FRCA Revision Material / UCL / http://www.emed-journal.com/fileadmin/content_images/emed/201503/047030104_t4.jpg
1. Three Main Classes
Natural (adrenaline, norad, dopamine) and synthetic (isoprenaline, dobutamine, dopexamine and salbutamol) catecholamines + phosphodiesterase 3 inhibitors (Milirinone, Enoximone) + 'others'.
2. Alpha and Beta Activity
Beta 1 effects = increased contractility and HR.
Beta 2 = smooth muscle relaxation and bronchodilation
Alpha effects = increased SVR and venous return
Alpha -2 agonist = clonidine = anti-hypertensive, causes suppression of catecholamine release.
3. Adrenaline & Noradrenaline
Adrenaline is an alpha and beta receptor agonist.
Noradrenaline is an alpha adrenergic agonist with some beta activity
4. Phenylephrine & Ephedrine
Phenylephrine is an alpha-1 agonist - causes increased venous return via SVR
5. Isoprenaline & Dobutamine - synthetics
Isoprenaline - unselected B agonist increases HR and cardiac output.
Peripheral and pulmonary vasoconstriction. Tachycardia may cause decreased myocardial oxygen delivery.
6. DPE 3 INHIBITORS
7. Other inotropic agents
Calcium - IV calcium salts improve BP for a few minutes - can be used in K+ and Calcium channel antagonist OD's.
8. Historical Drugs
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.
- its receptors are found centrally D1-3 in the basal ganglia/hypothalamus, CZT and spinal cord.
- peripheral receptors pre and post-synaptic are found in the heart, gut and kidneys
- it is NOT used in low doses for renal protective effect... it was previously.
- it is used for hypotension secondary to decreased SVR like in sepsis/anaphylaxis
- lower dose has some beta-1 effects
- arterial/venous constriction
- bronchodilation/increased MV
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
sympathomimetic - releasing norad from nerve endings (prone to tachyphylaxis though). Inhibits MAO release. Positive inotrope, chronotrope and increases BP.
Maintains uteroplacental blood flow. Causes bronchodilation.
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.
The drugs are usually used during and after cardiopulmonary bypass, in CCF and in low cardiac output states prior to transplant.
Decreases right atrial pressure. Beware in hepatic and renal impairment due to metabolism.
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.
Used in beta blocker OD.
Vasopressin is ADH and has V1 receptor activity in vascular
smooth muscle, increasing intracellular calcium.
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