15. Miscellaneous Cardiovascular Drugs

ANTILIPEMICS

Hypolipemic drugs are used in atherosclerosis-prone patients and with patients whose hyperlipi-dema is resistant to dietary treatment.³⁶ Hypolipemic drugs can be loosely divided into two groups. The first group lowers triglycerides (nicotinic add, clofi-brate, gemfibrozil). The second group lowers cholesterol (cholestyramine, colestipol, probucol). These agents do have multiple and overlapping pharmaco-logic actions.

Clofibrate (Atromid S) acts primarily to reduce the levels of very low density lipoproteins (VLDL). The effect of this agent on the low density lipoproteins (LDL) varies between patients. In most cases, the resultant activity is to lower serum triglycerides, but it has variable effect on the plasma cholesterol level. It is moderately effective in raising high density lipoproteins (HDL). Treatment with clofibrate is generally well tolerated. Prolonged administration is associated with increased cholelithiasis incidence and significant increase of cardiovascular symptoms in patients with coronary artery disease (CAD). Hepatic and intestinal disease have also been reported with long-term use of clofibrate. This drug is contraindi-cated in patients with severe renal or hepatic disease.

Gemfibrozil (Lopid) is a drug similar to clofibrate. It is used in treatment of hyperlipoproteinemia and is shown to be effective in reducing serum triglycerides but only mildly effective in lowering serum cholesterol. As the VLDLs are lowered, there is a concomitant increase in HDLs. Treatment with this agent is well tolerated; no serious adverse effects are reported. A few patients describe abdominal pain and distention if the drug is taken without food.

Nicotinic acid (Niacin) is a member of the B vitamins. In large doses it inhibits lipolysis from adipose tissue and suppresses free fatty acid flux into the liver for VLDL synthesis. This activity reduces plasma triglycerides that are available for conversion to LDLs. Adverse effects reported from nicotinic acid are pruritis and an initial flushing. This reaction subsides within 2 weeks. Also reported are gastrointestinal side effects if taken without food or liquids. Other adverse effects encountered are hepatic dysfunction, cholestatic jaundice, hyperuricemia, and gouty arthritis.

Cholestyramine (Questran) and colestipol (Coles-tid) are drugs that have very similar actions. Both of these agents act to bind bile acids (the end products of cholesterol) and increase fecal bile acid excretion. The result is a lowering of plasma LDLs and cholesterol. Treatment with either of these agents results in constipation as the most reported side effect. Other minor gastrointestinal symptoms such as nausea, dis-tention, and cramps have been reported. Long-term administration is well tolerated. Cholestyramine is in powdered form and is mixed with a beverage or wet food.

Probucol (Loreico) is recommended for treatment of hypercholesterolemia in patients with significant risk of CAD who have not responded to diet therapy. Probucol reduces plasma cholesterol concentrations but has variable effect on triglyceride concentrations. It is not useful in treatment for lowering triglycerides alone. This drug has a somewhat different route of activity. Probucol reduces serum cholesterol without an accompanying reduction of liver cholesterol. Side effects reported include bloating, diarrhea, nausea, vomiting, and abdominal cramping. To be effective, probucol should be taken with meals.

FIBRINOLYTIC ANTICOAGULANTS

Heparin sodium is an anticoagulant. The dosage is calculated according to patient weight. For open heart procedures, heparin is administered before the patient is placed on the bypass machine. The solutions used to prime the pump-oxygenator also contain heparin. Additionally, heparin is used in solution to flush or irrigate the lumen of blood vessels to be used for an anastomosis. The anticoagulant effect of heparin is immediate. Low-dose heparin is used in the postsurgery period prophylactically to prevent thrombophlebitis. Implanted heparin pumps have been used for continuous intravenous infusion in patients with recurrent venous thromboembolic disease.

Protamine sulfate, acting as a heparin antagonist, is used to reverse the activity of heparin. The amount used is dependent on the amount of heparin. Protamine will neutralize heparin within 5 minutes of injection. Heparin is also used as prophylaxis with bed-rest patients to prevent the possible formation of thromboembolic disease. It is given intravenously or subcutaneously.

The adverse effects reported for heparin include hypersensitivity, transient alopecia, rash, osteoporo-sis, fractures, hemorrhage, and thrombocytopenia.

Decreased renal function has also been reported. Protamine sulfate administration can be associated with dyspnea, bradycardia, and hypotension.

STREPTOKINASE

Streptokinase is used for the treatment of acute thromboembolic disease. The drug acts to promote dissolution of thromboemboli.^{13, 53, 6S} Streptokinase alters hemostasis radically. At present, it is used to treat extensive pulmonary emboli, ileofemoral thrombophlebitis, and coronary artery occlusion. The treatment is usually over a 24-72 hour period, followed by heparin or oral anticoagulant therapy. Protocols for dosage and administration differ in institutions. Treatment with Streptokinase is associated with percutaneous bleeding, febrile states, allergic reactions, anaphylaxis, and hemorrhage. Aminocaproic add is the specific antidote for Streptokinase overdose. It is given in an intravenous drip until the bleeding is controlled.

TISSUE PLASMINOGEN ACTIVATOR (TPA)

Tissue type plasminogen activator (TPA) is a new fibrinolytic agent that has shown to be more effective than Streptokinase in lysing a blood clot with minimal adverse effects. TPA is a fibrin-specific agent used to recanalize thrombosed coronary arteries. Fibrin sped-ficity is the special lysing property of TPA. It is administered by a peripheral intravenous line. Access is quick, and the drug can be administered at the bedside or in the cardiac catheter laboratory. TPA should be administered within 4-6 hours of the onset of pain to achieve lysis and to salvage myocardium tissue. Plasminogen activator is a natural substance in the system, but not enough is manufactured at one time to lyse clots in coronary arteries; therefore, it is bioengineered as a synthetic product. Although new, there is much promise anticipated for TPA. The sped-ficity of this drug for fibrin reduces the possibility of hemorrhage.

INCREASED CUTANEOUS BLOOD FLOW AGENT PENTOXIFYLLINE (TRENTAL)

Pentoxifylline is a vasodilator for treatment of intermittent claudication. The oral vasodilators are not effective in bringing relief for this problem. Pentoxifylline increases peripheral blood flow by reducing blood viscosity and by improving erythrocyte flexibility, microdrculatory flow, and oxygen concentration in tissues. It has been reported effective in increasing walking distance. Adverse effects associated with administration are dizziness, headache, and gastrointestinal discomfort. It is suggested that the drug be taken with meals to reduce side effects.

Nursing Management Priorities when administering an antilipemic agent are: Tell patient the importance of remaining on medication even though there is little dramatic change. Discuss benefits of the drugs. Teach methods for relief of side effects. For example, one method is to take small doses of nicotinic acid after meals to avoid heartburn, flatulence, and other gastrointestlnal symptoms common to these agents. Check for drug interactions if patient is taking several other drugs. Instruct patient on the time to take the medication (i.e., before, after, or with meals). Give patient a list of foods allowed and those to be avoided. Instruct patient and family about cholesterol and tri-glycosides. Monitor renal and hepatic function. Inform patient of the need to return to physician's office for blood studies for drug effectiveness. 10. Monitor other drugs given concomitantly with cholestyramine or colestipol; decreased absorption may occur. Priorities when administering an anticoagulation agent are: Encourage as much leg exercise as is allowable for postoperative and post-MI patients to prevent venous stasis and thrombophlebitis. Observe closely for signs of bleeding (e.g., epistaxsis, hematuria, tarry stools, oozing at puncture sites). Be aware that bleeding may occur because heparin is a rapid-action drug. Explain need for frequent assessment of bleeding time. Keep protamine sulfate and vitamin K at the bedside during an acute phase of treatment with heparin. Educate patient and family about precautions for bleeding after hospital discharge. Monitor closely while streptokinase is being infused. Discuss drug reactions and interactions with patients.

DRUGS USED IN CARDIOVASCULAR EMERGENCIES

Code Medications

The drugs most frequently called for to treat a code, or whatever title is used to describe an emergency cardiac arrest, include (Table 15.1);^{1, 12, 16, 62}

Epinephrine
Isoproterenol
Sodium bicarbonate
Calcium chloride
Atropine sulfate
Lidocaine
Bretylium tosylate
Dobutamine
Dopamine
Verapamil
Norepinephrine

During an arrest, many of these drugs are given by intravenous push. It is important to know that some cannot be given by IV push, and others are incompatible when given together. Dopamine, dobu-tamine, isoproterenol, and norepinephrine are prepared in diluent and administered via microdrop. Sodium bicarbonate precipitates in tubing when calcium chloride is given at the same time. Sodium bicarbonate should not be added to IVs containing dopamine, epinephrine, or norepinephrine. Dopamine and do-butamine are frequently administered at the same time. Dobutamine works to improve contractility by direct action on the beta receptors, and dopamine acts to elevate systolic blood pressure, cardiac output, and renal blood flow. Epinephrine is one of the most potent vasopressor and cardiac stimulant drugs used. It acts directly on the myocardial cells of conduction tissues. Norepinephrine is a powerful vasoconstrictor used in cardiac emergencies.

Table 15.1 Cardiovascular Emergency Drugs
Drug	Indication for Use	Dosage	Action
Epinephrine (adrenalin)	Cardiac arrest Ventricular fibrillation	IV bolus 5-10 ml (1-10,000) (0.5-1 mg)	1.	Stimulates spontaneous contraction
			2.	Increases amplitude of fine fibrillation (changes fine to coarse) to improve susceptibility to defibrillation
Sodium bicarbonate	Cardiac arrest Acidosis	IV bolus AMP 44.5-50 mEg Repeat p ABGs are drawn	1.	Reverses acidosis brought on by arrest
			2.	Facilitates defibrillation
Atropine	Severe bradycardia Complete block	IV bolus 0,5-1 mg q. 5 min to 2 mg	1.	Blocks vagal control of heart rate
			2.	Increases heart rate
Bretylium tosylate (Bretylol)	Ventricular fibrillation Ventricular tachycardia	IV bolus 5-10 mg/kg Maintenance at 500 mg/50 ml D5W Infuse 1-2 mg/min Maximum 40 mg/kg/day	1.	Reverses dysrrhythmias
Dopamine (Intropin)	Cardiogenic shock Severe hypotension	Titrated infusion 2-20 mcg/kg/min Dilution - 400 mg (2-200 mg vials) in 500 D5W (800 mcg/ml) May also be mixed in 1000 ml D5W (400 mcg/ml)	1.	Supports blood pressure
			2.	Improves renal perfusion
			3.	Increases cardiac output
Isoproterenol (Isoprel)	Asystole Bradyarrhythmia	Titrated infusion 1-8 mcg/kg/min 2 mg (2 amps 1 mg/5 ml) in D5W 500 ml (4 mcg/ml)	1.	Stimulates cardiac activity
			2.	Increases systolic blood pressure, heart rate, contractility, AV conduction
Calcium chloride	Asystole Electromechanical dissociation	IV bolus .5-1 g (1 g = 10 ml) at 1 ml/min	1.	Stimulates forceful contractions
			2.	Begins spontaneous electrical activity
Lidocaine (Xylocaine)	Acute Ventricular tachycardia, fibrillation, life-threatening PVCs	IV bolus 50-100 mg at 25-50 mg/min Repeat every 5 min; maximum 200 mg Infusion titrate 1-4 mg/min (2g - 50 ml) in 450 (D5W 4 mg/ml )	1.	Prevents ventricular premature contractions
			2.	Prevents reentry circuit of tachycardia! rhythm
Dobutamine	Cardiogenic shock	Infusion titrate 2,5-10 mcg/kg/min (250 mg in 500 D5W) 500 mcg/ml	1.	Increases contractility
			2.	Improves perfusion to vital organs
			3.	Supports blood pressure
Verapamil	Acute episode of supraventricular tachyarrhythmias	IV bolus 5-10 mg over 2 min Repeat in 30 min	1.	Reverses acute supraventricular arrhythmias
Norepinephrine (Levophed)	Acute hypotension	Infusion titrate 2-4 mcg/kg/min 4-8 mg in 500 ml D5W	1.	Increases vasoconstrictor of peripheral vasculature
			2.	Increases heart rate

The American Heart Association classifies drugs used for codes by the therapeutic results:

1. Epinephrine and calcium chloride are used to restore heartbeat and increase perfusion pressure, and they are used for inotropic effect. Epinephrine is used in a cardiac standstill or fine ventricular-fibrillation situation to correct the problem. Epinephrine may convert standstill to a sinus rhythm or to a fibrillation. Fine fibrillation may be converted to coarse fibrillation, so defibrillation becomes more likely. Calcium chloride may be useful to restore an electrical rhythm for a patient in standstill or to strengthen pumping activity when the contractions are ineffective. Calcium chloride is used cautiously in code situations.
2. Sodium bicarbonate is used to reverse acidosis. Sodium bicarbonate is given after the patient is oxygenated. It helps to reverse the lactic acidemia that occurs when there is a cardiac arrest. New protocols (American Heart Association) recommend guarded use of sodium bicarbonate until arterial blood gas reports are evaluated.
3. Atropine and isoproterenol reverse bradycardia and increase heart rate. Isoproterenol lowers peripheral vascular resistance, resulting in lowered diastolic blood pressure and increased cardiac output. This occurs as a result of increased venous return to the heart, combined with a positive inotropic and chronotropic effect. Atropine suppresses vagal tone and prevents the parasympa-thetic nervous system from slowing SA and AV nodal conduction time. This blocking action increases both heart rate and impulse conduction.
4. Bretylium and lidocaine are used to treat ventricu-lar arrhythmias. Bretylium is used in the management of ventricular tachycardias and ventricular fibrillation. It is useful as an assist to defibrillation. Bretylium is also a drug of choice in the management of fibrillation. Lidocaine is used to eliminate premature ventricular contractions during a cardiac arrest. Its activity is as an anesthetic that suppresses spontaneous electrical firing of cells.
5. Dopamine, dobutamine, and norepinephrine are used to restore blood pressure and cardiac output. Dopamine increases systolic and pulse pressure. It has little or no effect on diastolic pressure. Low or intermediate doses do not change total peripheral resistance. In low doses, renal blood flow is increased. For this reason, dopamine is useful in cardiovascular emergency situations to treat shock, as in cardiogenic or hypovolemic states when an increase in sympathetic activity may compromise renal function. Dobutamine increases myocardial contractility and cardiac output and decreases ventricular diastolic pressure. Additionally, dobutamine enhances AV conduction. Norepinephrine acts to cause vasoconstriction and elevation of blood pressure. It will also produce a positive inotropic effect on myocardial muscle.

Nursing Management Priorities when administering code medications are: Be familiar with drugs used during a code. Know the order in which the drugs will be called for and used. Recognize progress of the code so as to be efficient in preparing drugs. Record each drug used, time, and amount.