Transcript Pharmacology Slide Set - Respiratory Therapy Files

HW on Capnography
• DUE 3-25 instead of 18th
• Write a paper on the use and
indications of capnography
monitoring. What is it’s benefits? Is
there evidence to support it’s use?
Find a scientific/scholarly article
backing up your argument
1
• Preload-After load= Stroke Volume
• Stroke Volume + HR = Cardiac Output
•
(SV a product of inotropy/contraction), (HR product of
chronotropy/conduction)
• Cardiac output X CaO2 = DO2
•
(CaO2 determined primarily by Hb and ability of O2 to bind with it)
• Oxygen consumption (VO2)= C(a-v) CO
•
CvO2 determined by amount of O2 left in venous blood after tissue
consumption
• Tissue Perfusion/Oxygenation
dependent on all of the factors listed
above (SV, HR, EDV, ESV, Inotropy, Chronotropy,
Hb, PaO2, effective V/Q matching)
2
Clinical
Pharmacology Objectives
• Know basic ACLS drugs and usage
• Understand drugs, doses, and routes of
administration during cardiovascular
emergencies
• Learn to integrate basic drug
pharmacology into ACLS algorithms
© 2011 American Heart Association. Do not edit.
3
Drugs
• Epinephrine
• Vasopressin
• Amiodarone
• Lidocaine
• Magnesium
• Atropine
• Dopamine
• Adenosine
• Oxygen
• Aspirin
• Nitroglycerin
• Morphine
• Fibrinolytics
4
Priorities for Drug
Administration
First—CPR and Early Defibrillation
Then drug administration:
1. Intravenous
2. Intraosseous
3. Endotracheal
5
Drug Administration
Secondary
FYI Guidelines 2010: During cardiac
arrest, high-quality CPR and early
defibrillation are of primary importance,
and drug administration is of secondary
importance. Few drugs used in the
treatment of cardiac arrest are supported
by strong evidence. After provision of
CPR and early defibrillation, rescuers
can establish IV access, consider drug
therapy, and insert an advanced airway.
6
ETT route
• Although endotracheal administration
of some resuscitation drugs is
possible, IV or IO drug administration
is preferred because it will provide
more predictable drug delivery and
pharmacologic effect. If IV and IO
access cannot be established, some
resuscitation drugs may be
administered by the endotracheal
route.
7
ETT Route
• Administration of resuscitation drugs into the
trachea, however, results in lower blood
concentrations than the same dose given
intravascularly. Furthermore, recent animal studies
suggest that the lower epinephrine concentrations
achieved when the drug is delivered by the
endotracheal route may produce transient adrenergic effects. These effects can be detrimental,
causing hypotension, lower coronary artery
perfusion pressure and flow, and reduced potential
for return of spontaneous circulation (ROSC).
8
Intraosseous Infusion
• Drug delivery similar to central
venous access possible
• Average access time
<2 minutes
• Any drug given IV can be given IO
9
IO Route
• IO cannulation provides access to a
noncollapsible venous plexus,
enabling drug delivery similar to that
achieved by central venous access.
Two prospective trials, in children and
adults, and other studies documented
that IO access is safe and effective for
fluid resuscitation, drug delivery, and
blood sampling for laboratory
evaluation and is attainable in all age
10
groups
Mechanisms of Drug Actions
Sympathetic Nervous System
• Autonomic Nervous
System
 Sympathetic
Dilates pupil
Decreases
salivation
Constricts
blood
vessels
Accelerates
heartbeat
 Parasympathetic
Relaxes airways
Stimulates secretion
of epinephrine and
norepinephrine
11
Autonomic nervous system
• key component that regulates the cardiovascular
system and other organs. The sympathetic nervous
system is the “fight/flight” part of this system,
preparing the individual for stress. In certain
pathological conditions, the administration of
agents such as epinephrine stimulates the system,
increasing heart rate and blood pressure. In other
conditions drugs used to block this system are
important for the treatment of certain diseases and
symptoms, such as angina.
12
Mechanisms of Drug Actions
Parasympathetic Nervous System
• Autonomic Nervous
System
Constricts
pupil
Constricts
airways
 Sympathetic
 Parasympathetic
Slows
heartbeat
Stimulates
intestine
activity
13
Autonomic nervous system
The parasympathetic nervous system is
the “opposite” part of this system,
slowing body functions and organ
responses. In certain arrhythmias and
pathological conditions, the
administration of agents such as
atropine stimulates the system,
decreasing heart rate and terminating
arrhythmias under the influence of the
vagus nerve.
14
Mechanisms of Drug Actions
• Receptor
Stimulation
– α-Receptors
– β-Receptors
– Dopaminergic
Receptors
Drug or
agonist
Receptor
Physiologic response
• Heart rate
• Vasoconstriction
15
A physiologic stimulus or response interacts
at a receptor site and causes a response, such
as an increase in heart rate or slowing of a
conduction stimulus. Drugs can be used to
mimic an agonist or response or to block it.
Adrenergic receptors in the body regulate
cardiac, vascular, bronchiolar, and
gastrointestinal smooth muscle tone. The
major classes of adrenergic receptors are
• α-Adrenergic (α1 and α2) receptors
• β-Adrenergic (β1 and β2) receptors
• Dopaminergic (DA) receptors
16
• Albuterol/Xopenex/Serevent/Racemic
Epi/Foradil/Brovana
• These are our sympathomimic
bronchodilators, they are synthetic
variations of the catecholamine
Epinephrine that specialize on the Beta
2
• Minor Beta 1 side effects
• Beta 2 receptors when stimulated
cause bronchodilation
• Beta 1 when stimulated increase the
HR
17
Mechanisms of Drug Actions
Reproduced from Lange RA. N Engl J Med. 2001
© Massachusetts Medical Society
18
• This is an example showing how
norepinephrine serves as a
neurotransmitter. Norepinephrine is
made and stored in granules that are
released and stimulate receptors on
smooth muscle cells, causing muscle
stimulation and contraction. In the
case of blood vessels, smooth muscle
constriction increases peripheral
resistance and elevates blood
pressure. Cocaine can block reuptake
of norepinephrine and cause
hypertension or hypertensive crisis. 19
Mechanisms of Drug Actions
Receptor Stimulation
Constricts
blood vessels
• α-Receptors
Accelerates
heartbeat
20
α-Adrenergic receptors predominantly regulate
vascular smooth muscle tone. When α-adrenergic
agonists stimulate vascular α-receptors,
vasoconstriction occurs. α-Adrenergic receptors are
also located in myocardial muscle cells, and
stimulation of these receptors increases cardiac
chronotropic (heart rate) function. For clinical
purposes think in terms of one type of α-receptor, and
think of vasoconstriction as the response to
stimulation of α-receptors.
The potency of the major α-adrenergic agonists
(catecholamines) is as follows:
• Norepinephrine++++
• Epinephrine+++
• Isoproterenol++
• Phenylephrine+
21
Mechanisms of Drug Actions
Accelerates
heartbeat and
contractility
1
Dilates blood
vessels
2
Relaxes
airways
2
Receptor Stimulation
• -Receptors (1
and 2)
22
There are several types of β-adrenergic receptors. β1
and β2 are the most important:
• β1-Adrenergic receptors are the β-adrenergic
receptors of the heart. They concentrate in the
sinus node and ventricles. β1-Receptors are
excitatory. When agonists stimulate these
receptors, the heart responds with an increase
in rate plus an increase in strength of
contractility.
• β2-Adrenergic receptors are the β-adrenergic
receptors of the rest of the body. These
receptors in the periphery are
counterregulatory. They oppose α-adrenergic
vasoconstriction, leading to vasodilation.
23
Mechanisms of Drug Actions
Accelerates
heartbeat
Receptor Stimulation
• Dopaminergic
Receptors (dosedependent
effects)
Constricts
blood vessels
Stimulates secretion
of epinephrine and
norepinephrine
Vasodilates Renal
Splanchnic Vasculature
24
• Dopamine:
Chronotropic,
and a
vasoconstrictor
• Vasopressor:
Vasoconstrictor
only
• Epinephrine/nore
pinephrine:
inotropic/chronot
ropic and
vasoconstrictor
25
• Dopaminergic receptors are located in smooth
muscle cells in the cerebral, coronary, renal, and
splanchnic vascular beds. Dopaminergic receptors
are also present in proximal renal tubular cells and
in the pituitary gland. Activation of dopaminergic
receptors in the smooth muscle cells results in
cerebral, coronary, renal, and splanchnic
vasodilation. Activation of the dopaminergic cells in
the proximal renal tubular cells results in inhibition
of sodium ion reabsorption from tubular fluid, so
renal sodium excretion increases. Activation of
pituitary dopaminergic receptors modulates thyroid
and prolactin hormone release. The most significant
effect of dopaminergic receptor activation is
increased blood flow to the cerebral, coronary,
renal, and splanchnic circulations.
26
Dose-Dependent and ReceptorDependent Drug Effects
27
• The interaction of a drug with
receptors is complex. It varies from
person to person, and it is further
influenced by disease states, drug
dose, drug distribution, receptors, and
whether the patient is in cardiac arrest.
28
Note that most vasoactive drugs affect several types of
adrenergic receptors (β1, β2, α, and DA). The receptors are
affected with varying degrees of what is called receptor selectivity
(the binding affinity of agonists for one type of receptor over
another).
Other factors that contribute to the net effect of these drugs
include
•
Pharmacokinetics (affected by all processes that influence drug
diffusion, distribution, and uptake)
•
Receptor density (a variety of clinical conditions influence the
number of receptors present on the cell surface) and function
(may be affected by activation of other receptors and other
body processes)
•
Parasympathetic nervous system
•
Vasoactive platelet-mediated products such as thromboxane A2
and prostacyclin
•
Endothelial function (dysfunction may cause paradoxical
responses to vasodilating stimuli)
•
Loss of vasodilating substances such as endothelium relaxing
29
factor
Clinical Correlation
You have delivered 1 shock from a
defibrillator and immediately resumed
CPR with chest compressions. Two minutes
later you call for a rhythm check and see
this rhythm:
What is your next drug action?
30
When CPR and shocks have been
ineffective in terminating VF, a
vasopressor is used to increase
peripheral vasoconstriction and elevate
aortic diastolic pressure and therefore
coronary perfusion pressure in an
attempt to facilitate defibrillation.
31
Persistent or Recurrent VF/VT
Immediately resume CPR with compressions
Prepare to administer
•Epinephrine 1 mg IV/IO push, repeat every 3 to 5 minutes
or
•Vasopressin 40 units IV/IO, in place of first or second
dose epinephrine
32
Vasopressors in Persistent VF
Epinephrine 1 mg IV/IO push,
repeat every 3 to 5 minutes
or
Vasopressin 40 units IV/IO may be substituted
for first or second dose epinephrine
 Central Aortic
Pressure
 Coronary Perfusion
Pressure
33
• Peripheral vasoconstriction increases
coronary perfusion pressure, which
determines blood flow during cardiac
arrest. Experimental studies have
shown that coronary perfusion and
aortic diastolic pressure correlate with
resuscitation success.
34
Epinephrine
• Epinephrine is a naturally occurring
catecholamine with both - and adrenergic agonist activity
• Administer 1 mg (10 mL 1:10 000 IV
bolus) every 3 to 5 minutes during
cardiac arrest
• Stimulation of -adrenergic receptors
increases peripheral vasoconstriction
and as a result increases coronary and
cerebral blood flow
35
Epinephrine
•
The beneficial effects of epinephrine during cardiac arrest
come from its α-adrenergic effects.
– Stimulation of α-adrenergic receptors during CPR increases
myocardial and cerebral blood flow.
– During resuscitation epinephrine increases peripheral
vasoconstriction and improves coronary artery perfusion
pressure.
– Epinephrine produces significant renal vasoconstriction
even at very low doses, causing decreased renal blood flow
and urine output.
• Epinephrine makes ventricular fibrillation (VF) more responsive
to direct-current shock.
• Both beneficial and toxic physiologic effects of epinephrine
administration during CPR have been shown in animal and
human studies. Although epinephrine has been used
universally in resuscitation, there is a paucity of evidence to
show that it improves outcome in humans.
36
Epinephrine
Stimulation of -adrenergic receptors
• Increases heart rate, contractility, and
conduction velocity
• Increases conduction through the
atrioventricular node
• Decreases the ventricular muscle
refractory period: these latter effects
may increase the likelihood of
arrhythmias
37
Epinephrine
•
•
•
Epinephrine produces β-adrenergic effects of increased heart
rate, contractility, and conduction velocity. It increases heart
rate by increasing the spontaneous depolarization rate of the
sinoatrial node. It increases conduction through the
atrioventricular node and decreases the ventricular muscle
refractory period. These latter effects may increase the
likelihood of arrhythmias. Epinephrine does increase coronary
artery blood flow, but the β-adrenergic effects of epinephrine
increase myocardial work and reduce subendocardial
perfusion, so the net effect is a greater increase in oxygen
demand than oxygen delivery to the myocardium.
Epinephrine makes ventricular fibrillation (VF) more responsive
to direct-current shock.
Both beneficial and toxic physiologic effects of epinephrine
administration during CPR have been shown in animal and
human studies. Although epinephrine has been used
universally in resuscitation, there is a paucity of evidence to
show that it improves outcome in humans.
38
Epinephrine
in Cardiac Arrest
• Epinephrine may be
administered IV/IO
• Endotracheal
administration
provides uncertain
doses
• Remember to flush
with 20 mL of fluid
and elevate the arm
or leg
Special Considerations
Cautions—Contraindications
• High doses can
cause arrhythmias
• High doses do not
improve survival
and may contribute
to postresuscitation
myocardial
dysfunction
39
Vasopressin
• A naturally occurring hormone, also
known as antidiuretic hormone (ADH)
• Causes vasoconstriction by directly
stimulating smooth muscle receptors
• Causes no increase in myocardial
oxygen consumption during CPR—
no -receptor activity
Clinical studies have shown vasopressin
equivalent to epinephrine for treatment of cardiac arrest
40
Vasopressin
• Vasopressin can be
substituted for the
first or second dose
of epinephrine
• Give 40 units IV/IO
bolus

Coronary perfusion
pressure



Vital organ blood flow
Median frequency VF
Cerebral oxygen
delivery
41
Vasopressin
There is no evidence
on
• The value of
repeated
vasopressin doses
or
• The best approach
after
administration of a
single dose of
vasopressin
• no difference in
outcomes (ROSC,
survival to
discharge, or
neurologic
outcome) with
vasopressin (40
units IV) versus
epinephrine (1 mg)
42
Clinical Correlation
You have delivered a shock from a
defibrillator and administered a
vasopressor. Two minutes later you call
for a rhythm check and see this rhythm:
What is your next drug action?
43
Persistent or Recurrent VF/VT
Following Shocks, Vasopressor
Immediately resume CPR with compressions
Consider and prepare to administer
•Amiodarone 300 mg IV/IO push (Class IIb)
or
•Lidocaine 1 to 1.5 mg/kg (Class IIb)
44
IV amiodarone can be considered for the
first-line treatment of VF or pulseless VT
unresponsive to shock delivery, CPR,
and a vasopressor. Lidocaine is an
alternative antiarrhythmic of longstanding and widespread familiarity with
fewer immediate side effects than may be
encountered with other antiarrhythmics.
Lidocaine, however, has no proven
short-term or long-term efficacy in
cardiac arrest. Lidocaine should be
considered an alternative treatment to
amiodarone (Class IIb, LOE B).
45
Antiarrhythmic Agents
• Amiodarone
• Lidocaine
• Magnesium
46
Amiodarone
IV amiodarone affects sodium,
potassium, and calcium channels as well
as - and -adrenergic blocking
properties. It can be considered for the
treatment of VF or pulseless VT
unresponsive to shock delivery, CPR,
and a vasopressor.
47
Arrhythmias—
Antiarrhythmic Rx
Basic Mechanisms of Action
• Disturbed Automaticity
• Reentry
• Disturbed Conduction
48
Disturbed Automaticity.
• This may involve a speeding up or slowing down of
areas of automaticity such as the sinus node (sinus
tachycardia or sinus bradycardia), the
atrioventricular (AV) node, or the myocardium.
• Abnormal beats (more appropriately called
depolarizations rather than beats or contractions)
may arise through this mechanism from the atria,
the AV junction, or the ventricles. Abnormal
rhythms, such as atrial or ventricular tachycardia,
may also occur.
49
Disturbed Conduction
• Conduction may be either too rapid (as
in Wolff-Parkinson-White syndrome) or
too slow (as in atrioventricular block).
50
Combinations of Disturbed
Automaticity and Disturbed
Conduction
• Two examples are
–A premature atrial contraction (disturbed
automaticity) plus first-degree AV block
(disturbed conduction)
–Atrial flutter (disturbed automaticity) with
3:1 or higher grades of AV block (disturbed
conduction)
51
Mechanism PVCs
DELAYED CONDUCTION
REENTRY
IRRITABLE FOCUS
Unidirectional
Block
Purkinje Fiber


Reentry
Muscle Fiber
• Some forms of ventricular tachycardia are
initiated by a PVC and sustained by a
mechanism called unidirectional block, a
circus rhythm similar to other arrhythmias
using 2 pathways with different refractory
characteristics to propagate the
arrhythmia. This is also one method by
which antiarrhythmic agents work—by
altering refractory periods or converting
unidirectional block to bidirectional block.
A rapidly firing automatic focus is another
mechanism for VT.
Amiodarone
Cardiac Arrest Dose—300 mg IV/IO
Repeat Once—150 mg IV/IO
Amiodarone is approved for
• Refractory ventricular fibrillation
during cardiac arrest
• Recurrent ventricular fibrillation
• Recurrent hemodynamically
unstable ventricular tachycardia
54
Key Studies—Amiodarone
ARREST Trial, Kudenchuk 1999
Patient
group
n
Amiodarone 246
Placebo
258
Survival to
admission
Odds ratio for
admission
Survival to
discharge
44%
1.6
13.4%
34%
(P = .03)
1.0
(P = .02)
13.2%
(P = NS)
Kudenchuk PJ. N Engl J Med. 1999
55
ARREST Trial
Return of Spontaneous Circulation (ROSC)
70
60
50
%
40
30
20
10
0
64%
41%
ROSC
38%
33%
No ROSC
Amiodarone
Placebo
Kudenchuk PJ. N Engl J Med. 1999
56
ARREST Trial
Survival to Hospital Admission
60
50
40
%30
20
10
0
44%
34%
All
49%
39%
VF/VT
Amiodarone
17%
12%
Asys/PEA
Placebo
Kudenchuk PJ. N Engl J Med. 1999
57
Key Studies—Amiodarone
ALIVE Trial, Dorian 2002
Patient group
n
Survival to
admission
Survival to
discharge
Amiodarone
180
22.8%
5%
Lidocaine
167
12.0%
(P = .009)
3%
(P = .34)
Amiodarone 5 mg/kg vs lidocaine 1.5 mg/kg
Dorian P. N Engl J Med. 2002
58
ALIVE Trial
Survival to Hospital Admission
% of pts
25
Lidocaine (n = 167)
IV Amiodarone (n = 180)
20
15
10
5
0
12%
23%
All patients
P = .009
14% 25%
VF or VT
P = .03
59
Dorian P. N Engl J Med. 2002
Amiodarone
Special Considerations
Cautions—Contraindications
• Because of the
• For other uses, seek
potentially lifeexpert consultation
threatening side effects • Complex doseand difficulties
dependent side effects
associated with
managing its use,
amiodarone is
prescribed in ACLS for
only life-threatening
arrhythmias
60
Lidocaine
Initial Dose—1 to 1.5 mg/kg IV
Repeat Dose—0.5 to 0.75 mg/kg IV
every 5 to 10 minutes
Maximum—3 mg/kg
• Alternative to amiodarone in cardiac
arrest from VF/VT
• Can be used in stable monomorphic VT
• Remember to search for and correct
underlying causes of VT:
- Ischemia - Electrolyte abnormality
- Hypoxia - Proarrhythmia
(other drugs)
61
Lidocaine
• Prophylactic use in
acute coronary
syndromes is
contraindicated
• Reduce dose in the
elderly and those with
poor cardiac output,
heart failure, and liver
dysfunction
Special Considerations
Cautions—Contraindications
• Discontinue
immediately if signs of
toxicity develop
• Toxicity includes
altered mental status,
drowsiness, confusion,
disorientation, ringing
in ears
• Serious side effects
can include focal and
grand mal seizures
62
Lidocaine Metabolism
Hepatic Failure and CHF
63
Magnesium
Cardiac Arrest Dose—1 to 2 g over 5 to 20 minutes
Torsades—1 to 2 g IV/IO over 5 to 60 minutes
• Recommended in cardiac arrest if
torsades de pointes is present—
especially if baseline QT interval
prolongation is known to be present
• Also recommended if hypomagnesemia
is suspected
• Not routinely indicated for acute
coronary syndromes
64
Magnesium
• Magnesium is required
for proper function of
the membrane pump in
cardiac cells
• Magnesium depletion
causes cardiac cell
depolarization
• Torsades de pointes
may occur and persist
Special Considerations
Cautions—Contraindications
• Avoid rapid
administration because
hypotension may occur
• Use with caution if
renal failure is present
• Not routinely indicated
in acute myocardial
infarction
65
Agents to Control Rate
• Atropine
• Dopamine Infusion
• Epinephrine Infusion
• Adenosine
66
Agents to Control Rate
• Many new cardiovascular agents for the control of
rate and rhythm are available to the healthcare
provider. The provider must understand the clinical
pharmacology of these drugs in order to select the
proper drug and avoid serious complications in
emergency settings. Knowledge of side effects and
interactions with other drugs is important because
many drugs reduce the efficacy of other therapies
and add to unwanted effects, such as
atrioventricular (AV) nodal depression.
67
Atropine
Dose—0.5 mg bolus
Repeat every 3 to 5 min as needed
Maximum 3 mg
• First drug for symptomatic
bradycardia
• May be beneficial in AV nodal
blocks
• Do not rely on atropine for
infranodal blocks
• Atropine is useful when blockade of
the parasympathetic nervous
system can increase rate or improve
68
AV conduction.
•
Atropine sulfate reverses cholinergic-mediated decreases in heart rate
and should be considered a temporizing measure while awaiting a
transcutaneous pacemaker for those patients. Atropine is useful for
treating symptomatic sinus bradycardia and may be beneficial for any
type of AV block at the nodal level. Do not rely on atropine for
infranodal blocks (not likely to be effective for type II second-degree or
third-degree AV block or a block in non-nodal tissue). After 1 or 2
doses of atropine with no response, move to pacing, epinephrine
infusion, or a dopamine infusion as a second-line treatment.
• The recommended atropine dose for bradycardia is 0.5 mg IV every 3
to 5 minutes to a total dose of 3 mg. Doses of atropine sulfate of less
than 0.5 mg may paradoxically result in further slowing of the heart
rate. Atropine administration should not delay implementation of
external pacing for patients with poor perfusion.
• Use atropine cautiously in the presence of acute coronary ischemia or
myocardial infarction; increased heart rate may worsen ischemia or
increase the zone of infarction.
• Atropine may be used with caution and appropriate monitoring
following cardiac transplantation. It will likely be ineffective because
the transplanted heart lacks vagal innervation. One small, uncontrolled
study documented paradoxical slowing of the heart rate and highdegree AV block when atropine was administered to patients after
69
cardiac transplantation.
Atropine
Special Considerations
Cautions—Contraindications
• Use with caution in
• Use 0.5 mg
the presence of
incremental doses in
cardiac ischemia
the presence of
• Do not rely on
ischemia
atropine for
• Repeat every 3 to 5
infranodal blocks
minutes as needed to (not likely to be
a maximum of 3 mg
effective for type II
second-degree or
third-degree AV
block or a block in
non-nodal tissue)70
Atropine
• Excessive doses of atropine can cause an
anticholinergic syndrome of delirium, tachycardia,
coma, flushed and hot skin, ataxia, and blurred
vision. Administration of atropine in doses of less
than 0.5 mg can produce a paradoxical bradycardia
owing to the central or peripheral
parasympathomimetic effects of low doses in
adults.
• This effect can precipitate VF.
• When repeated doses of atropine are required,
restrict the total cumulative dose to the 3 mg (0.04
mg/kg) associated with full parasympathetic
blockade.
71
Dopamine
Infusion for
Rate
Bradycardia—2 to 10 mcg/kg per min
Hypotension—2 to 20 mcg/kg per min
• If bradycardia is unresponsive to
atropine, a chronotropic (heart rate)
agent can be given by infusion or
pacing
• Dopamine is also used at higher
doses for blood pressure control in
hypotension (inotropic agent)
72
Review:
Blood Pressure = Cardiac Output 
Peripheral Vascular Resistance
Cardiac Output = Heart Rate  Stroke
Volume
Stroke Volume = EDV - ESV
73
Dopamine
• Activates
dopaminergic
receptors and
causes vasodilation
in GI and renal
vasculature
• Ensure that
adequate preload
(volume) is present
or hypotension may
occur at low doses
Special Considerations
Cautions—Contraindications
Remember:
Blood Pressure =
Cardiac Output 
Peripheral Vascular
Resistance
Cardiac Output =
Heart Rate  Stroke
Volume
74
Dopamine
low-dose dopamine
may cause
vasodilation and
blood pressure may
fall if patients do not
have adequate filling
pressures.
• This may be
accentuated in
patients who have a
bradycardia
because heart rate
may not increase to
compensate for the
fall in cardiac
output due to a
decrease in venous
return.
75
Dopamine
Special Considerations
Cautions—Contraindications
• May increase heart • Tissue necrosis
may occur if
rate and exacerbate
interstitial
tachyarrhythmia
extravasation
occurs
• Nausea and
vomiting are
• Inactivated in
common side
alkaline solutions
effects
(bicarbonate)
76
Epinephrine Infusion
for Rate
2 to 10 mcg per minute
• If bradycardia is unresponsive to
atropine, a chronotropic
(heart rate) agent can be given
by infusion or pacing
• Epinephrine is initiated at 2 mcg
per minute and titrated to
patient response
77
Epinephrine
Special Considerations
Cautions—Contraindications
• Epinephrine is also
used in cardiac
arrest at higher
doses: 1 mg every
3 to 5 minutes IV/IO
• Dosing higher than
10 mcg per minute
can cause
vasoconstriction
• Raising blood
pressure and
increasing heart
rate can cause
myocardial
ischemia
• High doses can
cause angina,
arrhythmias
78
Adenosine
6 mg IV bolus
12 mg IV bolus
12 mg IV bolus
• Endogenous purine nucleotide
• Depresses sinus and AV
nodal activity
• Indicated for stable narrowcomplex supraventricular
tachycardias unresponsive to
vagal maneuvers
Adenosine

• Terminates reentry rhythms,
not indicated for ventricular or
pre-excited arrhythmias
79
Adenosine
•
•
SVT does not respond to vagal maneuvers, give 6 mg of IV
adenosine as a rapid IV push (Class I). Give adenosine rapidly
over 1 to 3 seconds through a large (eg, antecubital) vein,
followed by a 20 mL saline flush and elevation of the arm. If the
rate does not convert within 1 to 2 minutes, give a 12 mg
bolus. Give a second 12 mg bolus if the rate fails to convert
within 1 to 2 minutes after the first 12 mg bolus.
Amiodarone can achieve nearly 100% efficacy in the inhibition
of induced sustained reentrant SVT. Adenosine is safe and
effective in pregnancy. Adenosine, however, does have
several important drug interactions. Larger doses may be
required for patients with a significant blood level of
theophylline, caffeine, or theobromine. The initial dose should
be reduced to 3 mg in patients taking dipyrimadole or
carbamazepine, in those with transplanted hearts, or if given
by central venous access. Side effects with adenosine are
common but transient; flushing, dyspnea, and chest pain are
80
the most frequently observed.
Adenosine
Special Considerations
Cautions—Contraindications
• Administer rapid IV push
(1 to 3 seconds) with flush
• Initial bolus of 6 mg
• May repeat if no response
with 12 mg dose twice
• Transient periods of
bradycardia and PVCs
common after conversion
• Higher doses may be
required in patients taking
theophylline or caffeine
• Transient side effects
include chest discomfort,
flushing, nausea
• Safe in pregnancy
• Reduction of the initial
dose (to 3 mg) may be
required in patients
receiving dipyrimadole or
carbamazepine and those
with central vein
administration
81
Electrical Cardioversion
Immediate electrical
cardioversion is indicated for a
patient with serious signs and
symptoms related to a
tachycardia
82
Synchronized Cardioversion
Procedure:
1. Attach monitor leads to patient
2. Apply conductive material to
paddles if not using hands-free
defibrillation pads
3. Turn on defibrillator
83
Synchronized Cardioversion
Procedure (cont’d):
4. Turn on synchronization mode
5. Verify synchronization signal on
monitor screen
6. Select energy level
7. Place defibrillator pads or paddles
on chest and apply pressure
(if necessary)
8. Charge defibrillator
84
Synchronized Cardioversion
Procedure (cont’d):
9. “CLEAR!”
–Check yourself
–Check patient
–Check bed/stretcher
–Check flow of oxygen
10. Press button(s) until discharge
occurs
85
Cardioversion
Energy Recommendations
Biphasic Waveform
• Atrial Fibrillation
• Atrial Flutter & SVT
• Monomorphic VT
120-200 J Initial
50-100 J Initial
100 J Initial
• Increase the energy dose in a stepwise
fashion for any subsequent
cardioversion attempts
• Use manufacturer-recommended doses 86
Cardioversion
Energy Recommendations
Monophasic Waveform
• Atrial Fibrillation
• Atrial Flutter & SVT
• Monomorphic, Unstable
With Pulse
200 J
200 J
100 J
• Polymorphic or Pulseless VT—Treat as VF with
high-energy unsynchronized defibrillation
doses
(Do not use low energy—high likelihood of causing VF in
unsynchronized mode)
87
Synchronized Cardioversion
Premedicate with both a sedative and an
analgesic if appropriate. For example:
• Sedatives
─ Diazepam
─ Midazolam
─ Etomidate
• Analgesics
─ Fentanyl
─ Morphine
─ Hydromorphone
88
Reperfusion Therapy and
ACS Adjuncts
• Oxygen
• Aspirin
• Nitroglycerin
• Morphine
89
Immediate General Treatment
• Oxygen (if needed)
• Aspirin 160 to 325 mg
• Nitroglycerin SL or spray
• Morphine IV (if pain not relieved
with nitroglycerin)
90
Oxygen in ACS
• Administer to
patients who have an
oxygen saturation
<94% or respiratory
compromise
• If needed, initiate at 2
to 4 L/min with nasal
cannula
• Maintain O2 saturation
≥94%
91
Oxygen Use in
Acute Coronary Syndromes
Why?
• Increases supply of oxygen to
ischemic tissue
When?
• When O2 saturation <94% or respiratory
compromise
How?
• Start with nasal cannula at 2 to 4 L/min
Watch Out!
• Rarely COPD patients with hypoxic
ventilatory drive will hypoventilate
92
Platelet Role in ACS
Adhesion
Recruitment and Activation
Aggregation
FIBRIN
RUPTURED PLAQUE
X
PAF
X
HEPARIN
ASA
GP IIb-IIIa
GP IIb-IIIa
CLOPIDOGREL
PRASUGREL
TICAGRELOR
X
GP IIb-IIIa
93
• Rupture of an atherosclerotic plaque results in
exposure of the subendothelial matrix substrates,
triggering adhesion of platelets to the area of
disruption. Other platelet stimuli, such as thrombin,
serotonin (5-HT), and collagen, activate platelets to
secrete adenosine diphosphate (ADP) and
thromboxane A2 (TxA2), further amplifying activation
and thrombin generation.
• Acute coronary syndromes typically are initiated by
rupture of the thin fibrous cap over the lipid-laden
intracoronary plaque.
94
Antiplatelet Agents
• Blocks receptors on platelets
X
• Blocked receptors cannot attach
to fibrinogen
X
• Fibrinogen cannot aggregate
platelets to platelets
95
Platelet Receptor Blockade
Thromboxane A2
Thrombin
PLATELET
HEPARIN
ASPIRIN
GP IIb-IIIa
Platelet
Receptor
Fibrinogen
GP IIb-IIIa
PLATELET
Clot Formation
• As the activated platelets aggregate and cross-link,
they develop high affinity for prothrombin and
fibrinogen in the blood.
• Prothrombin, one of the essential clotting factors, is
converted by the activated platelets (among other
activators) to thrombin.
• Thrombin, in turn, acts to convert fibrinogen to fibrin.
As fibrin concentrations increase, the fibrin begins to
form fibrin strands.
• The fibrin strands give substance and structure to a
growing fibrin matrix. This matrix continues to attract
activated platelets and soon entraps passing red
blood cells
Aspirin and Clopidogrel
Indications: ACS examples
• STEMI
• NSTEMI
• Unstable angina
managed medically
• UA undergoing PCI
98
Aspirin in ACS
160 to 325 mg, chewed
• Administer to all patients with
suspected ischemic pain
• 2 - 4 “baby” aspirin can be given to
facilitate chewing
• Do not use enteric (coated)
preparations
• May be administered by
rectal suppository
99
Aspirin: Actions
• Actions
– Blocks formation of thromboxane
A2 (thromboxane A2 causes
platelets to aggregate and arteries
to constrict)
• These actions will reduce
– Overall mortality from AMI
– Nonfatal reinfarction
– Nonfatal stroke
100
Aspirin:
Indications, Dose
• Indications—As soon as possible!
− Standard therapy for all patients
with new pain/discomfort
suggestive of ACS
− Give within minutes of arrival
• Dose: 160 to 325 mg taken as soon
as possible
101
Aspirin: Precautions
• Relatively contraindicated in
patients with active peptic ulcer
disease or asthma
• Contraindicated in patients with
known aspirin hypersensitivity
• Bleeding disorders
• Severe hepatic disease
102
Nitroglycerin
• Administer to all patients
with suspected ischemic pain
unless contraindicated
• Remember to reassess and repeat
vital signs between doses
• Up to 3 sublingual or spray doses
may be given at 5-minute intervals
• IV initiated for specific indications
103
Nitroglycerin: Actions
• Decreases pain of ischemia
• Increases venous dilation
• Decreases venous blood return
to heart
• Decreases preload and cardiac
oxygen consumption
• Dilates coronary arteries
• Increases cardiac collateral flow
104
IV Nitroglycerin—STEMI:
Indications
• First 24 to 48 hours in patients with STEMI and
one or more of the following:
– Recurrent ischemic chest pain
– LV failure (acute pulmonary edema or CHF)
– Elevated BP (especially with signs of LV
failure)
– Large anterior infarction
– Persistent ischemia
• Administration does not interfere with other
agents known to decrease mortality (ACE-I)
105
Nitroglycerin: Dose
• Sublingual: 0.3 to 0.4 mg; repeat every
5 minutes
• Spray inhaler: 1 to 2 metered doses at
5-minute intervals
• Maximum of 3 sprays within 15
minutes
• IV infusion: 12.5 to 25 mcg bolus,
10 to 20 mcg/min infusion, titrated
106
Nitroglycerin: Precautions
• Contraindicated if systolic BP <90 mm Hg
• Contraindicated in RV infarction
– Suspect RV infarction with inferior
ST changes
• Limit BP drop to 10% if patient is normotensive
• Limit BP drop to 30% if patient is hypertensive
• Watch for headache, drop in BP, syncope,
tachycardia
• Tell patient to sit or lie down during
administration
107
Precautions
• Recent phosphodiesterase inhibitor. If the
patient has erectile dysfunction and has taken a
phosphodiesterase inhibitor within the previous
24 hours (48 hours for tadalafil), nitrates may
cause severe hypotension refractory to
vasopressor agents.
• Hypotension, bradycardia, or tachycardia.
Avoid use of nitroglycerin in patients with
hypotension (systolic BP <90 mm Hg), extreme
bradycardia (<50 bpm), or tachycardia (heart
rate >100 bpm).
108
Morphine Sulfate
• Administer to all patients with suspected
ischemic pain unresponsive to oxygen
and nitrates
• Remember to reassess and repeat vital
signs between doses
• Initial dose is 2 to 4 mg IV over
1 to 5 minutes
• Administer slowly and only titrate to effect
109
Morphine
• Produces CNS analgesia, which reduces the
toxic effects of neurohumoral activation,
catecholamine release, and heightened
myocardial oxygen demand
• Produces venodilation, which reduces LV
preload and oxygen requirements
• Decreases systemic vascular resistance,
thereby reducing LV afterload
• Helps redistribute blood volume in patients
with acute pulmonary edema
110
Morphine Sulfate:
Actions
• To reduce pain of ischemia
• To reduce anxiety
• To reduce extension of ischemia by
reducing oxygen demands
111
Morphine Sulfate:
Indications
• Continuing pain unresponsive
to nitrates
• Evidence of vascular congestion (acute
pulmonary edema)
• Systolic blood pressure >90 mm Hg
• No hypovolemia
112
Morphine Sulfate:
Precautions
• Drop in blood pressure, especially in patients
with
– Volume depletion
– Increased systemic resistance
– RV infarction
• Depression of ventilation
• Nausea and vomiting (common)
• Bradycardia
• Itching and bronchospasm (uncommon)
113
Fibrinolytic Therapy
• Breaks up the fibrin network that binds
clots together
• Indications: ST elevation in 2 or more contiguous
leads or new LBBB
– Threshold values: J-point elevation of 2 mm in V2
and V3* and 1 mm in all other leads
– Time of symptom onset must be <12 hours
– Caution: fibrinolytics can cause death from brain
hemorrhage
• Agents differ in their mechanism of action, ease of
preparation and administration, cost, need for
heparin
• 3 agents currently available: alteplase (tPA,
Activase), reteplase (Retavase), tenecteplase
(TNKase)
*2.5 mm in men <40 years; 1.5 mm in all women
114
Adjunctive Agents—ACS
• -Receptor blocking agents
• Clopidogrel
• Heparin
• ACE inhibitors and ARBs
• Statins
115
Advanced Adjunctive Agents—ACS
The use of ACS adjunctive agents is
NOT routine
• Timing and dose may depend on the
patient, selection of treatment
strategy, and a careful consideration
of risk-benefit
116
-Blockers
Mechanism of action
• Blocks catecholamines from binding to
-adrenergic receptors
• Reduces HR, BP, myocardial
contractility
• Decreases AV nodal conduction
• Decreases incidence of primary VF
117
-Blockers
Absolute
Contraindications
• Severe CHF
• SBP <100 mm Hg
• Acute asthma
(bronchospasm)
• Second- or thirddegree AV block
Cautions
•
•
•
•
•
Mild/moderate CHF
HR <60 bpm
History of asthma
IDDM
Severe peripheral
vascular disease
118
Heparin
• Mechanism of action
– Indirect thrombin inhibitor (with AT III)
• Indications
– PCI or CABG
– With fibrin-specific lytics
– High risk for systemic emboli
 Conditions with high risk for systemic
emboli, such as large anterior MI,
atrial fibrillation, or LV thrombus
119
ACE Inhibitors
• Mechanism of action
– Reduces BP by inhibiting angiotensinconverting enzyme (ACE)
– Alters post-AMI LV remodeling by
inhibiting tissue ACE
– Lowers peripheral vascular resistance
by vasodilatation
– Reduces mortality and CHF from AMI
120
Pharmacology
QUESTIONS?
121