Chapter 22 Antihypertensive Drugs Copyright 2014 by Mosby

Blood Pressure Blood pressure = CO × SVR CO = cardiac output Ø SVR

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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 1. Normal 2. Prehypertension 3. Stage 1 hypertension 4. Stage 2 hypertension *New guidelines pending Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 4

Classification of BP Hypertension can also be defined by its cause Unknown cause Essential, idiopathic, or primary hypertension Ø 90% of cases Ø Known cause Secondary hypertension Ø 10% of cases Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 5

Classroom Response Question The number of people with hypertension in the United States is estimated to be: A. 10 million. B. 50 million. C. 75 million. D. 100 million. Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 6

Autonomic Nervous System Parasympathetic nervous system Ø Stimulates smooth muscle, cardiac muscle, glands Sympathetic nervous system Ø Stimulates the heart, blood vessels, skeletal muscle Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 7

Location of the Nicotinic Receptors in the PNS and SNS Copyright © 2014 by

Antihypertensive Drugs Medications used to treat hypertension Categories Adrenergic drugs Ø Angiotensin-converting enzyme (ACE) inhibitors Ø Angiotensin II receptor blockers (ARBs) Ø Calcium channel blockers (CCBs) Ø Diuretics Ø Vasodilators Ø Direct renin inhibitors Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 9

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Adrenergic Drugs: Five Subcategories Centrally and peripherally acting adrenergic neuron blockers Centrally acting alpha 2 receptor agonists Peripherally acting alpha 1 receptor blockers Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 11

Adrenergic Drugs: Five Subcategories (cont’d) Peripherally acting beta receptor blockers (beta blockers) Cardioselective (beta 1 receptors) Ø Nonselective (both beta 1 and beta 2 receptors) Ø Peripherally acting dual alpha 1 and beta receptor blockers Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 12

Adrenergic Drugs Centrally acting alpha 2 receptor agonists Stimulate alpha 2 -adrenergic receptors in the brain Ø Decrease sympathetic outflow from the CNS Ø Decrease norepinephrine production Ø Stimulate alpha 2 -adrenergic receptors, thus reducing renin activity in the kidneys Ø Result in decreased blood pressure Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 13

Adrenergic Drugs (cont’d) Centrally acting alpha 2 receptor agonists (cont’d) clonidine (Catapres) Ø methyldopa (Aldomet) • Can be used for hypertension in pregnancy Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 14

Adrenergic Drugs (cont’d) Peripheral alpha 1 blockers/antagonists Block alpha 1 -adrenergic receptors Ø doxazosin (Cardura) Ø terazosin (Hytrin) Ø prazosin (Minipress) Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 15

Adrenergic Drugs (cont’d) Beta blockers Reduce BP by reducing heart rate through beta 1 blockade Ø Cause reduced secretion of renin Ø Long-term use causes reduced peripheral vascular resistance Ø Examples: nebivolol (Bystolic), propranolol (Inderal), atenolol (Tenormin), others Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 16

Adrenergic Drugs (cont’d) Dual-action alpha 1 and beta receptor blockers Reduce heart rate (beta 1 receptor blockade) Ø Cause vasodilation (alpha 1 receptor blockade) Ø carvedilol (Coreg) and labetalol Ø Result in decreased blood pressure Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 17

Adrenergic Drugs: Indications All used to treat hypertension Centrally acting alpha 2 receptor agonists Treatment of hypertension, either alone or with other drugs Ø Usually used after other drugs have failed because of adverse effects Ø Clonidine is useful in the management of withdrawal symptoms in opioid-dependent persons Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 18

Adrenergic Drugs: Indications (cont’d) Peripherally acting alpha 1 receptor agonists Treatment of hypertension Ø Some used to relieve symptoms of BPH • tamsulosin (Flomax) Ø Management of severe heart failure (HF) when used with cardiac glycosides and diuretics Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 19

Adrenergic Drugs: Adverse Effects High incidence of orthostatic hypotension Most common Ø Ø Ø Ø Bradycardia with reflex tachycardia Dry mouth Drowsiness, sedation Constipation Depression Edema Sexual dysfunction Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 20

Adrenergic Drugs: Adverse Effects (cont’d) Other Ø Ø Ø Headaches Sleep disturbances Nausea Rash

Classroom Response Question When administering an alpha-adrenergic drug for hypertension, it is most important for the nurse to assess the patient for the development of: A. hypotension. B. hyperkalemia. C. oliguria. D. respiratory distress. Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 22

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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 23

ACE Inhibitors (cont’d) captopril (Capoten) benazepril (Lotensin) enalapril (Vasotec) fosinopril (Monopril) lisinopril (Prinivil) moexipril (Univasc) quinapril (Accupril) Others Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 24

ACE Inhibitors: Mechanism of Action 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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 25

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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 26

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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 27

Classroom Response Question A patient with type II diabetes has a new prescription for the angiotensin-converting enzyme (ACE) inhibitor lisinopril. She questions this order because her physician has never told her that she has hypertension. What is the best explanation for this order? A. B. C. D. The doctor knows best. The patient is confused. This medication has cardioprotective properties. This medication has a protective effect on the kidneys for patients with type II diabetes. Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 28

ACE Inhibitors: Indications (cont’d) Drugs of choice in hypertensive patients with HF Drugs of

Classroom Response Question A patient with a history of pancreatitis and cirrhosis is also being treated for hypertension. Which drug will most likely be ordered for this patient? A. clonidine B. prazosin C. diltiazem D. captopril Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 30

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 Ø Captopril and lisinopril can be used if a patient has liver dysfunction, unlike other ACE inhibitors that are prodrugs Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 31

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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 32

Angiotensin II Receptor Blockers Also referred to as angiotensin II blockers or ARBs Well

Angiotensin II Receptor Blockers losartan (Cozaar) eprosartan (Teveten) valsartan (Diovan) irbesartan (Avapro) candesartan (Atacand) olmesartan (Benicar) telmisartan (Micardis) azilsartan (Edarbi) Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 34

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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 35

Angiotensin II Receptor Blockers: Indications Hypertension Adjunctive drugs for the treatment of HF May be used alone or with other drugs such as diuretics Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 36

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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 37

Classroom Response Question Which statement about angiotensin II receptor blockers does the nurse identify as being true? A. Hyperkalemia is more likely to occur than when using ACE inhibitors. B. Cough is more likely to occur than when using ACE inhibitors. C. Upper respiratory infection is a common adverse effect. D. Overdose is usually manifested by hypertension and bradycardia. Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 38

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 Ø Decreased systemic vascular resistance Ø Decreased blood pressure Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 39

Calcium Channel Blockers: Indications Angina Hypertension Dysrhythmias Migraine headaches Raynaud’s disease Copyright © 2014

Diuretics Decrease plasma and extracellular fluid volumes Results Decreased preload Ø Decreased cardiac output Ø Decreased total peripheral resistance Ø Overall effect Ø Decreased workload of the heart and decreased blood pressure Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 41

Diuretics (cont’d) Thiazide diuretics are the most commonly used diuretics for hypertension Listed as first-line antihypertensives in the JNC-7 guidelines Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 42

Vasodilators diazoxide (Hyperstat) hydralazine HCl (Apresoline) minoxidil (Loniten) sodium nitroprusside (Nipride, Nitropress) Copyright ©

Vasodilators: Mechanism of Action Directly relax arteriolar and/or venous smooth muscle Results in: Decreased systemic vascular response Ø Decreased afterload Ø Peripheral vasodilation Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 44

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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 45

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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 46

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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 47

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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 48

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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 49

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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 50

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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 51

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 Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 52

Nursing Implications (cont’d) Educate patients about lifestyle changes that may be needed Weight loss Ø Stress management Ø Supervised exercise Ø Dietary measures Ø Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 53

Nursing Implications (cont’d) Monitor for adverse effects (dizziness, orthostatic hypotension, fatigue) and for toxic effects Monitor for therapeutic effects Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 54