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CHAPTER 25 Antihypertensive Drugs 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 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 2 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 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 3 Compelling Indications Post-MI High cardiovascular risk Heart failure Diabetes mellitus Chronic kidney disease Previous stroke Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 4 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 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 5 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 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 6 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 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 7 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 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 8 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 9 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 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 10 Autonomic Nervous System Parasympathetic nervous system Stimulates smooth muscle, cardiac muscle, glands Sympathetic nervous system Stimulates the heart, blood vessels, skeletal muscle Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 11 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 12 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 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 13 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 14 Adrenergic Drugs: Five Subcategories Centrally and peripherally acting adrenergic neuron blockers Centrally acting alpha2-receptor agonists Peripherally acting alpha1-receptor blockers Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 15 Adrenergic Drugs: Five Subcategories (cont’d) Peripherally acting beta-receptor blockers (beta-blockers)—both cardioselective (beta1 receptors) and nonselective (both beta1 and beta2 receptors) Peripherally acting dual alpha1- and beta-receptor blockers Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 16 Adrenergic Drugs: Mechanism of Action Centrally acting alpha2-receptor agonists Stimulate alpha2-adrenergic receptors in the brain Decrease sympathetic outflow from the CNS Decrease norepinephrine production Stimulate alpha2-adrenergic receptors, thus reducing renin activity in the kidneys Results in decreased blood pressure Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 17 Adrenergic Drugs: Centrally Acting Alpha2-Receptor Agonists clonidine (Catapres) methyldopa (Aldomet) Can be used for hypertension in pregnancy Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 18 Adrenergic Drugs: Mechanism of Action Peripheral alpha1-blockers/antagonists Block alpha1-adrenergic receptors doxazosin (Cardura) terazosin (Hytrin) Results in decreased blood pressure Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 19 Adrenergic Drugs: Mechanism of Action (cont’d) Beta-blockers Reduce BP by reducing heart rate through beta1-blockade Cause reduced secretion of renin Long-term use causes reduced peripheral vascular resistance Propranolol, atenolol, others Newest: nebivolol (Bystolic)—beta1-selective Result: decreased blood pressure Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 20 Adrenergic Drugs: Mechanism of Action (cont’d) Dual-action alpha1- and beta-receptor blockers Block alpha1-adrenergic receptors • Reduction of heart rate (beta1-receptor blockade) • Vasodilation (alpha1-receptor blockade) carvedilol (Coreg) and labetalol Result in decreased blood pressure Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 21 Adrenergic Drugs: Indications Centrally acting alpha2-receptor agonists Treatment of hypertension, either alone or with other drugs Usually used after other drugs have failed because of adverse effects Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 22 Adrenergic Drugs: Indications (cont’d) Centrally acting alpha2-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 nicotinedependent persons Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 23 Adrenergic Drugs: Indications (cont’d) Peripherally acting alpha1-receptor agonists Treatment of hypertension Some used to relieve symptoms of BPH • tamsulosin (Flomax) Management of severe HF when used with cardiac glycosides and diuretics Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 24 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 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 25 Adrenergic Drugs (cont’d) Beta-blockers Act in the periphery Reduce heart rate owing to b1-blockade Examples: nebivolol (bystolic), propranolol (Inderal), atenolol (Tenormin), others Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 26 Adrenergic Drugs (cont’d) Dual alpha1- and beta-receptor blockers Act in the periphery at heart and blood vessels Reduce heart rate (beta1-receptor blockade) Cause vasodilation (alpha1-receptor blockade) Examples: labetalol (Normodyne), carvedilol (Coreg) Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 27 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 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 28 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 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 29 ACE Inhibitors: Mechanism of Action (cont’d) Aldosterone stimulates water and sodium resorption Result: increased blood volume, increased preload, and increased BP Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 30 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 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 31 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 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 32 ACE Inhibitors: Indications (cont’d) Drugs of choice in hypertensive patients with HF Drugs of choice for diabetic patients Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 33 ACE Inhibitors (cont’d) captopril (Capoten) enalapril (Vasotec) Available in oral and parenteral forms lisinopril (Prinivil and Zestril) and quinapril (Accupril), others Very short half-life Newer drugs, long half-lives, once-a-day dosing Several other drugs available Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 34 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 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 35 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! Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 36 Angiotensin II Receptor Blockers (A II blockers, or ARBs) Newer class Well tolerated Do not cause a dry cough Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 37 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 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 38 Angiotensin II Receptor Blockers losartan (Cozaar, Hyzaar) valsartan (Diovan) eprosartan (Teveten) irbesartan (Avapro) Others Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 39 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 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 40 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 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 41 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 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 42 Calcium Channel Blockers Benzothiazepines Phenylalkamines diltiazem (Cardizem, Dilacor) verapamil (Calan, Isoptin) Dihydropyridines amlodipine (Norvasc), bepridil (Vascor), nicardipine (Cardene) nifedipine (Procardia), nimodipine (Nimotop) Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 43 Calcium Channel Blockers: Indications Angina Hypertension Dysrhythmias Migraine headaches Raynaud’s disease Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 44 Calcium Channel Blockers: Adverse Effects Cardiovascular Gastrointestinal Hypotension, palpitations, tachycardia Constipation, nausea Other Rash, flushing, peripheral edema, dermatitis Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 45 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 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 46 Diuretics (cont’d) Thiazide diuretics are the most commonly used diuretics for hypertension Listed as first-line antihypertensives in the JNC-7 guidelines Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 47 Vasodilators: Mechanism of Action Directly relax arteriolar and/or venous smooth muscle Results in: Decreased systemic vascular response Decreased afterload Peripheral vasodilation Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 48 Vasodilators diazoxide (Hyperstat) hydralazine HCl (Apresoline) minoxidil (Loniten) sodium nitroprusside (Nipride, Nitropress) Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 49 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 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 50 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) Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 51 Vasodilators: Adverse Effects (cont’d) diazoxide Dizziness, headache, anxiety, orthostatic hypotension, dysrhythmias, sodium and water retention, nausea, vomiting, hyperglycemia in diabetic patients, others Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 52 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 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 53 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 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 54 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 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 55 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 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 56 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 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 57 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 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 58 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 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 59 Nursing Implications (cont’d) Educate patients about lifestyle changes that may be needed Weight loss Stress management Supervised exercise Dietary measures Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 60 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) Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 61
