Cardiovascular System Hypertension Lilley – Reading & Workbook, Chap 24

Antihypertensive Drugs Hypertension 50 million people in US Major risk factor for – Cardiovascular Disease Coronary Artery Disease Congestive heart failure Cerebrovascular Stroke Renal Failure Peripheral Vascular Disease/Arterial Disease

Antihypertensive Drugs Hypertension Classification SBP DBP Normal <120 <80 Prehypertension 120-129 80-89 Stage 1 HTN 140-159 90-99 Stage 1 HTN <160 <100 The previous labels of “mild,” “moderate,” and “severe” HTN have been dropped

Antihypertensive Drugs Hypertension - Definition BP = Cardiac Output x Systemic vascular resistance BP = CO x SVR CO = Amount of blood ejected from left ventricle per minute – measured in L/min SVR = the force or resistance the left ventricle has to overcome to eject its volume of blood.

Antihypertensive Drugs Hypertension Disease Process Hypertension and associated risk factors How does cigarette smoking contribute to high blood pressure? (Smoking causes vasoconstriction, which increases the heart’s work.) What effect does high cholesterol have on blood pressure? (Increased circulation of cholesterol causes plaque formation within the blood vessel walls, resulting in a narrowed lumen, which increases vascular resistance.) Can stress affect blood pressure? (Stress can increase the pulse rate, which increases the systolic pressure.) Of the major risk factors identified, which are those that can be controlled with lifestyle modifications? Identify the types of organ damage that occur with hypertension. How can the nurse approach education to those patients unwilling to modify lifestyle changes? Mosby items and derived items © 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

Hypertension Nutrition

Primary Hypertension Medical Management Lifestyle modification Nutritional therapy Alcohol consumption Physical activity Tobacco avoidance Stress management Drug Therapy

Hypertension Mechanisms that Regulate BP Sympathetic Nervous System Vascular Endothelium Renal System Endocrine System

Hypertension Mechanisms that Regulate BP Sympathetic Nervous System (SNS) – norepinephrine released from sympathetic nerve endings - to receptors alpha1, alpha2, beta 1 & beta2 Reacts within seconds Increases Heart Rate - chronotropic Increased cardiac contractility - inotropic Produces widespread vasoconstriction in peripheral arterioles Promotes release of renin from the kidney

Hypertension SNS Receptors Influencing B/P

Hypertension Mechanisms that Regulate BP Sympathetic Nervous System (SNS)– Sympathetic Vasomotor Center – located in the medulla – interacts with many areas of the brain to maintain BP within normal range under various conditions Exercise – changes to meet oxygen demand Postural Changes – peripheral vasoconstriction

Hypertension Mechanisms that Regulate BP Sympathetic Nervous System (SNS) – Baroreceptors: specialized nerve cells the carotid arteries and the aortic arch Sensitive to BP changes: Increased BP: Inhibits SNS – peripheral vessel dilation. Decreased heart rate & decreased contractility of the heart + increased parasympathetic activity (vagus nerve) decreased heart rate Decreased BP: Activates SNS – peripheral vessel constriction, increased heart rate, and increased contractility of the heart

Hypertension Mechanisms that Regulate BP Vascular Endothelium Single cell layer that lines the blood vessels Produce vasoactive substances: EDRF Endothelium-derive relaxing factor – Helps maintain low arterial tone at rest Inhibits growth of the smooth muscle layer Inhibits platelet aggregation Vasodilation – prostacyclin Endothelin (ET) potent vasoconstrictor Endothelial dysfunction may contribute to atherosclerosis & primary hypertension

Hypertension Mechanisms that Regulate BP Renal System Controls Na+ excretion & extracellular fluid volume Renal - Renin-angiotensin-aldosterone Renin converts angiotensinogen to angiotensin I Angiotensin-converting enzyme (ACE) converts I into angiotensin II Immediate: Vasoconstrictor – increased systemic vascular resistance Prolonged: Stimulates the adrenal cortex to secret Aldosterone – Na+ and Water retention Renal Medulla - Prostaglandins - vasodilator effect

Hypertension Mechanisms that Regulate BP Endocrine System Stimulates the SNS with Epinephrine – increases HR and contractility Activates B2-adrenergic receptors in peripheral arterioles of skeletal muscle = vasodilation Activates A1-adrenergic receptors in peripheral arterioles of skin and kidneys = vasoconstiction Adrenal Cortex – Aldosterone – stimulates kidneys to retain Na+ Increased Na+ stimulates posterior pituitary – ADH – reabsorbs ECF/water

Antihypertensive Drugs Compelling Indications to Treat HTN Post-MI High cardiovascular risk Heart failure Diabetes mellitus Chronic kidney disease Previous stroke

Antihypertensive Drugs Regulation of Blood Pressure CNS Autonomic Nervous System Adrenergic Drugs: Central & peripheral acting adrenergic neuron blockers Central acting a2 receptor blockers Peripherally acting a1 receptor blockers Peripherally acting b b receptor blockers Cardioselective beta1 receptor blockers Nonselective b1 and b 2 receptor blockers Peripherally acting dual a & b receptor blockers Angiotensin-Converting Enzyme Inhibitors (ACE Inhibitors) Calcium Channel Blockers Diuretics Vasodilators

Antihypertensive Drugs Regulation of Blood Pressure

Antihypertensive Drugs: Categories Adrenergic drugs Angiotensin converting enzyme (ACE) inhibitors Angiotensin II receptor blockers (ARBs) Calcium channel blockers (CCBs) Diuretics Vasodilators

Antihypertensive Drugs 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 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” Require lifestyle modifications to prevent CVD Thiazide-type diuretics-initial drug therapy for HTN Alone or with other medications

Antihypertensive Drugs Cultural Considerations b-blockers and ACE inhibitors have been found to be more effective in white patients than African-American patients CCBs and diuretics have been shown to be more effective in African-American patients than in white patients

Antihypertensive Drugs Classification of HTN Hypertension can also be defined by its cause Unknown cause Known as essential, idiopathic, or primary hypertension 90% of the cases Known cause Secondary hypertension 10% of the cases

Antihypertensive Drugs

Antihypertensive Drugs Adrenergic drugs B-Adrenergic Blockers Central Acting Adrenergic Antagonists Peripheral Acting Adrenergic Antagonists A-Adrenergic Blockers Angiotensin converting enzyme (ACE) inhibitors Angiotensin II receptor blockers (ARBs) Calcium channel blockers (CCBs) Diuretics Thiazide Loop K+ Sparing Vasodilators

Antihypertensive Drugs Adrenergic Drugs: Five Subcategories Centrally and peripherally acting adrenergic neuron blockers Centrally acting a2-receptor agonists Peripherally acting a1-receptor blockers Peripherally acting b-receptor blockers (b-blockers) cardioselective (b1 receptors) nonselective (both b1 and b2 receptors) Peripherally acting dual a1- and b-receptor blockers

Antihypertensive Drugs Adrenergics - Action-a2-Receptor Agonists Centrally acting a2-receptor agonists Stimulate a2-adrenergic receptors in the brain Sympathetic outflow from the CNS is decreased Norepinephrine production is decreased Stimulation of the a2-adrenergic receptors reduces renin activity in the kidneys Result: decreased blood pressure clonidine (Catapres) guanfacine (Tenex) methyldopa (Aldomet) Drug of choice for hypertension in pregnancy

Antihypertensive Drugs Adrenergic Drugs: Peripheral a1-blockers/antagonists Block the a1-adrenergic receptors doxazosin (Cardura) prazosin (Minipress) terazosin (Hytrin) Result: decreased blood pressure

Antihypertensive Drugs Adrenergic Drugs: b-blockers Reduce BP by reducing heart rate through b1-blockade Cause reduced secretion of renin Long-term use causes reduced peripheral vascular resistance metoprolol (Lopressor, Toprol XL) – IV (dysrhythmias) or po propranolol (Inderal) atenolol (Tenormin) Result: decreased blood pressure

Adrenergic Drugs: Dual-action a1- and b-receptor blockers Block the a1-adrenergic receptors Reduction of heart rate (b1-receptor blockade) Vasodilation (a1-receptor blockade) labetalol (Normodyne, Trandate) carvedilol (Coreg) Result: decreased blood pressure

Antihypertensive Drugs Centrally and Peripherally Acting Neuron Blocker Reserpine - The only centrally and peripherally acting neuron blocker still available in the United States, but is rarely used Seldom used because of frequent adverse effects

Antihypertensive Drugs Adrenergic Drugs Adverse Effects Most common: Dry mouth Drowsiness Sedation Constipation Other Headaches Sleep disturbances: Nausea Rash Cardiac disturbances (palpitations), others HIGH INCIDENCE OF ORTHOSTATIC HYPOTENSION

Antihypertensive Drugs Angiotensin Converting Enzyme Inhibitors (ACE inhibitors, or ACEIs) Large group of safe and effective drugs Often used as first-line drugs for HF & HTN May be combined with a thiazide diuretic or calcium channel blocker

Antihypertensive Drugs ACE Inhibitors 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 adrenals Aldosterone stimulates water and sodium reabsorption Result: increased blood volume, increased preload, and increased BP Prevent the breakdown of the vasodilating substance, bradykinin Result: decreased systemic vascular resistance (afterload), vasodilation, and therefore decreased blood pressure

Antihypertensive Drugs ACE Inhibitors-- Indications Hypertension Heart Failure (HF) (either alone or in combination with diuretics or other drugs) drug of choice To slow progression of left ventricular hypertrophy after an MI (cardioprotective) Renal protective effects in patients with diabetes drug of choice for DM patients

Antihypertensive Drugs ACE Inhibitors captopril (Capoten) Very short half-life Prevents - L ventricular dilation & dysfunction (ventricular remodeling) enalapril (Vasotec) lisinopril (Prinivil and Zestril) quinapril (Accupril) Newer drugs, long half-lives, once-a-day dosing ramipril (Altace)

Antihypertensive Drugs ACE Inhibitors - Considerations Captopril and lisinopril are NOT prodrugs Prodrugs are inactive in their administered form and must be metabolized in the liver to an active form in order to be effective Captopril and lisinopril can be used if a patient has liver dysfunction, unlike other ACE inhibitors that are prodrugs

Antihypertensive Drugs 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!

Antihypertensive Drugs Angiotensin II Receptor Blockers Allow angiotensin I to be converted to angiotensin II Block the receptors that receive angiotensin II Result: Block vasoconstriction and release of aldosterone losartan (Cozaar, Hyzaar) valsartan (Diovan) Both safe to use during pregnancy

Antihypertensive Drugs 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 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

Antihypertensive Drugs Calcium Channel Blockers Action: Cause smooth muscle relaxation: blocks the binding of calcium to its receptors, preventing muscle contraction Inhibit movement of calcium ions across the cell membrane This causes: decreased peripheral smooth muscle tone - vasodilation decreased systemic vascular resistance Slower rate of myocardial contraction Result: decreased blood pressure

Calcium Channel Blockers Classified by Structure Benzothiazepines diltiazem (Cardizem) Phenylalkamines verapamil (Calan, Isoptin, Verelan) Dihydropyridines amlodipine (Norvasc), bepridil (Vascor), nicardipine (Cardene) nifedipine (Procardia) nimodipine (Nimotop)

Antihypertensive Drugs Calcium Channel Blockers Indications: Angina Hypertension Dysrhythmias Migraine headaches Raynaud’s disease Adverse Effects: Cardiovascular: Hypotension, palpitations, tachycardia Gastrointestinal Constipation, nausea Other Rash, flushing, peripheral edema, dermatitis

Antihypertensive Drugs Vasodilators Action: Directly relax arteriolar and/or venous smooth muscle Result: decreased systemic vascular response, decreased afterload, and peripheral vasodilation diazoxide (Hyperstat) hydralazine HCl (Apresoline) minoxidil (Loniten) sodium nitroprusside (Nipride, Nitropress) Directly dilates arterial and venous smooth muscle

Antihypertensive Drugs Vasodilators Treatment of hypertension May be used in combination with other drugs Oral diazoxide may be used as an antihypoglycemic Sodium nitroprusside & IV diazoxide are reserved for the management of hypertensive emergencies given intravenously on monitored patients

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); solution must be protected from light Diazoxide Dizziness, headache, anxiety, orthostatic hypotension, dysrhythmias, sodium and water retention, nausea, vomiting, hyperglycemia in diabetic patients, others

Antihypertensive Drugs Nursing Implications Thorough health history & physical examination Assess for contraindications to specific antihypertensive drugs Assess for conditions that require cautious use of these drugs Administer IV forms with extreme caution and use an IV pump

Antihypertensive Drugs Patient Education Educate patients about the importance of not missing a dose and taking the medications exactly as prescribed Never double up on doses if a dose is missed Check with physician for instructions on what to do if a dose is missed Monitor BP during therapy; instruct patients to keep a journal of regular BP checks Men taking these drugs may not be aware that impotence is an expected effect. This may influence compliance with drug therapy

Antihypertensive Drugs Patient Education Remind patients that medication is only part of therapy. Encourage patients to watch their diet, stress level, weight, and alcohol intake Patients should avoid smoking and eating foods high in sodium Encourage supervised exercise Instruct patients to change positions slowly to avoid syncope from postural hypotension** 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

Antihypertensive Drugs Patient Education Avoid: 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 OTC drugs, without first getting the approval of their physician Contact physician: If patients are experiencing serious adverse effects, or believe that the dose or medication needs to be changed 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

Antihypertensive Drugs Nursing Implications Monitor for adverse effects (dizziness, orthostatic hypotension, fatigue) and for toxic effects Monitor for therapeutic effects Blood pressure should be maintained <130/90 mm Hg Patients with hypertension also has DM or renal disease: the BP goal is <130/80 mm Hg

Review 1. Angiotensin-converting enzyme (ACE) inhibitors include drugs such as _______________ and_____________.   2. Diazoxide and sodium nitroprusside are classified as __________________ and result in __________. 3. Prazosin (Minipress) is a(n) ____________________. 4. Propranolol works to decrease blood pressure by ___________________. 5. Nonpharmacologic treatment approaches to hypertension include ________________, ___________________, and _____________. 6. __________ and __________ are the only two ACE inhibitors that are not prodrugs.

Review Answers 1. ACE inhibitors include drugs such as captopril (Capoten), benazepril (Lotensin), enalapril (Vasotec), fosinopril (Monopril), lisinopril (Prinivil, Zestril), moexipril (Univasc), perindopril (Aceon), quinapril (Accupril), ramipril (Altace), and trandolapril (Mavik).   2. Diazoxide and sodium nitroprusside are classified as vasodilators and result in peripheral vasodilation, resulting in a reduction in systemic vascular resistance and reduced blood pressure. 3. Prazosin (Minipress) is a peripherally acting alpha1-blocker. 4. Propranolol works to decrease blood pressure by its β-blocking effects. It decreases heart rate and cardiac output, which are the components of blood pressure. 5. Nonpharmacologic treatment approaches to hypertension include weight loss, smoking cessation, sodium restriction, stress reduction, and supervised exercise. 6. Captopril and lisinopril are the only two ACE inhibitors that are not prodrugs.

Review: Match each definition with its corresponding term Review: Match each definition with its corresponding term. Not all terms will be used.   A. prodrug B. orthostatic hypotension C. secondary D. essential E. cardiac output F. diazoxide (Hyperstat) G. losartan (Cozaar) H. doxazosin (Cardura) I. captopril (Capoten) J. angiotensin II–receptor blockers M. ACE inhibitors N. α1-blockers O. Ejection fraction  1. _____ Drugs that primarily cause arterial and venous dilation through blocking the SNS 2. _____ Blood pressure is determined by the product of _______ and systemic vascular resistance (SVR) 3. _____ Drugs in this class cause a characteristic dry, nonproductive cough 4. _____ These drugs block vasoconstriction and the secretion of aldosterone. 5. _____ A drug that is inactive in its administered form and must be biotransformed in the liver to its active form. 6. _____ An example of a drug in the class mentioned in #1 7. _____ An example of a drug in the class mentioned in #3 8. _____ An example of a drug in the class mentioned in #4 9. _____ An elevated systemic arterial pressure for which no cause can be found 10. _____ A common adverse effect of adrenergic drugs that involves a sudden drop in blood pressure

Review - Matching Answers 4. J 5. A 6. H 7. I 8. G 9. D 10. B