1. Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. CHAPTER 25 Antihypertensive Drugs

2. 2 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Blood Pressure  Blood pressure = CO × SVR  CO = cardiac output  SVR = systemic vascular resistance  Hypertension = high blood pressure

3. 3 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7)* Four stages, based on BP measurements  Normal  Prehypertension  Stage 1 hypertension  Stage 2 hypertension *New guidelines pending

4. 4 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Compelling Indications  Post-MI  High cardiovascular risk  Heart failure  Diabetes mellitus  Chronic kidney disease  Previous stroke

5. 5 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. JNC-7: Significant Changes  High diastolic BP (DBP) is no longer considered to be more dangerous than high systolic BP (SBP)  Studies have shown that elevated SBP is strongly associated with heart failure, stroke, and renal failure

6. 6 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. JNC-7: Significant Changes (cont’d)  For those older than age 50, SBP is a more important risk factor for cardiovascular disease (CVD) than DBP  “Prehypertensive” BPs are no longer considered “high normal” and require lifestyle modifications to prevent CVD

7. 7 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. JNC-7: Significant Changes (cont’d)  Thiazide-type diuretics should be the initial drug therapy for most patients with hypertension (alone or with other drug classes)  The previous labels of “mild,” “moderate,” and “severe” have been dropped

8. 8 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Cultural Considerations  Beta-blockers and ACE inhibitors have been found to be more effective in white patients than in African American patients  CCBs and diuretics have been shown to be more effective in African American patients than in white patients

9. 9 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

10. 10 Classification of BP Hypertension can also be defined by its cause  Unknown cause  Essential, idiopathic, or primary hypertension  90% of cases  Known cause  Secondary hypertension  10% of cases

11. 11 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Autonomic Nervous System  Parasympathetic nervous system  Stimulates smooth muscle, cardiac muscle, glands  Sympathetic nervous system  Stimulates the heart, blood vessels, skeletal muscle

12. 12 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

13. 13 Antihypertensive Drugs  Medications used to treat hypertension  Categories  Adrenergic drugs  Angiotensin converting enzyme (ACE) inhibitors  Angiotensin II receptor blockers (ARBs)  Calcium channel blockers (CCBs)  Diuretics  Vasodilators

14. 14 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

15. 15 Adrenergic Drugs: Five Subcategories  Centrally and peripherally acting adrenergic neuron blockers  Centrally acting alpha 2 -receptor agonists  Peripherally acting alpha 1 -receptor blockers

16. 16 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Adrenergic Drugs: Five Subcategories (cont’d)  Peripherally acting beta-receptor blockers (beta-blockers)—both cardioselective (beta 1 receptors) and nonselective (both beta 1 and beta 2 receptors)  Peripherally acting dual alpha 1 - and beta-receptor blockers

17. 17 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Adrenergic Drugs: Mechanism of Action  Centrally acting alpha 2 -receptor agonists  Stimulate alpha 2 -adrenergic receptors in the brain  Decrease sympathetic outflow from the CNS  Decrease norepinephrine production  Stimulate alpha 2 -adrenergic receptors, thus reducing renin activity in the kidneys  Results in decreased blood pressure

18. 18 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Adrenergic Drugs: Centrally Acting Alpha 2 -Receptor Agonists  clonidine (Catapres)  methyldopa (Aldomet)  Can be used for hypertension in pregnancy

19. 19 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Adrenergic Drugs: Mechanism of Action  Peripheral alpha 1 -blockers/antagonists  Block alpha 1 -adrenergic receptors  doxazosin (Cardura)  terazosin (Hytrin)  Results in decreased blood pressure

20. 20 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Adrenergic Drugs: Mechanism of Action (cont’d)  Beta-blockers  Reduce BP by reducing heart rate through beta 1 -blockade  Cause reduced secretion of renin  Long-term use causes reduced peripheral vascular resistance  Propranolol, atenolol, others  Newest: nebivolol (Bystolic)—beta 1 -selective  Result: decreased blood pressure

21. 21 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Adrenergic Drugs: Mechanism of Action (cont’d)  Dual-action alpha 1 - and beta-receptor blockers  Block alpha 1 -adrenergic receptors Reduction of heart rate (beta 1 -receptor blockade) Reduction of heart rate (beta 1 -receptor blockade) Vasodilation (alpha 1 -receptor blockade) Vasodilation (alpha 1 -receptor blockade)  carvedilol (Coreg) and labetalol  Result in decreased blood pressure

22. 22 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Adrenergic Drugs: Indications  Centrally acting alpha 2 -receptor agonists  Treatment of hypertension, either alone or with other drugs  Usually used after other drugs have failed because of adverse effects

23. 23 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Adrenergic Drugs: Indications (cont’d)  Centrally acting alpha 2 -receptor agonists  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

24. 24 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Adrenergic Drugs: Indications (cont’d)  Peripherally acting alpha 1 -receptor agonists  Peripherally acting alpha 1 -receptor agonists  Treatment of hypertension  Some used to relieve symptoms of BPH tamsulosin (Flomax) tamsulosin (Flomax)  Management of severe HF when used with cardiac glycosides and diuretics

25. 25 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Adrenergic Drugs: Adverse Effects  High incidence of orthostatic hypotension  Most common  Dry mouth  Drowsiness, sedation  Constipation  Other  Headaches  Sleep disturbances  Nausea  Rash  Cardiac disturbances (palpitations), others

26. 26 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Adrenergic Drugs (cont’d)  Beta-blockers  Act in the periphery  Reduce heart rate owing to  1 -blockade  Examples: nebivolol (bystolic), propranolol (Inderal), atenolol (Tenormin), others

27. 27 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Adrenergic Drugs (cont’d)  Dual alpha 1 - and beta-receptor blockers  Act in the periphery at heart and blood vessels  Reduce heart rate (beta 1 -receptor blockade)  Cause vasodilation (alpha 1 -receptor blockade)  Examples: labetalol (Normodyne), carvedilol (Coreg)

28. 28 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Angiotensin Converting Enzyme (ACE) Inhibitors  Large group of safe and effective drugs  Often used as first-line drugs for HF and hypertension  May be combined with a thiazide diuretic or calcium channel blocker

29. 29 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. ACE Inhibitors: Mechanism of Action Renin-Angiotensin-Aldosterone System  Inhibit angiotensin-converting enzyme, which is responsible for converting angiotensin I (through the action of renin) to angiotensin II  Angiotensin II is a potent vasoconstrictor and causes aldosterone secretion from the adrenal glands

30. 30 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. ACE Inhibitors: Mechanism of Action (cont’d)  Aldosterone stimulates water and sodium resorption  Result: increased blood volume, increased preload, and increased BP

31. 31 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. ACE Inhibitors: Mechanism of Action (cont’d)  Block angiotensin-converting enzyme, thus preventing the formation of angiotensin II  Prevent the breakdown of the vasodilating substance, bradykinin  Result in decreased systemic vascular resistance (afterload), vasodilation, and therefore decreased blood pressure

32. 32 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. ACE Inhibitors: Indications  Hypertension  HF (either alone or in combination with diuretics or other drugs)  Slow progression of left ventricular hypertrophy after MI (cardioprotective)  Renal protective effects in patients with diabetes

33. 33 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. ACE Inhibitors: Indications (cont’d)  Drugs of choice in hypertensive patients with HF  Drugs of choice for diabetic patients

34. 34 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. ACE Inhibitors (cont’d)  captopril (Capoten)  Very short half-life  enalapril (Vasotec)  Available in oral and parenteral forms  lisinopril (Prinivil and Zestril) and quinapril (Accupril), others  Newer drugs, long half-lives, once-a-day dosing  Several other drugs available

35. 35 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. ACE Inhibitors (cont’d)  Captopril and lisinopril are NOT prodrugs  Prodrugs are inactive in their administered form and must be metabolized in the liver to an active form so as to be effective  Captopril and lisinopril can be used if a patient has liver dysfunction, unlike other ACE inhibitors that are prodrugs

36. 36 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. ACE Inhibitors: Adverse Effects  Fatigue  Dizziness  Headache  Mood changes  Impaired taste  Possible hyperkalemia  Dry, nonproductive cough, which reverses when therapy is stopped  Angioedema: rare but potentially fatal NOTE: First-dose hypotensive effect may occur!

37. 37 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Angiotensin II Receptor Blockers  (A II blockers, or ARBs)  Newer class  Well tolerated  Do not cause a dry cough

38. 38 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Angiotensin II Receptor Blockers: Mechanism of Action  Allow angiotensin I to be converted to angiotensin II, but block the receptors that receive angiotensin II  Block vasoconstriction and release of aldosterone

39. 39 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Angiotensin II Receptor Blockers Angiotensin II Receptor Blockers  losartan (Cozaar, Hyzaar)  valsartan (Diovan)  eprosartan (Teveten)  irbesartan (Avapro)  Others

40. 40 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Angiotensin II Receptor Blockers: Indications Angiotensin II Receptor Blockers: Indications  Hypertension  Adjunctive drugs for the treatment of HF  May be used alone or with other drugs such as diuretics  Used primarily in patients who cannot tolerate ACE inhibitors

41. 41 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Angiotensin II Receptor Blockers: Adverse Effects Angiotensin II Receptor Blockers: Adverse Effects  Upper respiratory infections  Headache  May cause occasional dizziness, inability to sleep, diarrhea, dyspnea, heartburn, nasal congestion, back pain, fatigue  Hyperkalemia much less likely to occur

42. 42 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Calcium Channel Blockers: Mechanism of Action  Cause smooth muscle relaxation by blocking the binding of calcium to its receptors, preventing muscle contraction  Results in  Decreased peripheral smooth muscle tone  Decreased systemic vascular resistance  Decreased blood pressure

43. 43 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Calcium Channel Blockers  Benzothiazepines  diltiazem (Cardizem, Dilacor)  Phenylalkamines  verapamil (Calan, Isoptin)  Dihydropyridines  amlodipine (Norvasc), bepridil (Vascor), nicardipine (Cardene)  nifedipine (Procardia), nimodipine (Nimotop)

44. 44 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Calcium Channel Blockers: Indications  Angina  Hypertension  Dysrhythmias  Migraine headaches  Raynaud’s disease

45. 45 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Calcium Channel Blockers: Adverse Effects  Cardiovascular  Hypotension, palpitations, tachycardia  Gastrointestinal  Constipation, nausea  Other  Rash, flushing, peripheral edema, dermatitis

46. 46 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Diuretics  Decrease plasma and extracellular fluid volumes  Results  Decreased preload  Decreased cardiac output  Decreased total peripheral resistance  Overall effect  Decreased workload of the heart, and decreased blood pressure

47. 47 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Diuretics (cont’d)  Thiazide diuretics are the most commonly used diuretics for hypertension  Listed as first-line antihypertensives in the JNC-7 guidelines

48. 48 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Vasodilators: Mechanism of Action  Directly relax arteriolar and/or venous smooth muscle  Results in:  Decreased systemic vascular response  Decreased afterload  Peripheral vasodilation

49. 49 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Vasodilators  diazoxide (Hyperstat)  hydralazine HCl (Apresoline)  minoxidil (Loniten)  sodium nitroprusside (Nipride, Nitropress)

50. 50 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Vasodilators: Indications  Treatment of hypertension  May be used in combination with other drugs  Sodium nitroprusside and intravenous diazoxide are reserved for the management of hypertensive emergencies

51. 51 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Vasodilators: Adverse Effects  hydralazine  Dizziness, headache, anxiety, tachycardia, nausea and vomiting, diarrhea, anemia, dyspnea, edema, nasal congestion, others  sodium nitroprusside  Bradycardia, hypotension, possible cyanide toxicity (rare)

52. 52 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Vasodilators: Adverse Effects (cont’d)  diazoxide  Dizziness, headache, anxiety, orthostatic hypotension, dysrhythmias, sodium and water retention, nausea, vomiting, hyperglycemia in diabetic patients, others

53. 53 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications  Before beginning therapy, obtain a thorough health history and head-to-toe physical examination  Assess for contraindications to specific antihypertensive drugs  Assess for conditions that require cautious use of these drugs

54. 54 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Educate patients about the importance of not missing a dose and taking the medications exactly as prescribed  Instruct patients to check with their physician for instructions on what to do if a dose is missed; patients should never double up on doses if a dose is missed  Monitor BP during therapy; instruct patients to keep a journal of regular BP checks

55. 55 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Instruct patients that these drugs should not be stopped abruptly because this may cause a rebound hypertensive crisis, and perhaps lead to stroke  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

56. 56 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Remind patients that medication is only part of therapy. Encourage patients to watch their diet, stress level, weight, and alcohol intake  Instruct patients to avoid smoking and eating foods high in sodium  Encourage supervised exercise

57. 57 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Teach patients to change positions slowly to avoid syncope from postural hypotension  Instruct patients to 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

58. 58 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Male patients who take these drugs may not be aware that impotence is an expected effect, and this may influence compliance with drug therapy  If patients are experiencing serious adverse effects, or if they believe the dose or medication needs to be changed, they should contact their physician immediately

59. 59 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  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 over-the-counter drugs, without first getting the approval of their physician

60. 60 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Educate patients about lifestyle changes that may be needed  Weight loss  Stress management  Supervised exercise  Dietary measures

61. 61 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Monitor for adverse effects (dizziness, orthostatic hypotension, fatigue) and for toxic effects  Monitor for therapeutic effects  Blood pressure should be maintained at less than 130/90 mm Hg  If a patient with hypertension also has diabetes or renal disease, the BP goal is less than 130/80 mm Hg (JNC-7)