Drugs affecting the circulatory system

Elsevier items and derived items © 2009 by Saunders, an imprint of Elsevier Inc. Some material was previously published.

Drugs That Affect the Circulatory System

Elsevier items and derived items © 2009 by Saunders, an imprint of Elsevier Inc. Some material was previously published.2

Learning ObjectivesLearning Objectives

• Discuss the ways drugs may affect the heart.

• Identify drugs used to treat heart failure.

• Identify drugs used to treat hypertension.

• Explain the action of antiarrhythmic agents.


Components and Function of the Circulatory System


• Circulatory system includes the heart and blood vessels

• Heart is a hollow, muscular organ– Situated near the center of thoracic cavity– Divided into four chambers– Muscular chambers pump blood– Left ventricle more muscular


Normal Blood CirculationNormal Blood Circulation

• Oxygenated blood comes into left atrium from lungs; passes into the left ventricle

• Ventricle contracts; blood is forced into aorta• Blood is carried to gastrointestinal tract, liver,

capillary beds • Oxygen (O2) and nutritive materials carried to

tissue• Carbon dioxide (CO2) and waste carried away

to lungs and kidneys for excretion


Drugs That Affect the HeartDrugs That Affect the Heart

• Cardiac drugs can affect the following:– Heart rate– Rhythm of the heartbeat– Amount of output of blood– Strength of the contraction– Intracellular energy production


Uses for Cardiac DrugsUses for Cardiac Drugs

• Three main conditions– Heart failure—heart is not circulating blood

at a satisfactory rate, fluid collects in lungs or extremities

– Myocardial infarction—blood supply to heart muscle is blocked

– Arrhythmias—abnormal electric conduction affects pumping action of heart


Heart FailureHeart Failure

• During heart failure the following occurs:– Capillaries and veins contain more blood– Hydrostatic pressure is greater– Blood in the periphery retains more CO2 and

wastes– Blood has less O2 with hemoglobin– Respiration in lungs is reduced– Cyanosis– Edema


Drugs That Affect the HeartDrugs That Affect the Heart

• Heart failure is treated with several classes of drugs:– Diuretic agents– Inotropic drugs– Angiotensin-converting enzyme (ACE)

inhibitor agents– Beta blockers


Diuretic AgentsDiuretic Agents

• Promote the formation and excretion of urine• Reduce fluid overload• Used in treatment of heart failure and

hypertension• Reduce orthopnea and dyspnea• Most helpful in combination with other drugs • Examples:

– Furosemide (Lasix)– Metolazone (Zaroxolyn)– Hydrochlorothiazide (HydroDIURIL)


Inotropic DrugsInotropic Drugs

• Inotropic drugs increase the contractibility of the myocardium.

• Digitalis was the first inotropic drug.– Crude digitalis leaf no longer used because

of problems with standardization.


Inotropic DrugsInotropic Drugs

• Digitalis – Strengthens heart musculature– Increases blood flow and allows heart to empty more

efficiently– Side effects indicating toxicity include nausea,

vomiting, and visual disturbances (objects may appear brighter than they actually are)

– Synthetic form is exclusively used.• Digoxin (Lanoxin, Digitek) in oral, intravenous, and

intramuscular forms

– Antidote• Digoxin immune Fab (Digibind)


ACE InhibitorsACE Inhibitors

• Inhibit angiotensin-converting enzyme • Used to treat congestive heart failure• Appear to minimize or prevent the left

ventricular dilation or dysfunction after myocardial infarction

• Also used to treat hypertension• Used in combination with other agents• May cause chronic cough, rarely

angioedema


ACE InhibitorsACE Inhibitors

• Examples:– Benazepril (Lotensin)– Captopril (Capoten)– Enalapril (Vasotec) – Fosinopril sodium (Monopril)– Lisinopril (Prinivil, Zestril)– Moexipril hydrochloride (Univasc)– Quinapril (Accupril)– Ramipril (Altace)


Beta-Blocking AgentsBeta-Blocking Agents

• Block beta-adrenergic receptors in the sympathetic nervous system

• Very beneficial in people who have had myocardial infarctions, especially those with low ejection fraction

• Reduce workload of heart• Increase survival rates, decrease

hospitalizations


Beta-Blocking AgentsBeta-Blocking Agents

• Examples:– Acebutolol hydrochloride (Sectral)– Atenolol (Tenormin)– Betaxolol (Kerlone)– Bisoprolol fumarate (Zebeta)– Carvedilol (Coreg)– Labetalol (Normodyne, Trandate) – Metoprolol (Toprol, Toprol-XL)– Nadolol (Corgard)– Propranoalol hydrochloride (Inderal)


Angiotensin II Receptor–Blocking Agents


• Used for patients after myocardial infarction or heart failure who cannot tolerate ACE inhibitors

• Reduce left ventricular dilation or dysfunction after myocardial infarction

• Less effective than ACE inhibitors




• Examples:– Candesartan cilexetil (Atacand)– Eprosartan mesylate (Teveten)– Irbesartan (Avapro)– Losartan (Cozaar)– Olmesartan (Benicar)– Telmisartan (Micardis)– Valsartan (Diovan)


Aldosterone Inhibitor AgentsAldosterone Inhibitor Agents

• Used to treat congestive heart failure if ACE inhibitor agents and angiotensin II receptor–blocking agents are not tolerated

• Cannot be used if patient has hyperkalemia or reduced renal function

• Also used to treat hypertension• Examples:

– Eplerenone (Inspra)– Spironolactone (Aldactone)


Cardiac ArrhythmiasCardiac Arrhythmias

• Sinoatrial (SA) node in right atrium controls rate and rhythm of heart

• Electrical conduction of heart– SA node generates electrical impulses– Impulses received by atrioventricular (AV) node– Impulses travel down to bundle of His and are transported to

ventricular muscles– Causes contraction

• Any deviation from normal called an arrhythmia

• Rate may be increased or decreased


Drug Used to Treat Arrhythmias


• Examples:– Amiodarone HCl (Cordarone, Pacerone)

• Treats supraventricular and ventricular arrhythmias• Can be used during cardiopulmonary resuscitation (CPR)• Side effects: bradycardia, heart block, hypothyroidism

– Disopyramide phosphate (Norpace)• Slows atrial contractions

– Dofetilide (Tikosyn)– Ibutilide fumarate (Corvert)– Lidocaine hydrochloride (Xylocaine)




• Examples:– Nadolol (Corgard)– Procainamide hydrochloride (Pronestyl)– Propranolol hydrochloride (Inderal)

• Beta blocker that decreases the irritability of the AV node and decreases myocardial contractility

– Quinidine sulfate– Sotalol hydrochloride (Betapace)


Chapter 20

Lesson 20.2



• Explain the action of vasoconstricting agents.

• Explain the action of vasodilating agents. • Identify the classes of antihypertensive

drugs and the general mechanism of action.

• Become familiar with side effects of antihypertensive drugs.


Vasoconstricting Agents Vasoconstricting Agents

• Constrict the muscle fibers in the walls of the blood vessels by doing the following:– Direct action on the vessels– Stimulation of vasomotor center in medulla

• May be used to do the following:– Stop superficial hemorrhage– Relieve nasal congestion– Raise blood pressure– Increase force of heart action


Vasoconstricting AgentsVasoconstricting Agents

• Drugs – Epinephrine injection, epinephrine solution

(Adrenalin)• Frequently used in eyes to constrict blood

vessels• Marked increase in blood pressure

– Midodrine hydrochloride (ProAmatine)• Treats symptomatic orthostatic hypotension


Vasodilating Agents Vasodilating Agents

• Cause the blood vessels to relax or increase in diameter

• Used to treat peripheral vascular diseases, heart conditions, hypertension

• Nitrates and nitrites– Chief use is to treat angina pectoris– Examples:

• Glyceryl trinitrate (nitroglycerin) (Nitrostat)• Topical nitroglycerin (Transderm-Nitro)• Amyl Nitrite


Antihypertensive Agents Antihypertensive Agents

• In the United States, about 58 million people are diagnosed with hypertension.

• Effective treatment of hypertension can reduce incidents of the following:– Stroke– Myocardial infarction– Heart failure– Kidney failure– Overall cardiovascular disease


Treatment of HypertensionTreatment of Hypertension

• Effective treatment reduces the risk of heart attack, stroke, and heart and kidney failure.

• Lifestyle changes are usually the first treatment option (i.e., diet, exercise).

• Organic causes include renal artery stenosis, pregnancy, oral contraceptives, and estrogen replacement therapy.

• Target blood pressure is usually no higher than 120/80 mm Hg.


Antihypertensive Drug Classes

Antihypertensive Drug Classes

• Diuretic agents• ACE inhibitor agents• Beta-blocking agents• Angiotensin II antagonist agents (also called

angiotensin II receptor blockers)• Aldosterone inhibitor agents• Central alpha agonists• Alpha-blocking agents• Calcium channel–blocking agents


Antihypertensive AgentsAntihypertensive Agents

• Central alpha agonists– Stimulate central alpha-adrenergic

receptors in the brain– Result in a decreased sympathetic outflow

from the brain to the peripheral circulatory system

– Reduce vasoconstriction



• Central alpha agonists– Clonidine (Catapres)

• Rapid onset, dry mouth

– Clonidine (Catapres TTS) • Transdermal patch• Lasts 1 week

– Guanabenz acetate (Wytensin) • Also used for opiate withdrawal and chronic pain

management

– Methyldopa (Aldomet)• Acts on CNS to decrease peripheral vascular resistance,

little heart rate change



• Alpha-blocking agents– Believed to work through the blockade of

the postsynaptic alpha-adrenergic receptors

– Cause a vasodilator effect, decrease peripheral resistance

– Not usually accompanied by increased heart rate

– Used for adults only, no children



• Calcium channel–blocking agents– Block the entry of extracellular calcium ions into

the myocardial and vascular smooth muscle cells– Lead to reduced cardiac output and reduced total

peripheral resistance– Effective for angina pectoris, supraventricular

arrhythmias, and cardiomyopathy– Should not be taken with grapefruit juice because

of increased effects of medications



• Calcium channel–blocking agents– Amlodipine besylate (Norvasc, Lotrel)– Diltiazem hydrochloride (Cardizem)– Isradipine (DynaCirc)– Nicardipine (Cardene)– Nifedipine (Procardia, Adalat)– Nimodipine (Nimotop)– Nisoldipine (Sular)– Verapamil hydrochloride (Calan, Isoptin)


Chapter 20

Lesson 20.3



• Identify drugs used to hasten the process of coagulation.

• Discuss the uses of anticoagulant agents.• Identify the specific antidote for an overdose

of sodium heparin.• Identify the specific antidote for an overdose

of warfarin sodium.• Identify drugs used as thrombolytic agents.


Coagulant AgentsCoagulant Agents

• Hasten the process of blood clotting

• Calcium salts– Needed for the reactions in blood

coagulation– May be given orally before surgery to

prevent excessive bleeding


Coagulant AgentsCoagulant Agents

• Vitamin K– Fat-soluble vitamin needed for normal blood

coagulation– Bile salts must be present in gastrointestinal

tract for absorption of natural vitamin K– In event of bile obstruction, an oral

preparation would be of no use– Antidote drug to warfarin (Coumadin)

overdose


Anticoagulant AgentsAnticoagulant Agents

• Increase the time it takes for blood to clot or coagulate

• Interfere with thrombin production and subsequent formation of fibrin from fibrinogen

• Used to treat thromboembolic (blood clot) disorders


HeparinHeparin

• Available as sodium heparin injection– Not active orally; must be given

parenterally (intravenously or subcutaneously)

• Used for the prevention and treatment of venous thrombosis

• Recommended when immediate effect is desired


HeparinHeparin

• Heparin-induced thrombocytopenia (HIT) is a significant side effect.

• Heparin induces formation of platelet antibodies.

• It should be discontinued if the platelets drop to 100,000/mm3.


Low–Molecular-Weight Heparin Agents


• Made by peroxide fragmentation of the heparin molecule

• Molecular weight is approximately one half of heparin

• Used for the prevention and treatment of thromboembolic disorders

• Administered by deep subcutaneous injection




• Tinzaparin sodium injection (Innohep)

• Ardeparin sodium injection (Normiflo)

• Dalteparin sodium injection (Fragmin)

• Enoxaparin sodium injection (Lovenox)


Direct Inhibitors of ThrombinDirect Inhibitors of Thrombin

• Lepirudin (Refludan)– Structurally and chemically unrelated to

heparin– Produces a similar pharmacologic effect to

heparin through direct interaction to thrombin

– Used for anticoagulation in patients with HIT to prevent further embolic complications


Coumarin Anticoagulant Agents


• Used in the prevention and treatment of thromboembolic disorders

• Alter the synthesis of blood coagulation factors

• Main advantage: May be taken orally

• Main disadvantage: Do not take effect for 2 to 7 days




• Sodium warfarin (Coumadin)– Agent commonly used for long-term prophylaxis of

deep vein thrombosis in patients with mechanical heart valves, atrial fibrillation.

– Its use decreases the risk for stroke, myocardial infarction, or recurrence of myocardial infarction.

– Common side effects include hemorrhage, alopecia, gastrointestinal upset, red-orange urine, and calcium loss leading to bone loss.


Thrombolytic Therapy for Myocardial Infarction

Thrombolytic Therapy for Myocardial Infarction

• A therapy used to dissolve blood clots.• It has been shown to do the following:

– Rescue the myocardium– Reduce mortality with acute myocardial infarction– Improve left ventricular function

• Examples:– Streptokinase (Streptase)– Urokinase (Abbokinase)– Alteplase (Activase, rt-PA, t-PA)


Chapter 20

Lesson 20.4



• Understand the role of platelets in blood clotting and cardiovascular disease.

• Identify drugs used in antiplatelet therapy.

• Identify drugs used in antilipidemic therapy.


Antiplatelet Therapy in Cardiovascular Disease Antiplatelet Therapy in

Cardiovascular Disease

• Blood platelets number about 250,000 to 350,000 per cubic millimeter of blood

• Three functions are as follows:– Stick to inner surfaces of damaged blood

vessels and plug leaks– When ruptured, release thromboplastin to

form a blood clot– Once a clot is formed, platelets change the

clot to a firm mass to stop bleeding


Antiplatelet Therapy in Cardiovascular DiseaseAntiplatelet Therapy in

Cardiovascular Disease

• Interfere with platelet aggregation on the surface of atherosclerotic plaques

• Prevent the formation of thrombi and emboli • Drugs

– Aspirin• If myocardial infarction is suspected, 325 mg; otherwise

81 mg daily

– Dipyridamole (Persantine)• Approved only for postoperative heart valve surgery

– Ticlopidine hydrochloride (Ticlid)• Used if aspirin is ineffective


Antilipidemic Drugs Antilipidemic Drugs

• A cholesterol level of 160 mg/dl is optimal for vessel health.

• Individuals are classified as high, medium, or low risk for death by coronary artery disease within 6 years.

• Antilipidemic drugs are contraindicated for pregnant and nursing women.

• They may cause skeletal muscle or liver damage.


Antilipidemic DrugsAntilipidemic Drugs

• Examples:– Atorvastatin calcium (Lipitor)– Cholestyramine (Questran) – Colestipol granules (Colestid)– Ezetimibe (Zetia)– Fenofibrate (Tricor)


Antilipidemic DrugsAntilipidemic Drugs

• Examples:– Gemfibrozil (Lopid)– Lovastatin (Mevacor)– Niacin (Niacor, Advicor) – Pravastatin (Pravachol)– Rosuvastatin (Crestor)– Simvastatin (Zocor)

Drugs affecting the circulatory system

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