Vasoactive Catecholamines

Chapter 176 Vasoactive Catecholamines



Jeffery P. Simmons, DVM, MS, DACVECC, James S. Wohl, DVM, MPA, DACVIM, DACVECC



KEY POINTS



• Naturally occurring catecholamines include dopamine, epinephrine, and norepinephrine. They share a common synthesis pathway and are formed most commonly in the sympathetic nervous system or the adrenal medulla.

• Catecholamines function by activating adrenergic receptors. The type of receptors (α or β) stimulated determines the function of the catecholamine.

• In the cardiovascular system, alpha receptor stimulation induces vasoconstriction. Beta receptor stimulation increases heart rate, enhances cardiac contractility, and causes peripheral vasodilation.

• Dobutamine is typically the preferred β-agonist in dogs. Because seizures may result from dobutamine administration to cats, dopamine may be preferable in this species.

• Norepinephrine may be the preferred α-agonist, although dopamine may be equally effective.

• If the clinician unsure whether a β-agonist or α-agonist is required, the former is typically the safest first choice.


INTRODUCTION


The use of vasoactive catecholamines is common in the therapeutic management of cardiovascularly unstable, critically ill patients. Proper use of these medications requires accurate understanding of their functions and effects. This knowledge begins with the understanding of in vivo catecholamine physiology and the function of the adrenergic receptors. Understanding the chemical properties of the adrenergic agonists, as well as the basis for their use, is also necessary to complete the foundation of knowledge for this subject.



PHYSIOLOGY OF CATECHOLAMINES



Catecholamine Synthesis


Catecholamines are neurotransmitters when they are produced in the sympathetic nervous system and brain and circulating hormones when synthesized in the adrenal medulla. The endogenous catecholamines include dopamine, epinephrine, and norepinephrine. The specific compound formed depends on the enzymes produced by the synthesizing tissue. All three of these catecholamines are synthesized in a similar fashion, beginning with tyrosine. The first and rate-limiting step in the production pathway is the conversion of tyrosine to L-dopa by tyrosine hydroxylase.1,2 L-dopa is converted to dopamine through the action of dopa decarboxylase. If dopaminergic receptors are the target, this is where the pathway stops.


However, if adrenergic receptors are the target of catecholamine synthesis, then conversion of dopamine to norepinephrine follows. Depending on the tissue type and species, norepinephrine may be converted to epinephrine. For instance, in the adrenal medulla of dogs and humans, most (80%) of the product synthesized is epinephrine. In cats, however, norepinephrine is the major product.3 When produced in the adrenal medulla, the catecholamine is then released into the blood. When synthesized in the sympathetic nervous system, release occurs near the effector cell from the axon.



Catecholamine Receptors


The effects of catecholamines are based more on their receptor profile than on the specific catecholamine. Adrenergic receptors are highly specific prosthetic groups on membrane proteins found on the effector cell. The function of the receptors depends on the effector organ, but can be generally divided into two main actions: (1) causing a change in the cell membrane permeability to one or more ions and (2) activating or inactivating an enzyme attached to the receptor.2 The most common ions affected are sodium, calcium, and potassium. Sodium and calcium typically depolarize the cell for excitation, whereas potassium usually exits the cell making the cell more electronegative. Activation or inactivation of an enzyme in a cell can cause many different effects depending on the enzyme and the cell type. One of the most common enzymes associated with these receptors is cyclic adenosine monophosphate (cAMP).2


Adrenergic receptors are typically divided into alpha1, alpha2, beta1, and beta2 receptors. The various catecholamines are not equal in their abilities to stimulate all receptors. Norepinephrine stimulates α-receptors more than β-receptors, and epinephrine stimulates both receptor types equally. Thus norepinephrine is not as effective as epinephrine in activating organs with predominantly β-receptors.



Catecholamine Effects


As previously discussed, the effects of catecholamines depend on the distribution, type, and action of the receptors. α-Receptors or β-receptors can be either excitatory or inhibitory. Actions of α-receptors include vasoconstriction, iris dilation, intestinal relaxation, and bladder sphincter contraction. α1-Receptor agonists cause vasodilation or vasoconstriction depending on the concentration and the specific vascular beds. α2-Agonists are pure vasoconstrictors, whereas the β-receptors are more dependent on the subtype. β1-Receptors cause increased heart rate, cardiac contractility, renin release, and lipolysis. The β2-receptors cause vasodilation, intestinal relaxation, bronchodilation, glycogenolysis, and bladder relaxation.


Thus specific receptor agonist drugs can be administered to achieve a desired effect. For instance, to treat hypotension due to a loss of systemic vascular resistance, an α-agonist may be superior to a beta drug or a nonspecific agonist. Meanwhile, managing hypotension caused by a decrease in cardiac function would be best accomplished using a β1-agonist.

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Sep 10, 2016 | Posted by in SMALL ANIMAL | Comments Off on Vasoactive Catecholamines

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