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Lilley Pharmacology Antihypertensive Drugs Blood Pressure Review • Blood pressure = CO × SVR • CO = cardiac output • SVR = systemic vascular resistance • Hypertension = high blood pressure 2 3 Stages of Blood Pressure 1. Normal <120 over </ 80 2. Prehypertension 120 or >/ 80 or > 3. Hypertension 140/90 4 Classification of BP • Hypertension • Unknown can also be defined by its cause Cause Essential, or Primary Hypertension 90-95% of cases • Known cause Secondary hypertension Approximately 10% of cases 5 Antihypertensive Drugs • Medications used to treat hypertension • Categories Adrenergic drugs Angiotensin-converting enzyme (ACE) inhibitors Angiotensin II receptor blockers (ARBs) Calcium channel blockers (CCBs) Beta blockers Diuretics Vasodilators Direct renin inhibitors 6 7 Adrenergic Drugs Actions Centrally acting alpha2 receptor agonists Stimulate alpha2-adrenergic receptors in the brain Decrease sympathetic outflow from the CNS Stimulate alpha2-adrenergic receptors, thus reducing renin activity in the kidneys Alpha blockers relax certain muscles and help small blood vessels remain open They work by keeping the hormone norepinephrine from tightening the muscles in the walls of smaller arteries and veins Blocking that effect causes the vessels to remain open and relaxed. This improves blood flow and lowers blood pressure Results in decreased blood pressure Example: doxazosin (Cardura) 8 Adrenergic Drugs • Peripheral alpha1 blockers/antagonists Block alpha1-adrenergic receptors doxazosin (Cardura) terazosin (Hytrin) prazosin (Minipress) First dose phenomena, tachycardia, dyspnea, feeling faint 9 Adrenergic Drugs • Beta blockers Reduce BP by reducing heart rate through beta1 blockade Cause reduced secretion of renin Long-term use causes reduced peripheral vascular resistance Examples: nebivolol (Bystolic), propranolol (Inderal), atenolol (Tenormin), metoprolol (Lopressor) 10 Adrenergic Drugs Dual-action alpha1 and beta receptor blockers Reduce BP & heart rate (beta1 receptor blockade) Cause vasodilation (alpha1 receptor blockade) Examples: carvedilol (Coreg) and labetalol (Normadyne, Trandate) Result in decreased blood pressure & HR 11 Adrenergic Drugs: Indications • All used to treat hypertension • 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 Clonidine is useful in the management of withdrawal symptoms in opioid-dependent persons (reduces anxiety and restlessness) 12 Adrenergic Drugs: Indications (cont’d) • Peripherally acting alpha1 receptor agonists Treatment of hypertension Some used to relieve symptoms of benign prostatic hyperplasia (BPH)- vasodilating effect Management of severe heart failure (HF) when used with cardiac glycosides and diuretics 13 Adrenergic Drugs: Adverse Effects • High • incidence of orthostatic hypotension Most common Bradycardia with reflex tachycardia Dry mouth Drowsiness, sedation Constipation Depression Edema Sexual dysfunction 14 Adrenergic Drugs: Adverse Effects • Other Headaches Sleep disturbances Nausea Rash Cardiac disturbances (palpitations) 15 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. 16 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 17 ACE Inhibitors Examples • captopril (Capoten) • benazepril (Lotensin) • enalapril (Vasotec) • fosinopril (Monopril) • lisinopril (Prinivil) • moexipril (Univasc) • quinapril (Accupril) 18 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 19 ACE Inhibitors: Mechanism of Action • 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 20 ACE Inhibitors: Indications • Hypertension • HF (either alone or in combination with diuretics or other drugs) • Slow progression of left ventricular hypertrophy after MI (cardio protective) • Renal protective effects in patients with diabetes 21 Classroom Response Question A patient with type II diabetes has a new prescription for the angiotensinconverting 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 cardio-protective properties. This medication has a protective effect on the kidneys for patients with type II diabetes. 22 ACE Inhibitors: Indications (cont’d) • Drugs of choice in hypertensive patients with • Drugs of choice for diabetic patients HF 23 ACE Inhibitors • 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 24 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 25 ACE Inhibitors: Adverse Effects • Fatigue • Dizziness • Headache • Mood changes • Impaired taste • Dry, nonproductive cough, which reverses when therapy is stopped • Angioedema: rare but potentially fatal • Potential hyperkalemia • First dose hypotension may occur 26 Angiotensin II Receptor Blockers • Also referred to as angiotensin II blockers or ARBs • Well tolerated • Rarely cause a dry cough 27 Angiotensin II Receptor Blockers • losartan (Cozaar) • valsartan (Diovan) • irbesartan (Avapro) • candesartan (Atacand) • olmesartan (Benicar) • telmisartan (Micardis) 28 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 – results in vasodilation 29 Angiotensin II Receptor Blockers: Indications • Hypertension • Adjunctive drugs for the treatment of HF • May be used alone or with other drugs such as diuretics 30 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 31 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. 32 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 33 Calcium Channel Blockers: Indications • Angina • Hypertension • Dysrhythmias • Migraine headaches • Raynaud’s disease 34 Beta Blockers • Beta-blockers are used for their antagonistic effect on cardiac beta-1 adrenoceptors • Two types of beta-blockers are available: beta-1 selective adrenoceptor antagonists (metoprolol, atenolol) • And nonselective beta-1/ beta-2 adrenoceptor antagonists cardiac & pulmonary effect (carvedilol, propranolol, sotalol, timolol). • Beta-2 receptor antagonism is associated with bronchoconstriction. • Many commercially available beta-1 selective blockers have high affinity for beta-2 receptors • So, both selective and nonselective beta-blockers may cause bronchoconstriction, which can lead some patients to experience a cough reflex. 35 Diuretics • Decrease volumes plasma and extracellular fluid • Results Decreased preload Decreased cardiac output Decreased total peripheral resistance • Overall effect Decreased workload of the heart and decreased blood pressure (from decreased volume) 36 Diuretics • Thiazide diuretics are the most commonly used diuretics for hypertension • Listed as first-line antihypertensives guidelines 37 Vasodilators • diazoxide (Hyperstat) • hydralazine HCl (Apresoline) • sodium nitroprusside used in ICU (Nipride, Nitropress) 38 Vasodilators: Mechanism of Action • Directly muscle • Results relax arteriolar and/or venous smooth in: Decreased systemic vascular response Decreased afterload Peripheral vasodilation 39 Vasodilators: Indications • Treatment • May of hypertension be used in combination with other drugs • Sodium nitroprusside and intravenous diazoxide are reserved for the management of hypertensive emergencies 40 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 41 Nursing Implications • 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 BP checks 42 Nursing Implications • Instruct patients that these drugs should not be stopped abruptly because this may cause a rebound hypertensive crisis, and perhaps lead to stroke • Administer IV forms with extreme caution, and use an IV pump • Oral forms should be given with meals or per label, so that absorption is more gradual 43 Nursing Implications • 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 44 Nursing Implications • 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 • Report weight gain or loss, chest pain, palpitations, or excessive fatigue (HF symptoms) 45 Nursing Implications • 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 46 Nursing Implications • Hot 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 over-the-counter drugs, without first getting the approval of their physician, and discuss all other medications they are taking 47 Nursing Implications Educate patients about lifestyle changes that may be needed • Weight loss Stress management Supervised exercise Dietary measures Nurses: Monitor for adverse effects including • dizziness, orthostatic hypotension • Monitor for therapeutic effects- which would be? 48