDL levels by 30 to 40% –Increase HDL levels by 2 to 15% –Reduce triglycerides by 10 to 30%

134. Antilipemics: HMG-CoA Reductase Inhibitors Side Effects Mild, transient GI disturbances Mild, transient GI disturbances Rash Rash Headache Headache Myopathy (muscle pain) Myopathy (muscle pain) Elevations in liver enzymes Elevations in liver enzymes

135. Antilipemics: Fibric Acid Derivatives clofibrate clofibrate gemfibrozil (Lopid) gemfibrozil (Lopid) fenofibrate (Tricor) fenofibrate (Tricor)

136. Antilipemics: Fibric Acid Derivatives Mechanism of Action Believed to work by activating lipase, which breaks down cholesterol Believed to work by activating lipase, which breaks down cholesterol Also suppress release of free fatty acid from the adipose tissue, inhibit synthesis of triglycerides in the liver, and increase the secretion of cholesterol in the bile Also suppress release of free fatty acid from the adipose tissue, inhibit synthesis of triglycerides in the liver, and increase the secretion of cholesterol in the bile

137. Antilipemics: Fibric Acid Derivatives Therapeutic Uses Treatment of type IV and V hyperlipemias Treatment of type IV and V hyperlipemias Treatment of type III, IV, and V hyperlipidemias Treatment of type III, IV, and V hyperlipidemias Decrease the triglyceride levels and increase HDL by as much as 25%

138. Antilipemics: Fibric Acid Derivatives Side Effects Abdominal discomfort Abdominal discomfort Diarrhea Diarrhea Nausea Nausea Blurred vision Blurred vision Increased risk of gallstones Increased risk of gallstones Prolonged prothrombin time Prolonged prothrombin time Liver studies may show increased function Liver studies may show increased function

139. Antilipemics: Niacin (Nicotinic Acid) Vitamin B 3 Vitamin B 3 Lipid-lowering properties require much higher doses than when used as a vitamin Lipid-lowering properties require much higher doses than when used as a vitamin Effective, inexpensive, often used in combination with other lipid-lowering agents Effective, inexpensive, often used in combination with other lipid-lowering agents

140. Antilipemics: Niacin (Nicotinic Acid) Mechanism of Action Thought to increase activity of lipase, which breaks down lipids Thought to increase activity of lipase, which breaks down lipids Reduces the metabolism or catabolism of cholesterol and triglycerides Reduces the metabolism or catabolism of cholesterol and triglycerides

141. Antilipemics: Niacin (Nicotinic Acid) Therapeutic Uses Effective in lowering triglyceride, total serum cholesterol, and LDL levels Effective in lowering triglyceride, total serum cholesterol, and LDL levels Increases HDL levels Increases HDL levels Effective in the treatment of types IIa, IIb, III, IV, and V hyperlipidemias Effective in the treatment of types IIa, IIb, III, IV, and V hyperlipidemias

142. Antilipemics: Niacin (Nicotinic Acid) Side Effects Flushing (due to histamine release) Flushing (due to histamine release) Pruritus Pruritus GI distress GI distress

143. Antilipemics: Nursing Implications Before beginning therapy, obtain a thorough health and medication history. Before beginning therapy, obtain a thorough health and medication history. Assess dietary patterns, exercise level, weight, height, VS, tobacco and alcohol use, family history. Assess dietary patterns, exercise level, weight, height, VS, tobacco and alcohol use, family history. Assess for contraindications, conditions that require cautious use, and drug interactions. Assess for contraindications, conditions that require cautious use, and drug interactions.

144. Antilipemics: Nursing Implications Contraindications include biliary obstruction, liver dysfunction, active liver disease. Contraindications include biliary obstruction, liver dysfunction, active liver disease. Obtain baseline liver function studies. Obtain baseline liver function studies. Patients on long-term therapy may need supplemental fat-soluble vitamins (A, D, K). Patients on long-term therapy may need supplemental fat-soluble vitamins (A, D, K). Take with meals to decrease GI upset. Take with meals to decrease GI upset.

145. Antilipemics: Nursing Implications Patient must be counseled concerning diet and nutrition on an ongoing basis. Patient must be counseled concerning diet and nutrition on an ongoing basis. Instruct on proper procedure for taking the medications. Instruct on proper procedure for taking the medications. Powder forms must be taken with a liquid, mixed thoroughly but not stirred, and NEVER taken dry. Powder forms must be taken with a liquid, mixed thoroughly but not stirred, and NEVER taken dry. Other medications should be taken 1 hour before or 4 to 6 hours after meals to avoid interference with absorption. Other medications should be taken 1 hour before or 4 to 6 hours after meals to avoid interference with absorption.

146. Antilipemics: Nursing Implications Clofibrate often causes constipation; instruct patients to increase fiber and fluid intake to offset this effect. Clofibrate often causes constipation; instruct patients to increase fiber and fluid intake to offset this effect. To minimize side effects of niacin, start on low initial dose and gradually increase it, and take with meals. To minimize side effects of niacin, start on low initial dose and gradually increase it, and take with meals. Small doses of aspirin or NSAIDs may be taken 30 minutes before niacin to minimize cutaneous flushing. Small doses of aspirin or NSAIDs may be taken 30 minutes before niacin to minimize cutaneous flushing.

147. Antilipemics: Nursing Implications Inform patients that these agents may take several weeks to show effectiveness. Inform patients that these agents may take several weeks to show effectiveness. Instruct patients to report persistent GI upset, constipation, abnormal or unusual bleeding, and yellow discoloration of the skin. Instruct patients to report persistent GI upset, constipation, abnormal or unusual bleeding, and yellow discoloration of the skin.

148. Antilipemics: Nursing Implications Monitor for side effects, including increased liver enzyme studies. Monitor for side effects, including increased liver enzyme studies. Monitor for therapeutic effects: Monitor for therapeutic effects: –Reduced cholesterol and triglyceride levels