IONOTROPES
AND
IONODILATERS
INTRODUCTION
➢An
inotrope is an agent, which increases
the force or energy of muscular
contractions of heart.
➢In 1785 the first inotrope-Digitalis was
discovered & used for CCF
➢they enhance myocardial contractility,
cardiac output, the amount of blood
ejected by the heart with each beat, will
also increase.
Three clinically approved inotropes
➢ Cardiac
Glycosides: - Digitalis Derivatives
Digoxin
➢ Sympathomimetics: Epinephrine
Dopamine (Intropin)
Dobutamine (dobutrex)
Norepinephrine (levophed)
Isoproterenol (isuprel)
➢
Phosphodiesterase Inhibitors: Amrinone (Inocor)
Milirinone (Primacor)
CARDIAC GLYCOSIDES
➢ The
first line of inotropes include all digitalis derivatives
➢ Digitalis Glycosides have
➢ A direct effect on cardiac muscle and the conduction
system.
➢ An indirect effect on the cardiovascular system
regulated by the
➢
autonomic nervous system which is responsible for
the effect on the sino-atrial (SA) and atrioventricular
(AV) nodes.
The result of these direct and indirect effects are: An increase in force and velocity of myocardial
contractility (positive inotrope effect).
Slowing of heart rate (negative chronographic
effect).
Decreased conduction velocity through the AV
node.
DIGOXIN
Digoxin is the most commonly prescribed cardiac
glycoside
➢ Convenient pharmacokinetics,
➢ Alternative routes of administration
➢ Widespread availability of serum drug level
measurement.
DIGOXIN ADMINISTRATION
➢Digoxin can be administered intravenously or orally.
➢IV injection should be carried out over 15 minutes to avoid
vasoconstriction responses.
➢Intramuscular Digoxin is absorbed unpredictably, causing
local pain, and is not recommended.
DIGOXIN LOADING DOSE
➢
Loading doses of Digoxin range from 10 – 15mg/kg.
➢
Digoxin can be given orally, but with a slower onset of
action and peak effect.
DIGOXIN MAINTENANCE DOSE:Initial therapy of Digoxin is usually started at 0.125 to
0.375mg/day.
NOTE: DRAW A SERUM DIGOXIN LEVEL AT LEAST
SIX HOURS AFTER THE LAST DOSE!
SIDE EFFECTS ASSOCIATED WITH TOXICITY:➢
GASTROINTESTINAL: Anorexia, nausea, vomiting,
diarrhea Rare: abdominal pain, hemorrhagic
necrosis of the intestines.
➢ CNS: visual disturbances, (blurred or yellow
vision), headache, weakness, dizziness, apathy
and psychosis.
➢ CARDIAC: Pulsus bigeminus,ventricular
extrasystole,ventricular tachycardia and
fibrillation,severe bradycardia,atrial
extrasystole,AF
➢ OTHER: Skin rash, gynecomastia
contraindication
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Hypokalemia(enhances digitalis toxicity by binding
to Na+-K+ATPase)
Elderly renal, hepatic disease
Myocardial infarction
Thyrotoxicosis
Myxoedema
Ventricular tachycardia
Partial AV block
Acute myocarditis
Slow digitalization
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Maintenance dose of digoxin(0.125-0.25 mg/day)
is given
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Full response seen after 5-7 days
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If no response after 1 wk, increase the dose to
0.375mg/day and then 0.5 mg after another wk.
RAPID ORAL DIGITALIZATION
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Digoxin 0.5-1 mg stat followed by 0.25 mg every 6
hrly
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Careful monitoring and watch for toxicity till the
response occurs in 6-24 hrs.
i.v. digitalization
Digoxin 0.25mg followed by 0.1 mg hrly by
slow i.v. inj. Till response occurs in 2-6 hrs.
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SYMPATHOMIMETICS (ADRENERGIC)
Sympathomimetic drugs exert potent
inotropic effects by
stimulating beta (B1 and B2), alpha
(A1 and A2) and dopaminergic receptors in the
myocardium, blood vessels, and sympathetic
nervous system.
ALPHA 1 (A1):
A1 receptor are present in vascular smooth muscle
➢ Stimulation of A1 receptors leads to vasoconstriction.
➢
ALPHA 2 (A2):➢ A2 receptors are located in large blood vessels.
➢
Stimulation of A2 receptors mediates arterial and venous
vasoconstriction.
BETA 1 (B1):Beta 1 receptors increase heart rate and myocardial
contractility.
BETA 2 (B2):Beta 2 receptors enhance vasodilation; relax bronchial, uterine
and gastrointestinal smooth muscle
DOPAMINERGIC: Related to the effect of dopamine.
DOPAMINE (INTROPIN)
(200mg/5ml ampule).
➢A
➢
chemical precursor of epinephrine.
Possessing alpha and beta and dopaminergic
receptor – simulating actions.
➢ The
specific effects are related to the dose delivered.
LOW DOSE
0.5- 2mcg/kg/minute (Dopaminergic effect).
➢ Vasodilation
of renal and mesenteric arteries.
➢ Promote
blood flow and increased GFR (glomerular
filtration rates in patients who become resistant to
diuretics).
➢ Urine
output may increase without significant effect on
blood pressure or heart rate.
INTERMEDIATE DOSE
2 to 10 mcg/kg/minute
➢Beta-adrenergic
receptor activity is
increased in the heart.
antagonism of alpha – adrenergic
receptors will mediate vasoconstriction.
➢Partial
➢Modest
increase in systemic vascular
resistance increases cardiac output &
CVP
DOPAMINE ADMINISTRATION
CONCENTRATIONS
Remove 5ml from 100ml 5% Glucose ,add 200 mg
Dopamine, final concentration 2000mcg/ml.
OR
Make the concentration half with 50 ml of 5% Dextrose.
Indication:
Renal protection.
➢ Hypotension/haemodynamic
compromise due to MI, trauma,
sepsis, CCF.
➢ Increases mesenteric flow in
mesenteric ischaemia.
Contraindication: -
➢Pregnancy.
➢Phaeochromocytoma.
➢Tachyarrhythmia.
➢Occlusive vascular disease.
WARNING:
Correct hypovolemiaprior to administration.
➢ Do not infuse peripherally.
➢ Extravasations can cause severe tissue necrosis.
➢ Monitor the patient carefully for decreased
circulation in the extremities.
If extravasates into tissues➢The infusion should be immediately stopped.
➢Infiltrate with 0-15ml 0.9% Sodium Chloride containing 5-10mg
Phentolalmine.
➢Regitine is then administered Sub cut. in the four 90°quadrants
around the site of extravasations.
ADVERSE EFFECTS:
➢Tachycardia
➢Supraventricular tachycardia
➢Ventricular arrhythmias
➢Pulmonary congestion
➢Nausea
➢Vomiting
➢Headache.
➢Increased myocardial oxygen demand.
➢Hypotension when used concomitantly with dilantin
DOBUTAMINE (Dobutrex)
(250mg in 20ml ampule)
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Drug class:Catecholamine.
Mechanism of action:➢Chemically related to dopamine.
➢Synthetic catecholamine.
➢Stimulates Beta 1 and Alpha-adrenergic receptors.
➢Increases myocardial contractility, stroke volume and
cardiac output.
➢Decreases preload and afterload (Vasodilatation)
➢Produces mild chronotropic, hypotensive and arrythmogenic
effects.
➢Increase renal and mesenteric blood flow by increasing
cardiac output.
➢Does not affect renal blood flow like dopamine.
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Initial dose: 2 to 3 mcg/kg/minute.
Usual dose: 2.5 to 10 mcg/kg/minute.
Desired effects include:
1. Increased cardiac output
2. Increased stroke volume
This dose will not increase heart rate or cause
vasoconstriction.
➢ Maximum
dose: 20 mcg/kg/minute.
➢ Dobutamine administration concentrations: Infusion pump: 500 mg per 250 cc normal
saline
Syringe pump: 250 mg (20cc) in total 50 cc
normal
saline (5 mg per cc)
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Contraindication:Idiopathic hypertrophic subaortic stenosis.
Nursing implication: ➢Monitor for hypertension, tachycardia, chest pain, and premature
ventricular contractions.
➢Monitor cardiac output, pulmonary artery pressure ECG
➢Correct hypovolemia before treating with this drug.
➢Patient with atrial fibrillation should be digitalized before giving this
drug to prevent ventricular tachycardia.
Warning: Increasing the rate past 20 mcg/kg/minute
could be detrimental because myocardial
oxygen consumption can cause tachycardias.
Adverse effects:➢ Tachycardia
➢ Arrhythmias
➢ Blood pressure fluctuation
➢ Myocardial ischemia
➢ Headache
➢ Nausea
➢ Tremors
➢ Hypokalemia
Dopexamine
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Analogue of dopamine
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Less beta-1 effect
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More selective for renal perfusion
FELODOPAM
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Have same benefits as dopamine
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Little alpha or beta receptor action
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Increases renal blood flow
EPHEDRINE
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NON CATECHOLAMINE AND HAS DIRECT
EFFECT ON B.P., HR contractility and cardiac
output
Mainly used as vasopressor, doesn’t decrease
uterine blood flow
Possess anti-emetic property because of
hypotension following spinal anaesthesia
NOREPHINEPHRINE (LEVOPHED)
Drug class: ➢ Catecholamine.
➢ Endogenous catecholamine released from nerve cells, synthesized by
adrenal medulla.
➢ Metabolized mainly by the liver.
Mechanism of action: ➢Potent alpha – receptor agonist, leads to arterial and venous
constriction.
➢Minimal effect on beta 2 receptors.
➢Increases myocardial contractility due to its beta 1 adrenergic effects.
➢Effective in septic shock and neurogenic shock after adequate
hydration.
➢Increases blood flow to the major organs including the kidneys and
helps in increases urine output.
➢ Initial
dose: 0.5 mcg/minute to 1 mcg/minute
Titrate to desired effect
➢ Average dose:2 to 12 mcg/minute
Doses greater than 30 mcg/minute
might be required during shock.
Norepinephrine administration concentration:Infusion pump: 4 mg per 250 c crystalloid (16
mcg/cc)
Nursing implication:-
➢Extravasations produces ischemic necrosis
and sloughing of superficial tissues.
➢Use of a central line is recommended due to
the risk of extravasations into surrounding
tissue.
➢Rebound hypotension occurs if it is
discontinued abruptly.
➢Its use should be temporary.
➢Monitor for bradycardia or arrhythmias.
EPINEPHRINE
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Drug class: Catecholamine.
Endogenous catecholamine, produced,
stored, and released by the adrenal medulla.
Mainly eliminated via kidneys.
Mechanism of action: ➢Stimulation of alpha and beta-adrenergic receptors causes
vasoconstriction.
➢Increases heart contractility and rate.
➢Causes bronchodilation.
➢Antagonizes histamine effect.
Dosage: Initial dose 0.5-1mg IV.
Or
1.5-3mg via ETT.
Maintain drip of 1-4 mcg/minute. Titrate to
BP.
Common contraindication: ▶
➢Hypertension.
➢Pheochromocytoma.
➢Caution with heart failure angina and hyperthyroidism.
Adverse effects: -
➢Cardiac Arrhythmias
➢ Palpitations
➢Tachycardia
➢ Sweating
➢ Nausea and vomiting
➢Respiratory difficulty
➢Pallor
➢Dizziness
➢Weakness
➢Tremors
➢Headache
➢Apprehension
➢Nervousness
➢ Anxiety
Nursing implication: -
➢Monitor ECG.
➢Observe for ventricular ectopy.
ISOPROTERENOL (ISUPREL)
➢Has nearly pure beta-adrenergic receptor activity.
➢Increase heart rate and contractility and cause peripheral
vasodilation.
➢Used for temporary control of symptomatic bradycardia.
➢Initial drug of choice for heart transplant.
➢Increases myocardial oxygen requirements and the possibility of
inducing or exacerbating myocardial ischemia is present.
➢The risk of arrhythmias is also increased.
➢It is not the first treatment of choice for bradycardias.
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Atropine, epinephrine or pacing should be initiated
first.
DOSE: ➢ Initial dose of 2 mcg/minute
➢ Titrate dose to a maximum of 10 mcg/min. or heart rate is 60
or greater.
➢ Decrease the rate if blood pressure is >120/60
➢ Decrease rate if PVC’s or Ventricular tachycardia is noted.
Isoproterenol administration concentration: ➢ 1 mg in 250 cc crystalloid (4 mcg/cc).
Adverse effects: ➢Arrhythmias.
➢Ventricular tachycardia.
➢Ventricular fibrillation.
Warning:➢ May exacerbate tachyarrhythmias due
to digitalis toxicity.
➢ May precipitate hypokalemia.
PHOSPHODIESTERASE INHIBITORS
Powerful positive inotropic agents.
The action is not fully understood.
➢ Inhibits phosphodiesterase, an enzyme that degrades (CAMP)
➢ Cyclic Adenosine Monophosphate.
➢ There is no effect on alpha or beta-receptors.
➢ Increase contractile force and velocity of relaxation of cardiac
muscle.
➢ Increasing cardiac output without increasing myocardial
➢
oxygen consumption.
➢ They cause vasodilation and a decrease in SVR (systemic
➢
vascular resistance) and PVR (Pulmonary vascular
➢
resistance & in afterload (resistance to ventricular ejection)
AMRINONE (INOCOR)
➢ Has
a hemodynamic effect similar to Dobutamine.
➢ Increase cardiac output and decrease pulmonary
vascular resistance.
➢ It should be used with caution in patients with ischemic
heart disease because it can exacerbate ischemia.
➢ It should be considered for use in patients with severe
congestive heart disease, which is no longer responsive
to other inotropes, diuretics, and vasodilators.
➢ It is also used after aorto-coronary bypass surgery.
➢ It is recommended that the lowest dose that produce
the desired hemodynamic effect to be used.
LOADING DOSE:
0.5 TO 0.75 mg/kg given over 2-3 min. IV
DO NOT EXCEED 1 mg/kg.
Maintenance dose: 5 to 10 mcg/kg/min
Maximum dose:10mg/kg/24hours.
Doses higher than 15 mcg/kg/minute can produce
tachycardia
NEVER DILUTE WITH DEXTROSE! ---Chemical
reaction occurs
Syringe pump: Use SALINE Solution
Concentration 5 mg/cc
Adverse reaction: -
➢Thrombocytopenia occurs in 10% of all patients seen 48
– 72 hours after infusion and resolves when drug is
discontinued.
➢Gastrointestinal upset
➢Myalgia
➢Fever
➢Hepatic dysfunction
➢Ventricular irritability
Nursing implication: -
➢Monitor for arrhythmias, hypotension, thrombocytopenia
& hepatotoxicity.
➢Monitor cardiac output, pulmonary artery pressure and
heart rate.
➢Effects last for 2 hours after drip is discontinued.
➢The loading dose may be given over 2 to 5 minutes, but
to prevent Hypotension it is recommended the loading
dose be given over 10 to 15 minutes.
MILRINONE (Primacor)
➢ Milrinone
is about 10 fold more potent than Amrinone.
➢ A positive inotropic agent that increases cardiac
output and decreases systemic vascular resistance.
➢ Because of its vasodilating effect, Milrinone is not
generally associated with an increase in myocardial
oxygen demand.
➢ Milrinone can be diluted in dextrose or saline solution.
LOADING DOSE:50 mcg/kg given IV over 10 minutes
MAINTENANCE DOSE:0.375 to 0.75 mcg/kg/minute
Warning; DOSES TO HIGH CAN CAUSE HYPOTENSION
AND TACHYCARDIA.
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VESNARINONE
MILRINONE IS INCOMPATIBLE WITH LASIX!
ADVERSE EFFECTS:
➢ Supraventricular
tachycardia
➢ Ventricular arrhythmias
➢ Ventricular ectopy
➢ Increased ventricular rate in atrial
fibrillation/flutter
➢ Headache
➢ Hypokalemia
➢ Tremors
➢ Thrombocytopenia
Levosimendan
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Sensitize trop.C to Ca.
Reduce peripheral vascular resistance
Enhance Lt. ventricular functions
Doesn’t increase myocardial O2 uptake
Reduces BNP , NT-proBNP ,plasma endothelin 1
levels
Acts on Mito. ATP senstive K+ channels (protects
cardiac ischemic perfusion damage)
Infused at 0.05-0.6mcg/kg/min i.v.
CONCLUSION
Cont…
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