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

OUTLINE  Physiology Review  Inotropes  Pressors  Antihypertensive

PHYSIOLOGY REVIEW

Google Images

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

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

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

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: Copyright © American Heart Association, Inc. All rights reserved.

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: Copyright © American Heart Association, Inc. All rights reserved.

INOTROPES

 Epinephrine (alpha + beta)  Cardiogenic shock, anaphylaxis, asystole/ACLS  Infusion dose ~ mcg/kg/min  Bolus dose 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

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

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: Copyright © American Heart Association, Inc. All rights reserved.

PRESSORS

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

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

ANTIHYPERTENSIVES

 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

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

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: , doi: /CIRCULATIONAHA