Cardiovascular MedicationsPICU Resident Talk
Stanford School of MedicinePediatric Critical Care Medicine
June 2014
ObjectivesDefine inotropy, chronotropy, lusitropy, and
vasopressor.List the determinants of BP and CO.Describe the receptor/ mechanism of action
of epi, norepi, dopamine, dobutamine, milrinone, phenylephrine, and nitroprusside.
List the major side effects of these medications.
DefinitionsInotropy—the force of muscle contraction,
most commonly cardiac muscle contractionChronotropy—affecting the heart rateLusitropy—relaxation function of cardiac
muscle and chambersVasopressor—producing a rise in blood
pressure through vasoconstriction
Definitions Bonus !
DromotropyBathmotropy
Definitions Bonus !
Dromotropy ~ running; increase AV conduction
Bathmotropy ~ threshold; increase excitability of cardiac cells
Determinants of Blood Pressure
Site of Action
Heart
Vascular Smooth Muscle
vasoconstriction
ChronotropyInotropy
Adrenoreceptors
vasodilation
Heart
β1 receptors:
Vascular Smooth Muscle
α1 receptors: vasoconstricti
onChronotropyInotropy
Adrenoreceptors
β 2 receptors: vasodilation
Heart
Vascular Smooth Muscle
NO & PDE Inhibitors
PDE3 Inhibitor: Vasodilation
NO → guanalyl cyclase:
vasodilation
PDE3 Inhibitor: Chronotropy
Inotropy
PDE Inhibitors
PDE 3 PDE 5
PDE Inhibitors
PDE 3 PDE 5
Milrinone SildenafilTadalafil
Milrinone
Increases CO
Diastolic relaxation Minimal increase HR and O2 demand
↓ SVR↓ PVR
T1/2 2-4 hrsFurther ↑ in renal impairment
The meds to choose from….
Dose: mcg/kg/min Mechanism /Therapeutic Effects Adverse Effects
Epinephrine
Norepinephrine
Dopamine
Dobutamine
Milrinone
Phenylephrine
Nitroprusside
β1 ↑ HR, ↑ inotropy β2 vasodilatationα1 vasoconstriction ↑ SVR
α1 vasoconstriction ↑ SVRβ1 ↑ HR, ↑ inotropy Min β 2 effects
D1 diuresis, natriuresis, renal vasodilatation, (No proven benefit in preventing AKI or ↓ mortality)
β1 ↑ HR, ↑ inotropy
α1 effects vasoconstriction ↑ SVRβ1 ↑ HR, ↑ inotropy Mild β2, α1 antagonist vasodilation ↓ PVR, SVR
Phosphodiesterase Inhibitor (PDE3 inhibitor):Myocardial : ↑ cAMP ↑contractility + lusiotropyVasculature: ↑ cAMP vasodilatation ↓ SVR/PVRα1 vasoconstriction ↑ SVR
NO activates guanalyl cyclase (in vasc smooth muscle) ↑cGMP vasodilation
Arrhythmia↑myocardial O2 demandIschemic injury due to potent vasoconstriction↑ After load
Arrhythmia↑myocardial O2 demand
Arrhythmia, hypotension↑myocardial O2 demandHypotension, arrhythmia T1/2 ↑ in renal impairment Ischemic injury due to potent vasoconstriction↑ afterloadCyanide toxicity↑ V/Q mismatch
0.01- 1
0.01- 1
< 5
5 -10
>10
5-20
0.25 -1
0.1-5
0.1-4
Dopamine Dobutamine Epinephrine
DopamineDobutamineEpinephrine
Norepinephrine
Milrinone
Increase SVRHigh dose EpiNorepinephrineHigh dose Dopa (>10)Phenylephrine
Decrease SVRLow dose Epi, NitroprussideMilrinoneDobutamine
Some interesting studies…Dopamine increases risk of infections - Inhibits anterior pituitary function & so ↓ prolactin, GH,
TSH. 1-3
- Prolactin and growth hormone have immunestimulatory properties.4
- Inhibits lymphocyte proliferation, immunoglobulin synthesis, cytokine production, and promote lymphocyte apoptosis. 5-8
- Chronotropic and inotropic effects increases myocardial oxygen demand, may not be adequately met by coronaries risk of tachycardia and tachy-arrhythmias. 9
- Beta adrenergic properties of dopamine predominate in sepsis10
Some interesting studies…Septic patients treated with dopamine had a higher incidence of
arrhythmias than those treated with norepinephrine.1
Norepinephrine is a more potent vasopressor than dopamine, with norepinephrine being more effective in reversing the hypotension of septic shock.2
In patients with sepsis, norepinephrine increases blood pressure, as well as cardiac output, renal, splanchnic, cerebral blood flow, and microvascular blood flow while minimally increasing heart rate.1,3,4
By achieving these hemodynamic goals, norepinephrine may be better than dopamine in maintaining organ perfusion.
We did not talk…Ionized calciumVasopressin Isoproterenol
Ionized Calcium Central role in maintaining myocardial
contractilityEffects mediated via intracellular
concentration, calcium requirements of the muscle cell, sensitivity of the myofilaments to calcium
Agents that increase intracellular cAMP increase intracellular calcium requirements for contraction, thus encouraging smooth muscle relaxation and vasodilation
Angiotensin IIHyperosmolarityDecreased atrial receptor firing sympethatic stimulation
Vasopressin
Vasoconstriction
Renal fluid reabsorption
Increased blood pressure
IsoproterenolSynthetic catacholamine. Non specific beta, no alpha. Causes inotropy, chronotropy, and systemic
and pulmonary vasodilatation. Indications: bradycardia, decreased cardiac
output, bronchospasm (bronchodilator).
THANK YOU !