Cardiac Medications: What’s With the Mixing &

Matching?

Michele B. Collins MSN RN CCRNSeptember 2009

Sodium-Potassium PumpSodium OUTSIDE cell & Potassium INSIDE cell before depolarization

Cell has NEGATIVE charge & must CONTRACT to become POSITIVE

SA node has less negativity so it serves as pacemaker

• With cell stimulation, cell permeability allows sodium INTO cell & potassium OUT of cell

• With sodium, can only have STAT (“fast channel”) contraction

• Calcium (“fast channel”) also enters cell, leading to total controlled contraction

Cardiac Repolarization

• Na+ - K+ pump uses energy (ATP) so SODIUM LEAVES cell and POTASSIUM RETURNS to cell

• Calcium also leaves cell at this time

Cardiac Repolarization

If the S-A node does not generate an impulse, another cardiac site WILL (“reentry phenomenon”)

Statistically, if you take six different drugs, you have an80% percent chance of at leastone drug-drug interaction.

Wayne K. Anderson, Dean,State University of New YorkSchool of Pharmacy

Medications Discussed

• Antiarrhythmics• Beta Blockers Ace Inhibitors • Calcium Channel Blockers • ACE Inhibitors• Angiotensin II Receptor Blockers (ARB)• Diuretics• Digitalis• Nitrates• Amiodarone

Why so Many?

• In atrial fibrillation, used to suppress arrhythmias

• Often done to relieve the symptoms associated with loss of the atrial component to ventricular filling (atrial kick) due to atrial fibrillation or flutter.

• In individuals with ventricular arrhythmias, used to suppress arrhythmias. Antiarrhythmic agents may be considered the first-line therapy in the prevention of sudden death in certain forms of structural heart disease

Automaticity• Refers to a cardiac muscle cell firing off

an impulse on its own• All cardiac cells can initiate an

action potential, however, only some of these cells are designed to routinely trigger heart beats

• Found in the 'conduction system' of the heart and include the SA node, AV node, Bundle of HIS and Purkinje fibers

• Sinoatrial node is a single specialized location in the atrium which has a higher automaticity (a faster pacemaker) than the rest of the heart, and therefore is usually responsible for setting the heart rate, and initiating each heart beat.

Re-entry• Occurs when an electrical

impulse recurrently travels in a tight circle within the heart, rather than moving from one end of the heart to the other and then stopping

• If conduction is abnormally slow in some areas, part of the impulse will arrive late and potentially be treated as a new impulse

• Can produce a sustained abnormal circuit rhythm. Re-entry circuits are responsible for atrial flutter, most paroxysmal supraventricular tachycardia, and dangerous ventricular tachycardia.

• Conditions that increase automaticity include sympathetic nervous system stimulation and hypoxia

• Resulting heart rhythm depends on where the first signal begins– if in sinoatrial node, the rhythm remains normal

but rapid– if an ectopic focus, many types of dysrhythmia

may ensue.

Positive Inotropes• THE EFFECTS OF STIMULATING ADRENERGIC RECEPTORS• RECEPTOR SITE ACTION• alpha peripheral blood vessels vasoconstriction of

peripheral arterioles• beta 1 myocardium increased heart rate (chronotropic)• increased contraction force

(inotropic) inc. conduction • • (dromotropic)• beta 2 peripheral blood vessels vasodilation of

peripheral arterioles & veins

• bronchioles bronchodilation

ANTIARRHYTMICS (Vaughan Williams classification)

• Class I – Membrane-stabilizing agents• Class II – Beta-blocking agents• Class III – Increase time for cell to

repolarize• Class IV – Calcium Channel blockers

• Class I agents interfere with the sodium (Na+) channel.

• Class II agents are anti-sympathetic nervous system agents. Most agents in this class are beta blockers.

• Class III agents affect potassium (K+) efflux. • Class IV agents affect calcium channels and the

AV node. • Class V agents work by other or unknown

mechanisms.

Class I Antidysrhythmics: • slow rate of spontaneous depolarization of cardiac

cells, thus decreasing automaticity, increasing refractory period, & decreasing susceptibility to escape beats

• Prolong QT interval.• Widen QRS interval: decreased Na+ influx into the

cell decreases conduction velocity and lengthens the QRS interval)

• CLASS I-A (quinidine, procainamide, disopyramide)Not often used today

Class 1c

• Increases blockage of sodium channel • Encainide, Tombocor, Rythmol• severe ventricular dysrhythmias

Class I: Sodium channel blockers

• Disopyramide (Norpace)Flecainide Procainamide Propafenone (Rythmol)Quinidine Tocainide

Beta blockers• Decrease mortality in patients with myocardial

infarction– Decrease infarct size– Decrease ventricular dysrhytmias

• Slow progression of heart failure (HF) and prolong lifespan in patients with HF

• Used in treatment of coronary artery disease, heart failure (HF), & dysrhythmia

Class II Agents: Beta Blockers

• Blockage of beta-1 receptors causes– Decreased force of contraction (- inotrope)– Decreased heart rate (-chronotrope)– Slowed conduction (-dromotrope)

• These 3 mechanisms of action combine to decrease myocardial oxygen demand

• decrease cardiac workload & myocardial oxygen needs

• Treatment of supraventricular tachycardias. They decrease conduction through the AV node.

Side Effects• Angina• Fatigue, nightmares, & slow HR• Males may experience impotence• Patients with asthma or emphysema may not be able to tolerate beta blockers because of an increase in symptoms of shortness

of breath and wheezing• Depression• Weight gain• Assess for cough, fatigue, edema, and other symptoms of

HF• may mask hypoglycemia in diabetics; check blood glucose

frequently• Removed from blood during hemodialysis; hold dose

until treatment finished

Cardioselectivity

• Acebutolol Sectrol• Atenolol Tenormin• Esmolol Brevibloc• Metoprolol Lopressor

Non Cardioselectivity

• Propranolol Inderal• Labetalol normodyne, Trandate (alpha

properties as well)• Carteolol Cartrol• Nadolol Corgard• Pindolol Visken• Timolol Blocadren

Beta Blockers

• Atenolol • Metoprolol • Propranolol • Sotalol • Bisoprolol • Nadolol

Carvedilol Timolol Nadolol Betaxolol Pindolol Labetolol

Calcium Channel Blockers• Block movement of calcium into smooth

muscle cells in vessel walls– Calcium required for muscle contraction;

calcium channel blockers cause relaxation and dilatation of arteries

– By this mechanism, lower BP– Dilate the coronary arteries so also used in

treatment of angina

• Reduce cardiac contractility, PVR, & myocardial O2 needs. Effective on reentrant dysrhythmias that require AV nodal conduction for their continuation

• In contrast to beta blockers, they allow the body to retain adrenergic control of heart rate and contractility.

• Some have a slowing effect on the heart rate and are used in the treatment of arrhythmia

• Used in treatment of hypertension, arrhythmia, and angina

Uses

• Paroxysmal SVT, rate control for a-fib and flutter

• Dilate coronary arteries/decreases BP • Potentiates effects of digoxin• Change position slowly.

Side Effects• Usually go away within a few hours to a day or so and are not said to be

permanent once the medication has "washed out" of the system• Common side effects of these drugs include constipation, dizziness, and

weakness• Swelling of the feet and ankles• Excessive lowering of the blood pressure

– Most common with first dose– Change position slowly

• Rarely an excessively slow heart beat • Worsening of HF• Many calcium channel blockers come in an extended release or sustained

release preparation ( XL, SR) that is convenient for once a day dosing. These tablets should not be cut in half or crushed, as this would affect the rate of drug release into the bloodstream.

Diltiazem (Cardizem)

• Less negative inotropic activity than verapamil• Dilates the coronary arteries

• Treatment of supraventricular arrhythmias

• Oral diltiazem is effective in treatment of reentry tachycardia

• Adverse Effects: fewest adverse effects of this category of drugs Hypotension- AV Block if patient is on Beta Blocker therapy

• Verapamil (Calan, Isoptin): severe hypotension & bradycardia

Calcium Channel Blockers

• Drugs in this class include:

• Nifedipine • Diltiazem • Verapamil • Amlodipine

Felodipine Isradapine Nicardipene Nimodipine Bepridil

ACE Inhibitors (“pril”)

• Used to treat both hypertension and Acute Coronary Syndrome

• Inhibit conversion of angiotension I to angiotension II >>> block release of aldosterone >>> reducing sodium & water retention

ACE Inhibitors• Act to lower the blood pressure

– Dilate blood vessels– Help with cardiac emptying in HF

• Good for patients with heart failure by lowering the net resistance in the vascular bed, thereby facilitating the heart’s task of pumping blood.

Indications

• Mild to severe hypertension• Treatment of heart failure• Given within 48 hours of MI to

prevent ventricular remodeling & development of HF

• Increase survival rate after MI

Side Effects• Hypotension

– have person lie down for 3 hrs after first dose

– temporarily D/C diuretics when starting therapya

– avoid potassium supplements/salt substitutes, diuretics (may cause severe hypotension)

• Hyperkalemia, renal tubular damage

• Cough• Angioedema

• Give one hour before meals• Hold enalapril or lisinopril until after

hemodialysis (both are removed by dialysis)

Ace Inhibitors

• Enalapril Vasotec• Lisinopril Zestril• Captopril Capoten• Quinapril Accupril• Benazopril • Fosinopril

ARBs• Related to ACE inhibitors• Used to treat hypertension• Block the action of angiotensin II to constrict

blood vessels– lower blood pressure– function in a similar way as the ACE

inhibitors, but do not cause the dry, hacking cough that is sometimes associated with ACE inhibitor use.

Angiotensin II Receptor Blockers (ARBs)

• Losartan • Valsartan • Candesartan • Irbesartan

Digitalis • First medication useful in treating

disorders of the heartbeat (1800s)• Digitalis leaf from the foxglove plant• Used to treat atrial fibrillation and heart

failure

Actions• Direct: increases myocardial contractility and CO

– Vagal effect on SA & AV nodes so decreases heart rate– Slows conduction through AV node (positive inotrope, negative

chronotrope and negative dromotrope)

• Indirect– decreases diastolic cardiac size– reduces cardiac wall tension– increases renal Na+ & H2O excretion– decreases peripheral vasoconstriction

•

• Slows HR so used in treatment of atrial fibrillation and atrial flutter– does not suppress or prevent arrhythmias

but only works to slow them down and relieve symptoms

of palpitations• Frequently used in heart failure (HF)

– Reduces frequency of HF exacerbations – Does not reduce mortality from HF

Digitalis Toxicity– anorexia, n & v, visual disturbances– lethargy, bradycardia, heart block,

tachydysrhythmias– Take apical heart rate for one full minute before

administering – Monitor digoxin levels: narrow therapeutic

window: 0.8-2.0 ng/ml– Monitor potassium levels: hypokalemia more

likely to become digtoxic

Drug Interactions

• Decreased digoxin absorption with antacids & laxatives

• Decreased digoxin effect: metoclopramide, aminoglycosides, thyroid supplements

• Increased digoxin effect Amphotericin B, corticosteroids, non-potassium-sparing diuretics, amiodarone

Digoxin Fab (Digibind)• Used for life-threatening digoxin toxicity

• Mechanism: antibody complex formation to digoxin

• Adverse Events– exacerbation of heart failure or a-fib due to withdrawal of

digoxin– potential for complex dissociation with repeat toxicity in end-

stage renal disease– digoxin levels meaningless for 7 days post Digibind use.

Nitrates

• Vasodilator: increases coronary blood flow by dilating coronary arteries and improving blood flow to ischemic regions of the heart– Decreases preload by dilating peripheral veins– Decreases afterload– Decreases myocardial oxygen demand to decrease

angina

• Used for angina, hypertension, MI• Used in heart failure to diminish symptoms

of shortness of breath• Do not reduce mortality in coronary artery

disease or heart failure. Their use is principally for symptom relief.

Short-acting: Nitroglycerin

• For acute anginal attacks. SL dosage (0.4mg):· Instruct patient to lie down· Repeat at 5 minute intervals; if pain not

relieved, up to 3 tablets· If anginal pain persists after 3 doses, go to ED· Stay with patient and monitor VS (esp. BP)· Headache & hypotension are major side effects

Long-acting Nitrates: Isordil, nitroglycerin ointment, nitroglycerin

transdermal patch

• Ointment: use appropriate application paper; don’t “rub in”

• Rotate sites (remove old patch, ointments)

• Avoid contact with skin

Nitrate-free periods (6 – 10 hrs/ 24 hr period) to prevent tolerance

Remove patch before defibrillating as patch may explode

Side Effects

• Hypotension, diaphoresis, nausea• Tachy- and bradydysrhythmias• Headache; reflex tachycardia

Drug Interactions

• Sympathomimetics, thyroid hormones, nicotine

• All increase cardiac workload so counteract NTG effects

Nitrates

• Drugs in this class include: • Isosorbide Dinitrate • Isosorbide Mononitrate

Amiodarone• Principal effect on cardiac tissue to increase time for cell to repolarize • Mainly block potassium channels, thereby prolonging

repolarization.• Do not affect the sodium channel so conduction velocity is

not decreased• Used to treat atrial arrhythmias (atrial fibrillation and atrial

flutter) as well as ventricular arrhythmias (ventricular fibrillation

• Prevent re-entrant arrhythmias• results in "chemical antifibrillatory" action

Side Effects

• Pulmonary fibrosis• Abnormal thyroid function• Photophobia,• Nausea, vomiting• Blue-gray skin color• Seeing halos around objects

• May take over 3 weeks to work; half-life about 50 days

• Monitor with patients in HF and elderly for decreased BP and pulse

• Assess for fluid retention

• Have patient swallow whole• Do not stop abruptly• Take one hour before meals or 2 hours after

meals• High fat meals elevate levels• Use sunscreens and sunglasses when outside

Drug Interactions

• Anticoagulants increase anticoagulation• Increased digoxin effects• Avoid grapefruit juice as it will increase serum

levels causing hypotension

Class III — Potassium Channel Blockers

• Amiodarone (Cordarone)

• Dofetilide (Tikosyn)

• Ibutilide (Corvert)

So How Does This Relate to My Patients? HTN

• Goal – Two primary regulatory factors

• Blood flow (volume) • Peripheral Vascular Resistance (PVR)

– Primary groups of drugs are used: • Diuretics • Adrenergic inhibitors (Beta-blockers) • Vasodilators • ACE inhibitors

• Calcium antagonists

Pharmacologic Treatment

• For patients with systolic dysfunction (ejection fraction <40%) – Angiotensin-converting enzyme (ACE) inhibitors

for all patients – Beta blockers for all patients except

• Hemodynamic instability or• Dyspnea at rest with signs of

congestion

–Aldosterone antagonist (ACE inhibitor or ARB) for those with• dyspnea at rest or• symptomatic patients who have suffered

a recent myocardial infarction • ARB as a substitute for patients intolerant

of ACE inhibitors

• Digoxin only for patients who remain symptomatic despite treatment with– Diuretics, ACE inhibitors, and beta blockers– or for those in atrial fibrillation – Diuretics for symptomatic patients to maintain

appropriate fluid balance .

• HF patients on multiple medications are at a risk of potential drug interactions and side effects– risk of hyperkalemia is increased with renal

insufficiency treated with an aldosterone antagonist and an ACE inhibitor.

Goals for Mgt of Heart Disease

• Maximize blood flow to heart muscle • Maximize preload & minimize afterload • Maximize cardiac contractility (inotropic

effect)

• Reduce chances of clot formation • Reduce overall blood volume if overload • Maintain heart rate between 60-80 beats/min

to maximize cardiac output and filling pressures

What Drugs Help to Meet these Goals?

• Maximize preload I.V. fluids, volume expanders

• Minimize afterloadACE inhibitors • Maximize cardiac contractility Digoxin, Dopamine • Decrease preload, inc coronary circulation & reduce pulmonary congestion Nitrates

What Drugs Help to Meet these Goals (cont’d)?

• Reduce chances of ASA or other anti-platelet clot formation agents • Reduce fluid volume overload Diuretics

• Keep heart rate btw Beta blockers & 60-80/min Calcium-channel blockers • Dysrhythmias Antidysrhytmics

Treatment Goals for HF

– Relieve symptoms & improve quality of life – Prevent readmission to hospital, and/or recurrent

ischemic events – Reduce mortality – Medications used:

• ACE Inhibitors • Beta Blockers • Diuretics • Vasodilators • Digitalis

ACE Inhibitors

• Increase lifespan of patients with heart failure

• Effects on blood vessels that seem to counteract the process of atherosclerosis and have been shown to reduce heart attack, stroke, and mortality in CAD

Beta-Blockers

• Lower blood pressure & slow heart rate (including protection against arrhythmias)

• Helps lower risk of stroke and heart attacks

Nitrates

• Used to treat angina • Vasodilates and

stops chest pain by increasing myocardial oxygen supply & decreasing demand

Antidysrhythmic Drugs

• Used to bring under control abnormal rhythms of the heart (including atrial fibrillation), so the heart can pump more effectively

Antihypertensives

• Used to control BP & risk of stroke & MI• Categories

– ACE Inhibitors– Beta-Blockers– Calcium-Channel Blockers

Managing the Cost

• Patients may be taking two to four drugs to

manage cardiac condition – in addition to meds for other health

issues such as diabetes

– Med treatment for a chronic condition becomes expensive with each drug added

• Even with worsening condition some people try to limit costs– May or may not ask which can be decreased or

stopped

• Best if medication regimen is kept simple so patients without insurance can purchase generic versions without rationing their doses.

Refill Red Tape

• Patients and HCPs often face red tape when it comes to refills and preapproved status.

• If desired med is not on insurance company's preferred list– Must complete preauthorization form– Also must talk with insurance company about why

that particular medication is needed

• Patients receiving non-formulary drugs often pay more– May only be able to get partially filled

prescriptions– Providers should seek generic or less

expensive alternatives whenever possible

Simple Steps: Lifestyle Changes

• Decrease sodium intake

• Exercise & weight loss

Preload or Afterload?Arterial vasoconstriction

BP 190/124

Administration of hydralazine or nitroprusside

Administration of Nitroglycerin

Diuretic therapy

Arterial vasodilation

• List some positive and negative aspects to the administration of beta blockers

• The desired effect from the use of diuretics in the patient with acute left ventricular failure is to …

• List some medications that decrease myocardial contractility

• What are some of the signs & symptoms of left sided heart failure?

• Your patient on digoxin has a morning heart rate of 56 BPM and is supposed to be discharged today. Your first priority is to…

• What are some positive and negative aspects related to Nitroglycerin administration?

A patient with a dysrhythmia is placed on digoxin and metoprolol (Lopressor). Because of the combined effects of these drugs, what area(s) need to be the most closely monitored?