Cardiovascular Medications

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 !