Unit 8 Part 1 Pharmacology

Intro to CV System

• Responsible for delivering oxygen & nutrients to all cells & for removing waste.

• Consists of a pump (heart) and an interconnected series of vessels, spanning about 60,000 miles, that moves blood continuously throughout the body via veins and arteries. 

• Divided into 4 chambers (2 atrium and 2 ventricles) partitioned by the septum and 2 valves (tricuspid and mitral). 

• 2 additional valves (pulmonic & aortic) allow blood flow to enter the great vessels and keep blood flowing in 1 direction.

Periods of the Cardiac Cycle

• Starling’s Law of the Heart (stretch & spring back theory).

• Systole

  • Period of cardiac muscle contraction

  • Oxygenated blood is pumped out of LV, through aorta, and to rest of body by arteries. 

• Diastole

  • Period of cardiac muscle relaxation

  • Deoxygenated blood is returned to the RA by veins.

Components of the Conduction System

• SA Node

  • Natural pacemaker 

  • Generates impulse 90-100 times/min

• Atrial Bundles

  • Conducts impulse through atrial muscle 

• AV Node 

  • Slows impulse allowing delay needed for atrial contraction & ventricular filling

  • Generates impulse at 40-50 times/min

• Bundle of His 

  • Transports impulse from atria to ventricles 

• Bundle Branches

  • Conducts impulses through ventricles 

• Purkinje Fibers 

  • Delivers impulses to ventricular cells, stimulating contraction

Automaticity

• Cells within the heart’s electrical system can generate action potentials or electrical impulses without being excited by an external stimuli 

• Each area of the heart appears to have a slightly different action potentials, causing different rates of automaticity

Conductivity

• Specialized cells of the heart can conduct an impulse rapidly through the system so that the muscle cells of the heart are stimulated at the approximately the same time.

Phases of Cardiac Action Potential

• Phase 0 

  • Occurs when the cell reaches a point of stimulation

• Phase 1 

  • Short period when the sodium ion concentrations are equal inside and outside the cell

• Phase 2 

  • Plateau stage: Occurs as the cell membrane becomes less permeable to potassium, allowing calcium to enter

• Phase 3 

  • Period of rapid repolarization as the gates are closed and potassium rapidly moves out of the cell

• Phase 4 

  • The cell comes to rest as the sodium-potassium pump returns the membrane to its previous state

Factors That May Affect the Cardiac Rate and Rhythm 

• Potential for causing arrhythmias/dysrhythmias (disruption in cardiac rate or rhythm) 

• Autonomic nervous system 

  • Parasympathetic nerves (10th cranial nerve/vagus)

  • Sympathetic nervous system

• Damage to conductive cells (MI, cardiomyopathy, etc.)

• Drugs

• Acidosis

• Decreased oxygen levels

• Changes in electrolyes in the area

• Buildup of waste products 

• Changes in automaticity or conductivity can interfere with the work of the heart and disrupt cardiac output

Courses of Circulation of the Blood

• Heart-Lung or Pulmonary Circulation

  • The right side of the heart sends blood to the lungs

  • Carbon dioxide and some waste products are removed from the blood. 

  • Oxygenation is picked up by the RBCs

• Systemic Circulation 

  • The left side of the heart sends oxygenated blood out to all cells in the body. 

Forces Determining Heart’s Oxygen Consumption

• HR

  • Harder the heart has to work, the more oxygen it requires

• Preload

  • Amount of blood returned to the heart so that it can be pumped throughout the body

  • Volume of blood is a determinant of preload. The more blood, the harder teh work to pump

• Afterload

  • Resistance against which the heart has to beat

  • BP pressure a measure of afterload

• Contractility

  • High influx of calcium can cause less relaxion of cardiac muscle, causing greater forces of contraction

BP is determined by

• HR

• Stroke Volume (Amount of blood pumped out of the ventricle with each heartbeat)

• Total Peripheral Resistance (Resistance of the muscular arteries to the blood being pumped through)

Baroreceptors

• Specialized cells within the aortic arch and carotid arteries 

• Communicates with the medulla to mediate changes in BP through the autonomic nervous system

Renin-angiotensin-aldosterone system (RAAS)

• Activated when BP within the kidney falls 

• Renin released, reacting with angiotensinogen 

Complications r'/t BP Control

• Hypertension (HTN)

  • Elevated bp above normal limits for sustained period of time

  • 90% of people have essential/primary htn- no known cause

  • Secondary htn- known cause (tumor)

• Hypotension 

  • Decreased bp below normal limits

  • Causes: 

    • When the heart muscle is damaged and unable to pump effectively

    • With severe blood or fluid loss leading to decreased volume 

    • When there is extreme stress and the body’s levels of norepinephrine are depleted, leaving the body unable to respond to stimuli to raise BP

  • Decreased oxygenated blood to vital centers in the brain and other vital organs/tissues can decrease functioning, leading to shock

Conditions r/t untreated htn

• CAD and cardiac death

• Stroke

• Renal Failure

• Loss of Vision

Factors known to increase BP

• High levels of psychological stress

• Exposure to high-frequency noise 

• High-salt diet

• Lack of rest

• Genetic predisposition 

Step Care Management of HTN

• Step 1

  • Lifestyle modifications are instituted 

    • Wt. reduction, smoking cessation, moderation of alcohol intake, reduction of dietary salt, increase in aerobic physical activity. 

• Step 2 

  • Inadequate response

    • Non-pharmacological therapy

    • Drug therapy added (diuretic, ACE inhibitor, calcium channel blocker, ARB)

• Step 3

  • Inadequate Response

    • Consider change in drug dose or class, or addition of another drug for combined effect.  

• Step 4 

  • Inadequate response

    • Second or third agent or diuretic is added to current regimen if not already prescribed. 

Antihypertensive Agents

• ACE Inhibitors 

• Angiotensin II Receptor Blockers

• Calcium Channel Blockers 

• Vasodilators 

• Renin Inhibitors 

• Diuretics

• Sympathetic Nervous System Blockers

Angiotensin Converting Enzyme (ACE) Inhibitors Common Drugs

• Benazepril (Lotensin)

• Captopril (Capoten)

• Enalapril (Vasotec)

• Lisinopril (Prinivil)

Angiotensin Converting Enzyme (ACE) Inhibitors Actions/Indications

• Act in the lungs to block conversion of angiotensin I to angiotensin II, leading to decrease in BP, a decrease in aldosterone production, and a small increase in serum potassium levels along with sodium and fluid loss. 

• Treatment of htn, HR, left ventricular dysfunction following an MI.

Angiotensin Converting Enzyme (ACE) Inhibitors Pharmacokinetics

Well absorbed, widely distributed, metabolized in liver, and excreted in urine and feces.

Angiotensin Converting Enzyme (ACE) Inhibitors Contraindications/Cautions

Allergies, impaired renal function, pregnancy and lactation, acute HF r/t changes in hemodynamics.

Angiotensin Converting Enzyme (ACE) Inhibitors Adverse Effects

R/t effects of vasodilation and alterations in blood flow (hypotension), reflex tachycardia, arrhythmias, GI irritation, renal insufficiency, unrelenting-nonproductive cough, contribute to hyperkalemia, and angioedema

Angiotensin Converting Enzyme (ACE) Inhibitors Nursing Considerations

• Assess contraindications

• Baseline assessment

• Encourage pt to implement lifestyle changes 

• Administer on empty stomach 1 hr before or 2 hrs after meals if taking captopril 

• Caution during surgical procedures r/t hypotention 

• Monitor renal functions and electrolytes 

• Monitor BP

• Educate pt on how to check BP and when to report issues 

Angiotensin II Receptor Blockers (ARBS) Common Drugs

• Losartan (Cozaar) 

• Olmesartan (Benicar)

• Valsartan (Diovan)

Angiotensin II Receptor Blockers (ARBS) Actions/Indications

• Selectively bind with the angiotensin II receptors in vascular smooth muscle of blood vessels in the adrenal cortex to block vasoconstriction and the release of aldosterone. 

• Can be used alone or in combination therapy to manage htn or HF

Angiotensin II Receptor Blockers (ARBS) Pharmacokinetics

Well absorbed and undergo metabolism in liver by the cytochrome P450 system. Excreted in feces and urine. 

Angiotensin II Receptor Blockers (ARBS) Contraindications/Cautions

Allergy, pregnancy, lactation, hepatic or renal dysfunction, and hypovolemia.

Angiotensin II Receptor Blockers (ARBS) Adverse Effects

Headache, dizziness, syncope, weakness r/t decrease in BP, GI complaints, skin rash or dry skin, dry mouth leading to tooth decay.

Angiotensin II Receptor Blockers (ARBS) Nursing Considerations

• Assess contraindications

• Baseline assessment

• Encourage pt to implement lifestyle changes 

• Administer without regard to meals 

• Caution during surgical procedures r/t hypotension 

• Encourage women to use barrier contraceptives to avoid pregnancy and use alternate methods of feeding baby

• Monitor pt response to therapy

• Educate pt how to check BP and when to report problems 

Calcium Channel Blockers (CCBs) Common Drugs

• Amlodipine (Norvasc)

• Nicardipine (Cardene)

• Diltiazem (Cardizem LA)

• Nifedipine (Procardia XL)

• Verapamil (Calan SR)

Calcium Channel Blockers (CCBs) Actions/Indications

• Inhibits movement of calcium ions across the membranes of cardiac and arterial muscle cells, depressing the impulse and leading to slowed conduction, decreased myocardial contractility, and dilation of arterioles, which lowers BP and decreases myocardial oxygen consumption. 

• Used alone or in combination to treat htn, tachyarrhythmias and to treat angina

Calcium Channel Blockers (CCBs) Pharmacokinetics

Well absorbed, metabolized in liver, and excreted in the urine. 

Calcium Channel Blockers (CCBs) Contraindications/Cautions

Allergy, heart block, sick sinus syndrome, renal or hepatic dysfunction, pregnancy, and lactation. 

Calcium Channel Blockers (CCBs) Adverse Effects

R/t effects on cardiac output, dizziness, headache, fatigue, GI symptoms, CV symptoms (Hypotension, bradycardia, peripheral edema).

Vasodilators Common Drugs

• Reserved for use in severe htn or hypertensive emergencies. 

• Hydralazine (generic): Maintains increased renal blood flow

• Minoxidil (generic)

• Nitroglycerine 

• Nitroprusside (Nitropress) 

Vasodilators Actions/Indications

• Act directly on vascular smooth muscle to cause muscle relaxation, leading to vasodilation, decreasing preload and afterload, and drop in BP. 

• Severe htn unresponsive to other therapy

Vasodilators Pharmacokinetics

Rapidly absorbed and widely distributed, metabolized in liver, and primarily excreted in urine. 

Vasodilators Contraindications/Cautions

Allergy, pregnancy, lactation, cerebral insufficiency, peripheral vascular disease, CAD, HF, or tachycardia (exacerbated r/t decreased bp).

Vasodilators Adverse Effects

R/t changes in BP, GI upset, and cyanide toxicity with nitroprusside (metabolized to cyanide). 

Calcium Channel Blockers and Vasodilators Nursing Considerations

• Assess contraindications

• Baseline assessment

• Encourage pt to implement lifestyle changes

• Monitor bp closely, HR

• Monitor serum electrolytes

• Educate pt to monitor bp and when to report problems

Other Antihypertensive Agents: Diuretics

• Often first agents used to treat mild htn 

• Increase the excretion of sodium and water from the kidney to lower bp 

• Thiazide and thiazide-like diuretics (first-line use): 

  • Hydrochlorothiazide (HydroDIURIL)

  • Metolazone (Zaroxolyn)

• Potassium-sparing diuretics: 

  • Spironolactone (Aldactone) 

Sympathetic Nervous System Blockers

• Beta blockers 

  • Atenolol (Tenormin) 

  • Metoprolol (Lopressor) 

  • Nadolol (Corgard) 

  • Nebivolol (Bystolic)

  • Propranolol (Indreal) 

  • Timolol (Generic)

• Alpha- and beta-blockers 

  • Carvedilol (Coreg) 

  • Labetalol (Transdate)

• Alpha1-blockers 

  • Doxazosin (Cardura)

  • Prazosin (Minipress)

  • Terazosin (Generic)

• Alpha2-agonists

  • Clonideine (Catapres)

Vasopressors Common Drugs

• Sympathomimetic drugs are first choice for treating severe hypotension or shock.

• Dobutamine 

• Dopamine

• Ephedrine

• Epinephrine (Adrenalin)

• Isoproterenol (Isuprel)

• Norepinephrine (Levophed) 

• Phenylephrine 

Vasopressors Action

• React with sympathetic adrenergic receptors to cause the effects of a sympathetic stress response (increased bp, increased blood volume and strength of cardiac muscle contraction). 

Vasopressors Adverse Effects

GI effects, changes in bp, headache, changes in peripheral blood flow.

BP Raising Agents Common Drug

• Midodrine

BP Raising Agents Action/Indications

• Activates alpha1-receptors in arteries and veins to produce increase in vascular tone and increase bp. 

• Used to treat symptomatic orthostatic hypotension

BP Raising Agents Contraindications/Cautions

Supine htn, CAD, acute renal disease, urinary retention 

BP Raising Agents Adverse Effects

Htn, bradycardia, and urinary retention 

Nursing Consideration for Antihypotensive Drugs

• Assess contraindications

• Baseline Assessment 

• Monitor bp and HR carefully 

• Administer/adjust dose carefully 

• Educate pt on adverse effects 

Agents for Treating HF

• Condition in which the heart fails to effectively pump blood throughout the body, leading to decreased cardiac output. 

• Usually involves dysfunction of the cardiac muscle. HF can occur with any of the disorders that damage or overwork the heart muscle: 

  • Coronary Artery Disease (CAD)

  • Cardiomyopathy leading to cardiomegaly 

  • Htn

  • Valvular Heart Disease 

Signs of Right sided HF

• Elevated jugular venous pressure

• Splenomegaly 

• Hepatomegaly 

• Decreased renal perfusion when upright

• Increased renal perfusion when supine → nocturia 

• Pitting edema 

• Weakness/fatigue 

Signs of Left sided HF

• Anxiety

• Tachypnea, dyspnea, orthopnea, hemoptysis rales

• Cardiomegaly S3, increased heart rate

• GI upset, N, abdominal pain 

• Decreased peripheral pulses, hypoxia 

Primary Treatment of HF

• Cardiotonic (inotropic) drugs

  • Cardiac glycosides 

  • Phosphodiesterase Inhibitors 

  • HCN Blocker 

  • ARN Inhibitor 

Heart Failure (HF)

• Allows the heart muscle to contract more efficiently, increasing cardiac output, in an effort to bring the system back into balance. 

• Other drugs used: 

  • Vasodilators 

  • ACE inhibitors

  • ARB’s

  • Diuretics

  • Beta-blockers

  • Beta-adrenergic agonists

  • Aldosterone antagonists

Cardiac Glycosides Common Drug

• Originally derived from foxglove or digitalis plant 

• Common drug

  • Digoxin (Lanoxin) 

Cardiac Glycosides Action/Indication

• Increases intracellular calcium and allows more calcium to enter myocardial cells during depolarization. 

• Leading to increased forces of myocardial contraction, cardiac output and renal perfusion, slows HR and conduction velocity through the AV node. 

• Used for treatment of HF, atrial flutter, atrial fibrillation, and paroxysmal atrial tachycardia

Cardiac Glycosides Pharmacokinetics

Rapidly absorbed and widely distributed throughout the body, primarily excreted unchanged in urine.

Cardiac Glycosides Contraindications/Cautions

Allergy, ventricular tachycardia or fibrillation, heart block, sick sinus syndrome, idiopathic hypertrophic subaortic stenosis, acute MI, renal insufficiency, electrolyte abnormalities, pregnancy and lactation.

Cardiac Glycosides Adverse Effects

Headache, weakness, drowsiness, vision changes (yellow halo around objects), GI upset and anorexia, arrhythmia development, and toxicity.

Cardiac Glycosides Nursing Considerations

• Assess contraindications

• Baseline assessment

• Assess cardiac and fluid status closely

• Loading dose when beginning therapy may be needed

• Monitor apical pulse for one full minute before administration, noting quality and rhythm. Hold dose if pulse less than 60 in adult client. 

• Check dose and preparation closely prior to administration

• Assess for signs of HF

• Avoid administering oral drug with food and antacids 

• Digoxin has a narrow margin of safety. Monitor therapeutic levels closely (0.5-2 ng/mL) and for signs of toxicity (anorexia, N, V, heart block, atrial or ventricular arrhythmias).  

• Digoxin Immune Fab (DigiFab) is an antigen-binding fragment derived from specific antidigoxin antibodies and is used as the antidote for toxicity.

• Educate pt how to monitor HR closely and when to report problems

Additional Drugs Used to Treat HF

• Phosphodiesterase Inhibitors 

  • Milrinone (generic) 

  • Block the enzyme phosphodiesterase, leading to increased calcium levels in the cell, increasing teh contraction and prolonging the effects of sympathetic stimulation. 

• HCN Channel Blockers

  • Ivabradine (Corlanor)

  • Affects of the pacemaker of the heart, reducing HR, allowing more time for ventricular filling without affecting BP

• ARN Inhibitors 

  • Sacubitril/Valsartan combo (Entresto)

  • Blocks the breakdown of neprilysin, increasing the loss of sodium and water

  • Combined with blocking of angiotensin II receptors, leads to decreased cardiac workload

Antiarrhythmic Agents

• Disruptions in impulse formation and in the conduction of impulses through the myocardium are called arrhythmias. 

• Arrhythmias occur because of the heart possess the property of automaticity and can generate excitatory impulses separate from the normal conductive pathway. 

• Disruptions in the normal rhythm of the heart can interfere with myocardial contractions and affect cardiac output. 

• Antiarrhythmics are drugs used to treat arrhythmias by suppressing automaticity or altering the conductivity of the heart. 

Causes of Cardiac Arrhythmias

• Electrolyte disturbances that alter the action potential

• Decreases in oxygen delivered to the cells 

• Structural damage changing the conduction pathway through the heart

• Acidosis or accumulation of waste products altering the action potential 

• Drugs that alter the action potential or cardiac conduction

Types of Cardiac Arrhythmias

• Tachycardia (Faster than normal HR >100 bpm)

• Bradycardia (Slower than normal HR <60 bpm)

• Premature atrial contractions (PACs) or premature ventricular contractions (PVCs)

• Atrial flutter

• Atrial fibrillation or ventricular fibrillation 

• Alterations in conduction through the muscle (heart blocks and bundle branch blocks)

Classifications of Antiarrhythmic Agents

• Antiarrhythmics affect the potential by altering automaticity, conductivity, or both. 

• 1- Class I (a, b, c): Block the sodium channels in the cell membrane during an action potential. 

• 2- Class II: Block beta-receptors, causing depression of phase 4 of the action potential. 

• 3- Class III: Block potassium channels, prolong phase 3 of the action potential. 

• 4- Class IV: Block calcium channels in the cell membrane.

Class I Antiarrhythmics

• Block sodium channels in cell membrane during an action potential 

• Class Ia: Depress phase 0 of the action potential and prolongs the action potential duration. 

  • Disopyramide (Norpace)

  • Procainamide

• Class Ib: Depress phase 0 somewhat and shortens the duration of teh action potential 

  • Lidocaine (Xylocaine)

• Class Ic: Markedly depress phase 0, resulting in extreme slowing of conduction, but has little effect on the duration of the action potential. 

  • Flecainide 

  • Propafenone (Rhythmol) 

Class I Antiarrhythmics Actions/Indications

• Stabilize the cell membrane by binding to sodium channels, depressing phase 0 of the action potential, and changing the duration of the action potential. 

• Management of acute, life threatening ventricular arrhythmias and symptomatic paroxysmal atrial arrhythmias. 

Class I Antiarrhythmics Pharmacokinetics

Widely distributed after injection or after rapid absorption through GI. Hepatic metabolism and excreted in urine.

Class I Antiarrhythmics Containdications/Cautions

Allergy, bradycardia, heart block, HF, hypotension or shock, electrolyte imbalances, renal or hepatic dysfunction or pregnancy.

Class I Antiarrhythmics Adverse Effects

CNS effects (dizziness, fatigue, slurred speech, and twitching), GI (N,V, changes in taste), CV (arrhythmias, hypotension), respiratory depression, rash, loss of hair, and potential bone marrow suppression. 

Class II Antiarrhythmics

• Many are beta-adrenergic blockers that block beta-receptors, causing a depression of phase 4 of the action potential. Others act on the autonomic nervous system if some way. 

• Common drugs: 

  • Propranolol (lInderal)

  • Esmolol (Brevibloc)

  • Atropine 

Class II Antiarrhythmics Actions/Indications

• Many competitively block beta receptor sites in the heart and kidneys. 

• Decreasing HR, cardiac excitability, and cardiac output, slowing conduction through the AV node. 

• Treatment of supraventricular tachycardia, htn, angina, atrial/ventricular arrhythmias. 

Class II Antiarrhythmics Pharmacokinetics

Absorbed from GI and undergo hepatic metabolism and excreted in urine.

Class II Antiarrhythmics Contraindications/Cautions

Sinus bradycardia, AV block, cardiogenic shock, HF, asthma, respiratory depression, pregnancy, lactation, diabetes, thyroid dysfunction, renal or hepatic dysfunction.

Class II Antiarrhythmics Adverse Effects

R/t effects of block beta receptors in the sympathetic nervous system, CNS (dizziness, insomnia, dreams, and fatigue), CV (hypotension, bradycardia, AV block, arrhythmias, alterations in perfusion), respiratory (bronchospasms and dyspnea), GI (N,V, and anorexia), loss of libido, decreased exercise tolerance, and alterations in blood glucose levels. 

Class III Antiarrhythmics Common Drugs

• Ammiodarone (Pacerone)

• Dofetilide (Tikosyn)

• Sotalol (Betapace)

Class III Antiarrhythmics Actions/Indications

• Block potassium channels and slow the outward movement of potassium during phase 3 of the action potential. This action prolongs the action potential. 

• Life threatening ventricular arrhythmias

• Maintenance of sinus rhythm after conversion of atrial arrhythmias

Class III Antiarrhythmics Pharmacokinetics

Absorbed and widely distributed, metabolized in liver and excreted in kidneys. 

Class III Antiarrhythmics Contraindications/Cautions

When used for life-threatening arrhythmias there are NO contraindications. Shock, hypotension, respiratory depression, prolonged QT interval, renal or hepatic disease. 

Class III Antiarrhythmics Adverse Effects

R/t changes caused in action potentials. N, V, weakness, dizziness, hypotension, arrhythmias. 

Class IV Antiarrhythmics Common Drugs

• Diltiazem (Cardizem)

• Verapamil (Calan)

Class IV Antiarrhythmics Actions/Indications

• Block movement of calcium ions across the cell membrane, depressing the generation of action potential, delaying phases 1 and 2 of repolarization, slowing conduction through the AV node. 

• Treatment of supraventricular tachycardia and control the ventricular response to rapid atrial rates. 

Class IV Antiarrhythmics Pharmacokinetics

Well absorbed, protein bound, metabolized in liver and excreted in urine.

Class IV Antiarrhythmics Contraindications/Cautions

Allergy, sick sinus syndrome, heart block, severe HF, hypotension, idiopathic hypertrophic subaortic stenosis, pregnancy, lactation, liver/kidney impairment.

Class IV Antiarrhythmics Adverse Effects

R/t vasodilation of blood vessels and slowing HR, dizziness, weakness, fatigue, depression, GI upset, hypotension, HF, and shock, arrhythmias, and edema.

Other Drugs Used to Treat Arrhythmias

• Adenosine (Adenocard)

  • Used to convert supraventricular tachycardia to sinus rhythm when vagal maneuvers have been ineffective. 

  • Slows conduction through the AV node, prolongs refractory period and decreases automaticity in AV node. 

  • Drug of choice for terminating SVTs due to its short duration (15 sec) and few adverse effects. 

• Digoxin 

  • Slows calcium from leaving the cell, prolonging the action potential and slowing conduction and HR. 

• Dronedarone (Multaq)

  • Has properties of all 4 classes of antiarrhythics 

  • Used to reduce risk of hospitalization in pts. with paroxysmal or persistent AF of flutter who have risk factors for CVD and are in sinus rhythm or scheduled to be converted to sinus rhythm. 

Nursing Considerations for Antiarrhythmics

• Assess contraindications

• Obtain comprehensive physical assessment including cardiac status, neuro status, GI and respiratory status.

• Utilize smallest dose needed to control arrhythmias

• Continually monitor cardiac rhythm when initiating or changing dose, monitor periodically during long term therapy.

• Monitor renal and hepatic function to determine need for dosing changes.

• Educate pt on adverse effects and warning signs of problems.