1. PRESSORS & ANTIHYPERTENSIVES Luis R. Sauceda-Cerda, MD PGY-4

2. OUTLINE  Physiology Review  Inotropes  Pressors  Antihypertensive

3. PHYSIOLOGY REVIEW

4. Google Images

5. ADRENERGIC RECEPTORS  α1: peripheral vasoconstriction  a2: pre-synaptic negative feedback. CNS depressant.  β1: +chronotropy, +inotropy, +dromotropy  β2: peripheral vasodilation, bronchodilation

6. DOPAMINERGIC RECEPTORS  D1: vasodilation to coronary, cerebral, mesenteric, renal vasculature  D2: vasodilation and increased blood flow to renal tissue

7. Figure 3. A, Endogenous catecholamine synthesis pathway. Christopher B. Overgaard, and Vladimír Džavík Circulation. 2008;118:1047-1056 Copyright © American Heart Association, Inc. All rights reserved.

8. Figure 2. Schematic representation of postulated mechanisms of intracellular action of α1- adrenergic agonists. α1-Receptor stimulation activates a different regulatory G protein (Gq), which acts through the phospholipase C system and the production of 1,2-diacylglycerol (DAG) and, via phosphatidyl-inositol-4,5-biphosphate (PiP2), of inositol 1,4,5-triphosphate (IP3). Christopher B. Overgaard, and Vladimír Džavík Circulation. 2008;118:1047-1056 Copyright © American Heart Association, Inc. All rights reserved.

9. Figure 1. Simplified schematic of postulated intracellular actions of β-adrenergic agonists. β- Receptor stimulation, through a stimulatory Gs-GTP unit, activates the adenyl cyclase system, which results in increased concentrations of cAMP. Christopher B. Overgaard, and Vladimír Džavík Circulation. 2008;118:1047-1056 Copyright © American Heart Association, Inc. All rights reserved.

10. INOTROPES

11.  Epinephrine (alpha + beta)  Cardiogenic shock, anaphylaxis, asystole/ACLS  Infusion dose ~0.01-0.1 mcg/kg/min  Bolus dose 5-1000 mcg  More beta activity at lower doses.  Pro-arrhythmic, lactic acidosis, hyperglycemia  Dobutamine (beta 1 + beta 2)  Cardiogenic shock, bradyarrythmias  Infusion dose 2-20 mcg/kg/min  Pro-arrhythmic, hypotension  Isoproterenol (beta 1 + beta 2)  Bradyarrythmias  Infusion dose 2-10 mcg/min  Pro-arrhythmic, hypotension

12. INOTROPES  Dopamine (dopamine, beta, alpha activity)  Shock, bradyarrythmias  Infusion dose 0.5-20 mcg/kg/min  Dopaminergic 0.5-3 mcg/kg/min  Beta 3-10 mcg/kg/min  Alpha 10-20 mcg/kg/min  Pro-arrhythmic, renal protection not proven  Milrinone (phosphodiesterase inhibitor)  Cardiogenic shock  Pro-arrhythmic, hypotension

13. Figure 4. Basic mechanism of action of PDIs. PDIs lead to increased intracellular concentration of cAMP, which increases contractility in the myocardium and leads to vasodilation in vascular smooth muscle. Christopher B. Overgaard, and Vladimír Džavík Circulation. 2008;118:1047-1056 Copyright © American Heart Association, Inc. All rights reserved.

14. PRESSORS

15.  Norepinephrine (predominantly alpha)  Vasodilatory and cardiogenic shock  Infusion dose 0.01-3 mcg/kg/min  Peripheral ischemia  Phenylephrine (alpha-1 agonist)  Vasodilatory shock  Infusion dose 0.1-9 mcg/kg/min  Bolus 100 mcg or more.  Reflex bradycardia, peripheral and visceral vasoconstriction

16. PRESSORS  Ephedrine  Indirect sympathomimetic  Vasopressin (V1, V2)  Vasodilatory and cardiogenic shock, cardiac arrest  Infusion dose 0.01-0.1 units/min  Sepsis 0.04 units/min  Bolus 1-40 units IV

17. ANTIHYPERTENSIVES

18.  β-blockers  Esmolol: B1 selective, short acting  Metoprolol: B1 selective  Labetalol: alpha1 and nonselective beta blocker  ACE-I  Captopril (ICU): short acting, easily titratable.  a2-agonists  Central receptors decrease sympathetic outflow.  PO Clonidine & IV Dexmedetomidine  Sedation, dry mouth, depression, hypertensive crisis on abrupt withdrawal

19. ANTIHYPERTENSIVES  Vasodilators  Nitroglycerin: short acting, primarily venodilator  Hydralazine: reflex tachycardia, primarily arteriodilator  Calcium Channel Blockers  Nicardipine: arterioles and cardiac muscle

20. REFERENCES  Contemporary Reviews in Cardiovascular Medicine: Inotropes and Vasopressors: Review of Physiology and Clinical Use in Cardiovascular Disease Christopher B. Overgaard and VladimírDžavík Circulation. 2008;118:1047-1056, doi:10.1161/CIRCULATIONAHA.107.728840