6. CV Pharmacology
Autonomic Cardiovascular Innervation
In order to have a better understanding of how cardiovascular drugs work, a brief review of how
the heart and circulation are regulated by the autonomic nervous system is needed. The
autonomic nervous system is composed of two branches; the sympathetic nervous system (SNS)
and the parasympathetic nervous system (PNS). The SNS and the PNS normally work together
to help maintain homeostasis in the body, including the cardiovascular system.
The fibers of the sympathetic nervous system affect the organs and tissues in which they are
located in by releasing norepinephrine (noradrenalin). These fibers are known as adrenergic
fibers in reference to their relationship to norepinephrine.
Some drugs are known as sympathomimetics because they mime or mimic the actions of the
sympathetic nervous system. These drugs may also be known as adrenergic agents because they
have the effects that stimulate the adrenergic fibers.
The sympathetic nervous system innervates all chambers of the heart. Sympathetic stimulation
(the “fight or flight” response) results in peripheral vasoconstriction, an increase in heart rate,
faster speed of electrical impulses conducted through the heart (conductivity), and an increase in
the strength with which the heart pumps blood (contractility).
While fibers of the parasympathetic nervous system do exist in both the atria and the ventricles,
they have a pronounced effect on the atria, while causing a minimal effect on the ventricles. The
fibers of the parasympathetic nervous system affect the organs and tissues that they innervate by
releasing acetylcholine. These fibers are known as cholinergic fibers in reference to their
relationship to acetylcholine. Parasympathetic stimulation results in a decrease in heart rate, a
slowing of electrical conduction through the AV node, and a mild decrease in the pumping action
of the ventricles.
Properties of Cardiac Cells
Automaticity is the ability of the cardiac pacemaker cells to spontaneously initiate an electrical
impulse without being stimulated from another source such as a nerve.
Excitability is the ability of the cardiac cells to respond to an external stimulus, such as from a
chemical, mechanical, or electrical source.
Conductivity is the ability of the cardiac cell to receive an electrical stimulus and conduct the
impulse to another cardiac cell. The conduction can be altered by factors such as sympathetic or
parasympathetic stimulation, cardiac muscle damage, electrolyte imbalances and medications.
Contractility is the ability of the cardiac cell to contract in response to an electrical stimulus.
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7. CV Pharmacology
The Adrenergic Receptor System
Adrenergic receptors are sites located within cell membranes that are sensitive to the
catecholamines, epinephrine and norepinephrine, as well as other sympathomimetic agents.
When an adrenergic agent reaches the adrenergic receptor site, it selectively changes the
permeability of the cell to various ions, thus causing the cell to react. This reaction is known as a
sympathetic response, since it is caused by the sympathetic nervous system, or a drug that
mimics it (sympathomimetic).
Adrenergic receptors are known by different names depending on where they are located, what
their primary action is, and which agents they respond to. Drugs that stimulate adrenergic
receptors are known as adrenergic agonists, while drugs that block the effect of adrenergic
stimulation are known as adrenergic antagonists.
Alpha (α)
Alpha (α) receptors are most abundant in the peripheral arteries and veins, although some αreceptors are located in the coronary arteries. Stimulation of α-receptors results in a
vasoconstrictive response which increases blood pressure and afterload (the force the ventricles
must push against to pump blood into the aorta and pulmonary vasculature).
Beta (β)
Beta (β) receptors are divided into cardiac (β1) and non-cardiac (β2) receptors. The β1 receptors
are located within the heart. Stimulation of the β1 receptors are responsible for the cardiac
effects caused by the sympathetic nervous system, such as increased heart rate, increased
conductivity, and increased strength of myocardial contraction. Stimulation of the β2 receptors
results in dilation of the peripheral arteries and dilation of the bronchial system in the lungs.
Dopaminergic
Dopaminergic receptors are located within the blood vessels of the kidneys, intestines, heart, and
brain. Stimulation of the dopaminergic receptors has a vasodilatory effect in these blood vessels,
increasing blood flow to those organs.
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8. CV Pharmacology
Check Yourself Pop Quiz
Match the definitions at the bottom with the terms at the top.
1.
Conductivity
2.
afterload
3.
Contractility
4.
alpha effect
5.
Norepinephrine
6.
parasympathetic stimulation
7.
alpha agonist
8.
alpha antagonist
9.
1 stimulant effects
10.
2 stimulant effects
a) The force the ventricles must push against to pump blood into the aorta and pulmonary
vasculature.
b) Blocks effects of adrenergic stimulation.
c) Dilation of peripheral arteries and the pulmonary bronchial system.
d) Faster speed of electrical impulses through the heart.
e) Vasoconstriction.
f) Stimulates adrenergic receptors.
g) Increased myocardial contraction and conductivity.
h) Refers to the strength with which the heart pumps blood.
i) Decreased AV node conductivity and myocardial contraction.
j) Drug released by the sympathetic nervous system.
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9. CV Pharmacology
Check Yourself Pop Quiz - Answers
1. d
2. a
3. h
4. e
5. j
6. i
7. f
8. b
9. g
10. c
Refer to previous section as a review for any incorrect answers. Reviewing
your incorrect answers will benefit your learning as you proceed in this
packet.
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10. CV Pharmacology
Oxygen
Oxygen is present in the air all around us at a concentration of approximately 21%, but it is
considered a drug. In fact, it is the most important drug contained in the ACLS protocols. All
tissues within the body require oxygen and will begin to suffer damage if deprived for more than
several minutes. The practice of cardiovascular medicine revolves around assuring the proper
balance between oxygen supply and demand throughout the body. Regardless of any other
actions taken during cardiovascular emergencies, if efforts fail to assure an adequate oxygen
supply, other efforts will be wasted.
Indications
Supplemental oxygen is indicated for patients who are experiencing acute chest pain regardless
of the cardiac cause. It is also used for patients with either demonstrated or suspected
hypoxemia, since this may lead to metabolic acidosis. In addition, oxygen is used in all cases
where CPR must be implemented. The best CPR you can provide only yields about 25-30% of
the normal cardiac output. Since blood flow is diminished, one way to prevent tissue damage is
to increase the oxygenation of the blood flow that you are providing.
Administration
Supplemental oxygen is given in a wide variety of doses and delivered in a number of ways
depending on the patient’s particular need.
Low Flow
Low flow oxygen systems include nasal cannulas, simple face masks, nonrebreathing masks, and
partial rebreathing masks. While partial rebreathing masks provide an oxygen concentration of
24-60%, nonrebreathing masks can provide an oxygen concentration between 55-95%.
Regardless of the concentration (%), low flow systems do NOT supply sufficient gas volume to
meet the patient’s needs. Therefore the patient must be able to inhale a sufficient amount of
room air along with the oxygen provided. Additionally, as the patient’s breathing pattern
changes, the oxygen concentration provided to the patient may need to be reassessed and
appropriately modified.
High Flow
High flow oxygen systems provide a high volume of gas that is sufficient to meet the patient’s
inspiratory need without inhaling additional room air. They supply a more accurate
concentration (%) of oxygen. The venturi mask is the most common high flow system, and
supplies oxygen at a rate of 24-40%.
Use of the Bag-Valve-Mask Devices
In a cardiac arrest, oxygen is delivered at a concentration of approximately 100% utilizing a bagvalve-mask (BVM) device. This concentration is used even in patients with chronic lung disease
(such as COPD) until the resuscitation is over.
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11. CV Pharmacology
Review of Antidysrhythmics
Antidysrhythmic drugs work by affecting the action potential (AP) of the myocardial cells. To
understand how antidysrhythmic drugs affect the heart, one must be familiar with the action
potential curve and its reflection of the cardiac cycle.
An action potential curve refers to the electrical changes in the myocardial cell during the
depolarization and the repolarization cycle. This activity can be compared to ourselves as we
work and rest. In the heart, the working period is the depolarization cycle (systole), and the
resting period is the repolarization cycle (diastole). These electrical charges are a result of
specific ions (sodium, potassium, and calcium) that shift between the myocardial cell and the
extracellular fluid via the sodium-potassium pump mechanism. The end result is the myocardial
electrical activity known as the cardiac cycle (depolarization-repolarization phases) observable
on the cardiac monitor or 12-lead EKG. The term “Refractory” is used to describe the extent to
which a cell is able to respond to a stimulus.
Absolute Refractory Period - During this period the cells cannot respond to any stimulus,
regardless of strength. This period corresponds with the onset of the QRS complex to the peak
of the T-wave. It is identified on the AP curve as phases 0, 1, 2, and the first half of phase 3.
Relative Refractory Period – This is the vulnerable period in which a strong stimulus may
produce ectopic depolarization. This period corresponds with the last half of the T-wave, and is
identified on the AP as the last half of phase 3 and phase 4.
The following chart briefly explains the different phases of the action potential.
R
Action Potential
T
Q
S
ECG
MV
0
1
2
Inside Cell
0
3
4
4
100
↓K
↑ Na
Cell Membrane
↑ Ca
↓K & ↓ Na
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Outside Cell
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12. CV Pharmacology
AP Phase
Phase 0
Rapid
Depolarization
Phase 1
Peak Phase
Phase 2
Plateau Phase
Response
ECG Waveform
The initial upswing indicates rapid depolarization
by the influx of sodium into the myocardial cell.
Potassium begins exiting cells.
QRS
This peak reflects the brief period that sodium
channels close.
Absolute Refractory Period
QRS
Absolute Refractory Period
Phase 4
Resting Phase
QRS
This rapid downswing marks the closure of sodium
and calcium channels to prevent any further entry
of sodium or calcium into the cell.
Potassium begins to move back into the cell.
Phase 3
Beginning
Repolarization
Phase
Calcium channels open for a slow influx of calcium
ions to prolong depolarization.
Calcium plays a key role in myocardial contraction.
QRS and first half of T wave
Absolute refractory period until
midpoint of T wave, then becomes
relative refractory period, the last
half of T-wave.
The cell is now ready for another depolarization
stimulus.
Last half of T wave as it returns to
isoelectric line
Absolute Refractory Period
Absolute Refractory Period
Relative Refractory Period
Relative Refractory Period
Keep in mind the ECG only represents electrical heart activity, not the actual contraction
of the heart.
Based on these previously mentioned principles, antidysrhythmic drugs are designed to modify
the movement of ions in the various AP phases by altering the electrophysiology of the cardiac
cell. Based on this principle, antidysrhythmics are classified based on their mechanisms of
action and effects on the action potential.
Currently there are four main classes of antidysrhythmics. The classification system (VaughanWilliams) can assist you in recalling the actions and adverse effects.
Class I - - Block sodium ion channel
o
Class Ia
o
Class Ib
o
Class Ic
Class II (beta-blockers) - Block beta receptors
Class III - Block potassium ion channels
Class IV (calcium channel blockers) - Block calcium ion channels
In general, drugs within the same class are similar in action and adverse effects and some drugs
may have properties of more than one class category. (Example: amiodarone, sotalol). It is also
important to note that all antidysrhythmics have the potential (some worse than others) to
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15. CV Pharmacology
General Rules
The QTI is normal if it is less than half of the R-R interval
The QTI is prolonged if it is more than half of the R-R interval
The QTI is borderline if it is approximately half of the R-R interval
(Remember, this rule applies to a regular HR in the normal range of 60-100)
A QTc > 0.44 is considered prolonged
Normal QT Intervals Corrected for given Heart Rate = (QTc)
Heart Rate/minute
R-R Interval/sec
QTC
40
1.5
0.41-0.51
50
1.2
0.38-0.46
60
1.0
0.35-0.43
70
0.86
0.33-0.41
80
0.75
0.32-0.39
90
0.67
0.30-0.36
100
0.60
0.28-0.34
120
0.50
0.26-0.32
150
0.40
0.23-0.28
180
0.33
0.21-0.25
200
0.30
0.20-0.24
Recommended Actions:
Remember to treat the patient not the monitor. Evaluate all the assessment data.
Record the QTI and the QTC as part of the routine documentation on patients in critical care
and telemetry monitoring areas.
Identify conditions and drugs associated with a prolonged QT interval, and increase
frequency in documenting the QTI/QTC. Example- a QTI/QTC on a patient receiving
procainamide should be measured q 4 hours and prn. This strip documentation is to include
the drug that patient is receiving.
Notify the appropriate person immediately (i.e. physician, nurse, charge nurse) if changes are
observed.
Documentation, continued assessment, and report to next shift.
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17. CV Pharmacology
Class I Antidysrhythmics
This class decreases the influx of sodium during phase 0 of depolarization. These drugs alter the
absolute refractory period to decrease the risk of premature impulses from ectopic foci. Class I
drugs also depress automaticity by slowing the rate of spontaneous depolarization of pacemaker
cells. This class of antidysrhythmics is further broken down into subclasses Ia, Ib and Ic,
depending on specific actions.
Class Ia
Blocks sodium to depress conductivity and prolong the refractory
period of the heart. These drugs are potent sodium channel
blockers (prolong QRS interval), and may prolong repolarization
(prolong QT interval) through blockade of potassium channels.
Examples of Drugs:
Indications
quinidine
disopyramide (Norpace)
procainamide (Pronestyl)
These antidysrhythmics are used to treat atrial dysrhythmias,
premature ventricular complexes, and ventricular tachycardia.
Procainamide ( Pronestyl) is available in both oral and intravenous forms. When used as an
intravenous bolus in the ACLS algorithm, it must be given no faster than 30mg/minute.
Indications that procainamide must be stopped:
Termination of the dysrhythmia
Hypotension
Reaching a total dose of 17 mg/kg
Widening of the QRS complex by 50%, which indicates slowing of electrical
conduction within the heart.
Precautions
Procainamide serum levels should be monitored in patients with renal failure or receiving
constant infusion.
All class I drugs depress myocardial contractility resulting in a lower cardiac output,
which may lead to profound hypotension.
Class Ia agents can prolong the QRS and QT intervals putting the patient at risk for
ventricular dysrhythmias such as ventricular tachycardia or torsades de pointes. This risk
is increased in patients with hypokalemia or hypomagnesemia. Consequently, it is
important to monitor the patient and the QTI or QTc intervals.
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19. CV Pharmacology
Antidysrhythmics: Class II
Class II antidysrhythmics are beta-blockers. They act indirectly on electrophysiological
parameters by blocking beta-adrenergic receptors (slow sinus rate, prolong the PR interval, with
no effect on QRS or QT intervals).
Beta-blockers compete for receptor sites with one’s naturally
occurring catecholamines such as epinephrine and
norepinephrine.
Examples of Drugs:
metoprolol (Lopressor)
The beta-blockers that are chosen for antidysrhythmic therapy esmolol (Brevibloc)
have a potent antidysrhythmic effect to inhibit dysrhythmias that
result from the increased irritability and automaticity caused by atenolol (Tenormin)
the sympathetic nervous system. Although their actions depend propanolol (Inderal)
on which catecholamine receptor (β1 versus β2) they block, these
drugs will have effects that are directly opposite to catecholamines by decreasing automaticity,
heart rate, conductivity, contractility, stroke volume, cardiac output and blood pressure and
myocardial workload.
Indications
Beta-blockers are used for rate control of sinus tachycardia, SVT, atrial tachycardia, and atrial
fibrillation. The early use of beta-blockers in Acute Myocardial Infraction (AMI) patients
reduces the likelihood of ventricular arrhythmias, recurrent ischemia, and reinfarction, thereby
decreasing mortality.
Precautions
Beta-blockers may precipitate hypotension, bradycardia, and heart failure, as well as
mask signs of hyperthyroidism and hypoglycemia.
During IV administration, carefully monitor BP, heart rate, and ECG due to their
mechanism of action.
Beta-blockers are used with extreme caution in patients with asthma and COPD because
they may lead to bronchospasms when non-selective beta-blockers interfere with the
stimulation of β2 receptors in the bronchial system.
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20. CV Pharmacology
Antidysrhythmics: Class III
Class III drugs prolong repolarization (phase 3) by preventing any further entry of sodium or
calcium into the cell. Potassium begins to move back into the cell.
Class III drugs are further known as either mixed or pure
class III. For example, although amiodarone is generally
prescribed because of its class III properties, it exhibits
electrophysiological characteristics of each of the other
classes of antidysrhythmics. Whereas sotalol combines the
class III property of prolonging the refractory period with
the beneficial beta-blocking effects of class II drugs. Strict
monitoring of the QTI/ QTc is essential for drugs within
this class.
Examples of Drugs:
Pure class III: ibutilide (Corvert),
dofetilide (Tikosyn)
Mixed class III: amiodarone
(Cordarone), sotalol (Betapace
and Betapace AF)
Amiodarone (Cordarone)
Amiodarone is an ACLS drug used for control of rapid ventricular rate due to an accessory
pathway conduction in pre-excited atrial arrhythmias; after defibrillation and epinephrine in
cardiac arrest with persistent ventricular tachycardia (VT) or ventricular fibrillation (VF); and
control of hemodynamically stable VT, polymorphic VT, or wide-complex tachycardia of
uncertain origin.
Dofetilide (Tikosyn®)
Dofetilide (Tikosyn) is indicated for the conversion of atrial fibrillation or atrial flutter to sinus
rhythm. It is also used to maintain sinus rhythm in patients with atrial fibrillation or atrial flutter.
Only prescribers (physicians, nurse practitioners, physician assistants) who have received
specialized training can prescribe dofetilide. Likewise, hospital pharmacists and nurses must
have received education prior to dispensing and administering this drug .
Therapy must be initiated in a hospital setting so the patient can be monitored for dysrhythmias.
Careful monitoring of serum potassium,magnesium, and renal function must be done for patients
receiving dofetilide.
Additionally, a baseline QTC interval must be measured and dofetilide is not be administered if
the baseline QTc is greater than 440 msec (>0.44) or greater than 500 msec (>0.50) in patients
with ventricular conduction abnormalities. An increase in the QTc measurement of greater than
15% over baseline or greater than 500 msec (0.50) necessitates either a dosage reduction or
discontinuation of dofetilide. Contact the cardiologist immediately if adverse signs occur.
ECG monitoring is continuous during the initial dosing period with strict measurement and
documentation of the QTc and patient tolerance. After a minimum three-day hospital stay with
dose adjustment, the patient can be discharged home with a 7-day supply of medication. It is
recommended that nursing collaborate with the hospital pharmacy for discharge planning.
Sotalol (Betapace®, Betapace AF®)
Sotalol is used for the treatment of documented ventricular arrhythmias (i.e. sustained ventricular
tachycardia) that in the judgment of the physician are life-threatening, and for maintenance of
normal sinus rhythm in patients with symptomatic atrial fibrillation or atrial flutter. Betapace
AF® is a modified version of Betapace, with specific manufacturer instructions that states
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22. CV Pharmacology
Antidysrhythmics: Class IV
Calcium is critical to heart function due to its effect on cardiac output by increasing contractility
and conductivity. Calcium channel blockers decrease contractility of the myocardium and slow
conduction through the SA and AV nodes by inhibiting the influx of calcium and sodium during
phase 2 of the action potential. These actions result in prolonging both the absolute and relative
refractory periods. Drugs in this class also produce vasodilation of the peripheral and coronary
arteries, thereby increasing the supply of oxygenated blood to the myocardium and reducing
myocardial workload to reduce myocardial oxygen demand.
Calcium channel blocker categories
Two types of calcium channel blockers exist because they exert different effects.
Calcuim channel blockers known as (nondihydropyridines): cause coronary artery
vasodilation, decrease heart rate, and decrease conduction through the SA and AV nodes. They
are utilized to treat atrial dysrhythmias, angina, and hypertension.
Diltiazem (Cardizem, Dilacor XR, Tiazac) verapamil (Calan, Isoptin, Verelan PM)
Calcuim channel blockers known as (dihydropyridines): dilate peripheral blood vessels
without affecting heart rate or contractility. They are utilized to manage hypertension and will
be discussed later in this SLP.
Nifedipine (Procardia, Adalat), amlodipine (Norvasc), felodipine (Plendil), isradipine
(DynaCirc), nicardipine (Cardene), and nisoldipine (Sular)
The following page has a summary chart on the actions and indications for calcium channel
blockers.
Precautions
Short acting nifedipine capsules (Procardia®, Adalat®) are not recommended for acute
blood pressure reduction nor for chronic hypertension management due to risk of
profound hypotension, cerebral ischemia or stroke, and/or death.
Nifedipine should NEVER be administered sublingually or as a “bite and swallow” order.
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23. CV Pharmacology
Summary chart of calcium channel blocker actions and indications
Calcium Channel Blockers Actions
Potent vasodilator of coronary vessels. This effect
increases coronary blood flow, and reduces coronary
vasospasm.
Vasodilator of peripheral vessels. Vasodilation occurs
predominantly in arterioles; there is no significant effect on
venous beds. Dihydropyridine agents reduce peripheral
resistance and afterload.
Indications
Angina
Hypertension
Negative inotropic effect. Nondihydropyridine agents cause
a modest decrease in contractility and reduction of myocardial
oxygen consumption. This effect is used to depress the
frequency of hyperactive tissue causing arrhythmias.
Supraventricular
Dysrhythmias
Angina
Negative chronotropic effect. Nondihydropyridine agents
cause a modest lowering of heart rate. This effect is due to
slowing of the SA node and results in reduced myocardial
oxygen consumption.
Supraventricular
Dysrhythmias
Angina
Negative dromotropic effect. By slowing conduction through
the AV node, nondihydropyridine agents increase the time
needed for each beat. This results in reduced myocardial
oxygen consumption.
Supraventricular
Dysrhythmias
Angina
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24. CV Pharmacology
Miscellaneous Antidysrhythmics
Adenosine (Adenocard)
Adenosine interrupts electrical conduction in the AV nodal reentry pathways making it effective
against supraventricular tachyarrhythmias and narrow complex tachyarrhythmias of unknown
origin. A rapid IV push bolus of adenosine causes complete depolarization of the myocardium,
resulting in a brief asystolic period that allows the heart's electrical activity to "reset" and return
to sinus rhythm. Because of this action, administration of adenosine is often referred to as a
"chemical cardioversion.”
Indications
Generally slow the rhythm down sufficiently to allow for correct interpretation of atrial
fibrillation or atrial flutter so that appropriate intervention may be made.
Precautions
Adenosine can induce a brief period of asystole, of 6-10 seconds. It is vital to have emergency
resuscitation equipment readily available.
Magnesium
Magnesium is essential for the functioning of the sodium-potassium pump to drive myocardial
electrical activity. A low serum magnesium level slows the return of potassium into the cell
during phase 4 of the action potential, resulting in a prolonged relative refractory period and QT
interval. Patients with a magnesium deficiency commonly have a high incidence of cardiac
dysrhythmias, including torsades de pointes (TdP) and sudden cardiac death.
Precautions
IV administration can cause hypotension and circulatory collapse if given too fast.
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25. CV Pharmacology
Check Yourself Pop Quiz
Match the definitions at the bottom with the terms at the top.
1. ________ Magnesium
2. ________ Class III
3. ________ Amiodarone
4. ________ Proarrythmic
5. ________ Class IV
6. ________ Class II
7. ________ Sotalol
8. ________ Dofetilide
9. ________ Absolute Refractory Period
10. ________ Relative Refractory Period
a) A drug class known to decrease the heart rate, conductivity, contractility.
b) A drug class which decreases contractility and slows conduction though the SA and AV
nodes.
c) Time frame when cardiac cells cannot respond to any stimulus from ectopic sources,
corresponds with the QRS and first half of the T wave.
d) Treatment of choice for the dysrhythmia torsades de pointes.
e) A mixed class III drug that is to be avoided with beta-blocker drugs.
f) A class III drug used to convert recent onset atrial fibrillation to sinus rhythm. Healthcare
providers must be inserviced prior to providing this agent.
g) Indicated in emergency therapy for ventricular tachycardia or ventricular fibrillation. may
also be used for PVC’s.
h) Describes a drug that may induce additional dysrhythmias.
i) A strong stimulus may produce ectopic depolarization in the cardiac cells. Corresponds with
the last half of the T-wave.
j) Strict monitoring of the QTI/QTc is essential for drugs within this class.
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26. CV Pharmacology
Check Yourself Pop Quiz -Answers
1.
d
2.
j
3.
g
4.
h
5.
b
6.
a
7.
e
8.
f
9.
c
10. i
Refer to previous section as a review for any incorrect answers. Reviewing
your incorrect answers will benefit your learning as you proceed in this
packet.
2010 Orlando Health Education & Development
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27. CV Pharmacology
Antihypertensives
Angiotensin Converting Enzyme (ACE) Inhibitors
Before discussing the ACE inhibitors, let us take a moment to review the renin-angiotensin
system. Renin is formed in the renal juxtaglomerular cells in response to certain types of stimuli.
These stimuli include salt depletion, β2 stimulation,
and a decrease in renal perfusion that might be found Examples of Drugs:
in hypotension or hypovolemia. Next, renin mediates
Capoten® (captopril), Vasotec®
the formation of angiotensin-I in the liver. When
(enalapril), Monopril® (fosinopril),
angiotensin-I reaches the lungs, it is converted by the
Lotensin® (benazepril), Mavik®
angiotensin converting enzyme into angiotensin-II. (trandolapril), Accupril® (quinapril),
Angiotensin-II causes vasoconstriction, promotes the Aceon® (perindopril), Prinivil®,
release of norepinephrine, and stimulates aldosterone Zestril® (lisinopril), Altace® (ramipril),
production resulting in sodium and water retention. Univasc® (moexipril)
Additional effects of angiotensin-II include increased
systemic vascular resistance, arterial blood pressure, and intravascular volume.
ACE inhibitor drugs work by blocking the angiotensin converting enzyme in the lungs so
angiotensin-I is prevented from being converted to angiotensin-II. The outcome is a decrease in
norepinephrine levels, prevention of systemic vasoconstriction and decreased blood pressure.
Furthermore, aldosterone production is no longer stimulated by Angiotensin II, which results in
decreased intravascular volume.
Indications
ACE inhibitors are used in the management of hypertension either alone or in combination with
other anti-hypertensive classes and also for patients with type 1 diabetes mellitus to slow the
progression of diabetic nephropathy.
Precautions
Due to their mechanism of action, ACE inhibitors may cause hypotension or symptoms
related to hypotension, such as dizziness and syncope.
It is important to understand that a number of patients who take ACE inhibitor drugs
develop a persistent nonproductive cough. Patients are to be cautioned about these effects
prior to initiating ACE inhibitor therapy.
ACE inhibitor therapy may compromise renal function and result in transient increases in
BUN and creatinine.
Angiotensin II Receptor Blockers (ARBs)
Angiotensin receptor blockade is a newer method of
renin-angiotensin blockade. Unlike the ACE inhibitor
drugs, they do not prevent the formation of
angiotensin-II. Instead, they bind to receptor sites to
prevent the effects of angiotensin-II. This results in a
decrease in norepinephrine levels, prevention of
2010 Orlando Health Education & Development
Examples of Drugs:
Cozaar® (losartan), Diovan®
(valsartan), Atacand® (candesartan),
Benicar® (olmesartan), Avapro®
(irbesartan), Micardis® (telmisartan),
Teveten® (eprosartan)
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29. CV Pharmacology
Beta-Adrenergic Blockers
Beta-blockers inhibit the response to adrenergic stimuli by competitively blocking beta-1
adrenergic receptors within the myocardium and by blocking beta-2 adrenergic receptors within
the bronchial and vascular smooth muscle. Some betaExamples of Drugs:
blockers are specific for beta-1 receptors (atenolol,
metoprolol, betaxolol, bisoprolol, esmolol). However, Lopressor®, Toprol-XL®
®
beta-1 selectivity is dose-dependent and is not seen (metoprolol), Coreg (carvedilol),
®
and Tenormin (atenolol). Zebeta®
with high doses of beta-1 selective drugs.
Indications
Used for hypertension, angina, MI’s, and heart failure,
dysrhythmias and rate control.
(bisoprolol),Inderal ®
(propranolol), Brevibloc®
(esmolol), Trandate® (labetalol),
Corgard® (nadolol)
Precautions
Beta-blockers may precipitate hypotension and bradycardia.
Oral beta-blocker therapy should not be withdrawn abruptly (particularly in patients with
CAD), but gradually tapered to avoid acute tachycardia, hypertension, and/or ischemia.
Concurrent use of beta-blockers, or the calcium channel blockers verapamil and diltiazem
because bradycardia or heart block can occur.
Beta-blockers should be avoided in patients with asthma and COPD because they may
lead to bronchospasm when non-selective beta-blockers interfere with the stimulation of
beta-2 receptors in the bronchial system.
Likewise, cautious use is indicated in diabetics because they can mask prominent
hypoglycemic symptoms.
Fenoldopam (Corlopam)
Fenoldopam is a rapid acting vasodilator because of its dopamine agonist properties. It is used as
an antihypertensive with the added bonus effects of natriuresis, sodium excretion, and improved
renal blood flow.
Indications
Used for short-term management of severe or malignant hypertension when rapid reduction of
blood pressure is needed.
Precautions
Due to its potent and rapid acting hypotensive properties, frequent blood pressure
monitoring is necessary.
Please review your institution’s policy regarding patient placement in an appropriate
telemetry unit.
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Sodium Nitroprusside (Nipride, Nitropress)
Sodium nitroprusside (Nipride) is a potent, fast acting drug producing vasodilation of both the
arteries and the veins. This action results in decreasing afterload by reducing systemic vascular
resistance and arterial blood pressure, and decreasing preload by increasing venous capacitance
and reducing blood return to the heart. The preload and afterload reduction results in both
decreased myocardial workload and myocardial oxygen demand. Nipride is used to managed
hypertensive crises and control blood pressure in patients after vascular surgeries,
coronary bypass surgery, dissecting aortic aneurysm.
Precautions
Sodium nitroprusside has a rapid onset and short duration of action making it very easy to
titrate. The effects of this drug are observed almost immediately and disappear within a
few minutes after it is discontinued.
Sodium nitroprusside has the potential to cause severe hypotension that can lead to
myocardial ischemia, myocardial infarction, or stroke. Patients must be monitored closely
during initiation and titration. Due to its short duration, discontinuing the drug and
elevating the patient’s legs should be sufficient to return arterial blood pressure to prior
levels within several minutes.
Cyanide is produced which is converted to thiocyanate in the liver and thiocyanate is
eliminated mainly in the urine. Patients receiving high doses and/or prolonged infusions
of nitroprusside, are at risk for cyanide and/or thiocyanate toxicity.
Clinical note: The patient is to be observed continuously for signs of cyanide toxicity,
which include metabolic acidosis (may be the earliest sign of toxicity), nausea, tinnitus,
blurred vision, changes in mental status, hyperreflexia, twitching, and seizures
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31. CV Pharmacology
Vasodilators
Nitroglycerin
Nitroglycerin is a potent vasodilator relaxing both the vascular smooth muscle of the arteries and
veins and has a more pronounced effect on the venous system. Nitroglycerin decreases systemic
arterial resistance and arterial blood pressure, increases
venous capacitance and reduces preload. As a result, Examples of Drugs:
nitroglycerin decreases myocardial workload and Tridil(IV), Nitro-Bid, Nitrostat,
myocardial oxygen demand.
isosorbide dinitrate (Isordil®),
Nitroglycerin also relieves vasospasm and dilates coronary
arteries to increase blood flow to the myocardium, helping
to relieve myocardial ischemia. Nitroglycerin is the drug
of choice for the relief of all types of angina, stable,
unstable, and prinzmetal.
isosorbide mononitrate,
(Imdur®, Monoket®, Ismo®),
Hydralazine, Nesiritide
(Natrecor)
Precautions
Because nitroglycerin is a powerful vasodilator, it may result in profound hypotension.
As a result, it should be initiated cautiously and the patient closely monitored during
titration.
Headaches are common with all forms of nitroglycerin, so patients need to be instructed
that this is an expected side effect.
Patients receiving nitrate therapy should not take selective phosphodiesterase inhibitors
used for erectile dysfunction (Viagra®, Levitra®, Cialis®). The combination can worsen
the hypotensive effects of nitrates, possibly resulting in potentially life-threatening
hypotensive/hemodynamic compromise.
In some cases, an intravenous nitroglycerin preparation may antagonize an IV infusion of
heparin and therefore close monitoring of its effects is required. This is important to
remember since these drugs may be administered concomitantly to patients diagnosed
with an acute myocardial infarction or acute coronary syndrome.
Isosorbide
Compared to nitroglycerin, isosorbide dinitrate (Isordil®) is a less potent vasodilator. Isosorbide
dinitrate, isosorbide mononitrate, and nitroglycerin are collectively known as nitrates. Isosorbide
dinitrate and one of its metabolites-isosorbide mononitrate (Imdur®, Monoket®, Ismo®) are
available orally, and sublingually. They are used for angina and for heart failure in combination
with hydralazine (BiDil®). Their mechanism of action is similar to nitroglycerin so they share
the same precautions, interactions, and adverse effects.
Nitrate tolerance – Tolerance to the vascular and antianginal effects of individual nitrates and
cross-tolerance among the drugs may occur with repeated prolonged use. Intermittent doses of
nitrates by use of a nitrate-free interval of 10-12 hours may minimize or prevent the development
of tolerance.
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34. CV Pharmacology
Check Yourself Pop Quiz
1.
Define parasympatholytic. What are the effects of this class of drugs on the
heart?
_________________________________________________________________
_________________________________________________________________
2.
Which class of drugs is used as a vasodilator and also blocks the conversion of
Angiotensin I to Angiotensin II?
______________________________________________________________
3.
Name 3 effects of Angiotensin II?
______________________________ ______________________________
______________________________
4.
Does Nitroglycerin have more effect on the venous or arterial system or equally on
both? (Circle correct answer)
Arterial system
Venous system
Equally on both system
Will this have more effect on ventricular preload or afterload? (Circle correct
answer)
Preload
5.
Afterload
Select which system Nitroprusside has more effect on: (Circle correct answer)
Venous system
Arterial system
Equally on both systems
List the effects Nitroprusside has on ventricular preload and afterload?
_________________________________________________________________
_________________________________________________________________
6.
State the vasodilator agent that is used as a potent antihypertensive and rapid
acting, but also has the effects of natriuresis?
_________________________________________________________________
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Check Yourself Pop Quiz -Answers
1. Parasympatholytic is defined as counteracting the effects of the parasympathetic
nervous system. This class of drug will enhance automaticity of the sinus node,
increase electrical conduction through the atria and the AV node and will enhance
conductivity. (Increases sinus and ventricular heart rate).
2. ACE inhibitor therapy blocks the conversion of angiotensin I to II, which occurs
primarily in the lungs. The ARB therapy blocks the effects of angiotensin II after
this conversion occurs.
3. Angiotensin-II causes vasoconstriction, promotes the release of norepinephrine,
and stimulates aldosterone production resulting in sodium and water retention.
Additional effects of angiotensin-II include increased systemic vascular
resistance, arterial blood pressure, and intravascular volume.
4. NTG relaxes vascular smooth muscle of arteries and veins, but has a more
pronounced effect on the venous system. Nitroglycerin will decrease systemic
arterial resistance and arterial blood pressure, but it increases venous capacitance
and reduces preload to a greater extent.
5. Sodium nitroprusside is a potent, fast acting drug which causes vasodilation of both
arteries and veins. Because of this action, it decreases afterload by reducing
systemic vascular resistance and arterial blood pressure, and decreases preload
by increasing venous capacitance and reducing blood return to the heart. This
preload and afterload reduction results in decreased myocardial workload and
myocardial oxygen demand.
6. Fenoldopam (Corlopam).
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36. CV Pharmacology
Vasopressor Therapy
Clinical Application
Vasopressor drugs must not be used until the patient’s volume status has been addressed.
The administration of vasopressors to hypovolemic patients does not increase blood
pressure; instead it can result in profound tachydysrhythmias and ventricular tachycardia or
ventricular fibrillation.
Should extravasation of this or any other alpha agonist occur, phentolamine (Regitine) may be
used to help minimize tissue damage. Refer to your hospital’s policy regarding the use of
phentolamine for intravenous extravasation of these drugs.
Dopamine
Dopamine (Intropin) is a chemical precursor of norepinephrine. Dopamine stimulates alpha, β1,
and dopaminergic receptors, depending on the administered dose, and also stimulates the release
of norepinephrine
Indications
Dopamine is used primarily for symptomatic hypotension and to increase organ perfusion.
According to the ACLS bradycardia algorithm, dopamine may also be considered in
hemodynamically significant bradycardia, with the dose beginning at 5 mcg/kg/minute,
following the use of transcutaneous pacing and/or atropine.
In patients with cardiogenic shock, left ventricular failure, and pulmonary edema, dopamine may
be used in conjunction with positive inotropic agents and vasodilators. This permits the
beneficial β1 effects to predominate and counteracts the increases in preload and afterload caused
by alpha stimulation.
At low doses (1 – 4 mcg/kg/minute), dopamine stimulates the dopaminergic receptors to produce
cerebral, renal, and mesenteric vasodilation. This dose is commonly thought to increase blood
flow to the kidneys and may sometimes be referred to as the renal dose dopamine. The efficacy
of dopamine for this indication is not supported in the literature.
NOTE: Many clinicians currently suggest that low dose dopamine therapy does NOT prevent or
ameliorate acute renal failure in patients.
At moderate doses (5 -10 mcg/kg/minute), dopamine stimulates the β1 receptors in the
myocardium. This increases contractility, cardiac output, and arterial blood pressure.
At higher doses (10 – 20 mcg/kg/minute), the alpha agonist properties of dopamine are much
more pronounced, resulting in significant increases in peripheral and venous vasoconstriction.
This results in an increase in preload, afterload, and myocardial workload. It also significantly
increases myocardial oxygen demand and negates the positive β1 and dopaminergic effects.
At doses of 20 mcg/kg/minute or more, significant arterial vasoconstriction results. If
hypotension continues, then other interventions should be considered.
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39. CV Pharmacology
Phenylephrine
Phenylephrine (Neo-Synephrine) is a sympathomimetic agent used primarily as an alpha agonist.
In usual therapeutic doses, it causes vasoconstriction to increase systemic vascular resistance and
arterial blood pressure.
Indications
From a cardiovascular perspective, phenylephrine is used in patients with hypotension and
shock.
Clinical Application
It is recommended that phenylephrine be administered through a central venous catheter
since extravasation of phenylephrine causes tissue necrosis.
Precautions and Interactions
In usual therapeutic doses, phenylephrine increases preload and afterload and resulting in
increased myocardial oxygen demand. Phenylephrine may cause a slowing of the heart rate
(reflex bradycardia) and is potentiated by tricyclic antidepressants and monoamine oxidase
(MAO) inhibitors.
Vasopressin
Vasopressin (Pitressin) is a naturally occurring antidiuretic hormone found in the posterior
pituitary. As a pharmacologic agent, vasopressin has several clinical applications, so our
discussion is limited to the application of vasopressin within the ACLS guidelines as a
vasopressor.
Indications
According to ACLS Guidelines, vasopressin “is an effective vasopressor and can be used as an
alternative for the first or second dose of epinephrine in the pulseless arrest algorithm.
Dosing for Cardiac Arrest is 40 Units IV push x 1. IV is the only route recommended
currently by AHA guidelines.
Vasopressin may be useful for hemodynamic support in vasodilatory shock (e.g., septic shock).
Precautions
The half-life of vasopressin is 10–20 minutes. As a result, after 10 minutes a decision needs to
be made to give epinephrine because vasopressin can only be given once. At this time,
vasopressin cannot be administered through the endotracheal tube, or as a continuous infusion.
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40. CV Pharmacology
Positive Inotropic Therapy
Digoxin
Our discussion of digitalis preparations will be limited to digoxin (Lanoxin, Digitek®) which is
the most commonly prescribed form of digitalis. Digoxin is a positive inotropic agent as it
increases the strength of myocardial contraction. Digoxin also decreases automaticity and
prolongs electrical conduction through the AV node.
Indications
Digoxin is used as maintenance therapy for symptom control in patients with heart failure to
increase myocardial contractility, stroke volume, and cardiac output. It also is used to control the
ventricular rate with atrial fibrillation or atrial flutter by slowing AV nodal conduction.
Note: For initial ventricular rate control in atrial fibrillation, IV calcium channel blockers and
beta-blockers are used before digoxin due to the length of time digoxin takes to produce a
slowing of the ventricular rate.
Precautions and Interactions
Digoxin has a very narrow therapeutic range and toxicity can develop rapidly. Symptoms of
digoxin toxicity include nausea, vomiting, diarrhea, visual disturbances, and changes in mental
status and level of consciousness. Toxicity also causes a wide variety of dysrhythmias, including
heart blocks, junctional rhythms, and ventricular dysrhythmias. Toxicity is precipitated by
hypokalemia, hyperkalemia, and hypomagnesemia. Many patients taking digoxin for heart
failure also take diuretics that can deplete potassium and lead to toxicity. Be sure to provide
patient education concerning the need to take any prescribed potassium supplements if the
patient is on diuretic therapy.
Digoxin is potentiated in such drugs as amiodarone, calcium channel blockers, and quinidine. In
patients taking these drugs, digoxin should be used with caution and the dose might be reduced
by 50%. Overdose of digoxin can be treated by the drug Digibind®.
Clinical Application
Digoxin should be avoided with those patients with sick sinus syndrome or significant
atrioventricular nodal heart blocks such as complete heart block and second degree AV
block.
Dobutamine
Dobutamine (Dobutrex) is a synthetic catecholamine. It is a potent β1 agonist to increase
myocardial contractility and cardiac output. It is also a mild alpha agonist; however, the alpha
effects are counteracted by the more potent β2 properties, resulting in a mild vasodilation effect.
This vasodilation will decrease preload and afterload with a beneficial effect on myocardial
oxygen supply and demand. At doses of 2–20 mcg/kg/min, it has only a minimal effect on the
heart rate. By increasing the cardiac output in the presence of mild vasodilation, it will increase
coronary, renal and mesenteric perfusion.
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42. CV Pharmacology
Isoproterenol
Sometimes called the “cardiac whip”, Isopreterenol (Isuprel) is a potent beta-adrenergic agonist
with essentially no alpha adrenergic activity. Isopreterenol produces large increases in
myocardial contractility, automaticity and conductivity. These actions profoundly increase
myocardial oxygen demand and increase the risk of myocardial ischemia, myocardial infarction,
and dysrhythmias. Because of its severe side effect profile Isopreterenol is now used only for
very specific indications, most commonly in cardiac transplantation. Because it is used so rarely,
Isopreterenol will not be discussed further in this packet. For further information please refer to
Lexicomp and Micromedex.
Sodium Bicarbonate
Sodium bicarbonate is used as a buffering agent in patients with a preexisting metabolic acidosis.
When bicarbonate combines with an acid, it forms carbonic acid, which usually dissociates to
water and carbon dioxide. In the presence of inadequate respiratory function (when carbon
dioxide is not rapidly cleared from the system) carbonic acid does not dissociate to carbon
dioxide and water. Instead, it remains carbonic acid, which can lead to an intracellular acidosis
and result in a decrease in myocardial contractility.
In general, the administration of sodium bicarbonate during a cardiac arrest situation is
associated with poor resuscitation outcomes. For this reason, sodium bicarbonate is no longer
routinely given as part of resuscitation efforts.
Indications
Sodium bicarbonate is indicated for several specific causes of pulseless electrical activity or
asystole within ACLS protocols. It is given to patients with a preexisting metabolic acidosis such
as patients in renal failure or diabetic ketoacidosis. However, it is not given to patients in
respiratory acidosis. It can also be given to patients with hyperkalemia or those who have
overdosed on tricyclic antidepressants or phenobarbital. A continuous infusion of sodium
bicarbonate given immediately prior to and post procedure has been shown to reduce the
incidence of contrast-induced nephropathy for patients undergoing cardiac catheterization,
computed tomography (CT), diagnostic or therapeutic arteriography, or transjugular intrahepatic
portal systemic shunt (TIPS) placement.
Precautions and Interactions
Sodium bicarbonate can lead to metabolic alkalosis if too much is administered. Because of the
high sodium content, it may cause hypernatremia and increase serum osmolality, resulting in
massive diuresis and cellular dehydration.
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43. CV Pharmacology
Check Yourself Pop Quiz
1) Choose the signs and symptoms of digoxin toxicity?
a) Nausea, vomiting, diarrhea
b) Heart blocks, junctional rhythms, ventricular dysrhythmias
c) Visual disturbances and changes in mental status
d) All of the above
2) Which of the following is an indication for the administration of sodium bicarbonate?
a) Hypokalemia
b) Tricyclic antidepressant overdose
c) Respiratory acidosis
d) Asystole
3) You are caring for a 71-year old male patient in heart failure. Which class of drugs is
used to increase contractility?
a) Beta blockade
b) Calcium channel blocker
c) Positive inotrope
d) Negative inotrope
4) Name a drug that has potent 1 agonist properties and is indicated for treatment of
left ventricular systolic dysfuntion.
_______________________ What is the usual starting dose? _____________
5) Stimulation of the dopaminergic receptors will cause which effect?
a) Peripheral vasoconstriction
b) Renal and mesenteric vasodilation
c) Bronchodilation
d) Bronchoconstriction
6) Choose the answer that best states the current ACLS Vasopressin dosage:
a) 80 units
b) 65 units
c) 40 units
d) 20 units
7) Identify a sympathomimetic drug that is used primarily as an alpha agonist.
___________________________________
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44. CV Pharmacology
Check Yourself Pop Quiz -Answers
1.
d
2.
b
3.
c
4.
Dobutamine / 5mcg/kg/min
5
b
6.
C
7.
Phenylephrine (Neo-Synephrine)
Refer to previous section as a review for any incorrect answers. Reviewing
your incorrect answers will benefit your learning as you proceed in this
packet.
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45. CV Pharmacology
Fibrinolytic Agents
Fibrinolytic agents activate plasminogen to form plasmin. Plasmin
digests or dissolves fibrin clots. The most commonly used
plasminogen activator (tPa, activase, alteplase, and Retavase
(reteplase r-PA) and TNKase (tenecteplase). Alteplase (tPA) and
reteplase (r-PA) are fibrin-selective agents, meaning that they act
primarily on plasminogen that is bound in blood clots.
Tenecteplase has an enhanced specificity for fibrin and is highly
clot selective, resulting in less degradation of circulating clotting
factors in comparison to other agents. All three agents have
shown similar efficacy.
is a fibrinolytic enzyme that
fibrinolytics include tissue
Examples of Drugs:
tPA, Activase, alteplase),
Retavase (reteplase, r-PA)
TNKase (tenecteplase).
Indications
All of the fibrinolytic agents are indicated in the management of acute myocardial infarction.
tPA is also approved for use in the management of acute stroke and in the management of acute
peripheral vascular thrombosis. Fibrinolytics may also be used in the emergency management of
acute pulmonary embolism.
Administration
Dosage and administration of fibrinolytics vary depending on the indication for which they are
being used and institutional protocols. In all cases they are to be mixed in normal saline or D5W.
They must not be mixed in bacteriostatic preparations. They also should be prepared gently to
avoid foaming and should be gently swirled, not shaken.
When used for acute myocardial infarction, tPA (Activase, Alteplase) the dosage is based on
weight with a total maximum dose of 100mg. For patient’s >67 kg an intravenous bolus dose of
15 mg is given over 1-2 minutes, then 50 mg infused over 30 minutes, followed by 35 mg over
the remaining hour. For patient’s < 67 kg, a 15 mg intravenous bolus is given, followed by 0.75
mg/kg infused over the next 30 minutes not to exceed 50 mg, and then 0.50 mg/kg over the next
60 minutes not to exceed 35 mg.
Reteplase (r-PA) is generally administered as an initial 10 unit intravenous bolus over two
minutes, with an additional 10 units as an intravenous bolus given 30 minutes following the
initial bolus. Reteplase (r-PA) has the advantage of reducing the nursing time involved in
administration since it requires no mixing or preparation, is not weight based, and there is no
continuous intravenous infusion to be monitored.
TNKase (tenecteplase) is provided in a kit containing a vial with 50 mg TNKase and sterile
water with a needleless injection system. It is given as a single IV push bolus over 5 seconds,
with the dose based on the patient’s weight. The total dose should not exceed 50 mg.
Precautions and Interactions
All fibrinolytic agents may cause bleeding from puncture sites, surgical sites, and areas of injury.
They also may result in intracranial hemorrhage leading to death. The risk of bleeding remains
for several hours to several days following administration.
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The American College of Cardiology/American Heart Association Guidelines for the
Management of Patients with ST-Elevation MI guidelines list the absolute and relative
contraindications of fibrinolytic therapy. These are viewed as advisory for clinical decision
making and may not be all-inclusive.
NOTE: See package insert or institutional guidelines for more information, as well as the
ACC/AHA Guidelines for the Management of Patients with ST Elevation Myocardial Infarction
(updated 7/1/04) via the ACC website as listed in the References section of this SLP.
Absolute contraindications to the use of fibrinolytics include:
ANY HISTORY OF INTRACRANIAL HEMORRHAGE
Known malignant intracranial neoplasm (primary or metastatic)
Known structural cerebral vascular lesion (e.g., AVM)
Ischemic stroke within 3 months EXCEPT acute ischemic stroke within 3 hours
Active internal bleeding or bleeding diathesis (excluding menses)
Suspected aortic dissection
Acute pericarditis
Significant closed head or facial trauma within 3 months
Relative contraindications must be weighed against potential benefits and include:
Severe uncontrolled hypertension (>180/110) or history of chronic severe
hypertension
History of prior ischemic stroke greater than 3 months, dementia, or known
intracranial pathology not covered in contraindications
Pregnancy
Active peptic ulcer or recent internal bleeding within the previous 2-4 weeks
Non-compressible vascular punctures
Current use of anticoagulants, the higher the INR, the higher the risk of bleeding
Traumatic or prolonged (greater than 10 minutes) CPR or major surgery with
the previous 3 weeks
For streptokinase/anistreplase: Prior exposure ( more than 5 days) or prior
allergic reaction to these agents
All patients are to be monitored closely for signs of bleeding, including changes in neurological
status, abdominal pain or rigidity, or hypotension. When used in the management of acute
myocardial infarction, the patient may experience chest pain or dysrhythmias when the coronary
artery opens and the supply of oxygenated blood to the myocardium is restored (reperfusion). It
is vital not to stop the administration of the fibrinolytic agent due to reperfusion symptoms. If
needed, symptoms are to be managed with morphine and antidysrhythmics.
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47. CV Pharmacology
Platelet Inhibitors
IIb/IIIa GP Platelet Inhibitors
Platelet inhibitors bind to the platelet receptor site named the glycoprotein IIb/IIIa site. These
receptor sites function at the end of final common pathway to block the binding of fibrinogen
and other components in the clotting cascade. Consequently, this action inhibits platelet
aggregation and blood clotting. Drugs in this class include Reopro (abciximab), Aggrastat
(tirofiban), and Integrilin (eptifibatide). Administration of these agents can result in reducing
refractory myocardial ischemia, myocardial infarction, and mortality. Recent research indicates a
significant decrease in complications and mortality from ischemic stroke, even when
administered up to 24 hours following the onset of symptoms.
Indications
Reopro, Aggrastat, and Integrilin are indicated in the treatment of refractory unstable angina, and
as an adjunct to percutaneous coronary interventions (PCI), such as angioplasty an planned
within 24 hours. These agents should not be used together and need to be used cautiously with
other drugs that effect clotting. It is important to note that all of these agents have been
administered in clinical trials with aspirin, clopidogrel (Plavix), unfractionated heparin and
enoxaparin (Lovenox), and bivalirudin (Angiomax).
Administration
Please consult Lexi-Comp, Micromedex, and PDR for dosage administration and usage. Please
contact a pharmacist at your facility for further information.
Precautions and Interactions
Also refer to fibrinolytics for the contraindications of GP IIb/IIIa inhibitors.
Patients are to be monitored closely for signs of bleeding, changes in neurological status,
abdominal pain or rigidity, and hypotension. A platelet assay count should be monitored daily
during therapy. One must obtain a platelet count within 4 hours of the bolus therapy.
In addition, Reopro is a monoclonal antibody derivative, meaning it has the potential to cause
allergic and anaphylactic reactions if the patient has had this drug in the past.
Platelet Aggregation Inhibitors
These drugs, include Plavix (clopidrogrel) and Ticlid (ticlopidine), work by modifying the
platelet membrane, to block the ADP pathway to prevent platelet aggregation and prolong
bleeding time.
Aspirin, another antiplatelet agent, does not work through the ADP pathway. Aspirin irreversibly
inactivates the COX-1 enzyme in platelets preventing the formation of thromboxane A2 (a
platelet aggregating substance).
The effect of all of these agents is irreversible for the life of the platelets modified.
Consequently, platelet function and bleeding time may take up to 2 weeks following
discontinuation of the drug to return to normal. Because ticlopidine can cause life-threatening
hematological reactions including neutropenia, thrombocytopenia, thrombotic thrombocytopenic
purpura (TTP), agranulocytosis, and aplastic anemia, its use is generally reserved for patients
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