Inotropic Agents: Submitted To

Inotropic agents
Submitted to:
Resp. Ms. Satinder mam
Associate professor
UCON Faridkot

Submitted by:
Dimple
M.Sc nursing 1st year
UCON Faridkot
ADNERGIC RECEPTORS:
 Adrenaline is the original name for what
we now call epinephrine. Stimulation of
the adrenal medulla by the sympathetic
nervous system causes the secretion of
both epinephrine (80%) and
norepinephrine(20%) into circulation.
Epinephrine is a hormone; norepinephrine
is both a hormone and a neurotransmitter .
CATEGORIES:
There are two categories of receptors, alpha and beta.
There are also subtype of each. Useful generalizations
concerning these are:
 Activation of alpha 1 and beta 2 receptors cause stimulatory

responses.
 Activation of alpha 2, beta 2 & beta 3 receptors cause inhibitory
responses.
 NE causes a greater response than E when activating alpha 2
receptors.
 E and NE cause equal responses when activating beta 1 receptors.
 E causes a significantly greater response than NE when activating
beta 2 receptors.
ALPHA RECEPTORS
 Alpha 1 receptors are more responsive to NE than to
E. This is interesting as alpha 1 receptors are
abundantly found on vascular smooth muscle. The
relationship between the activated receptor and the
cell’s response is direct- the activity(muscle tone) of
the cell is increased. Alpha 1 receptors are located on:
 All vascular smooth muscle, although densities vary
throughout the body.
 GI & urinary sphincters.
 Dilator muscle of the iris.
 Arrector pili muscle of hair follicles .

 Increase in tone of vascular smooth muscles
reduces the ability of blood pressure to
expand vessel diameter thus reducing blood
flow to downstream organs. Increased tone in
urinary and gastrointestinal sphincters
reduces the passage of contents past them.
Increased tone of the dilator muscle of the
iris enlarges the pupil. Increased tone of
arrector pili muscles pulls on the hair follicle
causing hair to ‘stand on end’.
ALPHA 2 RECEPTORS
 Alpha 2 receptors are located on secretory
terminals of some postsynaptic adnergic
neurons. When these terminals secrete
norepinephrine the neurotransmitter binds
with these receptors as well as with adnergic
receptors on the other side of the synapse.
The presynaptic neuron’s response is to
decrease the amount of NE being released it
is a negative feedback mechanism. Current
research is involved with determining if alpha
2 receptors are located elsewhere.
BETA RECEPTORS
Beta 1 receptors: the relationship
between beta 1 activation by E and/or NE is
direct the cell’s activity is increased. Beta 1
receptors are located on:
 cardiac peacemaker.
 Myocardium.
 Salivary gland ducts.
 Eccrine and apocrine sweat glands.
 The cardiac peacemaker responds by increasing the
heart rate. Simultaneously the myocardium
contracts more forcefully. The physiology of the
response of salivary duct cells to beta 1 activation is
unclear; it appears that beta 1 activation of certain
duct cells reabsorbs some water in the slowly
passing saliva making it more viscous. The secretory
portion of both types of sweat gland is stimulated
only by E and NE from the blood, not via nerves.
 Note that beta1 activation in the heart is both
neural and hormonal. In the salivary glands the
activation is sloely neural while in both type sweat
glands it is solely due to E and NE in the blood.
Beta 2 receptors are located on smooth
muscle. The relationship between E/NE.(neurological)
activation and the response of the cell is inverse
activity (muscle tone) of the cell is decreased. Beta 2
receptors are located on smooth muscle in:
i. The gastrointestinal tract
ii. The urinary bladder
iii. Skeletal muscle arteries
iv. The bronchial tree
Some coronary vessels Also notice there are beta 3
receptors on the smooth muscle cells of the urinary
bladder that decrease their tone in response to
receptor activation.
 Beta3 receptors:
specific actions of the beta3 receptor includes :
 Enhancement of lipolysis in adipose tissue. Beta3
activating drugs could theoretically be used as
weightloss agents, but are limited by the side effect
of tremors.
INOTROPE
 An inotrope is an agent that alters the force or energy
of muscular contractions. Negatively inotropic agents
weaken the force of muscular contraction. Positively
inotropic agents increase the strength of muscular
contraction.
 The term inotropic state is most commonly used in
reference to various drugs that affect the strength of
contraction of heart muscle. However , it can also
refer to pathological conditions. For example, enlarged
heart muscle can increase inotropic state, whereas
dead muscle can decrease it.
MEDICAL USES:
 Both positive and negative inotropes are used in the
management of various cardiovascular conditions.
The choice of agent depends largely on specific
pharmacological effects of individual agents with
respect to the condition. One of the most important
factors affecting inotropic state is the level of
calcium in the cytoplasm of the muscle cell. Positive
inotropes usually increase this level, while Negative
inotropes decrease it.
 However, not all positive and negative drugs affect
calcium release, and ,among those that do, the
mechanism for manipulating the calcium level can
differ from drug to drug
 While it is often recommended that vasopressors

are given through a central line due to the risk of
local tissue injury if the medication enters the local
tissues, they are likely safe when given for less
than two hours in a good peripheral IV.
POSITIVE INOTROPIC AGENTS:
 By increasing the concentration of intracellular
calcium or increasing the sensitivity of receptor
protein to calcium, positive inotropic agents can
increase myocardial contractility. Concentrations of
intracellular calcium can be increased by increasing
influx into the cell or stimulating release from the
sacroplasmic reticulum.
 Once in the cell, calcium can pass through one of two
channels; the L type calcium channel and the T
type calcium channel. These channels respond to
voltage changes across the membrane differently : L
–type channels respond to higher membrane
potentials, open more slowly, and remain open longer
than Ttype channels.
 Because e of these properties Ltype channels are
important in sustaining an action potential, while T
type channels are important in initiating them.
 By increasing intracellular calcium, via the action of
the L –type channels, the action potential can be
sustained for longer and therefore, contractility
increases.
 Positive inotropes are used to support cardiac
function in conditions such as decompensated
congestive heart failure, cardiogenic shock,
myocardial infraction, cardiomyopathy, etc.
 Examples of positive inotropic agents includes:
 Digoxin
 Amidarone
 Berberine
 Calcium
 Calcium sensitisers : levosimendan
 Catecholamines:
a. Dopamine
b. Dobutamine
c. Dopexamine
d. Epinephrine(adrenaline)
e. Isoprenaline (isoproterenol)
f. Norepinephrine (noradrenaline)
 Angiotensin II
 Prostagladins
 Phosphodiesterase inhibitors
a. Enoximon
b. Milirinone
c. Amrinone
d. Theophylline
o Glucagon
o Insulin .
NEGATIVE INOTROPIC AGENTS:
 Negative inotropic agents decrease myocardial
contractility, and are used to decrease cardiac
workload in conditions such as angina. While
negative inotropism may precipitate or
exacerbate heart failure, certain beta blockers
(e.g. carvedilol, bisoprolol and metoprolol) have
been believed to reduce morbidity and mortality
in congestive heart failure.
 Examples of negative inotropic agents include:
 Nondihydropyridine calcium channel
blockers
a. Diltiazem
b. Veraapamil
c. Clevidipine
 Class IA antiarrhythmias such as:
1. Quinidine
2. Procainamide
3. Disopyramide
o Class IC antiarrhythmics such as :
1. Flecanide.
EPINEPHRINE:
 Epinephrine, also known as adrenaline, is a
hormone, neurotransmitter, and medication.
Epinephrine is normally produced by both the
adrenal glands and certain neurons. It plays an
important role in the flight or –fight response by
increasing blood flow to muscles , output of the
heart, pupil dilation, and blood sugar . It does this
by binding to alpha and beta receptors. It is found
in many animals and some single cell organisms.
 As a medication, it is used to treat a number of
conditions including anaphylaxis, cardiac
arrest, and superficial bleeding. Inhaled
epinephrine may be used to improve the symptoms
of croup.
 It may also be used for asthma when other
treatments are not effective. It is given
intravenously, by injection into a muscle , by
inhalation, or by injection just under the skin.
Common side effects include shakiness, anxiety,
and sweating. A fast heart rate and high blood
pressure may occur. Occasionally it may result in
an abnormal heart rhythm. While the safety of its
use during pregnancy and breastfeeding is unclear,
the benefits to the mother must be into account.
PHYSIOLOGICAL EFFECTS:
 The adrenal medulla is a minor contributor to total

circulating catecholamines though it contributes over
90% of circulating epinephrine. Little epinephrine is
found in other tissues, mostly in scattered chromaffin
cells. Following adrenalectomy, epinephrine disappears
below the detection limits in the blood stream.
 The adrenal glands contribute about 7% of circulating
norepinephrine, most of which is a spill over from
neurotransmission with little activity as a hormone.
Pharamacological doses of epinephrine stimulate alpha
1,2,and beta 1,2, and 3 adrenoceptors of the sympathetic
nervous system,sympathetic nerve receptors are
classified as adnergic , based on their responsiveness to
adrenaline.
 Epinephrine does have a beta2 adrenoceptor
mediated effect on metabolism and the airway , there
being no direct neural connection from the
sympathetic ganglia to the airway.
 The concept of the adrenal medulla and the
sympathetic nervous system being involved in the
flight,fight and flight response was originally
proposed by cannon. But the adrenal medulla,in
contrast to the adrenal cortex, is not required for
survival. In adrenalectomized patients hemodynamic
and metabolic responses to stimuli such as
hypoglycemia and exercise remain normal.
PATHOLOGY:
 Increased epinephrine secretion is observed is

observed in phecohromocytoma, hypoglycemia,
myocardial infraction and to a lesser degree in
bening essential familial tremor. A general
increase in sympathetics neural activity is
usually accompained by increased adrenaline
secretion, but there is selectivity during hypoxia
and hypoglycemia , when the ratio of adrenaline
to noradrenaline is considerably increased.
Therefore, there must be some autonomy of the
adrenal medulla from the rest of the sympthetic
system.
 Myocardial infraction is associated with high levels of
circulating epinephrine, norepinephrine, particularly
in cardiogenic shock.
 Benign familial tremor is responsive to peripheral
beta adrenergic blockers and beta2 stimulation is
known to cause tremor. Patients with BFT were
found to have increased plasma epinephrine, but not
norepinephrine.
 Low,or absent, concentrations of epinephrine can be
seen in autonomic neuropathy or following
adrenalectomy.failure of the adrenal cortex, as with
addisons disease, can suppress epinephrine secretion.
MECHANISM OF ACTION
 As a hormone, epinephrine acts on nearly all body
tissues. Its actions vary by tissue type and tissue
expression of adnergic receptors. For example: high
level of epinephrine causes smooth muscle
relaxation in the airways but causes contraction of
the smooth muscle that lines most arterioles.
 Epinephrine acts by binding to a variety of adnergic
receptors. Epinephrine is a nonselective agonist of
all adnergic receptors, including the major subtypes
alpha1,alpha2, beta1,beta2, beta3.Epinephrine’s
binding to these receptors triggers a number of
metabolic changes. Binding to alpha adnergic
receptors inhibits insulin secretion by the pancreas,
stimulates glycogenolysis in the liver and muscle,
 And stimulates glycolysis and inhibits insulin
mediated glycogenesis in muscle. Beta adnergic
receptor binding triggers glucagon secretion in the
pancreas, increased adrenocorticotropic hormone
secretion by the pituitary gland, and increased
lipolysis by adipose tissue. Together, these effects
lead to increased blood glucose and fatty acids,
providing substrates for energy production within
cells throughout the body.
 Its actions are to increase peripheral resistance via
alpha1 receptor dependent vasoconstriction and to
increase cardiac output via its binding to beta1
receptors. The goal of reducing peripheral circulation
is to increase oxygen exchange at the cellular level.
 While epinephrine does increase aortic, cerebral, and
carotid circulation pressure, it lowers carotid blood
flow and end tidal co2 levels. It appears that
epinephrine may be improving macrocirculation at
the expense of the capillary beds where actual
perfusion is taking place.
DOSAGE
 Adrenalin 1ml single use and 30 ml multiple use
vial:
 Injection adrenalin intramuscular or subcutaneously
into anterolateral aspect of the thigh, through
clothing if necessary. When administering to a child,
to minimize the risk of injection related injury, hold
the leg firmly in place and limit movement prior to
and during an injection. The injection may be
repeated every 5 to 10 minutes as necessary. For IM ,
use a needle long enough(at least ½ inch to 5/8 inch)
to ensure the injection is administered into the
muscle. Monitor the patient for allergic reaction and
potential cardiac effects of the drug. Do not
administer repeated injections at the same site, as the
resulting vasoconstriction may cause tissue necrosis.
 Adults and children 30 kg or more 0.3 to 0.5 mg of
undiluted adrenalin administered IM or SC in the
anterolateral aspect of the thigh , up to a maximum of 0.5 mg
(0.5ml) per injection , repeated every 5 to 10 minutes as
necessary.
 Children less than 30 kg 0.01 mg/kg (0.01ml/kg) of undiluted
adrenalin administration IM or SC in the anterolateral aspect
of the thigh , up to a maximum of 0.3 mg (0.3ml) per injection,
repeated every 5 to 10 minutes as necessary.
 Adrenalin infusion pump preparation:
 Preparation:
 1 amp1ml (1:1000)= 1mg/ml
 Dilute 3.0mg(3ml) adrenalin with 47 mls of NS in 50 mls
syringe
 Rate : 1ml/hr=1mcq/min.
 Dose :110mcq/min. titrate accordingly to desired BP.
OVERDOSE:
 Epinephrine exerts its effects by interacting with
alpha and beta –adnergic receptors. Toxicity of
epinephrine in overdose is associated with
producing of so called “beta adnergic syndrome”.
Heart rate and cardiac contraction are increased
because of beta1 receptors stimulation, which
may lead to myocardial infraction , cardiac
arrest, and / or to potentially lethal arrhythmias.
Labetalol in the treatment of epinephrine
overdose. It is used to treat high blood pressure.
NOREPINEPHRINE
 Norepinephrine is similar to adrenaline. It works by
constricting (narrowing) the blood vessels and
increasing blood pressure and blood glucose levels.
 Norepinephrine is used to treat life threatening
low blood pressure that can occur with certain
medical conditions or surgical procedures. This
medication is often used during CPR.
 Contraindications:
 Vascular thrombosis
 Hypoxia, profound
 Hypercarbia
 Hslothane anesthesia
MECHANISM OF ACTION:
 It stimulate alpha1 and alpha2 adnergic receptors to
cause blood vessel contraction, thus increased blood
pressure. This effect also reduces the blood supply to
gastrointestinal tract and kidneys. Norepinephrine
acts on beta 1 adnergic receptors, causing increase
in heart rate and cardiac output.
 Interactions:
 See contraindications. Risk of ventricular

tachycardia or fibrillation with cyclopropane,
halothane anesthesia. Caution with MAOIs,
triptyline or imipramine antidepressants; may cause
prolonged hypertension.
 Dosage:
 Usual adult dose for hypotension:
 initial dose :8 to 12 mcg/min. continue IV infusion
 maintenance dose :2 to 4 mcg/min.
 continue IV infusion, until adequate blood pressure and
tissue perfusion are maintained without therapy
 Usual adult dose for sepsis: recommendations:0.01
to 3 mcg/kg/min.
 Use: for use in patients during sepsis or septic shock to
increase blood pressure.
 Usual adult dose for cardiac arrest:
Initial dose :8 to 12 mcg/min. continuous IV infusion
Duration of therapy: continue infusion until adequate
blood pressure and tissue perfusion are maintained
without therapy.
SIDE EFFECTS:
 Headache, a drop in the heart rate, arrhythmias, injury
to tissues or organs due to a reduction of oxygen,
anxiety, difficulty breathing.
 Norepinephrine drug preparation
through infusion pump:either add 2ml of
noradrenaline 1mg/ml to 48 ml 5% dextrose (or isotonic
dextrose saline) for administration by syringe pump,or
add 20 ml of noradrenaline 1mg/ml to 480ml 5% for
administration by drip counter.
.
ANTIDOTE OF OVERDOSE OF
NOREPINEPHRINE:
 Antidote for extravasation ischemia : to prevent
sloughing and necrosis in areas in which extraversion
has taken place, the area should be infiltrated as soon as
possible with 10ml to 15 ml of saline solution containing
from 5mg to 10 mg of Regitine (phentolamine), an
adnergic blocking agent. A syringe with a fine
hypodermic needle should be used , with the solution
being infiltrated liberally throughout the area which is
easily identified by its cold, hard, and pallid,
appearance. Sympathetic blockade with phentolamine
causes immediate and conpicuous local hyperemic
changes if the area is infiltrated within 12 hours.
Therefore, phentolamine should be given as soon as
possible after the extravasation is noted.
DOPAMINE:
 Dopamine is a medication form of a substance that
occurs naturally in the body. It works by improving
the pumping strength of the heart and improves
blood flow to the kidneys.
 Dopamine injection (intropin) is used to
treat certain conditions that occur when you are in
shock, which can be caused by heart attack, trauma,
surgery, heart failure, kidney failure, and other
serious medical conditions.
CONTRAINDICATIONS:
 Acidosis
 Heart ventricle rhythm problem
 Blockage or closing off of blood vessels
 Decreased oxygen in the tissues or blood
 Decreased blood volume.
 Allergies:
 Sympathomimetic agents.
 Its effects, depending on dosage, include an increase
in sodium excretion by the kidneys, an increase in
urine output, an increase in heart rate, and an
increase in blood pressure. At low dose it acts
through the sympathetic nervous system to increase
heart muscle contraction force and heart rate, there
by increasing cardiac output and blood pressure.
Higher doses also cause vasoconstriction that further
increases blood pressure.
 While some effects results from stimulation of
dopamine receptors , the prominent cardiovascular
effects result from dopamine acting at alpha1, beta1
and beta2 adnergic receptors.
DOSE:
 Dopamine is given by IV infusion.
 Low dose : 1 to 5 mcq/kg/min./IV to increase urine
output and kidney blood flow.
 Intermediate dose: 5 to 15 mcq/kg/min. IV to
increase kidney blood flow, cardiac output and
contractility, and heart rate.
 High dose: 20 to 50 mcq/kg/minute IV to increase
blood pressure and stimulate vasoconstriction: may
increase infusion by 1 to 4 mcq/kg/min. at 10 to 30
min. intervals until desired response (for example,
adequate blood pressure) is achieved.
USUAL ADULT DOSE FOR:
 Cardiothoracic surgery:
initial dose :2 to 10 mcg/kg/min. IV by continuous
infusion. Maintenance dose: 2 to 50 mcq/kg/min IV by
continue infusion.
 Congestive heart failure:
Initial dose:2 to 10 mcq/kg/min. IV by continuous infusion.
Maintenance dose: 2 to 50 mcq/kg/min IV by continue
infusion.
 Myocardial infraction:
Same dose.
 Renal failure , septicemia and shock:
same dose.
DRUG INTERACTION:
 Dopamine should not be used in patients with
abnormal heart rate and rhythm.
 Dopamine should not be used with medications like
selegiline,linezolid and MAIO inhibitors like
phenelzine isocarboxazid due to increased risk of a
hypertensive episode.
 Dopamine should not be used with tricyclic
antidepressants(for example, amitriptyline ) that
increase dopamine and norepinephrine due to
increased risk of hypertension and abnormal heart
rate and rhythm.
OVERDOSE:
 In the case of accidental overdose has occurred when high
doses were administered for prolonged periods or in
patients with occlusive vascular disease HCL until
patient’s condition stabilizes. If these measures fail to
stabilize the patient’s condition, use of the short –acting
alpha adnergic blocking agent phentolamine should be
considered.
 Suggested dilution: for the 40mg/ml
preparation, transfer by aseptic technique the contents
containing either 5ml,200mg or 10ml,400mg of dopamine
hydrochloride to either a 250ml or 500ml bottle of one of
the sterile I.V solutions. For the 80 mg/ml preparation,
transfer by aseptic techniques the contents containing
10ml, 800 mg of dopamine hydrochloride to a
250ml,500ml,or 1000ml bottle of one of the following
sterile I.V solutions
 Dosing consideration:
a. Strong beta1 adnergic, alpha adnergic, and
dopaminergic effects are based on dosing rate,
b. Beta1 effects: 210 mcq/kg/min.
c. Alpha effects:>10 mcq/kg/min.
d. Dopaminergic effects:0.52 mcq/kg/min.
Side effects:
 Dopamine may cause cardiac conduction
abnormalities (e.g., ventricular arrhythmia, atrial
fibrillation, widened QRS complex), tachycardia,
angina, palpitation, bradycardia, vasoconstriction,
hypotension, hypertension, dyspnea, nausea,
vomiting, headache, anxiety and gangrene of the
extremities.
DOBUTAMINE:
 Dobutamine is a sympathomimetic drug used in the

treatment of heart failure and cardiogenic shock. Its
primary mechanism is direct stimulation of beta1
receptors of the sympathetic nervous system.
 Clinical uses:
 Dobutamine is used to treat acute but potentially
reversible heart failure, such as which occurs during
cardiac surgery or in cases of septic or cardiogenic
shock, on the basis of its positive inotropic action.
 Dobutmine is used in cases of congestive heart failure
to increase cardiac output. It is indicated when
parenteral therapy is necessary for inotropic support
in the short term treatment of patients with cardiac
decompensation due to depressed contractility, which
could be the result of either organic heart disease or
cardiac surgical procedures. It is not useful in
ischemic heart disease because it increases heart rate
and thus increase myocardial oxygen demand.
 The drug is also commonly used in the hospital
setting as a pharmacologic stress testing agent to
identify coronary artery disease.
DOSAGE:
 At the time of administration, dobutamine injection
must be further diluted in an IV container. Dilute 20
ml of dobutamine in atleast 50ml of diluent and dilute
40 ml of dobutamine in atleast 100ml of diluent.
Dextrose injection 5%, dextrose 5% and sodium
chloride 0.45% injection, dextrose5% and sodium
chloride0.9% injection, dextrose injection 10%, isolyte
M with 5% dextrose injection, lactated ringer’s
injection intravenous solutions should be used with in
24 hours.
 Recommended dosage: the rate of infusion
needed to increase cardiac output usually ranged from
2.5 to 15 mcq/kg/min. on rare occasions, infusion rates
up to 40 mcq/kg/min. have been required to obtain the
desired effect.
HOW SUPPLIED:
 Dobutamine injection, USP, 12.5 mg/ml is
available as:
 20ml single dose vials containing 250 mg
dobutamine.
 40ml single dose vials containing 500 mg
dobutamine .
 Drug interaction:
 Nitroprusside : concomitant use of dobutamine
and Nitroprusside results in a higher cardiac
output and, a lower pulmonary wedge pressure
than when either drug is used alone.
 Dobutamine is a direct acting inotorpic agent whose
primary activity results from stimulation of the b
receptors of the heart while producing comparatively
mild chronotropic, hypertensive, arrhythmogenic, and
vasodilative effects. It does not cause the release of
endogenous norepinephrine, as does dopamine.
 Dobutamine Is contraindicated in patients with
idiopathic hypertrophic subaortic stenosis and in
patients who have shown previous manifestations of
hypersensitivity to dobutamine.
ADVERSE EFFECTS:
 Cardiovascular side effects are ectopic heartbeats,
increased heart rate, angina, chest pain,
palpitation and elevations in blood pressure. Less
frequent adverse events include nausea, vomiting,
tingling sensation, paresthesia, dysponea,
headache, reactions indicative of hypersensitivity
e.g. rash, fever, bronchospasm. Decreases in serum
potassium levels have been reported.
Overdose:toxicity from dobutamine is
usually due to excessive cardiac betareceptors
stimulation. The duration of action of dobutamine
is generally short because it is rapidly metabolized
by catecholo methytransferase.
 The symptoms may includes anorexia, nausea,
vomiting, tremor, headache, shortness of breath and
anginal symptoms.
 Treatment:
 The initial actions to be taken in a dobutamine overdose
are discontinuing administration, establishing an
airway, and ensuring ventilation and oxygenation.
Resusciative measures should be initiated promptly.
Severe ventricular tachyarrhythmias may be successful
treated with beta blocker or lidocaine . Hypertension
usually responds to a reduction in dose or
discontinuation of therapy. Protect the patient’s airway
and support ventilation and perfusion. Forced diuresis,
peritoneal or hemodialysis or charcol hemoperfusion
have not been established as beneficial for an overdose
of dobutamine.
DIGOXIN:
 Digoxin, sold under the brand name lanoxin among
others, is a medication used to treat various heart
conditions. Most frequently it is used for atrial
fibrillation, atrial flutter, and heart failure. Digoxin
is taken by mouth or by injection into a vein.
 Medical use:
 Irregular heart beat, heart failure, other digoxin is
also used intrafetally or aminotically during abortion
in the late second trimester and third trimester of
pregnancy. It typically causes fetal demise within
hours of administration.
 Digoxin inhibits sodium potassium ATPase, an enzyme
that regulates the quantity of sodium and potassium
inside cells. Inhibition of enzyme leads to an increase in
the intracellular concentration of sodium and thus an
increase in the intracellular concentration of calcium. The
beneficial effects of digoxin result from direct actions on
cardiac muscle as well as indirect actions on the
cardiovascular system mediated by effects on the
autonomic nervous system. It includes: a vagomimetic
action, which is responsible for the effects of digoxin on
the SA and AV nodes and baroreceptors sensitizaton,
which results in increased afferent inhibitory activity and
reduced activity of the sympathetic nervous system and
renin angiotensin system and renin angiotensin system
for any given increment in mean arterial pressure.
CONTRAINDICATIONS:
 Myxedema
 Low amount of magnesium in the blood
 High amount of calcium in the blood
 Heart attack
 Cor pulmonale
 Constrictive inflammation of sac surrounding the
heart
 Hypertrophic cardiomyopathy
 Ventricular fibrillation
 Sinus bradycardia
 Restrictive cardiomyopathy
 Kidney disease with likely reduction in kidney
function.
SIDE EFFECTS:
 Gynaecomastia (enlargement of breast tissue) due to
the estrogen like steroid moiety of digoxin molecule,
but when systematically sought. Loss of appetite,
nausea, vomiting trouble seeing , confusion, and the
irregular heart beat.
 Overdose:
 The usual supportive measures are needed. If
arrhytmias prove troublesome, or malignant
hyerkalaemia occurs , the specific antidote is digoxin
(antibody fragments against digoxin, trade names
digibind and digifab).
AMIODARONE
 Amiodarone is an antiarrhythmic medication used to treat
and prevent a number of types of irregular heartbeats. This
includes ventricular tachycardia, ventricular fibrillation
and wide complex tachycardia, as well as atrial fibrillation
and paroxysmal supraventricular tachycardia. It can be
given by mouth, intravenously , or intraosseously. When
used by mouth, it can take a few weeks for effects to begin.
 Medical uses:
 Amiodarone has been used both in the treatment of acute
lifethreatning arrthymias as well as the chronic
suppression of arrhythmias . It is used both in
supraventricular arrhythmias and ventricular
arrhythmias.
 Cardiac arrest, atrial fibrillation.
CONTRAINDICATIONS:
 Pregnancy
 Sinus nodal bradycardia
 Atrioventricular block
 Second or third degree heart block who do not have an
artificial pacemaker.
 Formulations of amiodarone that contain benzyl alcohol
should not be given to neonates, because the benzyl alcohol
may cause the potentially fatal “gasping syndrome”.
Mechanism of action:
 Increase the refractory periods in all cardiac tissues
 Decreases automaticity of fibers in the purkinje system
 Prolong AV conduction
 Can block potassium, sodium and calcium channels and

beta receptors.
Drug interaction:
 Amiodarone increases the plasma concentration of digoxin.
 Amiodarone increase the plasma concentration of
flecainide by inhibiting its metabolism
 Amiodarone can result in increased plasma concentration
of phenytoin
 It increase anticoagulant effect by inhibiting metabolism of
warfarin.
 Side effects:
 Hypothyroidism
 Hyperthyroidism
 Pulmonary fibrosis.
 Optic nerve neuropathy
 Loss of eyelashes
 Jaundice
 Hepatomegaly
 Hepatitis
 Blue –grey discoloration of skin
 Peripheral neuropathies
 Cancer specially main males with dose dependent effect
Dose:
Arrhythmias :
 Initial dose: 1000 mg over the first 24 hours of therapy.
loading infusions: 150mg over the first 10

minutes(15mg/min.), followed by 360 mg over the next 6 hours
(1mg/min).
Maintenance infusion: 540mg over the remaining 18
hours(0.5mg/min.).
 Maintenance dose: after the first 24 hours, Continue the
maintenance rate of 0.5mg/min , may increase infusion rate to
achieve effective arrhythmias suppression.
 Supplemental infusions: 150mg over 10 minutes(15
mg/min.) for breakthrough episodes of ventricular
fibrillation or hemodynamically unstable ventricular
tachycardia.
 Maximum dose: initial infusion rate :30 mg/min.
 Duration: until ventricular arrhythmias stabilize (most
patients require 48 to 96 hours); min can be continued for
up to 3 weeks. Mean dose greater than 2100 mg for the first
24 hours were associated with increased risk of hypotension.
 Oral: loading dose: 800to 1600 mg orally per day for 1 to 3
weeks.
 Overdose:therefore amiodarone side effects including
thyrotoxicosis may occur long after discontinuation of the
drug and may also be refractory. Cholestyramine, a bile
acid sequestrant has been shown to bind the thyroid
hormone excreted in the gut and prevent it from being
reabsorbed.
NEGATIVE INOTROPIC
AGENTS:
Beta blockers:
Beta blockers are particularly used to manage abnormal heart
rhythm, and to protect the heart from a second heart attack after
a first heart attack. They are also widely used to treat high blood
pressure , although they are no longer the first choice for initial
treatment of most patients.
Types:
There are three known types of beta receptors, known as beta1,
beta2, and beta3.
 Beta1 – adnergic receptors are located commonly in the heart
and kidneys.
 Beta2 – adnergic receptors are located mainly in the lungs ,
gastrointestinal tract , liver, uterus, vascular smooth muscle and
skeletal muscle.
 Beta3 – adnergic receptors are located in fat cells.
 List of examples of beta blockers:
a) Acebutolol
b) Atenolol
c) Betaxolol
d) Carteolol
e) Esmolol
f) Labetolol
g) Metoprolol
h) Nadolol
i) Propranolol
j) Sotalol
k) Timolol
 Beta blockers primarily block beta1 and beta2 receptors and
thereby the effects of norepinephrine and epinephrine. By blocking
the effects of norepinephrine and epinephrine, beta blockers reduce
heart rate, reduce blood pressure by dilating blood vessels, and may
constrict air passage by stimulating the muscles that surround the
air passages to contract considered an adverse side effects).
INDICATIONS:
 Cardiac arrhythmias
 Heart failure,
 high coronary artery disease risk
 Post heart attack
 Angina pectoris
 Hypertension.
 Mitral valve prolapse
 Essential tremor.
 Asthma, COPD
 Prinzmetala angina
 Bradycardia, heart block
 Acute decompensated heart failure
 Peripheral vascular disease.
SIDE EFFECTS:
 Beta blockers may causes:
 Diarrhea
 Stomach cramps
 Nausea
 Vomiting
 Others:
 Rashes
 Blurred vision
 Disorientation
 Insomnia
 Hair loss
 Weakness
 Muscle cramps and fatigue.
 Central nervous system effects:
 Headache , depression, confusion, dizziness,
nightmares, hallucination.
 Beta blockers that block beta2 receptors may cause
shortness of breath in asthmatics.
 Beta blockers may cause low or high blood glucose
and mask the symptoms of low blood glucose in
people with diabetes.
DRUG INTERACTIONS:
 Combining propranolol or with thioridazine or
chlorpromazine may result in low blood pressure and
abnormal heart rhythms because the drugs interfere with
each other’s elimination and result in increased levels of the
drugs.
 Dangerous elevations in blood pressure may occur when
clonidine is combined with a beta blockers. Blood pressure
should be closely monitor after initiation or discontinuation of
clonidine or beta blockers when they have been used
together.
 Aspirin and other NSAIDs like ibuprofen, may counteract the
blood pressure reducing effects of beta blockers by reducing
the effects of prostaglandins, which play a role in control of
blood pressure.
 Beta blockers may prolong hypoglycemia and mask symptoms
of hypoglycemia in diabetics who are taking insulin or other
diabetic medications
DOSAGE:
 Drug Loading dose Maintenance dose
 Atenolol 5 mg Oral, 50100mg
 Esmolo 0.5mg/kg/over15 min. 0.050.3mg/kg/min
 Labetalol 20mg in 2min. 210mg/min.
 Metoprolol – 2.55mg i.v. bolus oral, 25100mg/12h
over 2min.,
up to three doses
 Propranolol 0.15mg/kg 0.10 0.20mg/kg/min.
oral, 80240mg/day
BETA BLOCKERS OVERDOSE:
 Two beta blockers requires special consideration:
 Propanolol> cause sodium channel blockade> QRS
widening>treat with NaHCO3.
 Sotalol> causes potassium efflux blockade>long QT >
monitor for Torsades
 Clinical features:
 CVS :hypotension, bradycardia,Avblock, heart failure.
 Resp. bronhospasm
 Metabolic: hypoglycemia, hyperglycemia.
 Neuro: stupor, coma, seizures.
 Management:
 Resuscitation:
 Fluid, betaagonists, vasopressors, atropine, pacing.
 Acid base and electrolytes balance
 Decontamination : activated charcoal if <1hour.
 Antidotes:
 Glucagon 50mcg/kg up to 10mg>210mg/hr.
 High dose insulin euglycaemic therapy
 Consider intralipid if refractory to standard measures.
CALCIUM CHANNEL BLOCKERS:
 Calcium channel blockers prevent calcium from entering
cells of the heart and blood vessel walls, resulting in
lower blood pressure. Calcium channel blockers, also
called calcium antagonist, relax and widen blood vessels
by affecting the muscle cells in the arterial walls.
 Some calcium channel blockers have the added benefit
of slowing your heart rate, which can further reduce
blood pressure, relive chest pain and control an
irregular heartbeat.
 Example: some calcium channel blockers are available
in short – acting medications work quickly, but their
effects last only a few hours. Longacting medications
are slowly released to provide a longer lasting effects.
 Examples:
 Amlodipine
 Diltiazem
 Isradipine
 Nicardipine
 Nifedipine
 Nisoldipine
 Verapamil.
 In some cases , doctor may prescribe a calcium
channel blocker with other high blood pressure
medications or with cholesterol lowering drugs such
as statins.
 Calcium channel blockers are drugs that block the
entry of calcium into the muscle cells of the heart and
arteries.
 The entry of calcium is critical for condition of the
electrical signal that passes from muscle cell to muscle
cell of the heart, and signals the cells to contract.
 It also is necessary in order for the muscle cells to
contract and thereby pump blood.
 In the arteries , the entry of calcium into muscle cells
constricts the arteries.
 Thus, by blocking the entry of calcium, calcium channel
blockers reduce electrical conduction with in the heart,
decrease the force of contraction of the muscle cells, and
dilate arteries.
 Dilation of the arteries reduces blood pressure and
thereby the effort the heart must exert to pump
blood.
 Combined with decreases in the force of contraction,
this leads to a reduced requirement for oxygen by the
heart .
 Dilation of the arteries provide more oxygen carrying
blood to the heart.
 The combination of reduced demand for oxygen and
increased delivery of oxygen prevent angina or heart
pain.
 In addition, calcium channel blockers slow electrical
conduction through the heart and thereby correct
abnormal rapid heart beats.
USES OF CALCIUM CHANNEL
BLOCKERS:
 High blood pressure
 Coronary artery disease
 Chest pain
 Irregular heartbeats
 Some circulatory conditions such as Raynaud’s
disease.
 Heart failure
 Bradycardia
 Atrioventricular block
 Dihydropyridine calciumchannel blockers should not
be used in people with uncontrolled heart failure.
DRUG INTERACTIONS:
 Most of the interactions of calcium channel blockers
occur with verapamil or diltiazem. Because
verapamil and diltiazem decrease the elimination of
a number of drugs by the liver. Through this
mechanism they may reduce the elimination and
increase the blood levels of carbamazepine,
simvasatatin, atorvastatin and lovastatin. This can
leads to toxicity from these drugs. Grapefruit juice
(approximately: 200ml) may elevate blood
concentrations of felodipine, verapamil, nisolodipine,
nifedipine, and possibly amlodipine. Grapefruit juice
should not be consumed with in 2 hours before
calcium channel blockers.
DOSAGE
 Amlodipine:
 Hypertension :
 starting: 5mg once daily
 Maintenance: 510mg once daily
 Angina :
 Dosing: 510mg once daily
 Diltiazem:
 Angina:
 Starting: 30 mg four times a day
 Maintenance: 180360 mg a day
 Max.: 360 mg a day.
 FELODIPINE:
 Hypertension:
 Starting: 5 mg once daily
 Maintanence: 2.510 mg once daily
 Max. 10 mg once daily
 Nicardipine:
 Hypertension:
 Starting: 20mg three times a day
 Maintenance: 2040mg three times a day
 Max: 120mg a day
 Nifedipine:
 Angina:
 Starting: 10mg three times a day
 Maintenance: 1020 mg three times a day
 Max: 180 mg a day
 Nisoldipine:
 Hypertension:
 Starting:1720 mg once daily
 Maintanence: 17 40mg once daily
 Max.:40mg once daily.
 Varapamil:
 Hypertension:
 starting: 80 mg three timesa day
 Maintenance: 80120mg three times a day
 Max. 360 mg a day.
 Angina:
 Dosing: 80120mg three times a day
 Supraventricular arrhythmias:
 Dosing: 240480 mg a day
 Max. 480mg a day.
 Amlodipine:
 Hypertension:
 Starting: 2.5mg/10mg once daily
 Maintanence:2.5mg/10mg10mg/40mg once daily.
 Max.: 10mg/40mg once daily.
OVERDOSE:
 For severe overdose, treatment usually includes
close monitoring of vital signs and the additions
of vasopressive agents and intravenous fluids for
blood pressure support. Intravenous calcium
gluconate (or calcium chloride if a central line is
available) and atropine are first line therapies. If
the time of the overdose is known and
presentation is within two hours of ingestion,
activated charcoal, gastric lavage, and
polyethylene glycol may be used to
decontaminate the gut.
SIDE EFFECTS:
 Constipation
 Headache
 Palpitations
 Dizziness
 Rashes
 Flushing
 Nausea
 Swelling in the feet and lower legs
ANTIARRHYTHMIC AGENTS:
 Antiarrhythmic agents, also known as cardiac
dysrhythmia medications, are a group of pharmaceuticals
that are used to suppress abnormal rhythms of the heart
such as atrial fibrillation, atrial flutter, ventricular
tachycardia, and ventricular fibrillation.
 Classification:
 The five main classes in the vaughan williams
classification of Antiarrhytmic agents are:
 Class1 agents interfere with the sodium channel.
 Class2 agents are anti sympathetic nervous system agents.
Most agents in this class are beta blockers.
 Class3 agents affect potassium efflux.
 Class4 agents affect calcium channels and the AV node.
 Class5 agents work by other or unknown mechanisms.
 With regards to management of atrial fibrillation, classes 1
and 3 are used in rhythm control as medical cardioversion
agents, while classes 2 and 4 are used as ratecontrol agents.
 Class1 agents:
 The class 1 antiarrhythmic agents interfere with the sodium
channel. Class 1 agents are grouped by what effect they have
on the Na+ channel, and what effect they have on cardiac
action potentials. Class 1 agents are called membrane
stabilizing word is used to describe the decrease of
excitogenicity of the plasma membrane which is brought
about by these agents.
 Class 2 agents:
 Class2 agents are conventional beta blockers. They act by
blocking the effects of catecholamines at the beta1adnergic
receptors, thereby decreasing sympathetic activity on the
heart. These agents are particularly useful in the treatment
of supraventricular tachycardia. They decrease conduction
through the AV node.
 Class3: class 3 agents predominantly block the
potassium channels, thereby prolonging repolarization.
Since these agents do not affect the sodium channel,
conduction velocity is not decreased. The class3 agents
exhibit reverseuse dependence (their potency increases
with slower heart rates, and therefore improves
maintenance of sinus rhythm). Inhibiting potassium
channels, slowing repolarization, results in slowed atrial
ventricular myocyte repolarization. Class3 agents includes
amiodarone, sotalol, dofetilide,dronedarone.
 Class4 : class 4 agents are slow non dihydropyridine
calcium channel blockers. They decrease conduction
through the AV node, and shorten phase two of the cardiac
action potential . They thus reduce the cardiac action
potential. They thus reduce the contractility of the heart,
so may be inappropriate heart failure. These includes
verapamil and diltiazem.
 Class 5:agents includes:
 Digoxin ,which decrease conduction of electrical
impulses through the AV node and increases vagal
activity via its central action on the central nervous
system, via indirect action, leads to an increase in
acetylcholine production , leads to an increase in
acetylcholine production, overall decrease in speed of
conduction.
 Adenosine : is used intravenously for terminating
supraventricular tachycardia.
 Magnesium sulfate, an Antiarrhytmic drug, but only
against very specific arrhythmias which has been used
for torsades de pointes.
NURSING CONSIDERATIONS:
 Here are important nursing considerations when
administering cardiac glycosides:
 Nursing assessment:
 These are the important things the nurse should include in
conducting assessment, history taking, and examination.
 Assess for the mentioned contraindications to this drug to
prevent potential adverse effects.
 Conduct through physical assessment before beginning
drug therapy to establish baseline status, determine
effectivity of therapy and evaluate potential adverse effects.
 Obtain baseline status for weight while noting recent
manifestations that increase or decreases to determine
patient’s fluid status.
 Assess closely patient’s heart rate and blood pressure
to identify cardiovascular changes that may warrant
a change in digoxin drug dose.
 Auscultate heart sounds to note the presence of
abnormal sounds and possible conduction problems.
 Determine urinary pattern and output to assess gross
indication of renal function.
 Obtain baseline electrocardiogram to identify heart
rate and rhythm.
 Monitor serum electrolyte and renal function test
results to determine whether changes in drug dose is
needed or not.
SUMMARIZATION:
 It includes:
 Physiology of adnergic receptors
 Inotropic agents
 Positive inotropes
 Negative inotropes
 Epinephrine (positive agents)
 Norepinephrine
 Dopamine
 Dobutamine
 Digoxin
 Amiodarone
 Beta blockers (negative agents)
 Calcium channel blockers
 Antiarrhytmic drugs
 Nursing considerations

Inotropic Agents: Submitted To

Transféré par

Informations du document

Titre original

Copyright

Formats disponibles

Partager ce document

Partager ou intégrer le document

Options de partage

Avez-vous trouvé ce document utile ?

Ce contenu est-il inapproprié ?

Droits d'auteur :

Formats disponibles

Inotropic Agents: Submitted To

Transféré par

Droits d'auteur :

Formats disponibles

Inotropic agents

 Activation of alpha 1 and beta 2 receptors cause stimulatory

 Dilator muscle of the iris.

 Arrector pili muscle of hair follicles .

 While it is often recommended that vasopressors

 The adrenal medulla is a minor contributor to total

 Increased epinephrine secretion is observed is

 See contraindications. Risk of ventricular

 Dobutamine is a sympathomimetic drug used in the

 Can block potassium, sodium and calcium channels and

loading infusions: 150mg over the first 10

Vous aimerez peut-être aussi