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

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

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

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

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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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)