Mixed alpha and beta adrenergic agonists
Agonists like norepinephrine and adrenaline stimulate both alpha and beta receptors.
Norepinephrine (Noradrenaline)
Norepinephrine stimulates alpha-1, alpha-2 and beta-1 adrenergic receptors.
Cardiovascular effects
Norepinephrine has alpha-1 vascular effects (arterial and venous vasoconstriction) and beta-1 cardiac effects (inotropic, chronotropic, dromotropic and bathmotropic positive effects), responsible for an increase in arterial pressure, but it does not have beta-2 vascular effect.
Administered in perfusion, norepinephrine gives a rise in systolic and diastolic arterial pressure proportional to the dose. At the same time It induces a decrease of blood flow rate in the majority of organs: kidney, liver, brain…
Other effects
Norepinephrine has noncardiovascular effects not useful in therapeutics because of its hypertensive action previously described:
- on intestine: decrease of tone, suppression of peristaltic contractions.
- Mydriatic action on the eye.
- Uterotonic action (alpha-1): contraction.
- Metabolic effects less than those of adrenaline and isoprenaline:
Use
Norepinephrine is used in intravenous perfusion in the treatment of collapse, severe hypotension with peripheral vasodilation and normal blood volume.
Its principal disadvantage is vasoconstriction which reduces organs irrigation, but its use can be necessary in case of refractory vasodilation. It elicits necrosis when inadvertently administered outside the vein.
Antagonists of noradrenaline effects are alpha-1 antagonists for suppression of vasoconstriction and beta-1 antagonists for suppression of cardiac effects.
Epinephrine (adrenaline)
Adrenaline stimulates alpha-1, beta-1 and beta-2 adrenergic receptors.
Cardiovascular effects
An intravenous injection of adrenaline causes at low doses hypotension, at high doses hypertension. In perfusion, it elicits a rise of systolic pressure and a lowering of diastolic pressure. These variations of arterial pressure result from two components:
- Cardiac effects: by its beta-1 and beta-2 effects adrenaline accelerates and reinforces cardiac contractions and cardiac output increases. Moreover, it increases cardiac exitability and, in combination with certain compounds such as inhalational anesthetics, it can elicit rythm disorders. Its cardiac action is inhibited by beta- adrenolytics.
- Vascular effects: adrenaline has both alpha-1 (vasoconstriction) and beta-2 (vasodilation) effects. The vasoconstrictive effect overrides the vasodilatator effect and the peripheral resistances rise. After administration of an alpha-1 adrenolytic which inhibits vasoconstriction, adrenaline causes a fall of arterial pressure (inversion of effect), which implies that beta-1 cardiac effect is quantitatively less important than beta-2 vascular effect. In comparison, norepinephrine, which does not have a vascular beta effect, does not cause an hypotensive effect after administration of an alpha-1adrenolytic agent.
Other effects
Adrenaline has bronchodilator, mydriatic effets and inhibits peristaltic activity of the digestive tract.
It has metabolic effects: increase of plasma glucose, lactic acid, free fatty acids and glycerol.
It raises the temperature and increases oxygen uptake.
Use
Adrenaline is used, in injectable formulation, by general route in the treatment of anaphylactic shocks and cardiac arrest.
Epinephrine |
EPIPEN* Autoinjector |
It is very often combined with local anesthetics to reduce their diffusion from their injection site.
In an ophthalmic solution formulation, it was used as antiglaucomatous drug because it reduces blood flow rate in ciliary body and thus reduces the production of aqueous humor and in addition it increases its elimination.
In the form of aerosol, it was used in the treatment of asthma attack and glottis edema.
Dipivefrine, is a precursor of epinephrine whose catechol group is esterified by two molecules of pivalic acid, which makes it more lipophilic and facilitates its diffusion. Administered in the form of ophthalmic solution, it is hydrolyzed in pivalic acid and epinephrine which lowers intraocular pressure.
The regulation of aqueous humor circulation involves complex mechanisms and certain therapeutic attitudes based on clinical results can appear in contradiction with over simplified pharmacological explanations.
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