Chapters 7, 8, 24, 26 (Pharmacology)

Digoxin (Lanoxin) Inotropes (Cardiac Glycosides)

• Inotropes (cardiac glycosides) act to influence the contractility of the heart muscle. • Digoxin is the PROTOTYPE drug of this class. • Digoxin is derived from the digitalis plant. It is used to treat heart failure, atrial fibrillation, and atrial flutter. • Taking orally either as a tablet or elixir. The elixir is absorbed more effectively than the tablet and is used primarily with infants and children. Digoxin can also be given by injection. • Lanoxicaps - liquid-filled capsules. • Digitalization is the administration of a loading dose of digoxin. The administration of digoxin for rapid digitalization is usually done for atrial tachydysrhythmias rather than heart failure. • Rapid digitalization places the patient at risk for developing digoxin toxicity. Thus, the nurse must be alert to signs and symptoms of toxicity, which include very slow or very rapid ventricular rhythm, nausea, vomiting, loss of appetite, abdominal distention, blurred vision, and mental changes. • Decreased absorption of digoxin can result in digitalis toxicity (an accumulation of digitalis in the body that leads to nausea, vomiting, and atrial tachycardia). • Factors that decrease the absorption of digoxin include the presence of food in the GI tract, malabsorption syndromes, and the concurrent administration of antacids or cholestyramine. • NOTE: When digoxin is discontinued, it takes approx. 1 week for the drug to be eliminated from the body. • Action: A pt with heart failure is experiencing decreased contractility of the heart, which impairs the heart's ability to pump blood adequately. Digoxin produces a cardiotonic (positive inotropic) effect that improves the contractility and pumping ability of the heart. Digoxin increases the force of myocardial contractility by inhibiting sodium, potassium, adenosine triphosphatase (na, K-ATPase), an enzyme in cardiac cell membranes that decreases the movement of sodium out of myocardial cells after contraction. As a result, calcium enters the cell in exchange for sodium, causing additional calcium to be released from intracellular binding sites and increasing myocardial contractility. • Use: use of digoxin include the management of heart failure, atrial fibrillation, and atrial flutter. Digoxin is administered to patients with acute or chronic conditions, patients who are being digitalized, or for maintenance therapy. • In Children: Very small amounts are given to children (may be very little difference between a therapeutic dose and a toxic dose). Liquid digoxin must be precisely measured in a syringe and the dose should never be rounded. • Electrocardiographic monitoring is desirable when digoxin therapy is initiated. • Digoxin is primary excreted by the kdneys, and the dosage should be reduced in the presence of renal impairment. Divided daily doses should be given to infants and children younger than 10, and adult dosages adjust to weight should be given to children older than 10 years of age. • Neonates vary in tolerance of digoxin, depending on their degree of maturity. Premature infants are especially sensitive to drug effects. • Early signs of toxicity in newborns are undue slowing of the sinus rate, sinoatrial (SA) arrest, and prolongation of the P-R interval. • In Older Adults: Dosage must be reduced by approx. 50% with renal failure. The most common recommended dose is 0.125 mg daily. • Renal Impairment: Pts with advanced renal impairment can achieve therapeutic serum concentrations with a dosage of 0.125 mg three to five times per week. Digoxin toxicity develops more often and lasts longer in pts with renal impairment. • Hepatic Impairment: Hepatic function has little effect on digoxin clearance. • Home Care: instruct the patient and caregivers of symptoms of heart failure or digoxin toxicity develop, it is necessary to seek medical intervention immediately. • Adverse Effects: Patients with hypokalemia can develop digoxin toxicity even when the serum digoxin level is not considered to be elevated. Others include nausea, vomiting (digoxin stimulates the vomiting center of the brain), loss of appetite, abdominal pain, etc. • Factors that Contribute to Digoxin Toxicity: Electrolyte imbalance, hypothyroidism (slow metabolism). • If digoxin toxicity occurs, it is discontinued, not just reduced in dosage. In the presence of serious cardiac dysrhythmias - potassium chloride, which acts to decrease myocardial excitability. Atropine is used to manage bradycardia or conduction defects. • Digoxin immune fab (Digibind) is a digoxin-binding antidote. It is recommended only for serious toxicity. • Contraindications: contraindicated in those with severe myocarditis, ventricular tachycardia, or ventricular fibrillation. • Drugs that Increase the Effects of Digoxin: Adrenergic agents, such as epinephrine (Adrenaline), antidysrhythmics, calcium preparations, calcium channel blockers, such as diltiazem. Drugs that Decrease the Effects: Antacids, cholestyramine, colestipol hydrochloride (Colestid), oral laxatives. Herbs and Foods that Increase the Effects: Ginseng, hawthorne, licorice. Herbs and Foods that Decrease the Effects: Psyllium, St. John's wort. • Administering the Med: therapeutic serum digoxin level is 0.8 to 2.0 ng/mL. Blood sample is drawn at least 6 hours after the previous dose, BC distribution of digoxin to the tissues requires about 6 hours. Administration of digoxin requires the nurse to thoroughly assess the patient's cardiac status. Assess the apical pulse at the point of maximal impulse (PMI) for 1 full minute. If the rate is less than 60 beats/min in adults, 70 beats/min in older children, or 100 beats/min in younger children, the dose is omitted and the health care provider is notified. • Digoxin is administered with food or after meals. It minimizes gastric irritation and symptoms of anorexia nausea, vomiting. • Symptoms of digitalis toxicity: bradycardia and cardiac dysrhythmias, such as PVS, paroxysmal atrial tachycardia with heart block, AV tachycardia, and AV block (AKA second or third degree heart block), as well as headache, drowsiness, and confusion. Visual disturbances (blurred vision, photophobia, altered perception of color, and flickering dots). • Use the same brand and type of digoxin ALL THE TIME. Given daily at the same time. If you forget to take a dose and it is within 6 hours of the time you usually take it, take your daily dose. Take digoxin with food or after a meal. Dairy products will delay absorption. Tablets can be crushed. Capsules taken whole.

Drugs Used to Control Bleeding

• *Aminocaproic acid* and tranexamic acid are used to stop bleeding caused by overdoses of thrombolytic agents. • *Aminocaproic acid also may be used in other bleeding disorders caused by hyperfibrinolysis (in cardiac surgery, blood disorders, hepatic cirrhosis, prostatectomy, neoplastic disorders)*. • Transexamic acid also is used for short periods (2-8 days) in patients with hemophilia to prevent or decrease bleeding from tooth extraction. • *Protamine sulfate* is an antidote for standard heparin and LMWHs. BC heparin is an acid and protamine sulfate is a base, protamine neutralizes heparin activity. • Protamine dosage depends on the amount of heparin administered during the previous 4 hours. Each milligram of protamine neutralizes approximately 100 units of heparin or dalteparin and 1 mg of enoxaparin. • BLACK BOX WARNING: A single dose should not exceed 50mg due to the risk of severe hypotension, cardiovascular collapse, noncardiogenic pulmonary edema, catastrophic pulmonary vasoconstriction, and pulmonary hypertension with its use. The drug is given by slow IV infusion over at least 10 minutes. • Severe hypotensive and anaphylactoid reactions may result from protamine administration. Thus, the drug should be given in settings with equipment and personnel for resuscitation and management of anaphylactic shock. • *Vitamin K* is the antidote for warfarin overdosage. An oral dose of 10 to 20 mg usually stops minor bleeding and returns the INR to a normal range within 24 hours. INR serum levels less than 5 with no significant bleeding may be managed with withholding of the warfarin based on protocols; INR levels greater than 5 may require the use of oral vitamin K.

Argatroban Direct Thrombin Inhibitors (DTI)

• *Argatroban*: is the second agent, after lepirudin, to be indicated for HIT. Unlike lepirudin, *argatroban* is eliminated in the liver and can be used in people with end-stage renal disease. Administered IV.

Clopidogrel (Plavix) Adenosine Diphosphate Receptor Antagonists

• *Clopidogrel (Plavix)* is the PROTOTYPE ADP receptor antiantagonist. • Other ADP receptor antagonists, prasugrel and ticlopidine, are also used for their antiplatelet activity. • Clopidogrel has *THREE shortcomings: delayed onset of action, irreversible inhibitory effects on platelets with no reversing agent or antidote, and significant individual variability in platelet response*. • *Oral administration*. • Action: Clopidogrel irreversibly block the ADP receptor on platelet cell membranes. *Platelet aggregation progressively returns to baseline about 5 days AFTER discontinuing clopidogrel*. • Use: Reduction of MI, stroke, and vascular death in patients with atherosclerosis and in those after placement of coronary stents. Specific uses include prevention of vascular ischemic events in patients with symptomatic atherosclerosis or with acute coronary syndrome (with or without ST-segment elevation). In addition, after placement of an intracoronary stent for the prevention of thrombosis, *patients may take clopidogrel in conjunction with aspirin (dual antiplatelet therapy)*. • *People with atrial fibrillation who are unable to take vitamin K antagonists take clopidogrel instead*. • Adding clopidogrel to aspirin in people with atrial fibrillation reduces the rate of major vascular events compared with aspirin alone but is associated with a greater risk of bleeding. • In Children: Safety and efficacy has not been established. • In Older Adults: More likely than younger adults to experience bleeding and other complications of antiplatelet drugs. *Clopidogrel is commonly used to prevent thrombotic stroke but can increase the risk of hemorrhagic stroke*. • In Hepatic Impairment: BC clopidogrel is metabolized in the liver, *it may accumulate in people with hepatic impairment*. • Adverse Effects: pruritus, rash, purpura, and diarrhea. Thrombotic thrombocytopenia purpura, hemorrhage, and severe neutropenia have also occurred. • Contraindications: Patients with active bleeding in conditions such as intracranial hemorrhage or peptic ulcer disease. • *BLACK BOX WARNING: Use of clopidogrel in the 2% to 14% of the US population who are reduced metabolizers of the drug - the drug may be less effective in altering platelet activity in these people. These "poor metabolizers" may remain at risk for heart attack, stroke, and cardiovascular death, and alternate dosing of clopidogrel or the use of other antiplatelet drugs should be considered*. • Drugs that Increase the Effects of Clopidogrel: Aspirin, Atorvastatin, Barbiturates, rifampin, rifapentine, nonsteroidal anti-inflammatory drugs, platelet inhibitors, thrombolyrics. • Drugs that Decrease the Effects of Clopidogrel: Amiodarone, clarithromycin, erythromycin, ketoconazole, omeprazole, selective serotonin reuptake inhibitors. • Herbs and Foods that Increase the Effects: Garlic, ginkgo biloba, ginger, green tea, horse chestnut. • Administering the Medication: *Once daily without regard to food intake*. The FDA has approved a 300-mg tablet as a loading dose for appropriate patients. • *It is recommended that patients who receive implants with a bare-metal stent take clopidogrel for at least 1 month and that patients who receive a drug-eluting stent take dual antiplatelet therapy for at least 12 months*. • Assess for Therapeutic Effects: Assess for absence of vascular ischemic events (pain, cyanosis, coolness of extremities). • Assess for Adverse Effects: pruritus, rash, purpura, and diarrhea; thrombotic thrombocytopenia purpura and hemorrhage; and severe neutropenia. • Patient Teaching: Educate to take medication as directed and not to double the medication if a dose is missed.

Alteplase (Activase) Thrombolytic Drugs

• Alteplase (Activase) is the PROTOTYPE recombinant tissue plasminogen activator (rtPA). • The purpose of thrombolytic agents is to *dissolve thrombi*. These drugs stimulate conversion of plasminogen to plasmin, a proteolytic enzyme that breaks down fibrin, the framework of a thrombus. • Management of acute, severe thromboembolic disease, such as MI, pulmonary embolism, and iliofemoral thrombosis. • Alteplase is by *IV infusion*. • Whether alteplase crosses the placenta or is excreted into breast milk is unknown. • Action: Alteplase is a protein that lyses unwanted fibrin blood clots by catalyzing the conversion of plasminogen to plasmin. • Use: lysis of acute coronary arterial thromboembolism associated with evolving transmural MI or acute pulmonary thromboembolism. • Considered as a first-line therapy for the treatment of acute ischemic stroke in selected people. • Use in Older Adults: *Alteplase is not recommended in people older than 80 years of age*. • Adverse Effects: *Bleeding is the main adverse effect*. *The major risk of rtPA therapy is symptomatic brain hemorrhage, and when rtPA treatment is chosen, the prescriber should obtain informed consent signed by the stroke patient or family member. There is a 3% mortality rate and a 6% to 8% risk of symptomatic hemorrhage associated with its use*. • *In rtPA overdose, aminocaproic acid serves as an antidote*. • Contraindications: In patients with uncontrolled severe hypertension, aneurysm, arteriovenous malformation, known coagulopathy or internal bleeding, intracranial or intraspinal surgery or trauma within the past 3 months, recent major surgery, or current use of oral anticoagulants. • Nursing Implications: *it is necessary to minimize intramuscular injections in patients who are receiving systemic thrombolytic therapy, because bleeding, bruising, or hematomas may develop*. • *Assess patients for cardiac dysrhythmias, including sinus bradycardia, premature ventricular contractions, and ventricular tachycardia resulting from reperfusion following coronary thrombolysis*. • Drugs that Increase the Effects of Alteplase: Aspirin or other salicylates, abciximab, enoxaparin, eptifibatide, fondaparinux, heparin, nonsteroidal anti-inflammatory drugs, warfarin. • Herbs and Foods that Increase the Effects of Alteplase: Cat's claw, dong quai, evening primrose, feverfew, garlic, ginkgo, ginseng, green tea, horse chestnut, red clover. • Administering the Medication: Before starting a thrombolytic agent, it is essential to check INR, aPTT, platelet count, and fibrinogen to establish baseline values and to determine whether a blood coagulation disorder is present. Two or three hours after thrombolytic therapy is started, the nurse ensures that the fibrinogen level is measured to determine that fibrinolysis is occurring. During and following alteplase administration, the nurse monitors BP frequently and ensures that it is well controlled. • Administration is *IV as a bolus injection or infusion*. Administer all infusions using an IV infusion device. *It is necessary to reconstitute alteplase as indicated and not to shake it*. • Assess for Therapeutic Effects: Goal is to minimize total ischemic time and restore blood flow. • Assess for Adverse Effects: Assess for evidence of bleeding. If bleeding cannot be controlled or involves a vital organ, it is necessary to stop the thrombolytic drug and replace fibrinogen with whole blood plasma or cyoprecipitate. • *When the drugs are used in acute MI, cardiac dysrhythmias may occur when the blood flow is reestablished. Therefore, antidysrhythmic drugs should be readily available*. • Patient Teaching: Patients should take special care brushing their teeth to reduce bleeding at the gum line.

Patient Teaching About Angina and Antianginal Drugs

• Angina is chest pain that occurs BC your heart is not getting enough blood and oxygen. The most common causes are hypotension 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. • 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. • 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 BC they become ineffective. • Headache and dizziness may occur with nitrate antianginal drugs, especially sublingual nitroglycerin. • 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 antianginal drugs, avoid alcohol. Both drugs and alcohol dilate blood vessels, and an excessive reduction in BP (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. • Serum calcium channel blockers are available in both immediate-acting and long-acting (sustained-release) forms. • It is extremely important that the correct formulation is used consistently. • Self or Caregiver Administration: Take or give antianginal drugs on a regular schedule, at evenly spaced intervals. This increases drug effectiveness in preventing acute attacks of angina. • With nitroglycerin and other nitrate preparations: the dosage forms were developed for specific routes of administration and are not interchangeable. • Take your BP before administering the med as possible and anticipate that the drug can decrease BP from original reading. • 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. If pain continues or becomes more severe, notify your health care provider immediately or report to the nearest hospital emergency room. • For transmucosal tablets or nitroglycerin, place them under the upper lip or between the cheek and gum and allow them to dissolve slowly over 3 to 5 hours. • 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 (BC the ointment can irritate the skin) and wipe off the previous dose before applying a new dose. Wash hands afterward. • The drug is not as well absorbed from distal portions of the extremities BC of decreased blood flow. • Dispose of used patches properly BC 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. • If an oral nitrate and topical nitroglycerin are being used concurrently, stagger the times of administration. This minimizes dizziness from low BP and headache, which are common adverse effects of nitrate drugs.

Atenolol (Tenormin) Cardioselective Beta-Adrenergic Blockers

• Approx. only 50% of an oral dose is absorbed from the GI tract. • Use: Atenolol is useful in the treatment of angina and hypertension as well as for the prophylaxis and treatment of MI. • Long-term management to decrease the frequency and severity of angina attacks, decrease the need for sublingual nitroglycerin, and increase exercise tolerance. • NOTE: important to note that beta blockers should not be used in pts with variant angina BC they are ineffective and may increase the tendency to induce coronary vasospasm. • BLACK BOX WARNING in pts with CAD (coronary artery disease); withdrawing oral forms may result in exacerbation of angina, increased incidence of ventricular dysrhythmias, and the occurrence of MI. Therefore, it is essential to slowly TAPER beta blockers before discontinuing them. • In Older Adults: prevalence of CAD increases with age and is the major cause of disability, morbidity, and mortality in older adults. For this reason, beta blockers are one of the most frequent medications prescribed in older adults. Close monitoring of the pts heart rate is essential BC the incidence of sick sinus syndrome and chronotropic intolerance increases with age and predisposes these patients to bradycardia, syncope, and falls. • Renal Impairment: New study findings indicate beta blockers now slow the deterioration of renal function in chronic kidney disease. • IV administration should occur in a controlled setting equipped to monitor heart rate, BP, and ECG. Hypotension may also occur with use, so the pt should be closely monitored for symptoms of hypotension. Unlike nitroglycerin, IV beta-blockers are rarely used in the ICU for control of angina. • Adverse Effects: Heart failure and substantial negative chronotropy. Other adverse effects include slowing of the heart rate. • Contraindications: second-or third-degree heart block, and cariogenic shock, as well as severe bradycardia, heart failure, or hypotension. • Administering the Med: nurse should check the pts vital signs. It is important to withhold atenolol and notify the prescriber for a resting heart rate of 60 beats/min and/or systolic BP less than 90 mm Hg. • Continuous telemetry is necessary for pts receiving an IV bolus or a continuous drip. • The target heart should be 55 to 65 beats/min at rest. • The nurse monitors the BP every 5 minutes while the drip is being titrated. • Assess for Therapeutic Effects: Nurse evaluates for three main objectives. The patient's frequency and severity of angina is reduced. The patient has improved exercise capacity. There is a reduction or elimination in the use of sublingual nitroglycerin. • Assess for Adverse Effects: Closely monitors the pts BP 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 it pts with COPD who are taking beta blockers.

Other Antiplatelet Drugs Aspirin & Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

• Aspirin exerts pharmacologic actions by inhibiting synthesis of prostaglandins. • Aspirin may be used long term for prevention of MI or stroke in patients with prosthetic heart valves. Also used for the immediate treatment of suspected or actual acute MI, for TIAs, and for evolving thrombotic strokes. • Adverse Effects: uncommon with small doses used for antiplatelet effects. However, there is an increased risk of bleeding, including hemorrhagic stroke. • No antidote exists for the effects of aspirin BC it produces irreversible platelet effects; platelet transfusion may be required. • Nonsteroidal anti-inflammatory drugs (NSAIDs): including ibuprofen any many other aspirin-related drugs, inhibit cyclooxygenase reversibly. • Their antiplatelet effects subside when the drugs are eliminated from the circulation and the drugs usually are not used for antiplatelet effects. • Acetaminophen does NOT affect platelets in usual doses.

Pathophysiology of Coagulation and Clinical Manifestation

• Atherosclerosis is the basic disease process that often leads to pathologic thrombosis. Atherosclerosis begins with accumulation of lipid-filled macrophages (foam cells) on the inner lining of arteries. Foam cells develop in response to elevated blood lipid levels and eventually become fibrous plaques (foam cells covered by smooth muscle cells and connective tissue). Advanced atherosclerotic lesions also contain hemorrhages, ulcerations, and scar tissue. • Atherosclerosis can affect any organ or tissue but often involves the arteries supplying the heart, brain, and legs. Over time, plaque lesions become larger and extend farther into the lumen of the artery. Eventually, a thrombus may develop at plaque sites and partially or completely occlude an artery. • In coronary arteries, a thrombus may precipitate myocardial ischemia (angina or infarction); in carotid or cerebral arteries, a thrombus may precipitate a stroke; in peripheral arteries, a thrombus may cause intermittent claudication (pain in the legs with exercise) or acute occlusion. Thus, serious impairment of blood flow may occur with a large atherosclerotic plaque or a relatively small plaque with superimposed vasospasm and thrombosis. Consequences and clinical manifestations of thrombi and emboli depend primarily on their location and size. • Clinical manifestations of thrombosis vary depending on the size and location (arterial or venous system) of the thrombus. Symptoms are the result of decreased perfusion to an area due to the restriction of cessation of blood flow. • Arterial blood clots in the cerebral, pulmonary, or cardiac system can produce a cerebrovascular accident, pulmonary embolism, or MI, respectively. • Venous blood clots may lead to DVT; classic symptoms include leg swelling and pain on palpation in the calf or thigh. However, half of all affected patients do not have any symptoms of DVT.

Atorvastatin (Lipitor) HMG-CoA Reductase Inhibitors

• Atorvastatin is one of the most widely used drugs in the United States and is the PROTOTYPE of the class of drugs called hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, or statins. • By decreasing production of cholesterol, the statins decrease total serum cholesterol, LDL cholesterol, VLDL cholesterol, and triglycerides. • They reduce LDL cholesterol within 2 weeks and reach maximal effects in approximately 4 to 6 weeks. HDL cholesterol levels remain unchanged or may increase. • Atorvastatin is the most commonly prescribed statin. • Atorvastatin and other statins also reduce the risk of angina pectoris and peripheral arterial disease as well as the need for angioplasty and coronary artery grafting to increase or restore blood flow to the myocardium. • Food decreases the rate and extent of absorption. • Action: The statins inhibit an enzyme (HMG-CoA reductase) required for hepatic synthesis of cholesterol. • Use: Atorvastatin and other statins are indicated for the treatment of hypercholesterolemia and reducing cardiovascular events in people with multiple risk factors. • The statins are the MOST powerful drug class for reduction of LDL cholesterol but are expensive. • These drugs also decrease triglyceride levels and raise HDL levels. • In Children: Evidence indicates that atherosclerotic lesions can begin in childhood, and reccomendations support selectively screening for children and adolescents starting at age 2 who have a parent with a total cholesterol of 240 mg/dL or higher or a family history of premature cardiovascular disease (age 55 years or younger). • The FDA has approved atorvastatin for treatment of high cholesterol levels in children aged 10 to 17 years. Management of younger children with hypercholesterolemia focuses on lifestyle modifications. • In Older Adults: Diet, exercise, and weight control should be tried first to reduce cholesterol levels. When drug therapy is required, statins are effective for lowering LDL cholesterol and usually are well tolerated by older adults. • Renal Impairment: plasma levels are not affected and dosage reductions are not necessary. • Hepatic Impairment: Contraindications in patients with active liver disease or unexplained elevations of serum aspartate aminotransferase or alanine aminotransferase BC it may accumulate. Dosage reduction may need to be made for those with hepatic impairment and those who ingest substantial amounts of alcohol or who have a history of liver disease. • Home Care: BC liver enzymes may be elevated during atorvastatin use, patients need liver function tests and repeat lipid profile testing on a routine basis. • Adverse Effects: Statins are usually well tolerated; the most common adverse effects (nausea, constipation, diarrhea, abdominal cramps or pain, headache, skin rash) are usually mild and transient. Hepatic dysfunction has been a source of concern, although the actual risk appears to be small. Myopathy is an important adverse effect. Statins can injure muscle tissue, resulting in muscle ache or weakness. Factors that increase the risk of myopathy include advanced age, frail or small body frame, high dosage of statins, concomitant use of fibrates, hypothyroidism, and multiple systemic diseases such as renal insufficiency secondary to diabetic nephropathy. • Safety Alert: The risk of teratogenicity with the use of statins appears small, but the use of birth control measures with statin use is essential in sexually active women. • Contraindications: Potentially teratogenic (pregnancy category X). Careful consideration is necessary if used. • The statins are the MOST effective dyslipidemic agents for improving clinical outcomes when used for primary and secondary prevention of cardiovascular disease. • Drugs that Increase the Effects of Atorvastatin: magnesium, aluminum-containing antacids, erythromycin & macrolide abx. Drugs that Decrease the Effects: Cholestyramine, colestipol, Herbs and Foods that Increase the Effects: Grapefruit juice, Pomegranate juice, red yeast rice, sitostanol, vitamin B3. Herbs and Foods that may Decrease the Effects: Fibers such as oat bran and pectin. • Administering the Medication: The bulk of cholesterol synthesis appears to occur at night, administration of statins normally takes place in the evening or at bedtime. Though evidence suggests that atorvastatin casn be given without regard to time of day due to atorvastatin having a long half-life. • Assess for Therapeutic Effects: monitor lipid response to therapy, looking for decreased levels of total serum cholesterol, LDL cholesterol, and triglycerides, as well as increased levels of HDL cholesterol. Effects occur in 1 to 2 weeks with maximum effects in 4 to 6 weeks. • Assess for Adverse Effects: Nausea, diarrhea, abdominal pain, dyspepsia, and elevated liver function tests. Monitor for myopathy (muscle pain or weakness), mainly during the first months of therapy and when dosages are adjusted upward. • Patient Teaching: Contraceptive counseling. Liver function tests are recommended before starting a statin, at 12 weeks after starting the drug, at every increase in dose, and then periodically. • Other Drugs in the Class: Lovastatin and pravastatin are poorly absorbed, and fluvastatin has the highest rate of absorption. Patients may take pravastatin or simvastatin with or without food in the evening. They may take fluvastatin on an empty stomach or at bedtime. It is important to avoid taking them with grapefruit juice. It should be noted that concurrent use of cimetidine, ranitidine, and omeprazole increases the effects of fluvastatin.

Using Beta-Blockers for the Treatment of Angina

• Beta-adrenergic blockers have become the cornerstone of drug therapy regimens for people with angina, hypertension, heart failure, and dysrhythmias. They decrease cardiac workload by slowing heart rate, decreasing BP, and reducing contractility. The drugs are as effective as the organic nitrates in reducing the frequency and severity of anginal symptoms during exercise and present advantages to nitrate use. People taking the drugs do not develop tolerance during therapy as occurs with the organic nitrates. • With beta-blockers: do NOT stop taking the drug abruptly BC this can cause rebound tachycardia. If withdrawal of a beta blocker is planned by your prescriber, a gradual decrease in dose should occur and you should limit physical activity. • Move slowly from a sitting to a standing position to avoid orthostatic hypotension. • Learn how to take your own pulse and BP. Report heart rate less than 55 beats per minute to your health care provider, and withhold medication as instructed. • 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.

Bisoprolol (Zebeta) Cardioselective Beta-Adrenergic Blockers

• Bisoprolol (Zebeta) as well as Metoprolol are used to treat angina. These drugs block beta1 receptors. • Bisoprolol is also used to manage hypertension and heart failure. • Action: The drug reduces the workload of the heart and decreases myocardial oxygen demand by decreasing heart rate and the force of myocardial contractions. • Adverse Effects: It is generally well tolerated, and adverse effects are mild and transient; they include nausea, diarrhea, dizziness, fatigue, impotence, bradycardia, and hypotension. • At higher doses, bisoprolol can cause shortness of breath and wheezing. • The drug can mask early warning symptoms of hypoglycemia as does most of the beta blockers.

Nifedipine (Adalat, Procardia) Calcium Channel Blockers

• Calcium Channel Blockers are used to treat an assortment of cardiovascular disorders including stable angina pectoris and variant angina. • Nifedipine is the PROTOTYPE. • Nifedipine is well absorbed after ORAL administration. • Action: Nifedipine inhibits the influx of calcium entering through slow channels, producing vasodilation of the peripheral blood vessels and coronary arteries. Does NOT affect the heart rate. • Nifedipine has been shown to be effective in the treatment for stable, variant, and unstable angina, mild-to-severe hypertension, and Raynaud's phenomenon. • In Children: For primary hypertension, nifedipine and other long-acting calcium channel blockers are safe. They are especially useful in children who have asthma and cannot tolerate beta-adrenergic blockers. • In Older Adults: This age group is more prone to orthostatic hypotension and is at high risk for falls while taking calcium channel blockers. • Hepatic Impairment: Necessary to reduce dosage substantially and closely monitor patients for drug effects (including periodic measurements of liver enzymes). • Home Care: Check pts BP and heart rate at each visit. Suggest measures to minimize fall risk. • Adverse Effects: Cardiac adverse effects due to excessive vasodilation include hypotension, flushing, headache, dizziness, lower limb edema, and reflex tachycardia. • Contraindications: Do NOT use nifedipine in the treatment of angina related to overdose with cocaine, amphetamines, or other alpha-adrenergic receptors, causing vasoconstriction and severe, life-threatening hypertension. • Do NOT take grapefruit juice with nifedipin e BC a two-fold increase in the effects of the drug may occur. Nifedipine may interact with quinidine, decreasing plasma levels, and digoxin, increasing levels. • Administering the Med: can take with or without food. It is important not to crush or break sustained-release formulations. Take BP prior to administration and withhold the drug for a systolic BP less than 90 mm Hg. • Teach patients to NEVER stop taking nifedipine abruptly. May result in rebound tachycardia.

Cholestyramine Bile Acid Sequestrants

• Cholestyramine (Prevalite, Questran) is the PROTOTYPE bile acid sequestrant and has the ability to reduce LDL cholesterol. It has little to no effect on HDL cholesterol and either no effect or an increased effect on triglyceride levels. • No evidence of use as monotherapy, but can play a role as an add-on drug with statins or niacin in combination therapy. • Taken orally. • Action: Cholestyramine binds bile acids in the intestinal lumen, causing the bile acids to be excreted in feces, preventing recirculation to the liver. As more hepatic cholesterol is used to produce bile acids, more serum cholesterol moves into the liver to replenish the supply, thereby lowering serum cholesterol (primarily LDL). LDL cholesterol levels decrease within a week of starting cholestyramine and other bile acid sequestrants and reach maximal reductions within a month. When the drugs are stopped, pretreatment LDL cholesterol levels return within a month. • Use: Reduces LDL cholesterol levels and also produces a minimal elevation in HDL cholesterol. • In Children: The drug is given in two to three divided doses; dosing is based on 240 mg/kg/d not to exceed 8 g/d. • In Older Adults: These patients do NOT tolerate the adverse effects well. • Renal Impairment: Requires caution. • Adverse Effects: GI ones (abdominal fullness, flatulence, diarrhea, and constipation). Constipation is especially common. • Contraindications: Contraindicated in people with complete biliary obstruction, BC bile is not secreted into the intestine. The drug can bind with vitamin K; thus, use in people with any coagulopathy requires caution. • Cholestyramine may decrease absorption of MANY oral medications (digoxin, folic acid, glipizide, propranolol, tetracyclines, thiazide diuretics, thyroid hormones, fat-soluble vitamins—A, D, E, and K, and warfarin. • Herbs and Foods that Increase the Effects of Cholestyramine include fibers such as oat bran and pectin. No herbs and foods seem to decrease the effects of cholestyramine. • Administering the Medication: It is necessary to mix cholestyramine powder with water or other fluids, soups, cereals, or fruits such as applesauce and to follow with more fluid. Ensure that the drug is NOT taken in a dry form. It is essential that cholestyramine not be given with other drugs; to minimize altered absorption, people should take the other drugs 1 hour before or 4 to 6 hours after cholesyramine. Patients who take colestipol should swallow tablets whole, without cutting, crushing, or chewing. • Assess for Therapeutic Effects: Observe for decreased levels of total serum cholesterol, LDL cholesterol, and triglycerides, and increased levels of HDL cholesterol. Maximum effects occur in approximately 1 month. • Assess for Adverse Effects: Constipation is the most common adverse effect. Other conditions relate to GI effects: abdominal discomfort or pain, nausea, vomiting, flatulence, diarrhea, anorexia, and steatorrhea. Increased bleeding tendencies may result from vitamin K malabsorption. • Patient Teaching: Assess the adequacy of levels of fat-soluble vitamins A, D, E, K, supplementation may be required. Good dental hygiene is important BC holding the mixture in the mouth can damage the teeth. Some products may contain aspartamine or sugar, so caution is necessary in patients with phenylketonuria or diabetes mellitus • Teach the patient that these drugs are used mainly to reduce LDL cholesterol further in those who are already taking a statin drug.

Pathophysiology of Dyslipidemia and Clinical Manifestation

• Dyslipidemia (also called hyperlipidemia BC increased blood levels of lipoproteins accompany increased blood lipid levels), abnormal lipid levels in the blood, is associated with atherosclerosis and its many pathophysiologic effects (myocardial ischemia and infarction, stroke, peripheral arterial occlusive disease). • Elevated total cholesterol and LDL cholesterol and reduced HDL cholesterol are the abnormalities that are major risk factors for coronary artery disease. Elevated triglycerides also play a role in cardiovascular disease. For example, high blood levels reflect excessive calorie intake (excessive dietary fats are stored in adipose tissue; excessive proteins and carbohydrates are converted to triglycerides and also stored in adipose tissue) and obesity. • Very high triglyceride levels are associated with acute pancreatitis. • Dyslipidemia may be primary (genetic or familial) or second to dietary habits, other diseases (diabetes mellitus, alcoholism, hypothyroidism, obesity, obstructive liver disease), and medications (beta blockers, cyclosporine, oral estrogens, glucocorticoids, sertraline, thiazide diuretics, anti-human immunodeficiency virus [HIV] protease inhibitors). • Clinical Manifestations: A lipid profile consists of a total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides. For accurate interpretation, blood samples for laboratory testing of triglycerides should be drawn after the patient has fasted for 12 hours. Fasting is not required for cholesterol testing.

Eptifibatide Glycoprotein IIb/IIIa Receptor Antagonists

• Eptifibatide (and tirofiban) inhibit platelet aggregation by preventing activation of GP IIb/IIIa receptors on the platelet surface and the subsequent binding of fibrinogen and von Willebrand factor to platelets. • *Antiplatelet effects occur during drug infusion and stop when the drug is stopped*. • Use: Eptifibatide is indicated for acute coronary syndrome (unstable angina, MI) in patients who are to be treated medically or by angioplasty or atherectomy. • Contraindications: Eptifibatide is contraindicated in patients with hypersensitivity to any component of the product; current or previous bleeding (within previous 30 days); a history of thrombocytopenia after previous exposure to tirofiban; a history of stroke within 30 days or any history of hemmorhagic stroke; major surgery or severe physical trauma within the previous month; severe hypertension (systolic BP greater than 180 mm Hg). • Adverse Effects: *Bleeding is the most common*, with most major bleeding occurring at the arterial access site for cardiac catheterization. If bleeding occurs and cannot be controlled with pressure, the drug infusion and heparin should be discontinued. • Use cautiously if given with other drugs that affect hemostasis (warfarin, thrombolytics, and other antiplatelet drugs).

Ezetimibe (Zetia) Cholesterol Absorption Inhibitor

• Ezetimibe (Zetia) is the PROTOTYPE of the newest class of dyslipimedic drugs, which act in the small intestine to inhibit absorption of cholesterol and decrease the delivery of intestinal cholesterol to the liver, resulting in reduce hepatic cholesterol stores and increased clearance of cholesterol from the blood. • Ezetimibe reduces total cholesterol and triglycerides and increases HDL cholesterol. • Action: Blocks biliary and dietary cholesterol absorption at the brush border of the intestine without affecting absorption of fat-soluble vitamins and triglycerides. • Use: Ezetimibe is used together with dietary management for treatment of primary dyslipidemia. When given as monotherapy (without a statin), ezetimibe does not require dosage reduction in geriatric patients. • In Children: Safety and efficacy in children younger than 10 years of age has not been established. • Hepatic Impairment: Dosage adjustment is necessary in patients with mild hepatic impairment. • Adverse Effects: headache, diarrhea, hypersensitivity reactions such as rash and nausea. • Contraindications: pregnancy and lactation. • The nurse instructs the patient to maintain a low-cholesterol diet during ezetimibe therapy. • Drugs that Increase the Effects: Cylcosporine • Drugs that Decrease the Effects: Bile acid sequestrant drugs • Administering the Medication: Ezetimibe may be taken with or without food. Take the drug at the same time each day. At night if used in combination with a statin (can be given at the same time as the statin). But take either 2 hours before or 4 hours after bile sequestrants to prevent altered absorption. • Assess for Therapeutic Effects: desired results include decreases in total cholesterol, LDL cholesterol, and triglycerides, with increases in HDL cholesterol. A therapeutic response occurs within 2 weeks of initiation of therapy and lasts as long as the drug is continued. • Assess for Adverse Effects: Headache, dizziness, fatigue, diarrhea, and abdominal pain. • Patient Teaching: Patients should have periodic blood tests.

Furosemide (Lasix) Loop Diuretics

• Furosemide (Lasix) is the PROTOTYPE for the loop diuretics. • Administered to patients with moderate to severe heart failure to reduce edema. • Administered WITH food to prevent gastric upset. • The nurse weighs the patient daily and reports any increase in weight of greater than 2 pounds in 24 hours to the health care provider. • Fluid and electrolyte levels must be assessed frequently to identify extracellular fluid overload or dehydration. • The nurse assesses blood pressure, pulse, and respirations daily. • A potassium-rich, low-sodium diet is recommended, and potassium supplements may be ordered. • In patients with diabetes mellitus, the nurse assesses blood glucose levels frequently BC furosemide therapy may cause an increase in blood glucose levels.

Diet and Supplements Used to Lower Cholesterol

• Garlic: an herb, may lower cholesterol and triglycerides. However, there is little scientific support for this therapy. Bleeding may be increased when garlic is combined with anticoagulants, and insulin doses may need to be decreased as a result of the hypoglycemia effect on garlic. • Flax or Flax Seed: used internally as a laxative and a dyslipidemic agent. Absorption of all medications may be decreased when taken with flax, resulting in a less than therapeutic effect. • Soy: used as a food source and has been researched extensively. Use of soy to lower total and LDL cholesterol has been documented. Additionally, it is possible that an intake of soy proteins may have other beneficial vascular effects. • Plant-Derived Stanol and Sterol Esters: Which are added to margarine and other food products. These substances may also help lower total and LDL cholesterol. However, cholesterol-lowering margarines containing plant sterols cost approximately two to five times that of ordinary margarine. (Products such as orange juice and other beverages containing lecithin emulsified plant stanols have reduced total and LDL cholesterol to a similar degree as the margarines.) In addition, little is known about their long-term effects, and researchers have shown that plant sterol supplementation may have caused harmful vascular effects in animals. • Theaflavin: found in green tea, which has been shown to lower total cholesterol and low-density lipoprotein-cholesterol complex. • Red Yeast Rice: which has been shown to lower cholesterol. However, dosage standardization is a concern, and information about long-term safety is unavailable. • Start a low-fat diet. Use the "Mediterranean diet" which includes moderate amounts of monounsaturated fats (canola, olive oils) and polyunsaturated fats (safflower, corn, cottonseed, sesame, soybean, sunflower oils) to also decrease risks of cardiovascular disease. • Increase dietary intake of soluble fiber. • Start a weight-reduction diet if the patient is overweight or obese.

Pathophysiology and Clinical Manifestation of Heart Failure

• Heart failure results in low cardiac output and inadequate filling of the arteries. • The baroreceptors in the aortic arch and carotid sinus that normally inhibit sympathetic nervous system activity are blunted in the patient who is experiencing heart failure. This results in high levels of circulating catecholamines (active amines, such as epinephrine, norepinephrine, and dopamine that have an effect on the cardiovascular system). The circulating catecholamines increase the force and myocardial contractility, as does the increased activity of the sympathetic nervous system. The pts heart rate increases, and the blood vessels constrict. Levels of endothelin, a peptide secreted by the endothelial cells, are increased in heart failure. Endothelin is a potent vasoconstrictor and may exert direct toxic effects on the heart. • Renin is an enzyme produced in the kidneys in response to impaired blood flow and tissue perfusion. The release of renin stimulates the production of angiotensin II. Angiotensin II is a powerful vasoconstrictor. Arterial vasoconstriction impairs cardiac function by increasing the resistance (afterload) against which the ventricle ejects blood. This increases the filling pressures inside the heart, which in turn, increases the stress on the heart by stretching the walls of the heart muscle, predisposing the patient to subendocardial ischemia. • Right-Sided Heart Failure: Right-sided heart failure results from an accumulation of blood in the systemic venous system. The causes of right-sided heart failure are stenosis of regurgitation of the pulmonic or tricuspid valves, right-sided ventricular infarction, cardiomyopathy, or recurrent left-sided heart failure. • Left-Sided Heart Failure: Left-sided heart failure is most commonly caused by a MI or cardiomyopathy. • Clinical Manifestation: The cardinal manifestations of heart failure are dyspnea and fatigue, which can lead to exercise intolerance and fluid retention. Pts with compensated or asymptomatic heart failure usually no have symptoms at rest and no edema. In these pts, dyspnea and fatigue occur only with activities that require moderate- to high-level exertion. Pts with symptomatic heart failure have symptoms that occur with minimal exertion or failure have symptoms that occur with minimal exertion or at rest, ankle edema, and distention of the jugular vein. These signs reflect decompensation, which is the inability of the heart to adequately circulate oxygenated blood to the body's vital organs. • *Symptoms of Right-Sided Heart Failure*: Edema with lower extremities, weight gain, dyspnea, fatigue, hepatomegaly, ascites, anorexia, nausea or abdominal pain. • *Symptoms of Left-Sided Heart Failure*: Pulmonary congestion, dyspnea with possible orthopnea, cough, audible crackles in the bases of the lung, audible S3 or ventricular gallop.

Food Interactions with Statins

• Herbs and Foods that Increase the Effects: Grapefruit juice, pomegranate juice, red yeast rice, sitostanol, vitamin B3 (niacin). • Herbs and Foods that May Decrease the Effects: Fibers such as oat bran and pectin.

Hydrochlorothiazide (HCTZ, HydroDIURIL) Thiazide Diuretics

• Hydrochlorothiazide is the PROTOTYPE drug for the thiazide diuretics. • Hydrochlorothiazide inhibits the reabsorption of sodium and chloride in the distal renal tubule, increasing the excretion of sodium and water by the kidneys. • Administered for edema associated with early or mild heart failure. Decreasing the plasma volume increases cardiac output and decreases preload. • The nurse assesses the blood pressure and pulse before administering the medication and periodically following administration. • Hydrochlorothiazide is administered WITH food to prevent gastric upset. • Assess the patient's lungs (for adventitious sounds) heart (for an S3), and extremities (for peripheral edema); the patient's fluid and electrolyte status; and the patient's weight (daily). Any increase in weight of greater than 2 pounds in 24 hours must be reported to the primary health care provider.

Dyslipidemia Management

• Overall, the most effective blood lipid profile prevention or management of metabolic syndrome and its sequelae is high HDL cholesterol, low LDL cholesterol, and low total cholesterol. • A low triglyceride level is also desirable. • Note that therapeutic lifestyle changes, including exercise, smoking cessation, changes in diet, and drug therapy, are recommended at lower serum cholesterol levels in patients who already have cardiovascular disease or diabetes mellitus. Also, the target LDL serum level is lower in these patients.

Pathophysiology and Clinical Manifestation of Angina

• In CAD, there is a buildup of lipids and fibrous matter within the coronary artery. Increased blood levels of low-density lipoprotein (LDL) irritate and damage the inner layer (the intima) of the coronary artery. Eventually, the fatty streak and foam cell eventually transform into a fibrous plaque. This forms the fibrous cap, which is made up of smooth muscle cells, macrophages, foam cells, lymphocytes, collagen, and elastin. As the lumen of the vessel becomes smaller and blood is limited, especially during times of high oxygen demand (physical exertion) oxygen supply cannot keep up with demand. At this point, the pt may experience stable angina. • Angina pectoris is chest pain related to a lack of blood and oxygen supply to the heart muscle, producing myocardial ischemia. • Acute coronary syndrome (any condition brought on by sudden, reduced blood flow to the heart) may be seen when the fibrous cap ruptures, exposing thrombogenic material, producing a thrombus within the lumen. At this point, the intraluminal thrombi can occlude arteries outright or will detach, move into the circulation, and eventually occlude smaller, distal branches of the coronary artery causing thromboembolism and likely an acute MI or ST-segment elevation MI. • Coronary artery spasm is a transient, sudden narrowing of one of the coronary arteries. The spasm impedes blood flow through the artery, which in turn results in ischemia, leading to angina. Causes of coronary spasm include alcohol withdrawal, emotional stress, exposure to cold, vasoconstricting medications, and stimulants, such as cocaine. • Clinical Manifestation: Vary with the type of angina. The classical anginal pain is usually described as substernal chest pain of a constricting, squeezing, or suffocating nature. It may radiate to the jaw, neck, or shoulder; down the left or both arms; or to the back. The discomfort is sometimes mistaken for arthritis or for indigestion, BC the pain may be associated with nausea, vomiting, dizziness, diaphoresis, shortness of breath, or fear of impending doom. • Women, elderly people, and people with diabetes are more likely to have symptoms other than chest pain, including fatigue, weakness, and shortness of breath.

Isosorbide dinitrate (Isordil) Organic Nitrates

• Isosorbide dinitrate (Isordil) is useful for reducing the frequency and severity of acute angina episodes, not for acute relief of angina symptoms. • When given sublingually or in chewable tablets, 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.

Milrinone lactate (Primacor) Phosphodiesterase Inhibitors (Cardiotonic-Inotropic Agents)

• Milrinone lactate (Primacor) is the most commonly used phosphodiesterase inhibitor administered for short-term management of acute to severe heart failure in pts who do not respond to treatment with digoxin, diuretics, and vasodilators. • Milrinone can be used alone or with other drugs for the treatment of heart failure. • Is a potent inotropic agent that is given IV bolus injection followed by continuous infusion. • Action: Increase the force of contraction of the ventricles, providing a positive inotropic effect. It causes vasodilation by exerting a direct relaxant effect on the vascular smooth muscle, decreasing both preload and afterload. The effects of this drug are additive to those of digoxin and vasodilators, increasing cardiac output. • Use: for pts whose symptoms of heart failure are not controlled with digoxin, diuretics, and vasodilators. • In Children: Not recommended. • In Older Adults: Should not exceed 1.13 mg/kg/day. • Renal Impairment: the creatinine clearance level is used to determine the dosage administration for patients with renal impairment. • In Critical Illness: Milrinone lactate should be administered only in a cardiac intensive care unit. • Adverse Effects: the most serious is the development of potentially fatal ventricular dysrhythmias, which reportedly occur in 12% of pts. Hypotension, supraventricular dysrhythmias, chest pain, angina, headache, thrombocytopenia, and hypokalemia may also occur. Hypotension and headache occur in 3% of pts. • Contraindications: administered cautiously in pregnant and lactating women. Contraindicated in pts with severe aortic or pulmonic valvular disease. • Administering the Med: assess the patient for allergy to milrinone lactate or bisulfates. Also, nurse obtains an accurate weight and assess the patient for renal impairment to ensure that an accurate dosage of medication is administered. The patient's cardiac rhythm, blood pressure, and pulse are monitored continuously, and a baseline pulse and BP are recorded. If a marked decline in BP or pulse rate occurs, the rate of administration should be reduced. Assess for adventitious breath sounds prior to administration and periodically. Platelet count to rule out thrombocytopenia. Electrolyte levels are monitored.

Nesiritide (Natrecor) Human B-Type Natriuretic Peptides

• Nesiritide (Natrecor) is the PROTOTYPE drug in the human B-type natriuretic peptide class of drugs. • Nesiritide is a vasodilator and is identical to endogenous human B-type natriuretic peptide (BNP), which is secreted primarily by the ventricles in response to fluid and pressure overload. The medication is produced by recombinant DNA technology. • Nesiritide is administered as a bolus dose followed by a continuous infusion. • Nesiritide acts to compensate for deteriorating cardiac function by reducing cardiac preload and afterload. It produces a diuretic effect by increasing sodium secretion and suppressing the renin-angiotensin-aldosterone system. Nesiritide also decreases secretion of the neurohormones endothelin and norepinephrine, resulting in relaxation of the smooth muscle. • Use: Nesiritide is indicated for use in decompensated pts with acute heart failure (those who experience dyspnea at rest and on minimal exertion). • Adverse Effects: hypotension, headache, nausea, back pain, ventricular tachycardia, dizziness, anxiety, insomnia, bradycardia, and vomiting. • Contraindications: It should not be administered if the systolic BP is less than 90 mm Hg. • Nesiritide is used infrequently. The administration of antihypertensive agents with nesiritide will increase nesiritide's hypotensive effects. • Nesiritide administered with bayberry, black cohosh, cayenne, ephedra, ginger, kola, or licorice will increase BP. Nesiritide administered with goldenseal, Hawthorne, mistletoe, periwinkle, or quinine will enhance hypotension. • Administering the Med: In the event of severe hypotension, the administration should be discontinued. It is important that the patient be adequately hydrated during the administration of nesiritide. The reconstituted solution of the medication must be replaced every 24 hours. Hemodynamic monitoring of the pulmonary artery pressure is mandatory to determine drug effectiveness. • While you are taking this medication, frequent monitoring of your BP, pulse, and heart rhythm is necessary. • BC bed rest must be maintained, please call for assistance with toileting.

Niacin (nicotinic acid) Miscellaneous Dyslipidemic Agent

• Niacin (nicotinic acid) is a vitamin that decreases LDL and increases HDL cholesterol, and it serves as the PROTOTYPE. • Nicotinamide, another form of niacin, does not have the lipid-lowering properties of nicotinic acid. • Action: Niacin inhibits mobilization of free fatty acids from peripheral tissues, thereby reducing hepatic synthesis of triglycerides and secretion of VLDL, which leads to decreased production of LDL cholesterol. • Use: the most effective drug for increasing the concentration of HDL cholesterol, is the most helpful in preventing heart disease when used in combination with another dyslipidemic drug such as a bile acid sequestrant or a fibrate. • In Children: Niacin is a form of Vitamin B3. Use of niacin in children is often aimed at preventing vitamin B3 deficiency and related conditions such as pellagra. • In Older Adults: These pts do NOT tolerate the adverse effects of the drug well. • Hepatic Impairment: Niacin may cause hepatotoxicity; thus, it is contraindicated in pts with hepatic impairment. • Adverse Effects: Disadvantages of niacin are the high doses required for dyslipidemic effects and the subsequent adverse effects. Niacin commonly causes skin flushing, pruritis, and gastric irritation, and it may lead to tachycardia, hypotension, dizziness, hyperglycemia, hyperuricemia, elevated liver aminotransferase and hepatitis. • Contraindications: Active peptic ulcer. • The efficacy of oral hypoglycemic agents and insulin may be diminished by niacin, which may affect glucose control. • Herbs and foods that increase the effects of niacin include red yeast rice, which increases the risk of severe myopathy or rhabdomyolysis. • Drugs that Increase the Effects of Niacin: alcohol, leflunomide, statins, zidovudine. Drugs that Decrease the Effects of Niacin: Bile acid sequestrant drugs. • Formulations of niacin (immediate release, timed release) are not interchangeable. It is NECESSARY to give immediate release niacin with meals BC it may cause gastric irritation. In contrast, pts may take timed-release niacin without regard to meals. • Flushing may occur with niacin administration. This reaction can be reduced by starting with small doses, gradually increasing doses, taking doses with meals, and talking 325 mg of aspirin about 30 minutes before or 200 mg of ibuprofen about 60 minutes prior to administering niacin. • Assess for Therapeutic Effects: Effects occur in approximately 1 month. Assess for decreased levels of total serum cholesterol, LDL cholesterol, and triglycerides, as well as increased levels of HDL cholesterol. • Assess for Adverse Effects: Flushing of the face and neck, pruritius, and skin rash may occur, as well as tachycardia, hypotension, and dizziness. • Patient Teaching: nurse tells the patient that tablet strengths are not interchangeable and not to substitute immediate-release forms with long-acting ones. Patients should swallow sustained-release preparation whole.

Nitroglycerin (Nitro-Bid, Nitro-Dur) Organic Nitrates

• Nitroglycerin is the most widely used nitrate and is the PROTOTYPE of nitrates. • Available is multiple forms, and is indicated for the management and prevention of acute chest pain caused by myocardial ischemia. • Action: Nitrates are converted to nitric oxide, a potent vasodilator, which relaxes smooth muscle in blood vessel walls. Anginal pain is relieved by nitrates by several mechanisms: Venous dilation. Coronary artery dilation. Arteriole dilation. • Use: For relief of sudden-onset angina, fast-acting preparations of nitroglycerin include SL and chewable 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. To avoid development of tolerance, it is ESSENTIAL to observe a 10- to 12-hour nitrate-free interval. For example, in clinical practice, pts are usually nitrate free during the night, while sleeping. • PO form does not relieve acute chest pain and 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 usual PO dose. • Angina that is unresponsive to SL, PO, or transdermal preparations calls for IV nitroglycerin. Prescribers may typically order the IV form for 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. • In Children: IV nitroglycerin is the only form approved for use in children. May be used to treat hypertension and heart failure. • In Older Adults: May be more vulnerable to hypotension when taking nitroglycerin due to volume depletion, concurrent use of other medications, and loss of sympathetic tone. At greater risk for FALLING! • Close monitoring of vital signs, along with frequent titration of IV medications, is important. • 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. • Adverse Effects: the most common is a severe headache, which is typically treated with acetaminophen. Other common adverse effects include dizziness, bradycardia, syncope, hypotension, and orthostatic hypotension. • Contraindications: Severe anemia, hypotension, and hypovolemia. • NOTE: Men who take nitroglycerin or any other nitrate should not use phosphodiesterase enzyme type 5 inhibitors, such as Viagra and Levitra for erectile dysfunction, because nitrates and phosphodiesterase enzyme type 5 inhibitor decrease BP, and the combined effect can produce profound, life-threatening hypotension. • Herbs and Foods that Increase the Effects of Nitroglycerin: N-Acetyl cysteine, folate, vitamin E, Hawthorn. Herbs and Foods that Decrease the Effects of Nitroglycerin: Vitamin C. • Administering the Med: It is important to take a pts vital signs, prior to administration of any form of nitroglycerin. The nurse should withhold the medication with hypotension (systolic BP less than 90 or 30 mm Hg below the patient's normal BP) as well as tachycardia with a heart rate greater than 100 beats/min. Administration of SL nitroglycerin or transdermal 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. • 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-released preparations. It is ESSENTIAL to take vital signs frequently with IV administration and recheck them with each titration. • Assess for Therapeutic Effects: Pts should report that they feel better and demonstrate a higher activity tolerance.

Streptokinase (Streptase) Thrombolytics

• Pregnancy category C. • Use: Management of acute, severe pulmonary emboli or iliofemoral thrombophlebitis. Used to dissolve clots in the arterial or venous cannulas or catheters. May be injected into a coronary artery to dissolve a thrombus if done within 6 hours of onset of symptoms. • Routes and Dosages (Adults, unless specified): IV 250,000 units over 30 minutes, then 100,000 units/hour for 24-72 hours.

Propranolol (Inderal) Noncardioselective Beta-Adrenergic Blockers

• Propranolol (Inderal) is used to reduce the frequency and severity of acute attacks of angina. It is especially useful in preventing exercise-induced tachycardia, which can precipitate angina attacks. • Propranolol (Inderal) is a noncardioselective beta-adrenergic blocker which blocks beta1 and beta2 receptors (1 heart and 2 lungs). • Nonselective beta-adrenergic blockers such as propranolol can slow down the process of glycogenolysis (therefore, the occurrence of hypoglycemia increases). • Oral doses of propranolol are much higher than IV doses. • It is well absorbed after oral administration. • It is important to instruct patients to take the drug at the same time each day, preferably with or immediately following meals, BC food may enhance the bioavailability of propranolol. • Adverse Effects: Wheezing and erectile dysfunction. Patients should report shortness of breath, night cough, edema, slow pulse, confusion, rash, fever, or sore throat. • It is important that the pt understand that propranolol should NEVER be stopped abruptly.

Ranolazine (Ranexa) Metabolic Modulator

• Ranolazine (Ranexa) is an FDA-approved first-line treatment for chronic angina. The drug increases the energy production of the heart to preserve cardiac function but does not relieve acute angina attacks. • Ranolazine performs this action without decreasing blood pressure or heart rate. • Ranolazine decreases ischemia but does not possess negative inotropic or chronotropic effects. • Ranolazine is associated with a decreased frequency of ventricular dysrhythmias, bradycardia, and new-onset atrial fibrillation. • FDA has recommended that ranolazine should be reserved for patients who have not had an adequate response with other antianginal drugs due to the drug's dose-dependent ability to prolong the QT interval. Therefore, the drug is contraindicated in pts with preexisting QT-interval prolongation. It is also contraindicated in pts with hepatic disease and in pts taking other drugs that prolong the QT interval. • Dose reduction of digoxin and simvastatin may be necessary with concurrent use BC ranolazine affects the metabolic pathways of these drugs.

Fenofibrate (TriCor) Fibrates

• Serves as the PROTOTYPE of fibrates. • Is administered orally. • Action: Decrease hepatic production of triglycerides, decrease VLDL cholesterol, and increase HDL cholesterol. • Use: Fibrates are the most effective drugs for reducing serum triglyceride values, and their main indication for use is high serum triglyceride (greater than 500 mg/dL. They are also helpful for patients with low HDL cholesterol levels. • In Children: Have not yet established the safety and efficacy of fibrates in children. • In Older Adults: Lower starting dosages are recommended. • Renal Impairment: Accumulate in the serum of patients with renal impairment. Fenofibrate is contraindicated in patients with severe renal impairment, and the recommended starting dosage is 67 mg/d in patients with a creatinine clearance of less than 50 mL/min. Fibrates may cause a reversible elevated serum creatinine. • Hepatic Impairment: Fibrates may cause hepatotoxicity. Abnormal serum aminotransferases have occurred with both gemfibrozil and fenofibrate, but they usually subside after the drug is discontinued. • Contraindications: Severe hepatic impairment, including primary biliary cirrhosis, and persistent elevations in liver function tests and preexisting gallbladder disease. • It is necessary to monitor liver function during the first year of drug administration. • Adverse Effects: GI discomfort and diarrhea, which may occur less often with fenofibrate than with other fibrates. Also, formation of gallstones. • Fenofibrate and other fibric acid derivatives may enhance the hypothrombinemic effect of warfarin-type oral anticoagulants, increasing the risk of bleeding. • Drugs that Increase the Effects: Statins, cyclosporine. Drugs that Decrease the Effects: Bile acid sequestrant drugs. • Administering the Medication: Necessary to give WITH food to increase drug absorption. • Therapeutic effects: effects occur in approx. 1 month. Adverse Effects: GI disturbances and liver function.

Spironolactone (Aldactone) Aldosterone Antagonists

• Spironolactone (Aldactone) is the PROTOTYPE drug in this class - an aldosterone antagonist. • It reduces aldosterone-induced retention of sodium and water and impaired vascular function. • Overall, studies indicate that the addition of spironolactone improves cardiac function and reduces symptoms, hospitalizations, and mortality in pts with heart failure. • Spironolactone is used to decrease edema in patients with heart failure.

Warfarin Vitamin K Antagonists

• The most commonly used ORAL anticoagulant and is *the PROTOTYPE vitamin K antagonist*. •* Oral administration*. • *Action*: Acts in the liver to prevent synthesis of vitamin K-dependent clotting factors. • *Vitamin K serves as the ANTIDOTE for warfarin*. • Warfarin is most useful in long-term prevention or management. • Warfarin therapy after MI may decrease reinfarction, stroke, venous thromboembolism, and death. • *In Children*: After cardiac surgery, children receive warfarin to prevent thromboembolism, but there are no established doses or guidelines. • *In Older Adults*: As patient age increases, a lower dose of warfarin is usually required to produce a therapeutic effect. • *Hepatic Impairment*: More likely to cause bleeding in patients with hepatic disease BC of decreased synthesis of vitamin K and decreased plasma proteins. Also, only the liver eliminates warfarin; thus, it may accumulate in people with hepatic impairment, and dosage adjustment may be necessary. • *Home Care*: For prevention of DVT. Periodic office or clinic visits for blood tests and other follow-up care is required. • Medical conditions other than anticoagulation may cause bleeding during warfarin therapy. • *Adverse Effects*: *HEMORRHAGE*. • *Contraindications*: GI ulcerations, blood disorders associated with bleeding, severe kidney or liver disease, severe hypertension, and recent surgery of the eye, spinal cord, or brain. • *BLACK BOX WARNING: risk of causing major or fatal bleeding.* • *Drugs that Increase the Effects of Warfarin*: Acetaminophen (high doses), alteplase, androgens, aspirin, and other nonsteroidal anti-inflammatory drugs, azithromycin, bismuth, clarithromycin, heparin, macrolide antibiotics, direct thrombin inhibitors, tetracycline, thyroid hormones, tricyclic antidepressants, vancomycin, vitamin E, Antithrombin, Cephalosporins. • *Drugs that Decrease the Effects*: spirolactone, trazodone, chlordiazepoxide, haloperidol, IV lipid emulsions containing soybean oil • *Herbs and Dietary Interactions that Increase the Effects of Warfarin*: angelica, cat's claw, chamomile, chondroitin, cranberry juice, feverfew, garlic, ginkgo, goldenseal, grape seed extract, green tea, psyllium, turmeric. • *Herbs and Foods that Decrease the Effects*: ginseng, St. John's wort, vitamin K, foods high in vitamin K (broccoli, Brussels sprouts, cabbage, cauliflower, chives, collard greens, kale, lettuce, mustard greens, peppers, spinach, tomatoes, turnips, and watercress). • *Administering Warfarin*: Has a narrow therapeutic window of adequate anticoagulation without bleeding. *A therapeutic PT value is approximately 1.5 times control, or 18 seconds*. • *Nurse holds the dose if the INR is about 3.0 and notifies the health care provider*. • *Assess for Therapeutic Effects*: Assess for absence or reduction of signs and symptoms of thrombotic disorders (less edema and pain with DVT, less chest pain and respiratory difficulty with pulmonary embolism, absence of uncontrolled bleeding, hematuria or blood in the stools). • Ensure that the PT and INR values are within the therapeutic range. • *Assess for Adverse Effects*: asses for signs of bleeding, including excessive bruising of the skin, bleeding from IV sites or the gum line, and blood in urine and stool. *Vitamin K is the ANTIDOTE for warfarin and may be administered if the INR level is 5 or more and signs of bleeding are present*. • *Patient Teaching*: nurse reinforces instructions for safe use of warfarin, assists patients to obtain required lab tests, and teaches how to observe for signs and symptoms of bleeding.

Heparins Anticoagulant Drugs

• There are *THREE* types of anticoagulants: *heparins, vitamin K antagonists, and direct thrombin inhibitors (DTIs)*. • *Intravenously or subcut because the GI tract does not absorb the drug*. Hemodialysis does not remove it. • After thrombus has developed, *heparin can inhibit additional coagulation by inactivating thrombin*, preventing the conversion of fibrinogen to fibrin and inhibiting factor XIII (fibrin-stabilizing factor). Other effects include inhibition of factors V and VIII and platelet aggregation. • *Prophylactically*, patients at risk for certain disorders take low doses of heparin to prevent DVT and pulmonary embolism. • *Therapeutically*, patients receive heparin for management of acute thromboembolic disorders (DVT, thrombophlebitis, pulmonary embolism). In these conditions, *the aim of therapy is to prevent further thrombus formation and embolization*. Clinicians use heparin to prevent clotting during cardiac and vascular surgery, extra-corporeal circulation, hemodialysis, and blood transfusions and in blood samples to be used in lab tests. *Heparin does NOT cross the placental barrier and is NOT secreted in breast milk, making it the anticoagulant of choice for use during pregnancy and lactation*. • *In children*: use extreme caution to ensure that the vial concentration is correct. Fatalities in infants involving heparin overdoses have occurred. • *In Older Adults*: they are more likely than younger adults to experience bleeding and other complications associated with this therapy. • *In Critical Illness*: risk of bleeding is increased in the presence of other conditions. People who are critically ill, have a high risk of DVT and pulmonary embolism. • *Home Care*: subcut route and use of LMWHs of venous thrombosis has become standard practice. • *Adverse Effects*: *HEMORRHAGE* is the major side effect. Also, Heparin-induced thrombocytopenia (*HIT*) (Type II) - potentially life threatening. Leads to a decrease in platelet count and detectable HIT antibodies. Occurs in 1% to 3% of people receiving heparin at therapeutic levels for 4 to 14 days. • *Contraindications*: *GI ulcerations (peptic ulcer disease, ulcerative colitis), intracranial bleeding, dissecting aortic aneurysm, blood dyscrasias, severe kidney or liver disease, severe hypertension, etc*. • *Drugs that Increase the Effects of Heparin*: Alteplase, Antithrombin, Cephalosporins, Direct thrombin inhibitors, Penicillins, Platelet inhibitors, Warfarin. • *Drugs that Decrease the Effects of Heparin*: Antihistamines, Digoxin, Nicotine, Nitroglycerin (IV), Streptokinase, Tetracylcine. • *Herbs & Dietary Interactions*: Chamomile, garlic, ginger, ginkgo, ginseng, high-dose vitamin E. • *Administering Heparin*: use the activated partial thromboplastin time (aPTT), which is sensitive to changes in blood clotting factors, except factor VII, to regulate heparin dosage. Therapeutic values of adequate anticoagulation are 45 to 70 seconds. With continuous IV infusion, blood for the aPTT may be drawn at any time; with intermittent administration, blood for the aPTT should be drawn approximately 1 hour before a dose of heparin is scheduled. • *Disadvantages*: *parenteral injection is necessary, and the drug has a short duration of action, which means that there is a need for frequent administration*. • *Assess for Adverse Effects*: *PROTAMINE SULFATE is an ANTIDOTE for standard heparin and LMWHs*. • *Patient Teaching*: Education related to bleeding risk is essential. And teaching how to observe for signs and symptoms of bleeding. • *Other Drugs in the Class*: *Enoxaparin*: currently available LMWHs (low molecular weight heparins). Also dalteparin. They differ from standard heparin and each other and are NOT interchangeable. Given subcut and do NOT require close monitoring of blood coagulation, which allows for outpatient anticoagulant therapy. Also associated with LESS thrombocytopenia than standard heparin. However, platelet count monitoring IS necessary during therapy.

Combination Therapy Used to Treat Dyslipidemia

• When monotherapy is not effective in attaining target LDL cholesterol levels, combination therapies with lipid-lowering drugs that have different mechanisms of action are recommended. • In general, the drug combinations that are most effective in reducing total and LDL cholesterol are (1) a statin with a cholesterol absorption inhibitor or a bile acid sequestrant or (2) niacin with a bile acid sequestrant. • When a goal of therapy is to increase the level of HDL cholesterol, a fibrate, cholesterol absorption inhibitor, or niacin may be used. However, a fibrate-statin combination should be avoided BC of increased risks of severe myopathy, and a niacin-statin combination increases the risks of hepatotoxicity. • The adverse effects and contraindications associated with individual drugs also apply when they are used in combination. All combinations, like individual preparations, should be used in conjunction with a cholesterol-reducing diet.