Hypertensive Crises PDF

10/17/23, 4:12 PM Realizeit for Student Hypertensive Crises Two classes of hypertensive crisis that require immediate intervention include hypertensive emergency and hypertensive urgency, which occur when the SBP exceeds 180 mm Hg or the DBP exceeds 120 mm Hg. Hypertensive emergencies and urgencie...

10/17/23, 4:12 PM Realizeit for Student Hypertensive Crises Two classes of hypertensive crisis that require immediate intervention include hypertensive emergency and hypertensive urgency, which occur when the SBP exceeds 180 mm Hg or the DBP exceeds 120 mm Hg. Hypertensive emergencies and urgencies may occur in patients with secondary hypertension, and in those whose hypertension has been poorly controlled, whose hypertension has been undiagnosed, or in those who have abruptly discontinued their medications (i.e., rebound hypertension). Once the hypertensive crisis has been managed, a complete evaluation is performed to review the patient’s ongoing treatment plan, and strategies to prevent the occurrence of subsequent hypertensive crises are implemented (Whelton et al., 2017). Extremely close hemodynamic monitoring of the patient’s blood pressure and cardiovascular status is required during treatment of hypertensive emergencies and urgencies. The exact frequency of monitoring is a matter of clinical judgment and varies with the patient’s condition. Taking vital signs every 5 minutes is appropriate if the blood pressure is changing rapidly; taking vital signs at 15- or 30-minute intervals in a more stable situation may be sufficient. A precipitous drop in blood pressure can occur that would require immediate action to restore blood pressure to an acceptable level. Pharmacologic Therapy Research findings have demonstrated that appropriately prescribing antihypertensive pharmacologic agents lowers BP, and reduces the risk of CVD, cerebrovascular disease, and death (Whelton et al., 2017). Many classes of medications are available for hypertension management (Table 27-4). The medications that have been shown to prevent CVD are recommended as first-line agents for most patients. This first-line group includes thiazide or thiazide-type diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and calcium channel blockers (CCBs). African American patients with hypertension and without heart failure or CKD should be prescribed either a thiazide diuretic or a CCB as a first-line agent (not an ACE inhibitor or an ARB). The recommended first-line antihypertensive agents for patients with select comorbid disorders or who are pregnant are displayed in Table 27-5. Table 27-4 Oral Medication Therapy for Hypertension Medications Major Actions Advantages and Contraindications Effects and Nursing Considerations First-Line Antihypertensive Agents https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IWsgl87YCND5MlxcaDR%2bIXwVK92JaTnVop0r%2bp7e… 1/28 10/17/23, 4:12 PM Realizeit for Student Side effects include dry mouth, thirst, weakness, drowsiness lethargy, muscle aches muscular fatigue, Decrease of blood volume, Thiazide or Thiazide-Type Diuretics chlorthalidonea hydrochlorothiazide indapamide metolazone agent for its long half-life. Effective orally. renal blood flow, and cardiac Effective during long-term output. administration. Depletion of Mild side effects. extracellular fluid. Negative sodium balance (from natriuresis), mild a preferred Relatively inexpensive. hypokalemia. Directly affect vascular smooth muscle. tachycardia, GI disturbance. Orthostatic hypotension may be potentiated by alcohol, barbiturates, opioids, or hot weather. Enhance other antihypertensive medications. Because thiazides cause loss of sodium, Counter sodium retention potassium, and effects of other antihypertensive magnesium, and medications. increase in uric acid and calcium, monitor Contraindications: Gout, known for signs of electrolyte sensitivity to sulfonamide- imbalance. derived medications, severely impaired kidney function, and Encourage intake of history of hyponatremia. potassium-rich foods. Gerontologic considerations: Risk of orthostatic hypotension. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IWsgl87YCND5MlxcaDR%2bIXwVK92JaTnVop0r%2bp7e… 2/28 10/17/23, 4:12 PM Realizeit for Student Can cause ACE Inhibitors hyperkalemia. benazepril Side effect can include cough. Angioedema is a rare but captopril enalapril fosinopril lisinopril moexipril perindopril quinapril Inhibit potentially life-threatening Gerontologic complication. considerations: Require reduced dosages and conversion of angiotensin I to Contraindications: Concomitant the addition of loop angiotensin II. use of an ARB or a renin diuretics when there is inhibitor or a potassium-sparing renal dysfunction. Lower total diuretic or potassium peripheral supplements; bilateral renal May cause resistance. artery stenosis, pregnancy; upregulation of ACE2 history of angioedema with prior receptors, making use of an ACE inhibitor. patients more susceptible to infection ramipril trandolapril with SARS-CoV-2; however, may also mitigate deleterious effects of COVID-19. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IWsgl87YCND5MlxcaDR%2bIXwVK92JaTnVop0r%2bp7e… 3/28 10/17/23, 4:12 PM Realizeit for Student Monitor for hyperkalemia. Angiotensin Receptor Blockers Can be prescribed for Minimal side effects. azilsartan candesartan eprosartan Block the effects of angiotensin II at the receptor. irbesartan Reduce losartan olmesartan peripheral resistance. Contraindications: Concomitant use of an ACE inhibitor or a renin inhibitor or a potassiumsparing diuretic or potassium supplements; bilateral renal artery stenosis; history of angioedema with prior use of an ARB; pregnancy, lactation, renovascular disease. telmisartan valsartan patients with a history of angioedema from ACE inhibitor; however must wait 6 wks to take after ACE inhibitor stopped. May cause upregulation of ACE2 receptors, making patients more susceptible to infection with SARS-CoV-2; however, may also mitigate deleterious effects of COVID-19. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IWsgl87YCND5MlxcaDR%2bIXwVK92JaTnVop0r%2bp7e… 4/28 10/17/23, 4:12 PM Realizeit for Student Can cause pedal edema, which is more common in women. Inhibit calcium ion influx across Calcium Channel Blockers— Dihydropyridines amlodipine felodipine membranes. Administer on empty Rapid action. eating small, frequent Vasodilatory Effective by oral or sublingual effects on meals if complaint of route. nausea. arteries and No tendency to slow SA nodal Use with caution in peripheral activity or prolong AV node patients with diabetes. arterioles. conduction. coronary Muscle cramps, joint isradipine nicardipine SR Decrease Useful drug in treating isolated stiffness, sexual cardiac work systolic hypertension. dysfunction may and energy nifedipine LA nisoldipine stomach; recommend consumption, Contraindication: HFrEF (but increase can use amlodipine or delivery of felodipine, if necessary). disappear if dose decreased. Report irregular oxygen to heartbeat, myocardium. constipation, shortness of breath, edema. May cause dizziness. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IWsgl87YCND5MlxcaDR%2bIXwVK92JaTnVop0r%2bp7e… 5/28 10/17/23, 4:12 PM Realizeit for Student Do not discontinue suddenly. Observe for Calcium Channel hypotension. Blockers— Inhibit calcium Nondihydropyridines ion influx. diltiazem ER verapamil IR verapamil SR verapamil—delayed- Reduce cardiac Report irregular Avoid concomitant dosing with heartbeat, dizziness, beta-blockers. edema. Contraindications: HFrEF; sinus Instruct on regular node dysfunction, AV block. dental care because of afterload. Slow velocity of conduction of potential gingivitis. cardiac impulse. Metabolized via onset ER cytochrome p450 system; therefore, many potential drug interactions. Second-Line Antihypertensive Agents Volume Risk of volume and Diuretics—Loop depletion. bumetanide Block reabsorption of severe CKD. furosemide torsemide Preferred diuretics for patients electrolyte depletion; with symptomatic HF and for monitor for patients with moderate to hypokalemia. Gerontologic sodium, chloride, and Contraindications: Same as for considerations: Risk fo water in renal thiazide diuretics. orthostatic tubules. hypotension. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IWsgl87YCND5MlxcaDR%2bIXwVK92JaTnVop0r%2bp7e… 6/28 10/17/23, 4:12 PM Diuretics— Potassium-Sparing amiloride triamterene Realizeit for Student Not particularly effective Drowsiness, lethargy, antihypertensive drugs when headache. Block sodium prescribed as lone agents; can reabsorption. be effective when prescribed Monitor for with a thiazide diuretic in hyperkalemia if given Act on distal patients with hypokalemia; with ACE inhibitor or tubule causes potassium retention. ARB. Contraindications: Significant Diarrhea and other GI CKD, severe hepatic disease, symptoms—administer hyperkalemia. medication after meals independently of aldosterone. Drowsiness, lethargy, headache. Monitor for hyperkalemia if given with ACE inhibitor or Diuretics— Indicated for patients with Aldosterone Antagonists eplerenone spironolactone primary aldosteronism and Competitive inhibitors of aldosterone binding. resistant hypertension. Contraindications: Hyperkalemia and impaired renal function. ARB. Diarrhea and other GI symptoms—administer medication after meals Avoid the use of potassium supplements or salt substitutes. Spironolactone may cause gynecomastia. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IWsgl87YCND5MlxcaDR%2bIXwVK92JaTnVop0r%2bp7e… 7/28 10/17/23, 4:12 PM Realizeit for Student Similar to other beta-blockers with additional capacity for vasodilation. Beta-Blockers— Cardioselective nebivolol Blocks beta-1 adrenergic receptors and induces nitric oxide vasodilation. Contraindications: Similar to beta-blockers but with greater risk of severe bradycardia, heart Avoid sudden discontinuation. Sideeffect profile similar to other beta-blockers. block, cardiogenic shock, decompensated cardiac failure, sinus node dysfunction. Similar to other beta-blockers with additional capacity for Beta-Blockers— Cardioselective and Vasodilatory nebivolol Blocks beta-1 vasodilation. adrenergic receptors and Contraindications: Similar to induces nitric beta-blockers but with greater oxide risk of severe bradycardia, heart vasodilation. block, cardiogenic shock, Avoid sudden discontinuation. Sideeffect profile similar to other beta-blockers. decompensated cardiac failure, sinus node dysfunction. Beta-Blockers— Noncardioselective nadolol propranolol propranolol LA timolol Avoid sudden Nonselectively block the betaadrenergic receptors of the sympathetic nervous system with intended effects of slowing the heart rate and lowering the blood pressure. discontinuation. Side effects may Contraindications: Asthma, reactive airway disease, COPD, heart block, symptomatic bradycardia. include insomnia, lassitude, weakness, fatigue and occasionally nausea, vomiting, and epigastric distress. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IWsgl87YCND5MlxcaDR%2bIXwVK92JaTnVop0r%2bp7e… 8/28 10/17/23, 4:12 PM Realizeit for Student Block both Beta-Blockers— beta-1 and Intrinsic beta-2 Sympathomimetic receptors. Avoid sudden discontinuation. Activity Also has acebutolol penbutolol pindolol antiarrhythmic Contraindications: Avoid use in patients with HFrEF. activity by Side-effect profile similar to other betablockers. slowing atrioventricular conduction. Block alphaBeta-Blockers— and beta- Combined Alpha- adrenergic Carvedilol is a preferred agent and Beta-Receptor receptors. for patient with HFrEF. Blockers carvedilol carvedilol phosphate CR labetalol Avoid sudden discontinuation. Cause Contraindications: Asthma, peripheral reactive airway disease, COPD, Side-effect profile dilation and heart block, symptomatic similar to other beta- decrease bradycardia, cardiogenic shock, blockers. peripheral severe tachycardia. vascular resistance. Blocks the Direct Renin Inhibitor Aliskiren conversion of angiotensinogen to angiotensin I by inhibiting the activity of the enzyme renin. Cannot be given in combination with ACE inhibitors or ARBs. Very long acting. Contraindicated in pregnancy. Monitor for hyperkalemia, especially for patients with CKD, or patients taking potassium supplements. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IWsgl87YCND5MlxcaDR%2bIXwVK92JaTnVop0r%2bp7e… 9/28 10/17/23, 4:12 PM Alpha-1 Blockers doxazosin Realizeit for Student Peripheral vasodilator acting directly on the blood prazosin terazosin vessel; action similar to direct May be second-line agent in men with BPH. Contraindication: CAD. Associated with orthostasis, especially in older adults. vasodilators. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IWsgl87YCND5MlxcaDR%2bIXwVK92JaTnVop0r%2bp7… 10/28 10/17/23, 4:12 PM Realizeit for Student clonidine: Exact mode of action is not understood, but acts through the central nervous system, Dry mouth, apparently drowsiness, sedation, through and occasional centrally Central Alpha2Agonists and Other Centrally Acting Drugs clonidine clonidine patch guanfacine methyldopa headaches and fatigue mediated alphaadrenergic stimulation in the brain, producing blood pressure reduction. guanfacine: Stimulates central alpha2adrenergic receptors. methyldopa: Anorexia, malaise, and Generally last-line agents— vomiting with mild sometimes can be effective disturbance of liver when other medications fail to function have been lower blood pressure. reported. Methyldopa may be drug of Rebound hypertension choice during pregnancy. or hypertensive crisis is relatively common with Contraindication: Severe withdrawal of coronary artery disease. clonidine; medication dosage should be tapered down when discontinuing clonidine and BP monitored carefully. Dopa decarboxylase inhibitor; displaces norepinephrine from storage sites. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IWsgl87YCND5MlxcaDR%2bIXwVK92JaTnVop0r%2bp7… 11/28 10/17/23, 4:12 PM Realizeit for Student Sodium and fluid retention and reflex Direct Vasodilators hydralazine minoxidil Direct Typically used in combination vasodilatory with other medications action on (diuretics, beta-blockers). smooth muscle of blood Used also in pregnancy-induced vessels, causing hypertension. decreased peripheral Contraindications: Angina or vascular coronary disease, heart failure, resistance. hypersensitivity. tachycardia are common effects; headache, flushing, and dyspnea may occur. Hydralazine may produce lupus erythematosus–like syndrome. Minoxidil may cause hirsutism. ACE: angiotensin-converting enzyme; ARB: angiotensin receptor blocker; AV: atrioventricular; BP: blood pressure; BPH: benign prostatic hyperplasia; CAD: coronary artery disease; CKD: chronic kidney disease; COPD: chronic obstructive pulmonary disease; COVID-19: coronavirus disease 2019; CR: controlled release; ER: extended release; GI: gastrointestinal; HF: heart failure; HFrEF: heart failure with reduced ejection fraction; IR: intermediate release; LA: long acting; SA: sinoatrial; SARS-CoV2: severe acute respiratory syndrome coronavirus 2; SR: sustained release. Adapted from Comerford, K. C., & Durkin, M. T. (2020). Nursing 2020 drug handbook. Philadelphia, PA: Wolters Kluwer; Guo, J., Huang, Z., Lin, L., et al. (2020). Coronavirus disease 2019 (COVID-19) and cardiovascular disease: A viewpoint on the potential influence of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers on onset and severity of severe acute respiratory syndrome coronavirus 2 infection. Journal of the American Heart Association, 9, e016219. doi:10.1161/JAHA.120.016219; Sommerstein, R., Kochen, M. M., Messerli, F. H., et al. (2020). Coronavirus disease 2019 (COVID-19): Do angiotensin-converting enzyme inhibitors/angiotensin receptor blockers have a biphasic effect? Journal of the American Heart Association, 9, e016509. doi:10.1161/JAHA.120.016509; Vaduganathan, M., Vardeny, O., Michel, T., et al. (2020). Renin-angiotensin-aldosterone system inhibitors in patients with COVID-19. The New England Journal of Medicine, 382(17), 1653–1659; Whelton, P. K., Carey, R. M., Aronow, W. S., et al. (2017). 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension, 71(6), e13–e115. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IWsgl87YCND5MlxcaDR%2bIXwVK92JaTnVop0r%2bp7… 12/28 10/17/23, 4:12 PM Realizeit for Student Patients are first prescribed low doses of medication. If blood pressure does not fall to less than 130/80 mm Hg, the dose is increased gradually and additional medications are included as necessary to achieve control. The simplest treatment schedule possible is ideal as it promotes adherence to the regimen (e.g., one pill once each day, two or more agents combined into a single pill). Resistant hypertension is diagnosed when a patient takes at least three antihypertensive medications from different classes (including a diuretic) and the blood pressure is still not controlled (i.e., not less than 130/80 mm Hg). A patient with controlled blood pressure but who requires at least four antihypertensive medications in order to maintain that control is also considered to have resistant hypertension (Whelton et al., 2017). Risk factors for resistant hypertension include older age, being African American, and having obesity, CKD, or diabetes. Treatment of patients with suspected resistant hypertension first revolves around ensuring that they are indeed adhering to their prescribed medication regimen, including ensuring that their finances do not preclude them from purchasing their prescriptions, that they understand the purpose of the medications, and that medication side effects are tolerable. Patients with suspected resistant hypertension should also be evaluated for possible secondary hypertension (Whelton et al., 2017). Drug Management If lifestyle modifications alone do not produce the target blood pressure (or a systolic blood pressure ≥140 mm Hg or a diastolic blood pressure ≥90 mm Hg), it is important to initiate antihypertensive drug therapy and continue lifestyle modifications. Drugs used in the management of primary hypertension belong to several different groups, including ACE inhibitors; angiotensin II receptor blockers (ARBs), also called angiotensin II receptor antagonists; antiadrenergics; calcium channel blockers (CCBs); diuretics; and direct vasodilators. In general, these drugs act to decrease blood pressure by decreasing cardiac https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IWsgl87YCND5MlxcaDR%2bIXwVK92JaTnVop0r%2bp7… 13/28 10/17/23, 4:12 PM Realizeit for Student output or peripheral vascular resistance. Evidence indicates that management strategies need to account for race in drug selection for initial therapy. For instance, recommendations for treatment of hypertension in individuals of African American descent, including those with diabetes, includes initial therapy with a CCB and/or thiazide-type diuretic. In non–African American populations, including those with diabetes, there is evidence to support initial drug therapy with an ACE inhibitor, ARB, CCB, and/or a thiazide-type diuretic. This module focuses on ACE inhibitors, ARBs, CCBs, and select adjuvant drugs (direct renin inhibitors, alpha1adrenergic blockers, alpha2 agonists, beta-adrenergic blockers, alpha-/beta-adrenergic blockers, and diuretics). Current guidelines ( Whelton et al., 2018 ) suggest that thiazide diuretics (e.g., chlorthalidone, hydrochlorothiazide) be used as first-line therapy, either alone (monotherapy) or with an ACE inhibitor, ARB, or CCB. Monotherapy is reasonable if the patient has stage 1 hypertension and a BP goal less than 130/80 mm Hg. If the initial drug (and dose) does not produce the desired blood pressure within 1 month of initiating treatment, options for further management include increasing the dose, substituting another drug, or adding a second drug from a different group ( James et al., 2014 ). If the patient has a systolic pressure greater than 140 mm Hg or a diastolic blood pressure greater than 90 mm Hg, initial drug therapy with a combination of two antihypertensives is recommended ( Whelton et al., 2018 ). To minimize the impact of medication side effects, two or three medications may be combined at lower doses, rather than increasing doses of monotherapy, to achieve blood pressure treatment goals. If the response is still inadequate, addition of a third drug, including a diuretic if not previously prescribed, is recommended. When current management is ineffective, it is necessary to reassess the patient’s adherence to lifestyle modifications and drug therapy. In addition, it is also important to review other factors that may decrease the therapeutic response, such as the use of over-the-counter appetite suppressants, dietary or herbal supplements, or nasal decongestants, which raise blood pressure. Regardless of the medication selected, the primary determining factor in selecting the appropriate antihypertensive medication(s) and dose(s) is patient response to treatment, with attained blood pressure control being the ultimate outcome measure (Whelton et al., 2018 ). Holistic management of hypertension should include consideration of age, ethnicity, and concomitant cardiovascular disorders when choosing an antihypertensive drug. Starting with a single drug, in the lowest available dose; changing to a drug from a different group, rather than increasing dosage of the first drug or adding a second drug, if the initial drug is ineffective or not well tolerated; and using long-acting drugs (i.e., a single dose effective for 24 hours) are prudent considerations. Many patients require two or more drugs to achieve adequate blood https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IWsgl87YCND5MlxcaDR%2bIXwVK92JaTnVop0r%2bp7… 14/28 10/17/23, 4:12 PM Realizeit for Student pressure control. When this is the case, fixed-dose combinations or long-acting agents may be preferred, because they decrease the number of individual drugs and doses that are required and may increase compliance. Variation exists in the response to drug therapy for hypertension in ethnic populations. Experts credit nearly 70% of the familial considerations related to blood pressure to shared genes rather than to shared environment. For most antihypertensive drugs, research studies comparing effects have indicated differences among different genetic or ethnic groups. For example, several studies indicate that beta-adrenergic blockers have greater effects in people of Asian heritage compared with those of Caucasian background. For hypertension, Asians in general need much smaller doses because they metabolize and excrete beta-adrenergic blockers slowly. Other populations known to metabolize beta-adrenergic blockers slowly include Arab and Egyptian Americans and possibly German Americans. In African Americans, thiazide diuretics and CCBs are effective and recommended as initial drug therapy. CCBs, alpha1 receptor blockers, and the alpha-/beta-adrenergic blocker labetalol are reportedly equally effective in African Americans and Caucasians. ACE inhibitors, some ARBs (e.g., losartan and telmisartan), and beta-adrenergic blockers are less effective as monotherapy in African Americans. When beta-adrenergic blockers are used, they are usually one component of a multidrug regimen, and higher doses may be necessary. Overall, African Americans are more likely to have severe hypertension and require multiple drugs as a result of having low circulating renin, increased salt sensitivity, and a higher incidence of obesity. Angiotensin-Converting Enzyme Inhibitors Experts recommend captopril, the prototype ACE inhibitor, and other drugs in this class as first-line agents for treating hypertension, particularly in patients with heart failure or asymptomatic left ventricular dysfunction. ACE inhibitors reduce proteinuria and slow progression of renal impairment in people with this disease. (However, they may cause or aggravate proteinuria and renal damage in people who do not have diabetes.) ACE inhibitors may be used alone or in combination with other antihypertensive agents, such as thiazide diuretics, CCBs, and beta-blockers, based on the patient’s blood pressure. Pharmacokinetics Captopril is well absorbed with oral administration (with absorption reduced by food), produces effects within 1 to 1½ hours, and has a prolonged serum half-life with impaired renal function. The drug is metabolized and excreted in the urine (half as unchanged drug) and is excreted in https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IWsgl87YCND5MlxcaDR%2bIXwVK92JaTnVop0r%2bp7… 15/28 10/17/23, 4:12 PM Realizeit for Student breast milk. QSEN Alert: Safety The metabolism of captopril is highly dependent on a patient’s genetics and ethnicity. Current guidelines recommend that all nonblack individuals, including those with diabetes and chronic kidney disease, receive an ACE inhibitor as part of their drug therapy. ACE inhibitors are not recommended for treatment of hypertension in black patients unless they have chronic kidney disease. Action ACE inhibitors such as captopril block the enzyme that normally converts angiotensin I to the potent vasoconstrictor angiotensin II. (ACE [also called kininase] is mainly located in the endothelial lining of blood vessels, which is the site of production of most angiotensin II. This same enzyme also metabolizes bradykinin, an endogenous substance with strong vasodilating properties.) By blocking production of angiotensin II, the ACE inhibitors decrease vasoconstriction (thus having a vasodilating effect) and decrease aldosterone production (thus reducing retention of sodium and water). In addition to inhibiting formation of angiotensin II, ACE inhibitors also inhibit the breakdown of bradykinin, prolonging its vasodilating effects. Use Health care providers use captopril to prevent or reverse the remodeling of heart muscle and blood vessel walls that impairs cardiovascular function and exacerbates cardiovascular disease processes. Widely used to treat heart failure and hypertension, the drug may also decrease morbidity and mortality in other cardiovascular disorders. Captopril may be effective as monotherapy in Caucasian patients with hypertension or in combination with a diuretic in African American hypertensive patients, but the 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults recommends thiazide diuretics or CCBs as preferred for monotherapy in the absence of comorbidities ( Whelton et al., 2018 ). Clinicians also recommend captopril and other ACE inhibitors for adults with hypertension and diabetes mellitus and kidney damage because they slow the progression of albuminuria. In addition, captopril improves post-MI survival when added to the standard therapy of aspirin, a beta-adrenergic blocker, and a thrombolytic. Use in Patients with Renal Impairment Captopril and other ACE inhibitors are usually effective in patients with renal impairment, but responses may vary. Careful monitoring is required, especially during the first few weeks of therapy, to prevent irreversible renal failure. Manufacturer recommendations include a reduction https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IWsgl87YCND5MlxcaDR%2bIXwVK92JaTnVop0r%2bp7… 16/28 10/17/23, 4:12 PM Realizeit for Student in initial dosage and then slow titration over 1- to 2-week intervals to determine the minimum effective dose necessary to achieve desired blood pressure outcome. For some patients, it may not be possible to normalize blood pressure and maintain adequate renal perfusion. Use in Patients with Critical Illness Health care providers may use captopril in patients who are critically ill. However, oral dosing may restrict use to patients who can tolerate oral medications. Urgent or emergent needs to reduce significant hypertension may require more effective management with drugs that can be administered intravenously or have a more rapid onset of action. Adverse Effects Captopril is well tolerated and has a low incidence of serious adverse effects (e.g., neutropenia, agranulocytosis, proteinuria, glomerulonephritis, angioedema [sudden deep swelling or welts under skin, particularly around the eyes and lips]). However, a persistent cough develops in a significant number of patients, and this problem may lead to discontinuation of the drug. Also, acute hypotension may occur when captopril is started, especially in patients with fluid volume deficit. Starting with a low dose taken at bedtime or by stopping diuretics and reducing dosage of other antihypertensive drugs temporarily may prevent this reaction. Hyperkalemia may develop in patients with diabetes mellitus or renal impairment or who are taking nonsteroidal anti-inflammatory drugs (NSAIDs), potassium supplements, or potassium-sparing diuretics; these patients should be monitored for this condition. Contraindications Contraindications to captopril and other ACE inhibitors include pregnancy, and it is important to discontinue them when pregnancy is detected. The U.S. Food and Drug Administration (FDA) has issued a BLACK BOX WARNING for use of drugs that directly affect the renin–angiotensin system, such as ACE inhibitors, during pregnancy because their use can cause injury and even death to a developing fetus. Additional contraindications to captopril include known hypersensitivity to the drug or occurrence of angioedema with previous treatment with an ACE inhibitor. Nursing Implications Preventing Interactions Many medications interact with captopril, increasing or decreasing its effects. Additionally, captopril may increase serum concentrations of digoxin and lithium and increase the risk of elevated serum levels and toxicity. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IWsgl87YCND5MlxcaDR%2bIXwVK92JaTnVop0r%2bp7… 17/28 10/17/23, 4:12 PM Realizeit for Student QSEN Alert: Safety Reportedly, taking captopril and other ACE inhibitors at the same time as potassiumcontaining salt substitutes (No Salt, Morton Salt Substitute, and others) or large amounts of high-potassium foods (bananas, oranges, and other fruit) increases the risk of hyperkalemia. Administering the Medication People should take captopril 1 hour before or 2 hours after meals to enhance absorption. If they have difficulty swallowing, they may crush the tablets. It is necessary to assess blood pressure and pulse on an ongoing basis with initial dosage adjustment and intermittently during therapy. Assessing for Therapeutic Effects The nurse monitors response to therapy, looking for a return of blood pressure to target limits without significant adverse effects. Assessing for Adverse Effects The nurse observes acute hypotension when captopril is started, to make sure the patient does not have a fluid volume deficit that would worsen the likelihood of hypotension. He or she assesses for a persistent cough. Also, it is important to check serum potassium levels to ensure a decreased risk of hyperkalemia. QSEN Alert: Safety It is important to instruct women of childbearing age to take measures to prevent pregnancy while taking captopril or other ACE inhibitors because the drugs are teratogenic. Self or Caregiver Administration Take or give antihypertensive drugs at prescribed time intervals, about the same time each day. For example, take once-daily drugs as close to every 24 hours as you can manage; twice-a-day drugs should be taken every 12 hours. If ordered four times daily, take approximately every 6 hours. Taking doses too close together can increase dizziness, weakness, and other adverse effects. Taking doses too far apart may not control blood pressure adequately and may increase risks of heart attack or stroke. Take oral captopril on an empty stomach; food decreases drug absorption. If you are a sexually active woman, use birth control measures when taking angiotensinconverting enzyme (ACE) inhibitors. Take most other oral antihypertensive agents with or after food intake to decrease gastric irritation. Candesartan (Atacand), irbesartan (Avapro), losartan (Cozaar), telmisartan (Micardis), and valsartan (Diovan) may be taken with or without food. When taking losartan, take the following precautions: Avoid potassium supplements and salt substitutes containing potassium, unless directed by prescriber. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IWsgl87YCND5MlxcaDR%2bIXwVK92JaTnVop0r%2bp7… 18/28 10/17/23, 4:12 PM Realizeit for Student Use birth control measures if you are a woman and you are sexually active. Contact your health care provider immediately if you suspect that you are pregnant. Discuss with your prescriber if you are considering breast-feeding. When taking aliskiren, use birth control measures if you are a woman and you are sexually active. When taking ACE inhibitors, angiotensin II receptor blockers (ARBs), and aliskiren, immediately report hypersensitivity reactions, especially lip or eyelid swelling, throat tightness, and difficulty breathing. Avoid taking aliskiren with a high-fat meal because this significantly decreases the amount of available drug. With prazosin, doxazosin, or terazosin, take the first dose and the first increased dose at bedtime to prevent dizziness and possible fainting. With the clonidine skin patch, apply to a hairless area on the upper arm or torso once every 7 days. Rotate sites. Other Drugs in the Class Because of their effectiveness in hypertension and beneficial effects on the heart, blood vessels, and kidneys, the ACE inhibitors are widely used with patients diagnosed with cardiovascular disorders. Drugs in this class also are used in the management of hypertension and heart failure because they decrease peripheral vascular resistance, cardiac workload, and ventricular remodeling. Adverse effects for the class are similar to those outlined with captopril. Specifically, there is an increased risk of cough, hyperkalemia, and angioedema, and the drugs pose a significant risk to a fetus if taken during pregnancy. Benazepril (Lotensin) is indicated for the treatment of hypertension. Patients may take the drug alone or in combination with thiazide diuretics. Peak plasma concentrations occur within 30 minutes to 1 hour. Once-a-day dosing means that steady-state concentrations of the drug are reached after two or three doses. Enalapril (Vasotec) is a prodrug used in the treatment of hypertension and heart failure (see Chap. 30). Prescribers may order the drug for use alone or in combination with antihypertensive agents, particularly thiazide diuretics. QSEN Alert: Safety Patients started on enalapril who are taking a diuretic occasionally may have symptomatic hypotension following the initial dose of enalapril. The nurse should advocate for the patient’s safety and monitor adverse effects. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IWsgl87YCND5MlxcaDR%2bIXwVK92JaTnVop0r%2bp7… 19/28 10/17/23, 4:12 PM Realizeit for Student Fosinopril (Monopril) is indicated for the treatment of hypertension and heart failure. Patients may take the drug alone or in combination with thiazide diuretics. As with enalapril, symptomatic hypotension may occur following the initial dose if the patient has been taking a diuretic. A prodrug, fosinopril is absorbed very slowly after oral administration and is highly bound to protein. Time to peak concentration is about 3 hours. Lisinopril (Prinivil, Zestril) is indicated for the treatment of hypertension and heart failure, and the drug is an adjunctive therapy in the management of MI. Prescribers may order it as monotherapy or in combination with thiazide diuretics. Peak serum concentrations of lisinopril occur within about 7 hours. The drug does not undergo metabolism and is excreted unchanged entirely in the urine. Moexipril (Univasc), which is administered orally and intravenously, is used in the treatment of hypertension. People may take the drug alone or in combination with thiazide diuretics. Peak serum concentrations occur within about 30 minutes. However, absorption is significantly delayed in the presence of food, and it is important to take the drug in a fasting state. In patients who are currently taking a diuretic, symptomatic hypotension may occasionally occur following the initial dose of moexipril. The nurse should advocate for the patient’s safety. Perindopril (Coversyl) is used alone or in combination with other therapies to treat mild to moderate essential hypertension. People should take it at least 1 hour prior to eating. Its peak effect occurs within 1 to 2 hours. Caution is necessary in patients older than 65 years of age; metabolism slows with age, and increased serum plasma levels of the mediation exacerbate fluid retention and hyponatremia. Quinapril (Accupril) may be used as monotherapy or in combination with thiazide diuretics in the treatment of hypertension or heart failure. The blood pressure–lowering effect is greater in combination than that seen with either quinapril or the thiazide diuretic alone. Following oral administration, peak concentrations are reached within 1 hour; absorption is decreased with administration with a fatty meal. The drug is highly protein bound and is primarily excreted in the urine. Ramipril (Altace) is used alone or in combination with other medications, including thiazide diuretics, in the treatment of hypertension. It is also used to reduce the risk of heart attack and stroke in at-risk patients as well as to improve survival in patients with heart failure after a heart attack. After oral administration, peak concentration is reached in 1 hour. Trandolapril (Mavik) is indicated for the treatment of hypertension alone or in combination with other antihypertensive agents such as hydrochlorothiazide. It is also used post-MI in patients who demonstrate left ventricular systolic dysfunction or in those who are symptomatic from https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IWsgl87YCND5MlxcaDR%2bIXwVK92JaTnVop0r%2bp7… 20/28 10/17/23, 4:12 PM Realizeit for Student heart failure immediately following an MI. The majority of drug is excreted in the stool, and the remainder is excreted in the urine. The extent of biliary excretion has not been determined. Angiotensin II Receptor Blockers Scientists developed ARBs to block the strong blood pressure–raising effects of angiotensin II. These drugs resemble ACE inhibitors in their effects on blood pressure and hemodynamics and are as effective in the management of hypertension and possibly heart failure. However, they are less likely to cause hyperkalemia than ACE inhibitors, and the occurrence of a persistent cough is rare. The prototype ARB is losartan (Cozaar), the first ARB. Pharmacokinetics Both losartan and its metabolite are highly bound to plasma albumin, and the drug’s active metabolite is 40 times more potent than losartan and largely responsible for the duration of action. The drug undergoes extensive first-pass metabolism, has an onset of 6 hours, and reaches maximum concentrations 1 to 2 hours. Absorption is good. Metabolism is rapid; the cytochrome P450 liver enzymes process losartan to an active metabolite. Excretion is through the kidneys and the liver. Action Instead of decreasing production of angiotensin II, like the ACE inhibitors, losartan blocks vasoconstricting and aldosterone-secreting effects of angiotensin II at various receptor sites and prevents angiotensin II from combining at various receptors sites. The drug also increases renal flow and enhances the excretion of chloride, calcium, magnesium, and phosphate. Although multiple types of receptors have been identified, the angiotensin II receptors, type 1 (AT1) located in brain, renal, myocardial, vascular, and adrenal tissue, determine most of the effects of angiotensin II on cardiovascular and renal functions. ARBs block the AT1 receptors and decrease arterial blood pressure by decreasing systemic vascular resistance. Use Prescribers primarily order losartan for use in the treatment of hypertension; the drug is effective in people with type 2 diabetes who have diabetic nephropathy. After drug therapy begins, maximal effects usually occur within 3 to 6 weeks. It is important to recognize that in African Americans, losartan and other ARBs may be ineffective when used alone. If losartan alone does not control blood pressure, a low dose of a diuretic may be added. A combination product of losartan and hydrochlorothiazide is available. Use in Older Adults https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IWsgl87YCND5MlxcaDR%2bIXwVK92JaTnVop0r%2bp7… 21/28 10/17/23, 4:12 PM Realizeit for Student Losartan and other ARBs are metabolized by the liver and do not need dose reduction for adults with renal impairment. Use is not recommended in children who have a glomerular filtration rate less than 30 mL/min/1.73 m2. Use in Patients with Hepatic Impairment Caution is warranted for use of all ARBs in biliary tract obstruction or hepatic impairment. Experts recommend a lower starting dose for losartan in affected patients because plasma concentrations of the drug and its active metabolite are increased and clearance is decreased approximately 50% with hepatic dysfunction. Use in Patients with Critical Illness Health care providers may administer losartan to critically ill patients, but monitoring is necessary to ensure that the drug produces the desired outcome without significant adverse effects. Also, it has significant drug–drug interactions and the potential to produce hyperkalemia, which could have potentially serious outcomes in the critically ill. Adverse Effects Overall, losartan is generally well tolerated. Adverse effects include dizziness, muscle cramps or weakness, heartburn, diarrhea, and decreased sensitivity to touch. There are reports of angioedema, and it is important to evaluate this condition immediately. Contraindications Contraindications to losartan include known hypersensitivity to the drug. Additionally, the FDA has issued a BLACK BOX WARNING ♦ regarding the use of losartan and other ARBs, which directly affect the renin–angiotensin system, because their use can cause injury and even death to a developing fetus. Therefore, pregnancy is a contraindication to use of losartan and other ARBs, and it is essential that the drugs be discontinued as soon as pregnancy is detected. Nursing Implications Preventing Interactions Many medications and herbs interact with losartan, increasing or decreasing its effects. Administering the Medication People may take losartan without regard to meals. Assessing for Therapeutic Effects The nurse monitors blood pressure to evaluate drug efficacy. Also, he or she observes for the presence of lifestyle modifications that will improve baseline blood pressure readings (e.g., weight loss, smoking cessation, restricted salt intake). https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IWsgl87YCND5MlxcaDR%2bIXwVK92JaTnVop0r%2bp7… 22/28 10/17/23, 4:12 PM Realizeit for Student Assessing for Adverse Effects The nurse assesses kidney and liver function tests, as well as serum electrolyte levels, particularly potassium. Also, he or she observes for the presence of angioedema and other hypersensitivity reactions. Calcium Channel Blockers CCBs are first-line agents for controlling hypertension and may be used as monotherapy or in combination with other drugs. They may be especially useful for people with hypertension who also have angina pectoris, other cardiovascular disorders, or pulmonary disorders. Current guidelines recommend that CCBs be used alone or in combination with a thiazide diuretic to treat hypertension. These drugs are especially appropriate as the first-line treatment of hypertension for black patients. They may be used alone or in combination with thiazide-type diuretics. For the purposes of this discussion, amlodipine (Norvasc) serves as the prototype. Note that sustained-release forms of nifedipine, diltiazem, verapamil, and other long-acting drugs (e.g., amlodipine, felodipine) are recommended rather than the short-acting forms because they do not cause precipitous lowering of pressure. In hypertension, CCBs mainly dilate peripheral arteries and decrease peripheral vascular resistance by relaxing vascular smooth muscle. As a group, the CCBs are well absorbed from the GI tract following oral administration and are highly bound to protein. The drugs are metabolized in the liver and excreted in the urine. Most of the available CCBs have received FDA approval for use in hypertension. Nifedipine, a short-acting CCB, has been used to treat hypertensive emergencies or urgent hypertensive events. Note that CCBs (e.g., verapamil) are used for several other cardiovascular disorders. Pharmacokinetics Amlodipine is well absorbed with oral administration. Absorption is not reduced by the presence of food. Peak plasma concentration is achieved between 6 and 12 hours after oral administration. Significant initial reductions in blood pressure are achieved with 24 to 48 hours of the initial dose. Therapeutic plasma levels are reached in approximately 7 days with consistent daily dosing. The drug is metabolized in the liver and excreted in the urine. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IWsgl87YCND5MlxcaDR%2bIXwVK92JaTnVop0r%2bp7… 23/28 10/17/23, 4:12 PM Realizeit for Student Action Amlodipine inhibits the influx of calcium ions across cardiac and smooth muscle during depolarization, resulting in relaxation and vasodilation. This leads to lowered blood pressure. Use Health care providers use amlodipine to treat hypertension alone or in combination with other antihypertensives. Note that no dosage adjustment is necessary for patients with renal impairment. Use in Older Adults Older patients have decreased clearance of the drug. Therefore, dosing should start with the lowest possible dose and be titrated as necessary. Use in Patients with Hepatic Impairment Amlodipine is metabolized extensively by the liver. Consideration of the possibility of prolonged half-life and delayed clearance, resulting in drug accumulation, may be warranted. Reduced dosing is advised; titrate slowly if necessary. Adverse Effects Amlodipine is generally well tolerated. Possible adverse effects include headache; drowsiness; fatigue; dizziness; edema of the hands, ankles, and feet; flushing; palpitations; nausea; and abdominal pain. Contraindications Contraindications include hypersensitivity to amlodipine or any of its components. Nursing Implications Preventing Interactions Many medications interact with amlodipine, increasing or decreasing its effects. Conivaptan, CYP3A4 strong inhibitors (e.g., ketoconazole), may increase plasma concentration levels. Avoid concurrent use. Cyclosporine may decrease the metabolism of CCBs. Monitor for hypotension. Amlodipine also affects the action of several drugs. Simvastatin serum concentrations may increase when taken concurrently. Concurrent use should be avoided if possible and the simvastatin dose limited to 20 mg/d if patients must take the two drugs concurrently. Foods that affect the action of amlodipine include grapefruit juice (a CYP3A4 inhibitor), which may increase the serum level of the drug. St. John’s wort (a CYP3A4 inducer) should be avoided because the herbal supplement may decrease the serum level of the drug. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IWsgl87YCND5MlxcaDR%2bIXwVK92JaTnVop0r%2bp7… 24/28 10/17/23, 4:12 PM Realizeit for Student Administering the Medication The drug can be given without regard for food. Assessing for Therapeutic Effects The nurse monitors blood pressure to evaluate drug efficacy. Also, he or she observes for the presence of lifestyle modifications that will improve baseline blood pressure readings (e.g., losing weight, stopping smoking, restricting salt intake). Assessing for Adverse Effects The nurse monitors blood pressure and assesses for chest pain frequently on initiation of drug therapy. In patients with severe CAD and/or heart failure, very close monitoring for chest pain, pulmonary edema, and peripheral edema is necessary. QSEN Alert: Safety Authorities no longer recommend puncturing a nifedipine capsule, because this practice is associated with an increased risk of adverse cardiovascular events precipitated by a rapid and severe decrease in blood pressure. QSEN Alert: Safety Abrupt discontinuation of CCBs may increase frequency and duration of chest pain. Adjuvant Medications Used to Treat Hypertension Prescribers may order other drugs for the treatment of hypertension. Direct Renin Inhibitors Aliskiren (Tekturna), the only direct renin inhibitor, decreases plasma renin activity and inhibits the conversion of angiotensinogen to angiotensin I. The drug is used as monotherapy or in combination with other antihypertensive agents for the treatment of hypertension but should never be used in combination with an ACE inhibitor or an ARB. A fixed-dose combination with valsartan (Valturna) is available. Aliskiren is poorly absorbed, and steady-state blood levels are reached in about a week. Following oral administration, peak plasma levels are reached in 1 to 3 hours. If taken with a high-fat meal, bioavailability and peak levels are decreased by about 75%. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IWsgl87YCND5MlxcaDR%2bIXwVK92JaTnVop0r%2bp7… 25/28 10/17/23, 4:12 PM Realizeit for Student The drug is excreted in the urine. Aliskiren is contraindicated in patients with chronic kidney disease because of the increased risk of renal impairment, hyperkalemia, and hypotension. Angioedema may occur. Antiadrenergics Antiadrenergic (sympatholytic) drugs inhibit activity of the SNS. When the SNS is stimulated, the nerve impulse travels from the brain and spinal cord to the ganglia. From the ganglia, the impulse travels along postganglionic fibers to effector organs (e.g., heart, blood vessels). Although SNS stimulation produces widespread effects in the body, the effects relevant to this discussion are the increases in heart rate, force of myocardial contraction, cardiac output, and blood pressure that occur. When the nerve impulse is inhibited or blocked at any location along its pathway, the result is decreased blood pressure. Alpha1-adrenergic receptor blockers (e.g., prazosin) dilate blood vessels and decrease peripheral vascular resistance. These drugs can be used alone or in multidrug regimens but are not routinely used as initial antihypertensive agents. One adverse effect, called the first-dose phenomenon , results in orthostatic hypotension, with palpitations, dizziness, and perhaps syncope 1 to 3 hours after the first dose or an increased dose. To prevent this effect, first doses and first increased doses are taken at bedtime. Another effect, associated with long-term use or higher doses, leads to sodium and fluid retention and a need for concurrent diuretic therapy. Centrally acting sympatholytics (e.g., clonidine) stimulate presynaptic alpha2 receptors in the brain and are classified as alpha2 receptor agonists. Taking these drugs leads to the release of less norepinephrine and a reduction of sympathetic outflow from the vasomotor center. Stimulation of presynaptic alpha2 receptors peripherally may also contribute to the decreased sympathetic activity. Reduced sympathetic activity leads to decreased cardiac output, heart rate, peripheral vascular resistance, and blood pressure. Chronic use of clonidine and related drugs may result in sodium and fluid retention, especially with higher doses. Beta-adrenergic blockers are useful in the treatment of hypertension in patients with ischemic heart disease, especially in those (a) younger than 50 years of age with acute coronary syndrome or recent MI and (b) who have heart failure with reduced ejection fraction. Experts do not recommend beta-blockers as initial monotherapy unless they are specifically indicated; they are most effective when used in combination with ARBs ( Mann et al., 2018, Sept 19 ). Most beta-adrenergic blockers have FDA approval for use in hypertension and are probably equally effective. However, the cardioselective drugs are preferred for people with hypertension who also have asthma, peripheral vascular disease, or diabetes mellitus. Research studies demonstrate reduced morbidity and mortality with diuretics and beta-adrenergic blockers used in combination, especially after an MI. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IWsgl87YCND5MlxcaDR%2bIXwVK92JaTnVop0r%2bp7… 26/28 10/17/23, 4:12 PM Realizeit for Student Beta-adrenergic blockers (e.g., propranolol) decrease heart rate [chronotropy], force of myocardial contraction [inotropy]), cardiac output, and renin release from the kidneys. The FDA has issued a BLACK BOX WARNING for patients with CAD taking oral forms of atenolol, metoprolol, nadolol, propranolol, and timolol; abrupt withdrawal has resulted in exacerbation of angina, the incidence of ventricular dysrhythmias, and the occurrence of MIs. Beta-adrenergic blockers that normally undergo extensive first-pass hepatic metabolism (e.g., acebutolol, metoprolol, propranolol, timolol) may produce excessive blood levels in patients with cirrhosis because the blood containing the drug is shunted around the liver into the systemic circulation. It is necessary to start at a low dose and titrate the dosage carefully. Also, dosage reduction with bisoprolol and pindolol is important in patients with cirrhosis or other hepatic impairment. Labetalol can be used as monotherapy for initial management of uncomplicated hypertension; however, thiazide diuretics are preferred by JNC 8. Administration is intravenous or oral. Occasionally following intravenous administration, orthostatic hypotension with loss of consciousness reportedly occurs; the hypotension can last for 3 hours or longer. Other Vasodilators (Direct Acting) Vasodilator antihypertensive drugs directly relax smooth muscle in blood vessels, resulting in dilation and decreased peripheral vascular resistance. As they reduce afterload, they may be used in management of heart failure. The direct-acting vasodilators are effective in managing a hypertensive emergency. Nitroprusside (Nitropress) is a potent vasodilator that acts on arterioles and venules. Given by continuous intravenous infusion, the drug has a rapid onset and short duration of action, and it requires continuous blood pressure monitoring. Intra-arterial blood pressure monitoring is the most effective during the infusion. Nitroprusside is metabolized to thiocyanate, and it is necessary to measure serum thiocyanate levels if the drug is given longer than 72 hours. If the serum thiocyanate level is more than 12 mg/dL, it is important to stop the infusion after 72 hours. The infusion should last no longer than 48 hours in patients with renal impairment. Hemodialysis reverses the symptoms of thiocyanate toxicity (e.g., nausea, vomiting, muscle twitching or spasm, seizures). Hydralazine (Hydra-Zide, BiDil) and minoxidil act mainly on arterioles. These drugs have a limited effect on hypertension when used alone because the vasodilating action that lowers blood pressure also stimulates the SNS and triggers reflexive compensatory mechanisms (vasoconstriction, tachycardia, and increased cardiac output), which raise blood pressure. It is possible to prevent this effect during long-term therapy by also giving a drug that inhibits excessive sympathetic stimulation (e.g., propranolol, an adrenergic blocker). These drugs also https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IWsgl87YCND5MlxcaDR%2bIXwVK92JaTnVop0r%2bp7… 27/28 10/17/23, 4:12 PM Realizeit for Student cause sodium and water retention, which may be minimized by concomitant diuretic therapy. The FDA has issued a BLACK BOX WARNING for minoxidil because the drug can exacerbate angina and precipitate pericardial effusion (which can progress to cardiac tamponade). Diuretics For mild to moderate hypertension, diuretics, particularly thiazide diuretics, are often first-line drugs. In cases of stage 1 hypertension, diuretics alone may lower blood pressure. When diuretic therapy begins, blood volume and cardiac output decrease. After long-term administration, cardiac output returns to normal, but there is a persistent decrease in peripheral vascular resistance. Authorities have attributed this to a persistent small reduction in extracellular water and plasma volume, decreased receptor sensitivity to vasopressor substances such as angiotensin, direct arteriolar vasodilation, and arteriolar vasodilation secondary to electrolyte depletion in the vessel wall. In hypertension that does not respond to a diuretic alone, the practitioner usually continues the diuretic and adds another antihypertensive drug or tries monotherapy with a different type of antihypertensive drug. Current hypertension management guidelines recommend initial drug therapy with two antihypertensive agents for patients with a blood pressure 20/10 mm Hg above goal, and diuretics are frequently part of this combination. Health care providers prefer diuretics for initial therapy in all people with hypertension but specifically older adults and African Americans. They should be included in any multidrug regimen for these and other populations. Hydrochlorothiazide is most commonly used, although chlorthalidone reduces cardiovascular events. Diazoxide, usually in parenteral form, is indicated for short-term treatment of malignant hypertension. The selective aldosterone blocker, eplerenone, has demonstrated efficacy in African Americans. Loop diuretics (e.g., furosemide) or potassium-sparing diuretics (e.g., spironolactone) may be useful in some circumstances. Loop diuretics are indicated in people with renal insufficiency. Potassium-sparing diuretics may precipitate hyperkalemia. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IWsgl87YCND5MlxcaDR%2bIXwVK92JaTnVop0r%2bp7… 28/28