Antihypertensive Drugs

Antihypertensive Drugs
Chapter 22 Antihypertensive Drugs Copyright © 2017, Elsevier Inc. All rights reserved.

Copyright © 2017, Elsevier Inc. All rights reserved.
Blood Pressure Blood pressure (BP) = CO × SVR CO = cardiac output SVR = systemic vascular resistance Hypertension = high BP Copyright © 2017, Elsevier Inc. All rights reserved.

Blood Pressure (Cont.) 60 years or older: systolic blood pressure (SBP) of greater than 150 mm Hg or diastolic blood pressure (DBP) greater than 90 mm Hg Younger than 60 years and those who have chronic kidney disease or diabetes: SBP greater than 140 and DBP greater than 90 Copyright © 2017, Elsevier Inc. All rights reserved.

Normal regulation of blood pressure and corresponding medications
Copyright © 2017, Elsevier Inc. All rights reserved.

Eighth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-8)* Four stages based on BP measurements Normal Prehypertension Stage 1 hypertension Stage 2 hypertension *Released December 2013. Copyright © 2017, Elsevier Inc. All rights reserved.

Eighth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-8)* (Cont.) According to the JNC 8, therapy should be started if BP is at or greater than150/90 for patients older than 60 years and 140/90 for patients younger than 60 and those who have chronic kidney disease or diabetes. *Released December 2013. Copyright © 2017, Elsevier Inc. All rights reserved.

Classification of Blood Pressure
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 Copyright © 2017, Elsevier Inc. All rights reserved.

Audience Response System Question
The number of people with hypertension in the United States is estimated to be 10 million. 25 million. 50 million. 70 million. Correct answer: D Rationale: Hypertension affects approximately 70 million people in the United States and approximately 1 billion people worldwide, designating it as the most common disease state. Copyright © 2017, Elsevier Inc. All rights reserved. Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint of Elsevier Inc.

Autonomic Nervous System
Parasympathetic nervous system (PNS) Stimulates smooth muscle, cardiac muscle, glands Sympathetic nervous system (SNS) Stimulates the heart, blood vessels, skeletal muscle Copyright © 2017, Elsevier Inc. All rights reserved.

Location of the Nicotinic Receptors in the PNS and SNS

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 Direct renin inhibitors Copyright © 2017, Elsevier Inc. All rights reserved.

Site and mechanism of action of the various antihypertensive drugs

Adrenergic Drugs: Five Subcategories
Adrenergic neuron blockers (central and peripheral) Alpha2 receptor agonists (central) Alpha1 receptor blockers (peripheral) Beta receptor blockers (peripheral) Combination alpha1 and beta receptor blockers (peripheral). Copyright © 2017, Elsevier Inc. All rights reserved.

Centrally Acting Adrenergic Drugs
Clonidine and methyldopa Stimulate alpha2-adrenergic receptors in the brain Decrease sympathetic outflow from the central nervous system Decrease norepinephrine production Stimulate alpha2-adrenergic receptors, thus reducing renin activity in the kidneys Result in decreased BP Copyright © 2017, Elsevier Inc. All rights reserved.

Peripherally Acting Alpha1 Blockers
Doxazosin, prazosin, and terazosin Block alpha1-adrenergic receptors When alpha1-adrenergic receptors are blocked, BP is decreased. Dilate arteries and veins Alpha1 blockers also increase urinary flow rates and decrease outflow obstruction by preventing smooth muscle contractions in the bladder neck and urethra. Use: benign prostatic hyperplasia (BPH) Copyright © 2017, Elsevier Inc. All rights reserved.

Beta Blockers Propranolol, metoprolol, and atenolol Reduction of the heart rate through beta1 receptor blockade Cause reduced secretion of renin Long-term use causes reduced peripheral vascular resistance. Copyright © 2017, Elsevier Inc. All rights reserved.

Dual-Action Alpha1 and Beta Receptor Blockers
Labetalol and carvedilol Dual antihypertensive effects of reduction in heart rate (beta1 receptor blockade) and vasodilation (alpha1 receptor blockade) Copyright © 2017, Elsevier Inc. All rights reserved.

Adrenergic Drugs: Indications
All used to treat hypertension Glaucoma BPH: doxazosin, prazosin, and terazosin Management of severe heart failure (HF) when used with cardiac glycosides and diuretics Copyright © 2017, Elsevier Inc. All rights reserved.

Adrenergic Drugs: Adverse Effects
High incidence of orthostatic hypotension Most common Bradycardia with reflex tachycardia Dry mouth Drowsiness, sedation Constipation Depression Edema Sexual dysfunction Copyright © 2017, Elsevier Inc. All rights reserved.

Adrenergic Drugs: Adverse Effects (Cont.)
Other Headaches Sleep disturbances Nausea Rash Cardiac disturbances (palpitations), others Copyright © 2017, Elsevier Inc. All rights reserved.

When administering an alpha-adrenergic drug for hypertension, it is most important for the nurse to assess the patient for the development of hypotension. hyperkalemia. oliguria. respiratory distress. Correct answer: A Rationale: These drugs have strong vasodilating properties and may cause severe hypotension, especially at the beginning of therapy. Copyright © 2017, Elsevier Inc. All rights reserved. Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint of Elsevier Inc.

Alpha2-Adrenergic Receptor Stimulators (Agonists)
Clonidine and methyldopa Not typically prescribed as first-line antihypertensive drugs High incidence of unwanted adverse effects: orthostatic hypotension, fatigue, and dizziness Adjunct drugs to treat hypertension after other drugs have failed Used in conjunction with other antihypertensives such as diuretics Copyright © 2017, Elsevier Inc. All rights reserved.

Alpha1 Blockers doxazosin (Cardura) prazosin (Minipress) tamsulosin (Flomax)* terazosin (Hytrin) *Tamsulosin is not used to control BP but is indicated solely for symptomatic control of BPH. Copyright © 2017, Elsevier Inc. All rights reserved.

Dual-Action Alpha1 and Beta Receptor Blockers
Carvedilol (Coreg) Widely used drug that is well tolerated Uses: hypertension, mild to moderate HF in conjunction with digoxin, diuretics, and ACE inhibitors Contraindications: known drug allergy, cardiogenic shock, severe bradycardia or HF, bronchospastic conditions such as asthma, and various cardiac problems involving the conduction system Copyright © 2017, Elsevier Inc. All rights reserved.

Beta Receptor Blocker Nebivolol (Bystolic) Uses: hypertension and HF Action: blocks beta1 receptors and produces vasodilatation, which results in a decrease in SVR Less sexual dysfunction Do not stop abruptly; must be tapered over 1 to 2 weeks. Copyright © 2017, Elsevier Inc. All rights reserved.

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 CCB Copyright © 2017, Elsevier Inc. All rights reserved.

ACE Inhibitors (Cont.) captopril (Capoten) benazepril (Lotensin) enalapril (Vasotec) fosinopril (Monopril) lisinopril (Prinivil) moexipril (Univasc) perindopril (Aceon) quinapril (Accupril) ramipril (Altace) trandolapril (Mavik) Copyright © 2017, Elsevier Inc. All rights reserved.

ACE Inhibitors: Mechanism of Action
Inhibit ACE, 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 © 2017, Elsevier Inc. All rights reserved.

ACE Inhibitors: Mechanism of Action (Cont.)
Block ACE, thus preventing the formation of angiotensin II Prevent the breakdown of the vasodilating substance bradykinin Result in decreased SVR (afterload), vasodilation, and therefore decreased BP Copyright © 2017, Elsevier Inc. All rights reserved.

ACE Inhibitors: Indications
Hypertension HF (either alone or in combination with diuretics or other drugs) Slow progression of left ventricular hypertrophy after myocardial infarction (MI) (cardioprotective) Renal protective effects in patients with diabetes Copyright © 2017, Elsevier Inc. All rights reserved.

A patient with diabetes has a new prescription for the 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? 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 diabetes. Correct answer: D Rationale: ACE inhibitors have been shown to have a protective effect on the kidneys because they reduce glomerular filtration pressure. This property makes them the cardiovascular drug of choice for patients with diabetes. Copyright © 2017, Elsevier Inc. All rights reserved. Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint of Elsevier Inc.

ACE Inhibitors (Cont.) 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. Copyright © 2017, Elsevier Inc. All rights reserved.

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? Clonidine Prazosin Diltiazem Captopril Correct answer: D Explanation: Captopril is not a prodrug; therefore, it does not need to be metabolized by the liver to be effective. This is an advantage in patients with liver disease. Copyright © 2017, Elsevier Inc. All rights reserved. Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint of Elsevier Inc.

ACE Inhibitors: Mechanism of Action
Inhibit ACE ACE: converts angiotensin I (A1) (formed through the action of renin) to angiotensin 2 (AII). AII: potent vasoconstrictors that induce aldosterone secretion by the adrenal glands Aldosterone: stimulates sodium and water resorption, which can raise BP Renin-angiotensin-aldosterone system ACE Inhibitors thus lower BP. Copyright © 2017, Elsevier Inc. All rights reserved.

Primary Effects of the ACE Inhibitors
Cardiovascular and renal BP: reduce BP by decreasing SVR HF Prevent sodium and water resorption by inhibiting aldosterone secretion Diuresis: decreases blood volume and return to the heart Decreases preload, or the left ventricular end-diastolic volume Decreases work required of the heart Copyright © 2017, Elsevier Inc. All rights reserved.

Cardioprotective Effects of the ACE Inhibitors
ACE inhibitors decrease SVR (a measure of afterload) and preload. Used to prevent complications after MI Ventricular remodeling: left ventricular hypertrophy, which is sometimes seen after MI ACE inhibitors have been shown to decrease morbidity and mortality in patients with HF. Drugs of choice for hypertensive patients with HF Copyright © 2017, Elsevier Inc. All rights reserved.

Renal Protective Effects of the ACE Inhibitors
ACE inhibitors: reduce glomerular filtration pressure Cardiovascular drugs of choice for patients with diabetes ACE inhibitors reduce proteinuria. Standard therapy for diabetic patients to prevent the progression of diabetic nephropathy Copyright © 2017, Elsevier Inc. All rights reserved.

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 © 2017, Elsevier Inc. All rights reserved.

Captopril (Capoten) Uses: prevention of ventricular remodeling after MI; reduce the risk of HF after MI Shortest half-life Must be administered multiple times throughout the day Copyright © 2017, Elsevier Inc. All rights reserved.

Enalapril (Vasotec) Only ACE inhibitor available in both oral and parenteral preparations. Enalapril intravenous (IV) does not require cardiac monitoring Oral enalapril: prodrug Improves patient’s chances of survival after an MI Reduces the incidence of HF Copyright © 2017, Elsevier Inc. All rights reserved.

Angiotensin II Receptor Blockers
Also referred to as angiotensin II blockers Well tolerated Do not cause a dry cough Copyright © 2017, Elsevier Inc. All rights reserved.

Angiotensin II Receptor Blockers (Cont.)
losartan (Cozaar) eprosartan (Teveten) valsartan (Diovan) irbesartan (Avapro) candesartan (Atacand) olmesartan (Benicar) telmisartan (Micardis) azilsartan (Edarbi) Copyright © 2017, Elsevier Inc. All rights reserved.

Angiotensin II Receptor Blockers: Mechanism of Action
ARBs affect primarily vascular smooth muscle and the adrenal gland. Selectively block the binding of AII to the type 1 AII receptors in these tissues ARBs block vasoconstriction and the secretion of aldosterone Copyright © 2017, Elsevier Inc. All rights reserved.

Comparison of ACE Inhibitors and Angiotensin II Receptor Blockers
ACE inhibitors and ARBs appear to be equally effective for the treatment of hypertension. Both are well tolerated. ARBs do not cause cough. Evidence that ARBs are better tolerated and are associated with lower mortality after MI than ACE inhibitors Not yet clear whether ARBs are as effective as ACE inhibitors in treating HF (cardioprotective effects) or in protecting the kidneys, as in diabetes Copyright © 2017, Elsevier Inc. All rights reserved.

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 © 2017, Elsevier Inc. All rights reserved.

Angiotensin II Receptor Blockers: Adverse Effects
Most common adverse effects of ARBs Chest pain Fatigue Hypoglycemia Diarrhea Urinary tract infection Anemia Weakness Hyperkalemia and cough are less likely to occur than with the ACE inhibitors. Copyright © 2017, Elsevier Inc. All rights reserved.

Which statement about ARBs does the nurse identify as being true? Hyperkalemia is more likely to occur than when using ACE inhibitors. Cough is more likely to occur than when using ACE inhibitors. Chest pain is a common adverse effect. Overdose is usually manifested by hypertension and bradycardia. Correct answer: C Rationale: The most common adverse effects of ARBs are chest pain, fatigue, hypoglycemia, diarrhea, urinary tract infection, anemia, and weakness. Hyperkalemia and cough are less likely to occur than with the ACE inhibitors. Overdose may manifest as hypotension and tachycardia; bradycardia occurs less often. Treatment is symptomatic and supportive and includes the administration of IV fluids to expand the blood volume. Copyright © 2017, Elsevier Inc. All rights reserved. Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint of Elsevier Inc.

Losartan (Cozaar) Beneficial in patients with hypertension and HF Used with caution in patients with renal or hepatic dysfunction and in patients with renal artery stenosis Copyright © 2017, Elsevier Inc. All rights reserved.

Calcium Channel Blockers
Primary use: treatment of hypertension and angina. Hypertension: cause smooth muscle relaxation by blocking the binding of calcium to its receptors, thereby preventing contraction Copyright © 2017, Elsevier Inc. All rights reserved.

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 SVR Decreased BP Copyright © 2017, Elsevier Inc. All rights reserved.

Calcium Channel Blockers: Indications
Angina Hypertension: amlodipine (Norvasc) Dysrhythmias Migraine headaches Raynaud’s disease Prevent the cerebral artery spasms after subarachnoid hemorrhage: nimodipine Copyright © 2017, Elsevier Inc. All rights reserved.

Diuretics First-line antihypertensives in the JNC 8 guidelines for the treatment of hypertension Decrease plasma and extracellular fluid volumes Results Decreased preload Decreased CO Decreased total peripheral resistance Overall effect Decreased workload of the heart and decreased BP Copyright © 2017, Elsevier Inc. All rights reserved.

Vasodilators: Mechanism of Action
Directly relax arteriolar or venous smooth muscle (or both) Results in: Decreased SVR Decreased afterload Peripheral vasodilation Copyright © 2017, Elsevier Inc. All rights reserved.

Vasodilators: Indications
Treatment of hypertension May be used in combination with other drugs Sodium nitroprusside and IV diazoxide are reserved for the management of hypertensive emergencies. Copyright © 2017, Elsevier Inc. All rights reserved.

Vasodilators: Adverse Effects
Hydralazine: dizziness, headache, anxiety, tachycardia, edema, dyspnea, nausea, vomiting, diarrhea, hepatitis, systemic lupus erythematosus, vitamin B6 deficiency, and rash Minoxidil: T-wave electrocardiographic changes, pericardial effusion or tamponade, angina, breast tenderness, rash, and thrombocytopenia Copyright © 2017, Elsevier Inc. All rights reserved.

Vasodilators: Adverse Effects (Cont.)
Sodium nitroprusside: bradycardia, decreased platelet aggregation, rash, hypothyroidism, hypotension, methemoglobinemia, and (rarely) cyanide toxicity Copyright © 2017, Elsevier Inc. All rights reserved.

Vasodilators: Hydralazine (Apresoline)
Orally: routine cases of essential hypertension Injectable: hypertensive emergencies BiDil: specifically indicated as an adjunct for treatment of HF in African-American patients Copyright © 2017, Elsevier Inc. All rights reserved.

Vasodilators: Sodium Nitroprusside (Nitropress)
Used in the intensive care setting for severe hypertensive emergencies; titrated to effect by IV infusion Contraindications: known hypersensitivity to the drug, severe HF, and known inadequate cerebral perfusion (especially during neurosurgical procedures) Copyright © 2017, Elsevier Inc. All rights reserved.

Miscellaneous Antihypertensive Drugs
Epleronone (Inspra) New class of drugs called selective aldosterone blockers Reduces BP by blocking the actions of aldosterone at its corresponding receptors in the kidney, heart, blood vessels, and brain Indications: routine treatment of hypertension and for post-MI HF Copyright © 2017, Elsevier Inc. All rights reserved.

Treatment of Pulmonary Hypertension
Bosentan (Tracleer) Specifically indicated only for the treatment of pulmonary artery hypertension in patients with moderate to severe HF Action: blocks receptors of the hormone endothelin Copyright © 2017, Elsevier Inc. All rights reserved.

Treatment of Pulmonary Hypertension (Cont.)
Other drugs used to treat pulmonary hypertension epoprostenol treprostinil iloprost ambrisentan macitentan sildenafil and tadalafil Copyright © 2017, Elsevier Inc. All rights reserved.

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 © 2017, Elsevier Inc. All rights reserved.

Nursing Implications (Cont.)
Educate patients about the importance of not missing a dose and taking the medications exactly as prescribed. Instruct patients to check with their physicians 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 © 2017, Elsevier Inc. All rights reserved.

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 © 2017, Elsevier Inc. All rights reserved.

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 © 2017, Elsevier Inc. All rights reserved.

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; and excessive fatigue. Copyright © 2017, Elsevier Inc. All rights reserved.

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 physicians immediately. Copyright © 2017, Elsevier Inc. All rights reserved.

Hot tubs, showers, or baths; hot weather; prolonged sitting or standing; physical exercise; and alcohol ingestion may aggravate low BP, 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 physicians. Copyright © 2017, Elsevier Inc. All rights reserved.

ACE Inhibitors and Laboratory Values
ACE inhibitors can cause renal impairment, which can be identified with serum creatinine. ACE inhibitors can also cause hyperkalemia, so potassium levels need to be monitored. Copyright © 2017, Elsevier Inc. All rights reserved.

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