Student Notes on Antianginal Drugs PDF

1/16/24, 10:24 PM Realizeit for Student Introduction Antianginal drugs are used to help restore the appropriate oxygen delivery supply-and-demand ratio to the myocardium unrelieved by rest. These drugs can work to improve blood delivery to the heart muscle in one of two ways: (1) by dilating blood...

1/16/24, 10:24 PM Realizeit for Student Introduction Antianginal drugs are used to help restore the appropriate oxygen delivery supply-and-demand ratio to the myocardium unrelieved by rest. These drugs can work to improve blood delivery to the heart muscle in one of two ways: (1) by dilating blood vessels (i.e., increasing the supply of oxygen) or (2) by decreasing the work of the heart (i.e., decreasing the demand for oxygen). The demand for oxygen by the heart muscle is influenced by heart rate (a faster heart rate requires more energy), the preload (the more blood returned to the heart, the more pumping will be done to empty it, which requires more energy), the afterload (the more pressure the heart has to pump against the more energy is required), and contractility of the heart muscle cells. The primary drugs used to treat angina include nitrates, beta-adrenergic blockers, calcium channel blockers, and the anti-ischemic metabolic modulator ranolazine. In this section, previous knowledge of angina and review pharmacological treatment will be built upon. Pharmacologic Therapy Nitroglycerin Nitrates are a standard treatment for angina pectoris. Nitroglycerin is a potent vasodilator that improves blood flow to the heart muscle and relieves pain. Nitroglycerin dilates primarily the veins and, to a lesser extent, the arteries. Dilation of the veins causes venous pooling of blood throughout the body. As a result, less blood returns to the heart, and filling pressure (preload) is reduced. If the patient is hypovolemic (does not have adequate circulating blood volume), the decrease in filling pressure can cause a significant decrease in cardiac output and blood pressure (Frandsen & Pennington, 2021). Nitrates also relax the systemic arteriolar bed, lowering blood pressure and decreasing afterload. These effects decrease myocardial oxygen requirements, bringing about a more favorable balance between supply and demand. Nitroglycerin may be given by several routes: sublingual tablet or spray, oral capsule, topical agent, and intravenous (IV) administration. Sublingual nitroglycerin is generally placed under the tongue or in the cheek (buccal pouch) and ideally alleviates the pain of ischemia within 3 minutes. Chart 23-3 provides more information on self-administration of sublingual nitroglycerin. Oral preparations and topical patches are used to provide sustained effects. A regimen in which the patches are applied in the morning and removed at bedtime allows for a nitratefree period to prevent the development of tolerance. A continuous or intermittent IV infusion of nitroglycerin may be given to the hospitalized patient with recurring signs and symptoms of ischemia or after a revascularization procedure. The rate of infusion is titrated to the patient’s pain level and blood pressure. It usually is not given if the systolic blood pressure is less than 90 mm Hg. Generally, after the patient is symptom-free, the nitroglycerin may be switched to an oral or topical preparation within 24 hours. A common adverse effect of nitroglycerin is headache, which may limit the use of this drug in some patients. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbfuwFjUs0mdxkPeVey4KH2F7i%2fH0LC0NH7inQLoUzK%2f… 1/13 1/16/24, 10:24 PM Realizeit for Student Beta-Adrenergic Blocking Agents Beta-blockers such as metoprolol reduce myocardial oxygen consumption by blocking beta-adrenergic sympathetic stimulation to the heart. The result is a reduction in heart rate, slowed conduction of impulses through the conduction system, decreased blood pressure, and reduced myocardial contractility (force of contraction). Because of these effects, beta-blockers balance the myocardial oxygen needs (demands) and the amount of oxygen available (supply). This helps control chest pain and delays the onset of ischemia during work or exercise. Beta-blockers reduce the incidence of recurrent angina, infarction, and cardiac mortality. The dose can be titrated to achieve a resting heart rate of 50 to 60 bpm (Frandsen & Pennington, 2021). Cardiac side effects and possible contraindications include hypotension, bradycardia, advanced atrioventricular block, and acute heart failure. If a beta-blocker is given IV for an acute cardiac event, the ECG, blood pressure, and heart rate are monitored closely after the medication has been given. Side effects include depressed mood, fatigue, decreased libido, and dizziness. Patients taking beta-blockers https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbfuwFjUs0mdxkPeVey4KH2F7i%2fH0LC0NH7inQLoUzK%2f… 2/13 1/16/24, 10:24 PM Realizeit for Student are cautioned not to stop taking them abruptly, because angina may worsen, and MI may develop. Beta-blocker therapy should be decreased gradually over several days before being discontinued. Patients with diabetes who take beta-blockers are instructed to monitor their blood glucose levels as prescribed because beta-blockers can mask signs of hypoglycemia. Beta-blockers that are not cardioselective also affect the beta-adrenergic receptors in the bronchioles, causing bronchoconstriction, and therefore are contraindicated in patients with significant chronic pulmonary disorders, such as asthma. Calcium Channel Blocking Agents Calcium channel blockers have a variety of effects on the ischemic myocardium. These agents decrease sinoatrial node automaticity and atrioventricular node conduction, resulting in a slower heart rate and a decrease in the strength of myocardial contraction (negative inotropic effect). These effects decrease the workload of the heart. Calcium channel blockers also increase myocardial oxygen supply by dilating the smooth muscle wall of the coronary arterioles; they decrease myocardial oxygen demand by reducing systemic arterial pressure and the workload of the left ventricle (Frandsen & Pennington, 2021). The calcium channel blockers most commonly used are amlodipine and diltiazem. In addition to their use to treat angina, they are commonly prescribed for hypertension. Hypotension may occur after the administration of any of the calcium channel blockers, particularly when administered IV. Other side effects may include atrioventricular block, bradycardia, and constipation. Antiplatelet and Anticoagulant Medications Antiplatelet medications are given to prevent platelet aggregation and subsequent thrombosis, which impedes blood flow through the coronary arteries. Aspirin Aspirin prevents platelet aggregation and reduces the incidence of MI and death in patients with CAD (Frandsen & Pennington, 2021). A 162- to 325-mg dose of aspirin should be given to the patient with a new diagnosis of angina and then continued with 81 to 325 mg daily. Patients should be advised to continue aspirin even if they concurrently take other analgesics such as acetaminophen. Because aspirin may cause GI upset and bleeding, the use of histamine-2 (H2) blockers (e.g., famotidine) or proton pump inhibitors (e.g., omeprazole) should be considered concomitant with continued aspirin therapy (Ibanez, James, Agewall, et al., 2018). Adenosine Diphosphate Receptor Antagonists (P2Y12) These medications act on different pathways than aspirin to block platelet activation. However, unlike aspirin, these agents may take a few days to achieve antiplatelet effects. Clopidogrel is commonly prescribed in addition to aspirin in patients at high risk for MI. Newer oral agents such as prasugrel and ticagrelor may be used in place of clopidogrel during coronary events and interventions (Frandsen & Pennington, 2021). Both carry the risk of bleeding from the GI tract or other sites. Heparin Unfractionated IV heparin prevents the formation of new blood clots (i.e., it is an anticoagulant). Treating patients with unstable angina with heparin reduces the occurrence of MI. If the patient’s signs and symptoms indicate a significant risk for a cardiac event, the patient is hospitalized and may be given an IV bolus of heparin and started on a continuous infusion. The dose of heparin given is based on the results of the activated partial thromboplastin time (aPTT). Heparin therapy is usually considered therapeutic when the aPTT is 2 to 2.5 times the normal aPTT value. A subcutaneous injection of low-molecular-weight heparin (LMWH; enoxaparin or dalteparin) may be used instead of IV unfractionated heparin to treat patients with unstable angina or non–ST-segment elevation myocardial infarction (NSTEMI) (Frandsen & Pennington, 2021). LMWH provides effective and stable anticoagulation, potentially reducing the risk of rebound ischemic events, and eliminating the need to monitor aPTT results. LMWHs may be beneficial before and during PCIs as well as for ACS. Because unfractionated heparin and LMWH increase the risk of bleeding, the patient is monitored for signs and symptoms of external and internal bleeding, such as low blood pressure, increased heart rate, and decreased serum hemoglobin and hematocrit. The patient receiving heparin is placed on bleeding precautions, which include: •Applying pressure to the site of any needle puncture for a longer time than usual •Avoiding intramuscular (IM) injections •Avoiding tissue injury and bruising from trauma or use of constrictive devices (e.g., continuous use of an automatic blood pressure cuff) A decrease in platelet count or evidence of thrombosis may indicate heparin-induced thrombocytopenia (HIT), an antibody-mediated reaction to heparin that may result in thrombosis. Patients who have received heparin within the past 3 months and those who have been receiving unfractionated heparin for 4 to 14 days are at high risk for HIT (Frandsen & Pennington, 2021). As an alternative to LMWH and https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbfuwFjUs0mdxkPeVey4KH2F7i%2fH0LC0NH7inQLoUzK%2f… 3/13 1/16/24, 10:24 PM Realizeit for Student unfractionated heparin, argatroban, a direct antithrombotic agent might be prescribed (Frandsen & Pennington, 2021; see Chapter 29 for further discussion of HIT). Glycoprotein IIb/IIIa Agents IV administration of glycoprotein (GP) IIb/IIIa agents, such as abciximab or eptifibatide, is indicated for hospitalized patients with unstable angina and as adjunct therapy for PCI. These agents prevent platelet aggregation by blocking the GP IIb/IIIa receptors on the platelets, preventing adhesion of fibrinogen and other factors that crosslink platelets to each other and thus form intracoronary clots (Urden, Stacy, & Lough, 2019). As with heparin, bleeding is the major side effect, and bleeding precautions should be initiated. Organic Nitrates The most widely used nitrate is the prototype nitroglycerin (Nitro-Bid, Nitro-Dur). Available in multiple forms, it is indicated for the management and prevention of acute chest pain caused by myocardial ischemia. Pharmacokinetics Nitroglycerin is 60% bound to protein, undergoes extensive first-pass metabolism in the liver, and has a half-life of 1 to 4 minutes. Excretion occurs in the urine. The onset of action, peak, and duration of action varies with the route of administration: Intravenous (IV) drip: onset, immediate; peak, immediate; duration of action, 3 to 5 minutes Sublingual (SL): onset, 1 to 3 minutes; peak, 4 to 8 minutes; duration of action, at least 25 minutes Translingual spray: onset, 1 to 3 minutes; peak, 4 to 10 minutes; duration of action, at least 25 minutes Oral (PO) tablets or capsules (sustained release): onset, about 60 minutes; peak, 2½ to 4 hours; duration of action, 4 to 8 hours Topical ointment: onset, 15 to 30 minutes; peak, 60 minutes; duration of action, 7 hours Topical transdermal disk: onset, about 30 minutes; peak, 120 minutes; duration of action, 10 to 12 hours Action Organic nitrates are converted to nitric oxide, a potent vasodilator, which relaxes smooth muscle in blood vessel walls. The drugs relieve anginal pain by several mechanisms: Venous dilation: reduces venous pressure and decreases venous return to the heart. This decreases blood volume and pressure within the heart ( preload ), which in turn decreases cardiac workload and oxygen demand. This is the main mechanism by which nitroglycerin relieves angina. Coronary artery dilation at higher doses: can increase blood flow to ischemic areas of the myocardium. Arteriole dilation: lowers peripheral vascular resistance ( afterload ). This results in lower systolic blood pressure and, consequently, reduced cardiac workload and balancing supply and demand in the heart. Use For relief of sudden-onset angina, fast-acting preparations of nitroglycerin include SL tablets and transmucosal spray. Indications for these preparations include acute-onset chest pain and prophylaxis prior to activities known to provoke angina, such as walking, dancing, or mowing the lawn. For management of recurrent, chronic angina, long-acting preparations include PO sustained-release tablets and transdermal ointment. With these longer-acting forms, intolerance to their hemodynamic effects may develop, and therefore, the drugs do not relieve chest pain. QSEN Alert: Safety To avoid development of tolerance to nitroglycerin, it is essential to observe a 10- to 12-hour nitrate-free interval. In clinical practice, patients taking nitrates are usually nitrate free during the night, while sleeping, to prevent nitrate tolerance. The oral form of the drug undergoes rapid metabolism in the liver, and relatively small portions ultimately reach the systemic circulation. Thus, the PO form does not relieve acute chest pain but may be useful prophylactically in chronic chest pain. Nitroglycerin ointment is indicated for prevention of chronic angina. This route is convenient to use when the patient can have nothing by mouth (NPO) before surgery and cannot take the usually PO dose. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbfuwFjUs0mdxkPeVey4KH2F7i%2fH0LC0NH7inQLoUzK%2f… 4/13 1/16/24, 10:24 PM Realizeit for Student Angina that is unresponsive to SL, PO, or transdermal preparations calls for IV nitroglycerin. Prescribers may typically order the IV form for management of pain associated with an MI. IV nitroglycerin is useful in the management of angina that is unresponsive to organic nitrates via other routes or to beta-adrenergic blockers. It also may be used to control blood pressure in perioperative or emergency situations and to reduce preload and afterload in severe heart failure. Use in Children IV nitroglycerin is the only form of nitroglycerin approved for use in children. It may be used to treat hypertension and heart failure. Caution and close monitoring are necessary. Use in Older Adults Older adults may be more vulnerable to hypotension when taking nitroglycerin as a result of volume depletion, concurrent use of other medication, and loss of sympathetic tone. QSEN Alert: Safety Therefore, older adults may be at greater risk of falling than younger patients at the therapeutic doses of nitroglycerin because of the risk of hypote Use in Patients With Critical Illness IV nitroglycerin is commonly used in the critical care setting. Angina related to MI may be a patient's principal issue in the intensive care unit (ICU). However, he or she may also have heart failure, hypertension, renal failure, and/or anemia and therefore could be receiving multiple drugs such as heparin, epoetin alfa, and dobutamine. QSEN Alert: Safety The nurse must always check IV compatibility when administering drugs by that route. Close monitoring of vital signs along with frequent titration of IV medications is important in the critically ill. Adverse Effects https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbfuwFjUs0mdxkPeVey4KH2F7i%2fH0LC0NH7inQLoUzK%2f… 5/13 1/16/24, 10:24 PM Realizeit for Student The majority of adverse effects of nitroglycerin are related to the hemodynamic changes responsible for preload reduction and vasodilation. The most common adverse effect is a severe headache, which is typically treated with acetaminophen. Other common adverse effects include dizziness, bradycardia, syncope, hypotension, and orthostatic hypotension. Contraindications Contraindications to nitroglycerin include hypersensitivity reactions, severe anemia, hypotension, and hypovolemia. QSEN Alert: Safety Men who take nitroglycerin or any other nitrate should not use phosphodiesterase enzyme type 5 inhibitors, such as sildenafil (Viagra) and vardenafi combined effect can produce profound, life-threatening hypotension. Caution is necessary in the following situations: In the presence of head injury or cerebral hemorrhage because it may increase intracranial pressure. With the use of other antihypertensive agents, such as beta-adrenergic blockers, as it is essential to observe for extreme episodes of hypotension. With renal impairment. Nursing Implications Preventing Interactions Many drugs interact with nitroglycerin, increasing or decreasing its effects. Several herbs interact with nitroglycerin and cause profound hypotension or negate the effects of nitroglycerin. Drug Interactions: Nitroglycerin Drugs That Increase the Effects of Nitroglycerin Adalat and other calcium channel blockers, alcohol, aripiprazole, benazepril and other angiotensin-converting enzyme inhibitors, codeine and oth Increase the risk of orthostatic hypotension Sildenafil, tadalafil, vardenafil Increase the risk of life-threatening hypotension Drugs That Decrease the Effects of Nitroglycerin Acetaminophen, chloral hydrate, dihydroergotamine, sulfonylureas, vasopressin Decrease vasodilating effects Herb and Dietary Interactions: Nitroglycerin Herbs and Foods That Increase the Effects of Nitroglycerin N-Acetyl cysteine Arginine, folate, vitamin E Hawthorn Herbs and Foods That Decrease the Effects of Nitroglycerin Vitamin C Administering the Medication It is important to take a patient’s vital signs prior to administration of any form of nitroglycerin. The nurse should withhold the medication with hypotension (systolic blood pressure less than 90 or 30 mm Hg below the patient’s normal blood pressure) as well as tachycardia with a heart rate greater than 100 beats/min. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbfuwFjUs0mdxkPeVey4KH2F7i%2fH0LC0NH7inQLoUzK%2f… 6/13 1/16/24, 10:24 PM Realizeit for Student Administration of SL nitroglycerin or translingual spray is essential as soon as chest pain develops. If a patient is hospitalized, it is necessary to call the patient’s health care provider and obtain a 12-lead ECG at the onset of chest pain. The SL nitroglycerin container should stay in a dry, cool, dark environment, and replacement every 6 months is necessary. Exposure to light deactivates the nitroglycerin tablets. Once opened, the translingual spray has a shelf life of 2 to 3 years. In acute coronary syndromes, after three SL doses, administered 5 minutes apart, patients outside of the hospital should seek medical attention. While hospitalized, IV dosing should be started and titrated to desired effect. Nitrate tolerance commonly develops within 24 hours in patients on a continuous infusion of nitroglycerin. Extended-release oral nitrate preparations are used post-MI if angina persists after revascularization. Application of nitroglycerin ointment requires using the dose-measuring application papers supplied with ointment. It is necessary to do the following: Squeeze the ointment onto a measuring scale printed on paper; typically, this is 1 or 1/2 inch, depending on the practitioner’s order. Use the paper to spread ointment onto a nonhairy area of skin (chest, abdomen, thighs; avoid distal extremities) in a thin, even layer, covering a 2- to 3-inch area. Do not allow the ointment to come in contact with the hand. Do not massage the ointment into the patient’s skin because absorption will be increased and interfere with the sustained action. People should take PO nitrates in the morning after a nitrate-free interval (typically during the night). They should take the tablets or capsules 1 to 2 hours before meals. It is important not to break, crush, or chew sustained-release preparations. IV nitroglycerin preparations come in glass bottles, polyvinyl chloride (PVC)-free partial-additive bags, and di(2-ethylhexyl) phthalate (DEHP)free, PVC-free plastic EXCEL containers. Nurses should use these only with special tubing provided by the manufacturer because PVC tubing absorbs up to 80% of the nitroglycerin. Inline IV filters that adsorb nitroglycerin should be avoided. In addition, nurses should ensure that IV nitroglycerin is administered via infusion pump and that patients are placed on cardiac monitors. Many hospitals require patients to be in ICUs or step-down units while the nitroglycerin drip is actively being titrated. As previously stated, it is essential to take vital signs frequently with IV administration and recheck them with each titration. Assessing for Therapeutic Effects Therapeutic effects of some forms of nitroglycerin may include the relief of acute chest pain as well as a modest decrease in blood pressure. With oral preparations, a decreased frequency of chronic chest pain should occur. Overall, patients should report that they feel better, have no symptoms of cardiac ischemia (i.e., chest pain), and have a higher activity tolerance. Patient Teaching Patient teaching guidelines regarding drugs for the management of coronary heart disease, including nitroglycerin. Patient Teaching Guidelines for Drugs Used for Coronary Heart Disease General Considerations Angina is chest pain that occurs because the heart is not getting enough blood and oxygen. The most common causes are hypertension and atherosclerosis of the coronary arteries. The chest pain usually lasts less than 5 minutes, and episodes can be managed for years without causing permanent heart damage. However, if the pain is severe or prolonged, a heart attack and heart damage may develop. Seek information about the heart condition to prevent or decrease episodes of angina and prevent a heart attack. Several types of drugs are used in coronary heart disease, and there may need to be a combination of drugs for the best effects. Most patients take one or more long-acting drugs to prevent anginal attacks and a fast, short-acting drug (usually nitroglycerin tablets that you dissolve under your tongue or a nitroglycerin solution that you spray into your mouth) to relieve acute attacks. Seek emergency care immediately if rest, and three sublingual tablets or oral sprays 5 minutes apart do not relieve chest pain. The long-acting oral medications are not effective in relieving sudden anginal pain. As with any medications for serious or potentially serious conditions, it is extremely important to take antianginal medications as prescribed. Do not increase dosage or discontinue the drugs without specific instructions from a health care provider. With sublingual nitroglycerin tablets, keep them in the original container; carry them so that they are always within reach but not where they are exposed to body heat; and replace them approximately every 6 months because they become ineffective. It may be helpful to record the number and severity of anginal episodes, the number of nitroglycerin tablets required to relieve the attack, and the total number of tablets taken daily. Such a record can help a health care provider know when to change medications or dosages. Headache and dizziness may occur with nitrate antianginal drugs, especially sublingual nitroglycerin. These effects are usually temporary and dissipate with continued therapy. If dizziness occurs, avoid strenuous activity and stand up slowly for approximately an hour after taking the drugs. If the headache is severe, aspirin or acetaminophen may be taken with the nitrate drug. Do not reduce drug dosage or take the drug less often to avoid headache; loss of effectiveness may occur. Keep family members or support people informed about the location and use of medications for heart disease in case help is needed. Avoid over-the-counter decongestants, cold remedies, and diet pills, which stimulate the heart and constrict blood vessels and thus may cause angina. With nitrate drugs, avoid alcohol. Both the drugs and alcohol dilate blood vessels, and an excessive reduction in blood pressure (with dizziness and fainting) may occur with the combination. With a metabolic modulator, avoid concurrent intake of grapefruit juice: grapefruit juice increases serum drug levels. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbfuwFjUs0mdxkPeVey4KH2F7i%2fH0LC0NH7inQLoUzK%2f… 7/13 1/16/24, 10:24 PM Realizeit for Student Several calcium channel blockers are available in both immediate-acting and long-acting (sustained-release) forms. The brand names often differ very little (e.g., Procardia is a brand name of immediate-release nifedipine; Procardia XL is a long-acting formulation). It is extremely important that the correct formulation is used consistently. Keep all appointments with a health care provider. Self or Caregiver Administration Take or give drugs for heart disease as instructed; specific instructions differ with the type of drug being taken. Take or give drugs for heart disease on a regular schedule, at evenly spaced intervals. This increases drug effectiveness in preventing acute attacks of angina. The only exception may be nitroglycerin transdermal paste, which you may be directed not to take at night. With nitroglycerin and other nitrate preparations: Use according to instructions for the particular dosage form. The dosage forms were developed for specific routes of administration and are not interchangeable. Take your blood pressure before administering the medication as possible, and anticipate that the drug can decrease blood pressure from original reading. For sublingual nitroglycerin tablets, place them under the tongue until they dissolve. Take at the first sign of an anginal attack, before severe pain develops. Notify your health care provider immediately, report to the nearest hospital emergency room or call 911 after the first dose. Sit down when you take the medications. This may help relieve pain and prevent dizziness from the drug. If chest pain is not relieved in 5 minutes, dissolve a second tablet under the tongue. If pain is not relieved within another 5 minutes, dissolve a third tablet. Do not take medications for erectile dysfunction when taking nitroglycerin and other nitrate preparations. For the translingual solution of nitroglycerin, spray onto or under the tongue; do not inhale the spray. For transmucosal tablets of nitroglycerin, place them under the upper lip or between the cheek and gum and allow them to dissolve slowly over 3 to 5 hours. Do not chew or swallow the tablets. For nitroglycerin ointment, use the special paper to measure the dose. Place the ointment on a nonhairy part of the upper body and apply with the applicator paper. Cover the area with plastic wrap or tape. Rotate application sites (because the ointment can irritate the skin) and wipe off the previous dose before applying a new dose. Wash hands after applying the ointment. Use the measured paper for accurate dosage. Use the paper to apply the ointment because the drug is readily absorbed through the skin. Avoid skin contact except on the designated area of the body. Plastic wrap or tape aids absorption and prevents removal of the drug. It also prevents soiling of clothes and linens. For nitroglycerin patches and ointment, apply at the same time each day to clean, dry, hairless areas on the upper body or arms. Note whether the directions require you to remove the patch or ointment at night. Rotate sites. Avoid applying below the knee or elbow or in areas of skin irritation or scar tissue. Correct application is necessary to promote effective and consistent drug absorption. The drug is not as well absorbed from distal portions of the extremities because of decreased blood flow. Rotation of sites decreases skin irritation. Also, dispose of used patches properly because there is enough residual nitroglycerin to be harmful, especially to children and pets. Take oral nitrates on an empty stomach with a glass of water. Oral isosorbide dinitrate is available in regular and sustained-release tablets; be sure each type is taken appropriately. Do not crush or chew sustained-release nitrate tablets. For sublingual isosorbide dinitrate tablets, place them under the tongue until they dissolve. If an oral nitrate and topical nitroglycerin are being used concurrently, stagger the times of administration. This minimizes dizziness from low blood pressure and headache, which are common adverse effects of nitrate drugs. Report all new dietary supplements to the prescriber because some herbs interact with nitroglycerin. With beta-adrenergic blockers: Do not stop taking the drug abruptly because this can cause rebound tachycardia. If withdrawal of a beta-adrenergic blocker is planned by your prescriber, a gradual decrease in dose should occur, and you should limit physical activity to a minimum during this period. Move slowly from a sitting to a standing position to avoid orthostatic hypotension. Learn how to take your own pulse and blood pressure, report heart rate less than 55 beats/min to your health care provider, and withhold medication as instructed. Take your pulse and blood pressure more frequently when the medication is initiated and titrated up or down. Be aware of possible adverse effects, including dizziness, wheezing, and low heart rate. Take atenolol at the same time each day and avoid drinking large amounts of orange juice. If you are a diabetic, especially if you are prone to low blood sugar levels, you may need to check your blood sugar levels more frequently and eat consistently because beta-adrenergic blockers mask symptoms of low blood sugar. With calcium channel blockers: Increase water and fiber intake as tolerated to decrease constipation. Elevate your feet during the day to avoid ankle swelling. With sustained-release forms, which are usually taken once daily, do not take more often than prescribed and do not crush or chew. Other Drugs in the Class Isosorbide dinitrate (Isordil) is useful for reducing the frequency and severity of acute anginal episodes, not for acute relief of anginal symptoms. When given sublingually, it acts in about 2 minutes, and its effects last for 2 to 3 hours. When higher doses are given orally, more drug escapes metabolism in the liver and produces systemic effects in approximately 30 minutes. Therapeutic effects last about 4 hours after PO administration. The effective PO dose is usually determined by increasing the dose until headache occurs, indicating the maximum tolerable dose. Sustained-release capsules also are available. Isosorbide mononitrate is the metabolite and active component of isosorbide dinitrate. It is well absorbed after PO administration and almost 100% bioavailable. Unlike other PO nitrates, this drug is not subject to first-pass hepatic metabolism. Onset of action occurs within 1 hour, peak effects occur between 1 and 4 hours, and the elimination half-life is approximately 5 hours. It is used only for prophylaxis of angina; it does not act rapidly enough to relieve acute attacks. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbfuwFjUs0mdxkPeVey4KH2F7i%2fH0LC0NH7inQLoUzK%2f… 8/13 1/16/24, 10:24 PM Realizeit for Student Beta-Adrenergic Blockers Beta-adrenergic blockers have become the cornerstone of drug therapy regimens for people with angina, MI, hypertension, heart failure, and dysrhythmias. They inhibit the chronotropic, inotropic, and vasoconstrictor responses to the catecholamines epinephrine and norepinephrine by exerting effects on the three adrenergic receptors (beta1, beta2, and alpha). In the cardiac system, these drugs decrease cardiac workload by slowing heart rate, decreasing blood pressure, and reducing contractility. The drugs are as effective as the organic nitrates in reducing the frequency and severity of anginal symptoms during exercise. People taking the drugs do not develop tolerance during therapy as occurs with the organic nitrates. The 2013 ACCF/AHA Guidelines for the Management of Acute MI reported evidence from randomized controlled trials demonstrating that when beta-adrenergic blockers are started early in patients without signs of heart failure with acute MI (primarily STEMI), they reduce infarction size and early mortality. Also, with long-term use, these drugs lower the risk of death. The ability of a drug in this class to selectively block beta1 receptors, principally found in the myocardium, is known as cardioselectivity . Therefore, cardioselective beta-adrenergic blockers, such as atenolol, metoprolol, bisoprolol, and esmolol, offer the potential advantage of not interfering with bronchodilation or peripheral vasodilation. In addition to beta1-blockade, noncardioselective beta-adrenergic blockers block beta2 receptors found in smooth muscle in the lungs, blood vessels, and other organs. Examples of noncardioselective betaadrenergic blockers include propranolol, labetalol, nadolol, carvedilol, and timolol. Labetalol and carvedilol block both beta- and alphareceptors, thereby decreasing peripheral and coronary vascular resistance. During beta-adrenergic blocker therapy, the beta receptors undergo receptor up-regulation. This means that the number of receptors on the surface of target cells (the beta cells) becomes more sensitive to catecholamines. Pharmacokinetics With PO administration, atenolol undergoes limited first-pass metabolism in the liver. Absorption is rapid and consistent but incomplete. Approximately only 50% of an oral dose is absorbed from the gastrointestinal (GI) tract. The drug is modestly (6%–16%) bound to plasma, is distributed to the placenta, and is secreted in breast milk. It does not readily cross the blood–brain barrier. Peak blood levels occur between 2 and 4 hours after ingestion. With IV atenolol, the onset of action is immediate, duration of action is dose dependent (half-life 6–7 hours), and peak blood levels are reached in 5 minutes. The drug is not metabolized and is excreted in the urine and feces. Action Atenolol is a cardioselective beta-adrenergic blocker. The cardioselectivity is diminished at higher doses, where it inhibits beta2 receptors in the bronchial and vascular musculature. Use Atenolol is useful in the treatment of angina and hypertension as well as for the prophylaxis and treatment of MI. Health care providers use atenolol and other beta-adrenergic blockers in long-term management to decrease the frequency and severity of anginal attacks, decrease the need for sublingual nitroglycerin, and increase exercise tolerance. Evidence supports the use of a cardioselective beta-adrenergic blocker, such as atenolol, within the first 24 hours following an acute MI. QSEN Alert: Safety It is important to note that nonselective beta-adrenergic blockers should not be used in patients with variant angina because they are ineffective an coronary artery vasospasm. The U.S. Food and Drug Administration (FDA) has issued a BLACK BOX WARNING ♦ relating to the use of beta-adrenergic blockers in patients with CAD; abrupt withdrawal of oral forms may result in exacerbation of angina, increased incidence of ventricular dysrhythmias, MI, or death. Therefore, it is essential to slowly taper beta-adrenergic blockers before discontinuing them. Use in Older Adults The prevalence of CAD increases with age and is the major cause of disability, morbidity, and mortality in older adults. The elderly have a higher incidence of multivessel coronary disease, decreased left ventricular function, and comorbid conditions. For this reason, betaadrenergic blockers are one of the most frequently medications prescribed in older adults. Close monitoring of the patient’s heart rate is essential because the incidence of sick sinus syndrome and chronotropic intolerance increases with age and predisposes these patients to bradycardia, syncope, and falls. Use in Patients With Renal Impairment https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbfuwFjUs0mdxkPeVey4KH2F7i%2fH0LC0NH7inQLoUzK%2f… 9/13 1/16/24, 10:24 PM Realizeit for Student Atenolol is well tolerated in patients with renal impairment, but dosage reduction may be necessary. Study findings indicate beta-adrenergic blockers slow the deterioration of renal function in chronic kidney disease. Use in Patients With Critical Illness Administration of atenolol in the critical care setting may occur to reduce cardiovascular mortality in the management of hemodynamically stable patients with definite or suspected acute MI. IV administration should occur in a controlled setting equipped to monitor heart rate, blood pressure, and ECG. Hypotension may also occur with use, so the patient should be closely monitored for symptoms of hypotension. Unlike nitroglycerin, IV beta-adrenergic blockers are rarely used in the ICU for the control of angina. Adverse Effects The major cardiac adverse reactions related to beta-adrenergic blockers such as atenolol include heart failure and substantial negative chronotropy (causing slowing of the heart rate). A small number of people with chronic heart failure may have an exacerbation of heart failure when they begin taking atenolol or other beta-adrenergic blockers. In these people, sympathetic drive is maintaining cardiac output. The beta-adrenergic blockers decrease this sympathetic drive and therefore cause a low cardiac output state and heart failure. The majority of patients with heart failure do benefit from beta-blockade, and symptoms of heart failure abate. To manage the negative chronotropy, dosage adjustments may be necessary; the target heart rate should be 55 to 65 beats/min at rest. Use of beta-adrenergic blockers can lead to serious bradydysrhythmias and depression of the atrioventricular node. Noncardiac adverse effects include bronchospasm, especially in patients with chronic obstructive pulmonary disease (COPD) receiving high dosages because of beta2 receptor blockade. Note that many of the earlier signs of hypoglycemia are adrenergic warning symptoms (e.g., tremors, palpitation, tachycardia). Therefore, the use of beta-adrenergic blockers in patients with diabetes can mask the early warning symptoms of hypoglycemia. Contraindications Contraindications to atenolol include known hypersensitivity to the drug, second- or third-degree heart block, and cardiogenic shock, as well as severe bradycardia, heart failure, or hypotension. Caution is warranted with milder bradycardia, heart failure, or hypotension, and asthma. Nursing Implications Preventing Interactions Many medications interact with atenolol, increasing or decreasing its effects. Additionally, some herbs decrease the effects of atenolol. Drug Interactions: Atenolol Drugs That Increase the Effects of Atenolol Alcohol Increases the risk of hypotension Atazanavir, dolasetron, saquinavir Increase the risk of heart block Digoxin Increases the risk of bradycardia Diltiazem, verapamil Increase the risk of bradycardia, heart block, and increased left ventricular end-diastolic pressure Reserpine Increases the risk of hypotension and significant bradycardia Sildenafil, tadalafil, vardenafil Increase the risk of life-threatening hypotension Drugs That Decrease the Effects of Atenolol Adrenergic drugs (e.g., epinephrine, isoproterenol) Reverse bradycardia Anticholinergic drugs (e.g., diphenhydramine, ipratropium) Increase heart rate, offsetting slower heart rates of atenolol Indomethacin Decreases the hypotensive effects https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbfuwFjUs0mdxkPeVey4KH2F7i%2fH0LC0NH7inQLoUzK%2f… 10/13 1/16/24, 10:24 PM Realizeit for Student Herb and Dietary Interactions: Atenolol Herbs and Foods That Decrease the Effects of Atenolol Betel palm Calcium salts Orange juice Administering the Medication Prior to giving atenolol, the nurse should check the patient's vital signs. It is important to withhold atenolol and notify the prescriber for a resting heart rate of 60 beats/min and/or systolic blood pressure less than 90 mm Hg. The nurse gives IV beta-adrenergic blockers over 2.5 minutes. Continuous telemetry is necessary for patients receiving an IV bolus or a continuous drip. The effectiveness of beta-adrenergic blockers in relation to relieving angina is dose dependent. It is necessary to titrate the dose of the beta-adrenergic blocker for a target heart rate of 50 to 60 beats/min with normal blood pressure. The nurse monitors the blood pressure every 5 minutes, while the drip is being titrated and assesses for signs of bronchoconstriction at higher drug dosages where cardioselectivity may be lost. Assessing for Therapeutic Effects The nurse evaluates for three main objectives in the patient with chronic angina. One, the patient's frequency and severity of angina is reduced. Two, the patient has improved exercise capacity. Three, there is a reduction or elimination in the use of sublingual nitroglycerin. Ideally, achievement of these goals results in fewer adverse effects. Assessing for Adverse Effects The nurse closely monitors the patient's blood pressure and heart rate 2 to 4 hours after the first dose of atenolol. Signs of hypotension include dizziness and blurred vision; syncope is indicative of bradydysrhythmias. Increased shortness of breath and wheezing are adverse effects seen in patients with COPD who are taking noncardioselective beta-adrenergic blockers or high doses of cardioselective betaadrenergic blockers. In patients with diabetes prone to hypoglycemia, more frequent assessment of serum glucose levels may be necessary. Adjuvant Medications Ranolazine The anti-ischemic metabolic modulator ranolazine (Ranexa) is an approved first-line treatment for chronic angina. However, the drug does not relieve acute angina symptoms and has not shown a benefit in acute coronary syndromes. Conventional antianginal drugs significantly decrease one or more of the determinants of myocardial oxygen demand, such as heart rate, preload, afterload, or myocardial contractility, thus reducing myocardial ischemia. Ranolazine increases the energy production of the heart to preserve cardiac function without decreasing blood pressure or heart rate, but it does not relieve acute anginal attacks and does not have any benefit in treating acute coronary syndromes. Although its mechanism of action is not clearly understood, ranolazine works by preventing both calcium overload and the subsequent increase in diastolic tension. This is all related to inhibition of the late inward sodium channel. Because this sodium channel frequently fails to inactivate in a number of important myocardial disease states such as ischemia and hypertrophy, excess entry of sodium ions leads to activation of the sodium–calcium exchanger, thereby raising calcium concentration. Unlike the other classes of antianginal drugs, ranolazine decreases ischemia but does not possess negative inotropic or chronotropic effects. When compared to placebo in patients with CAD, ranolazine is associated with a decreased frequency of ventricular dysrhythmias, bradycardia, and new-onset atrial fibrillation. Ranolazine should be reserved for use in two groups of patients: (1) in those who have not had an adequate response to beta-adrenergic blockers or (2) in combination with the blockers for relief of symptoms when initial treatment with the blockers has not been successful. Ranolazine has a dose-dependent ability to prolong the QT interval. Therefore, the drug is contraindicated in patients with preexisting QTinterval prolongation. It is also contraindicated in patients with hepatic disease and in patients taking other drugs that prolong the QT interval. Dose reduction of digoxin and simvastatin may be necessary with concurrent use because ranolazine affects the metabolic https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbfuwFjUs0mdxkPeVey4KH2F7i%2fH0LC0NH7inQLoUzK%2f… 11/13 1/16/24, 10:24 PM Realizeit for Student pathways of these drugs. Aspirin, antilipidemics, and antihypertensives are used in conjunction with antianginal drugs to prevent progression of myocardial ischemia to MI. The Nursing Process A concept map below outlines the nursing process related to drug therapy considerations in this chapter. Additional nursing implications related to the disease process should also be considered in care decisions. Example YouTube: Pharmacology - Nitroglycerin & Angina - for RN NCLEX https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbfuwFjUs0mdxkPeVey4KH2F7i%2fH0LC0NH7inQLoUzK%2f… 12/13 1/16/24, 10:24 PM Realizeit for Student You tube: Nitroglycerin (Nitro) Nursing Drug Card (Simplified) – Pharmacology Nurseslabs. Antianginal Drugs. Retrieved from https://nurseslabs.com/antianginal-drugs/ Drugs.com Nitroglycerin. Retrieved from https://www.drugs.com/ppa/nitroglycerin.html RNpedia. Nitroglycerin Nursing Considerations & Management. Retrieved from https://www.rnpedia.com/nursing-notes/pharmacology-drug-study-notes/nitroglycerin/ Summary This section discusses the drugs used to treat angina. Individual drugs used in the treatment of coronary heart disease include the organic nitrates, beta-adrenergic blockers, calcium channel blockers, and adjuvant drugs, including the anti-ischemic metabolic modulator ranolazine. Nitroglycerin is the prototype drug and is available in multiple formulations. These drugs relieve anginal pain by increasing blood supply to the myocardium as well as reducing the oxygen demand of the myocardium. Nitroglycerin relieves pain of stable angina by dilating veins, which decreases venous return, which decreases preload, which decreases oxygen demand. Nitroglycerin causes three characteristic side effects: headache, orthostatic hypotension, and reflex tachycardia. All three occur secondary to vasodilation. All antianginal agents are effective and may be used in combination to achieve good pain control. The type of drug that is best for a patient is determined by tolerance of adverse effects and response to the drug. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbfuwFjUs0mdxkPeVey4KH2F7i%2fH0LC0NH7inQLoUzK%2f… 13/13