#EPINEPHRINE ( #Adrenaline) : Pharmacological Highlights

🔻Epinephrine is an agonist of alpha 1, β1 , and β2 adrenoceptors. An intravenous infusion of epinephrine produces an increase in mean arterial pressure (MAP) characterized by selectively enhanced systolic pressure with no change in diastolic pressure. 

🔻Epinephrine exerts positive chronotropic and inotropic actions by stimulation of β1 adrenoceptors

🔻Epinephrine also increases the rate of myocardial relaxation and enhances early LV filling, thereby improving diastolic function. These combined effects result in a dramatic increase in cardiac output.

🔻Epinephrine (0.01–0.03 ug kg –1 min –1 ) has been shown to produce similar hemodynamic effects with less pronounced tachycardia than dobutamine (2.5–5.0 ug kg–1 min–1 ) in patients after coronary artery bypass graft (CABG) surgery

🔻Predictable increase in cardiac output, favours the use of epinephrine as the primary inotropic drug for the management of LV dysfunction after cardiopulmonary bypass

🔻Epinephrine causes direct positive dromotropic effects ( leading to increase in conduction velocity and reduction of the refractory period of the AV node, His bundle, Purkinje fibers, and ventricular muscle)

🔻This may contribute to detrimental increases in ventricular rate in patients with atrial flutter or fibrillation and the occurrence of ventricular arrhythmias

🔻The overall effect of epinephrine on blood flow to a specific organ depends on the relative balance of alpha 1 and β2 adrenoceptors located in the vasculature.

🔻β2 -Adrenoceptors are sensitive to lower doses of epinephrine and, as a result, peripheral vasodilation and modest reductions in arterial pressure are observed with such doses

🔻In contrast, the effects of epinephrine on alpha 1 -adrenoceptors predominate at greater doses with marked increases in systemic vascular resistance and arterial pressure.

🔻The intense vasoconstriction produced by high doses of epinephrine may adversely impede LV ejection by increasing after load after cardiopulmonary bypass. Thus, greater doses of epinephrine may be used in combination with arterial vasodilators such as sodium nitroprusside to optimize contractile performance in such situations .

🔻Adrenaline via alpha 1 receptors also mediates (1) venoconstriction & enhanced venous return (2) Pulmonary vasoconstriction and increases in pulmonary arterial pressures.

🔻 Pre-existing β-blockade by nonselective β-blocker propranolol abolishes the decrease in systemic vascular resistance from epinephrine-induced stimulation of β2 adrenoceptors and potentiates peripheral vasoconstriction mediated by unopposed alpha 1 adrenoceptors.

🔻The positive inotropic and chronotropic effects of epinephrine are also attenuated in the presence of pre-existing β-blockade and greater doses of epinephrine are required to overcome this competitive blockade

🔻Complete pharmacologic blockade of β1 and β2 adrenoceptors may theoretically make the hemodynamic effects of epinephrine indistinguishable from those of the pure alpha 1 adrenoceptor agonist phenylephrine.

#NorAdrenaline , #CriticalCare , #vasopressors , #TheLayMedicalMan , #IntensiveCare , #Pharmacology, #anesthesia , #anaesthesia, #drugs

(Reference: Paul S. Pagel and David C. Warltier, Essential drugs in anesthesia practice Positive inotropic drugs, Anesthetic Pharmacology, 2nd edition)