1. Three Main Classes
Natural (adrenaline, norad, dopamine) and synthetic
(isoprenaline, dobutamine, dopexamine and salbutamol) catecholamines + phosphodiesterase 3 inhibitors (Milirinone, Enoximone) + 'others'.
Beta 1 effects = increased contractility and HR.
Alpha -2 agonist = clonidine = anti-hypertensive, causes suppression of catecholamine release.
Adrenaline is an alpha and beta receptor agonist.
Noradrenaline is an alpha adrenergic agonist with some beta activity
Phenylephrine is an alpha-1 agonist - causes increased venous return via SVR
Isoprenaline - unselected B agonist increases HR and cardiac output.
Peripheral and pulmonary vasoconstriction.
Tachycardia may cause decreased myocardial oxygen delivery.
Calcium - IV calcium salts improve BP for a few minutes - can be used in K+ and Calcium channel antagonist OD's.
What gets your blood pressure up?
Catecholamines work by stimulating adenylate cyclase, increasing cAMP levels, which increase intracellular calcium and contraction force. Inhibition of phosphodiesterase 3, prevents cAMP degredation and increases slow calcium inward current during cardiac action potential.
Dopamine acts on receptors via G proteins leading to increased or decreased cAMP.
- it is used for hypotension secondary to decreased SVR like in sepsis/anaphylaxis
Both metabolised by COMT in the liver with some MAO metabolism within adrenergic neurones - more MAO metabolism of norad.
Reflex bradycardia, used in spinal anaesthesia and alongside SE's of IV drugs
Ephedrine is a mixed alpha and beta agonist - it actually is a direct and indirect
Metaraminol boasts A1 and some B2 activity. It tends to last slightly longer than phenylephrine
Dobutamine has mainly B1 effects with some B2 - usually increases BP despite the small fall in BP. Less tachycardias than other catecholamines.
Avoid in patients with outflow obstruction due to arrhythmia potential.
Enoximone & milrinone prevent hydrolysis of intracellular cyclic AMP, augmenting its effects. Increased cardiac contractility and stroke volume. Many isoenzymes of phosphodiesterase – PDE III is the target vasodilatation for inotropic actions.
Digoxin - cardiac glycoside - thought to increase calcium intracellularly. Increases cardiac output and reduces heart rate- may cause vasoconstriction.
Thyroxine has positive inotropic and chronotropic effects via intracellular mechanisms.
Glucagon - increased cAMP through G proteins and stimulation of adenylate cyclase.
Vasopressin is ADH and has V1 receptor activity in vascular
Levosimendan - Calcium sensitizer. Increases the sensitivity of myocardial troponin to intracellular calcium, possible inhibition of PDE III. Increased cardiac contractility without increasing myocardial oxygen demand.
Dr. D. Lyness