1. Cardiovascular Medications PICU Resident Talk Stanford School of Medicine Pediatric Critical Care Medicine June 2010

2. Objectives After this lesson, the participant will be able to: Define 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.

3. Definitions Inotropy—the force of muscle contraction, most commonly cardiac muscle contraction Chronotropy—affecting the heart rate Lusitropy—relaxation function of cardiac muscle and chambers Vasopressor—producing a rise in blood pressure through vasoconstriction

4. Why do we use vasoactives/ionotropes? To improve blood pressure Why do we want to improve blood pressure? To improve oxygen delivery to tissues What determines blood pressure?

6. Where do cardiovascular medications work?

7. Heart β1 receptors: Vascular Smooth Muscle α 1 receptors: vasoconstriction Chronotropy Inotropy Adrenoreceptors β 2 receptors: vasodilation

8. Heart Vascular Smooth Muscle NO & PDE Inhibitors PDE 3 Inhibitor: vasodilation NO → guanalyl cyclase: vasodilation PDE 3 Inhibitor: Chronotropy Inotropy

9. The meds to choose from….

10. Dose: mcg/kg/minMechanism /Therapeutic EffectsAdverse Effects Epinephrine Norepinephrine Dopamine Dobutamine Milrinone Phenylephrine Nitroprusside β1  ↑ HR, ↑ inotropy β2  vasodilatation α1  vasoconstriction  ↑ SVR β1  ↑ 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  ↑ SVR β1  ↑ HR, ↑ inotropy Mild β2, α1 antagonist  vasodilation  ↓ PVR, SVR Phosphodiesterase Inhibitor (PDE 3 inhibitor): Myocardial : ↑ cAMP  ↑contractility + ↑lusiotropy Vasculature: ↑ cAMP  vasodilatation  ↓ SVR/PVR α1  vasoconstriction  ↑ SVR NO activates guanalyl cyclase (in vasc smooth muscle)  ↑cGMP  vasodilation Arrhythmia ↑myocardial O 2 demand Ischemic injury due to potent vasoconstriction ↑ afterload Arrhythmia ↑myocardial O 2 demand Arrhythmia ↑myocardial O 2 demand Hypotension Arrhythmia Ischemic injury due to potent vasoconstriction ↑ afterload Cyanide toxicity ↑ V/Q mismatch 0.01- 1 < 5 5 -10 >10 5-20 0.25 -1 0.1-5 0.1-4

11. Summary of Key Points Dopamine Dobutamine Epinephrine Dopamine Dobutamine Epinephrine Norepinephrine Milrinone Increase SVR High dose Epi Norepinephrine High dose Dopa (>10) Phenylephrine Decrease SVR Low dose Epi, Nitroprusside Milrinone Dobutamine