Only $35.99/year

Pharmacology Cardiovascular Drugs

Terms in this set (124)

Cardiac glycosides occur widely in nature or can be prepared synthetically.
These glycosides act directly on the myocardium to increase the force of myocardial contractions.

Digoxin is the only clinical drug currently used in the cardiac glycoside family.

Cardiac glycosides are used primarily in the treatment of heart failure in patients with symptoms that persist after optimization of treatment with an ACE inhibitor, a beta-adrenergic blocker, and/or a diuretic.
They are sometimes also used alone or in conjunction with other medications (such as calcium channel blockers) to slow the ventricular response in patients with atrial fibrillation or flutter.

A small percentage of patients with heart failure will go on to develop atrial fibrillation. Two disabling and devastating complications of atrial fibrillation are ischemic stroke and systemic embolism.

In patients with heart failure, the cardiac glycosides act by increasing the force of the cardiac contractions without increasing oxygen consumption, thereby increasing cardiac output.
Cardiac glycosides also lower norepinephrine levels, which are elevated in heart failure and are toxic to the failing heart.
As a result of increased efficiency, the heart beats slower, the heart size shrinks, and the concurrent diuretic therapy decreases edema.

Digoxin (Lanoxin) is the only product still marketed for clinical use because it can be administered orally and parenterally and has an intermediate duration of action.

There is a very narrow margin between effective therapy with digoxin and dangerous toxicity.
Careful monitoring of cardiac rate and rhythm with EKG (electrocardiogram), cardiac function, side effects, and serum digoxin levels is required to determine the therapeutic maintenance dose.

Checking the apical pulse before administering digoxin is an important part of this monitoring process.
If the apical pulse rate is less than 60, digoxin may need to be withheld until the physician is consulted.

Modification of dosage is based on individual requirements and response as determined by general condition, renal function, and cardiac function, monitored by EKG
Antiarrhythmic agents include a variety of drugs that act in different ways to suppress various types of cardiac arrhythmias, including atrial or ventricular tachycardias, atrial fibrillation or flutter, and arrhythmias that occur with digoxin toxicity or during surgery and anesthesia.

The choice of a particular antiarrhythmic agent is based on the careful assessment of many factors, including the type of arrhythmia; frequency; cardiac, renal, or other pathological condition; and current signs and symptoms.

The role of the health care practitioner is critical in this area in accurate and timely reporting of vital signs, pertinent observations regarding the effectiveness of medications and adverse side effects, and modification of precipitating causes.

Keep in mind that most of the drugs given to counteract arrhythmias have the potential for lowering blood pressure and slowing heartbeat.
Therefore, it is especially important to be alert for the signs of hypotension and bradycardia, which could lead to cardiac arrest.

Although the antiarrhythmics commonly slow the heart rate, there are exceptions (e.g., procainamide and quinidine, which may cause tachycardia).
When other cardiac drugs are administered concomitantly, cardiac effects may be additive or antagonistic.

Antiarrhythmic agents can worsen existing arrhythmias or cause new arrhythmias, and therefore careful monitoring is essential.

Arrhythmia detection or monitoring can include EKG rhythm strips and 24-h Holter monitoring as indicated.

Electrolyte surveillance, especially for disorders of potassium and magnesium, is very important for patients on antiarrhythmic agents.
Patients taking antihypertensives should be instructed regarding:

-Routinely monitoring blood pressure at home, keeping a log of their blood pressure readings, and sharing this information with their physician
-Immediate reporting of any adverse side effects, especially slow or irregular heartbeat, dizziness, weakness, breathing difficulty, gastric distress, and numbness or swelling of extremities
-Taking the medication on time as prescribed by the physician; not skipping a dose or doubling a dose; not discontinuing the medicine, even if the patient is feeling well, without consulting the physician first
-Rising slowly from a reclining position to reduce lightheaded feeling
-Taking care in driving a car or operating machinery if the medication causes drowsiness (ask the physician, nurse, or pharmacist about the specific medication, since medicines
differ and individual reactions differ; older people are more susceptible to this effect)
-Potentiation of adverse side effects by alcohol, especially dizziness, weakness, sleepiness, and confusion
-Reduction or cessation of smoking to help lower blood pressure
-Importance of lifestyle modifications, such as exercise, quitting smoking, limiting alcohol usage, and eating a healthy diet in control of blood pressure; following the physician's instructions regarding appropriate diet for the individual, which may include a low-salt or low-sodium or weight-reduction diet if indicated
-Avoiding hot tubs and hot showers, which may cause weakness or fainting
-Mild exercise on a regular basis as approved by the physician
-Always swallowing the extended-release products intact. -Quick release of the medication into the system can cause the blood pressure to drop suddenly, causing loss of
consciousness and possible shock.
-Avoiding grapefruit juice while taking calcium channel blockers, which can increase the risk of hypotension and other adverse cardiac effects
Coronary vasodilators are used in the treatment of angina.

Vasodilators are administered to dilate these blood vessels (thus increasing myocardial oxygen supply) and stop attacks of angina or reduce the frequency of angina when administered prophylactically.

Coronary vasodilators used in the treatment and prophylactic management of angina include nitrates, beta-blockers, and calcium channel blockers.

The nitrates used most commonly for relief of acute angina pectoris, as well as for long-term prophylactic management, are nitroglycerin and isosorbide (e.g., Isordil, Imdur). Nitroglycerin is available in several forms and can be administered in sublingual tablets allowed to dissolve under the tongue or a sublingual spray for the relief of acute angina pectoris. If chest pain is not relieved or worsens 5 min after a dose, EMS should be activated because unrelieved chest pain can indicate an acute myocardial infarction.
Although the traditional recommendation is for patients to take up to three SL nitroglycerin doses over 15 min before accessing the emergency system, recent guidelines suggest an alternative strategy to reduce delays in emergency care. New guidelines recommend instructing a patient with a prior prescription for nitroglycerin to call 911 immediately if chest discomfort or pain is persistent or worsened 5 min after one dose of nitroglycerin. Self-treatment with nitrates has been identified as a factor resulting in delays in emergency evaluation.
Nitroglycerin is also available in timed-release capsules and tablets and in an injectable formulation that must be diluted carefully according to the manufacturer's instructions for IV administration. Nitroglycerin tablets and capsules must be stored only in glass containers with tight-fitting metal screw tops away from heat. Plastic containers can absorb the medication, and air, heat, or moisture can cause loss of potency. Impaired potency of the SL tablets can be detected by the patient if there is an absence of the tingling sensation under the tongue common to this form of administration.

For the long-term prophylactic management of angina pectoris, nitroglycerin is frequently applied topically as a transdermal system.
One type of nitroglycerin that is absorbed through the skin is Nitro-Bid ointment, applied with an applicator-measuring (Appli-Ruler) paper.
Usual dosage is 0.5-2 inches applied every 8 h.
Remove old paper first.
The ointment is spread lightly (not massaged or rubbed) over any hairless skin area, and the applicator paper is taped in place.
Care must be taken to avoid touching the ointment when applying (accidental absorption through the skin of the fingers can cause headache).
If nitroglycerin ointment is discontinued, the dose and frequency must be decreased gradually to prevent sudden withdrawal reactions.

Another topical nitroglycerin product, which has a longer action, is in transdermal form (e.g., Nitro-Dur).
The skin patch is applied every 24h (on in a.m./off 12h later in the p.m.) to clean, dry, hairless areas of the upper arm or body.
Do not apply below the elbow or knee.
The sites should be rotated to avoid skin irritation, and raw, scarred, or callused areas should be avoided.
Patch dosage varies widely, from 0.1 to 0.8 mg/h daily.
Check prescribed dosage carefully.
Remove old patch.

Another nitrate used for the acute relief of angina pectoris and for the prophylactic long-term management is isosorbide.
It is available in SL tablets, regular- release tablets, and timed-release capsules and tablets.
When using long-acting nitrates, a 12-14h nitrate-free interval between the last dose of the day and the first dose of the following day is recommended to lessen the risk of nitrate tolerance.
Patients receiving coronary vasodilators (nitrates) should be instructed regarding:

-Administering fast-acting preparations (sublingual tablets or spray) while sitting down because the patient may become lightheaded
-Rising slowly from a reclining position
-Not drinking alcohol or taking PDE inhibitors while taking these medicines, which can cause a serious drop in blood pressure
-Using timed-release capsules or tablets to prevent attacks (they work too slowly to help once an attack has started)
-The fact that nitrates taken for chronic angina may require periods of drug-free intervals to avoid the development of nitrate tolerance and lessening of antianginal effects
-Taking timed-release capsules or tablets on an empty stomach with a full glass of water
-Allowing sublingual tablets to dissolve under the tongue or in the cheek pouch and not chewing or swallowing them
-Repeating sublingual tablets or spray in 5-10 min for a maximum of three tablets or sprays (if no relief or worsening of chest pain within 5 min after the first tablet, activate EMS, or if EMS is unavailable, report to the emergency department); for patients known to have frequent angina, physicians may provide individualized instructions for the use of SL nitroglycerin, based on the characteristics of the patient's angina, time course, and response to the treatment
-Not discontinuing the medication suddenly if administered for several weeks (dosage must be reduced gradually under the physician's supervision)
-Sensations to be expected, including facial flushing, headache for a short time, and lightheadedness upon rising too suddenly (if these symptoms persist or become more severe, or other symptoms occur, such as irregular heartbeat or blurred vision, notify the physician at once)
-Preventing attacks of angina by administering a sublingual tablet or spray before physical exertion or emotional stress (it is preferable to avoid physical or emotional stress when possible)
Low-density lipoproteins (LDLs; "bad cholesterol") carry the largest amount of the cholesterol in the blood and are responsible for transporting and depositing it in the arterial walls.

Very low-density lipoproteins (VLDLs; triglycerides) are precursors of the LDL and compose the largest proportion of lipids in the diet, adipose tissue, and the blood.

Triglycerides (TGs) are a source of energy; excess dietary calories are converted to TGs and stored as fat in the adipose tissue for future energy needs.

Excess TGs (greater than the normal 150 level) can be an independent risk factor leading to atherosclerosis and CHD, as well as pancreatitis.

High-density lipoproteins (HDLs; "good cholesterol") help transport LDL cholesterol from the walls of the arteries through the bloodstream to the liver for excretion.

An HDL level of below 40 mg/dL is considered low, and each 1 mg/dL increase in the HDL level is associated with a 6% lower risk of cardiovascular dis-ease.

LDL cholesterol is the primary target of treatment in clinical lipid management.

The use of therapeutic lifestyle changes (TLCs), including LDL-lowering dietary management (e.g., restriction of saturated and trans fats or cholesterol intake, including fiber and soy protein in diet), weight control, appropriate exercise, limiting alcohol intake, and smoking cessation, will achieve the therapeutic goal (LDL below 100 mg/dL) in many persons.

If these measures are inadequate, drug therapy may be added.

Drug therapy aimed at reducing cholesterol levels either reduces hepatic production or intestinal absorption of cholesterol.

Six categories of antilipemic agents used to lower blood cholesterol levels are available: HMG-CoA reductase inhibitors (the statins), bile acid sequestrants, nicotinic acid (niacin), fibric acid derivatives, cholesterol absorption inhibitor, and omega-3 fatty acids.
There are two types of heparin: the standard or unfractionated type (UFH) and the low-molecular-weight heparins (LMWHs).

Heparin is not absorbed from the GI tract, and the standard type (UFH) must be administered intravenously or subcutaneously.

The LMWH type is usually only administered subcutaneously but may be given IV as well.

Heparin acts on thrombin, inhibiting the action of fibrin in clot formation.

Theantidote for serious bleeding complications during heparin therapy is protamine sulfate.

When administered IV, the action of heparin is immediate.

A dilute flushing solution of heparin is also used to maintain the patency of indwelling venipuncture devices used to obtain blood specimens and of catheters used for arterial access (arterial lines).

Be sure to check that it is a dilute flushing solution before injection, and not full-strength heparin.
However, 0.9% sodium chloride (normal saline) injection alone is used to flush peripheral venipuncture devices, for example PRN adapters.
Heparin is not normally used to flush these devices because of possible drug incompatibilities and laboratory test interferences.

The LMWHs include enoxaparin (Lovenox) and dalteparin (Fragmin).
When administered subcutaneously, monitoring of anticoagulant effect is not necessary, but periodic complete blood counts (CBCs), stool occult blood tests, and platelet counts are recommended during treatment.
Unlike UFH, in the case of clinically significant bleeding, no agent fully reverses the activity of the LMWHs, although protamine has some activity and should be given for life-threatening bleeding along with packed red blood cells and fresh frozen plasma transfusions if indicated.

Fondaparinux (Arixtra), a closely related pentasaccharide, is not generally classified as an LMWH (although often discussed with the same).
It is an indirect clotting factor Xa inhibitor and lacks a specific antidote in the event of excessive anticoagulation.

Enoxaparin was the first LMWH to be approved in the United States. It is currently approved for the prevention of deep vein thrombosis (DVT) in patients undergoing hip or knee replacement or abdominal surgery, for the treatment of unstable angina and ST-elevation myocardial infarction (STEMI), and for the in- patient treatment of acute DVT and pulmonary embolism (PE).
It is also used in the outpatient treatment of acute DVT not associated with pulmonary embolism and is combined with warfarin (until INR reaches 2-3).

When heparin is administered subcutaneously, especially if the patient is discharged and the medication will be administered at home, be sure to stress patient education.

Measurement of the activated partial thromboplastin time (aPTT) is the most common laboratory test for monitoring heparin therapy.

When long-term anti-coagulant therapy is begun with warfarin, there is a short-term overlap period in which both heparin and warfarin are administered concurrently.
It is very important that patients on anticoagulant therapy be instructed regarding:

-Reading the FDA-approved Medication Guide dispensed with the oral anticoagulants Importance of compliance with taking medications as prescribed and required laboratory monitoring (if any)
-The fact that this medication does not dissolve clots and that it decreases the clotting ability of the blood and helps prevent the formation of harmful blood clots in the blood
vessels and heart
-Taking the medication as prescribed at the same time every day
-Not changing brands of the medication without the physician's approval
-Avoiding eating large amounts of grapefruit or drinking grapefruit juice or cranberry juice
-Avoiding shots such as flu shots, shingle vaccine, and pneumonia vaccine (Talk with your healthcare provider before getting shots.)
-Avoiding activities and contact sports that may cause injury, cuts, or bruises
-Using a soft toothbrush and an electric razor to shave to prevent cuts
-Always wearing closed-toe shoes
-Using a night light to prevent falls
-Immediately reporting unusual bleeding, bruising, brown spots, or blood-tinged secretions, injury, trauma, dizziness, abdominal pain or swelling, back pain, headaches, and joint pain and swelling to their physician
-If prescribed, carrying vitamin K for emergency use
-Using a reliable birth control method
-Reporting allergic reactions such as skin rash to their physicians
-Avoiding smoking, the use of alcohol, and over-the-counter medications
-Wearing identifications and alerts at all times
-Keeping all follow-up appointments with their physician for laboratory work and for needed dosage changes

In addition to drug therapy, patients should be educated on modifying risk factors for CHD and stroke, that is, abstinence from all forms of tobacco, weight control, low-fat and low-cholesterol diet, and aerobic exercise on a regular basis.
ADP receptor antagonists block the activation of the platelet's receptor surface, thereby inhibiting platelet activation.

Clopidogrel (Plavix) was the first agent approved in this class.
It is used to reduce atherosclerotic events (myocardial infarction, stroke, and vascular death) in patients with a history of recent stroke, recent MI, or established peripheral vascular disease.

Clopidogrel is also used in combination with aspirin to prevent thrombosis of stents that are used to prop open diseased coronary arteries.

Prasugrel (Effient) is a more potent antiplatelet agent with no clinically significant drug interactions identified to date.

The newest agent in this class, ticagrelor (Brilinta), is the first reversible oral ADP receptor antagonist.
It's quicker onset of antiplatelet activity allows the platelet function to return to baseline quicker and may result in fewer coronary artery bypass surgery-related bleeding events in patients requiring emergent intervention.
Ticagrelor's shorter half-life necessitates twice-daily dosing compared with once-daily dosing of clopidogrel and prasugrel.
Ticagrelor is contraindicated in severe hepatic impairment.

All ADP receptor antagonists are contraindicated in patients with active pathological bleeding (such as peptic ulcer) or a history of intracranial hemorrhage.

Interactions of all platelet inhibitors with other anticoagulants, for example aspirin and NSAIDs, other platelet inhibitors, or thrombolytic agents, may increase the risk of bleeding.

The use of certain PPIs (esomeprazole, omeprazole, including Prilosec OTC), azole antifungals, most macrolide antibiotics (except azithromycin), certain SSRIs (fluoxetine, fluvoxamine), and HIV NNRTIs may make clopidogrel less effective by inhibiting the enzyme that converts clopidogrel to the active form of the drug.

The plasma concentrations of ticagrelor may be elevated by azole antifungals, HIV protease inhibitors, and some macrolide antibiotics; they may be reduced by carbamazepine, phenobarbital, phenytoin, and rifampin.

Ticagrelor can increase digoxin concentrations (monitor levels) and increase lovastatin and simvastatin concentrations (avoid doses > 40 mg).
The body maintains a process to dissolve clots (fibrinolysis) after they have formed.

Tissue plasminogen activator (t-PA) is a natural peptide that initiates fibrinolysis.

Thrombolytic agents actually dissolve and liquefy the fibrin of the existing clot.

Thrombolytic drugs (e.g., reteplase and alteplase) potentiate t-PA, resulting in clot dissolution, reperfusion of organs, and restoration of blood flow to tissues.

Thrombolytic agents, given IV, reduce mortality when used as early as possible but within the first 12h after the onset of acute STEMI.

Alteplase is also used to treat acute ischemic stroke (within 3 to 4.5h of the onset of stroke symptoms) and acute pulmonary embolism.

Administered in an ER or ICU setting, close monitoring of hemodynamics and vital signs is generally considered standard with thrombolytic therapy, particularly during the initial 24-48h.

Intracranial hemorrhage is the most serious complication of thrombolytic therapy, but bleeding can occur at any site in the body.

Bleeding occurs most commonly at access sites such as catheter insertion sites or venipuncture sites.

Patients with preexisting coagulation problems, uncontrolled hypertension, severe chronic heart failure, and recent stroke are at the highest risk for developing bleeding complications during thrombolytic therapy.

Hemorrhage can result from concomitant therapy with heparin or other platelet-aggregation inhibitors.

If severe bleeding occurs during therapy, the drug should be discontinued promptly.

Rapid coronary lysis can result in the development of arrhythmias; however, they are generally transient in nature.