Catecholamines

Catecholamines

Because of their common basic chemical structure, all catecholamines share certain properties’they stimulate the nervous system, constrict peripheral blood vessels, increase heart rate, and
dilate the bronchi. They can be manufactured in the body or in a laboratory.

Common catecholamines include:

• dobutamine
• dopamine
• epinephrine, epinephrine bitartrate, and epinephrine hydrochloride
• norepinephrine (levarterenol)
• isoproterenol hydrochloride and isoproterenol sulfate

Pharmacokinetics

Catecholamines can’t be taken orally because they’re destroyed by digestive enzymes. In contrast, when these drugs are given sublingually (under the tongue), they’re absorbed rapidly through the mucous membranes. Any sublingual drug not completely absorbed is rapidly metabolized by swallowed saliva.

Subcutaneously slow

SubQ absorption is slowed because catecholamines cause the blood vessels around the injection site to constrict.

I.M. absorption is more rapid because there’s less constriction of local blood vessels.

Distribution and metabolism

Catecholamines are widely distributed in the body. they’re metabolized and inactivated predominantly in the liver but can also be metabolized in the:

• GI tract
• lungs
• kidneys
• plasma
• other tissues.

Excretion

Catecholamines are excreted primarily in urine; however, a small amount of isoproterenol is excreted in feces and some epinephrine is excreted in breast milk.

Pharmacodynamics

Catecholamines are primarily direct-acting. When catecholamines combine with alpha receptors or beta receptors, they cause either an excitatory or an inhibitory effect. Typically, activation of alpha receptors generates an excitatory response, except for intestinal relaxation. Activation of beta receptors typically produces an inhibitory response, except in heart cells, where norepinephrine produces excitatory effects.

How heartening

The clinical effects of catecholamines depend on the dosage and administration route. Catecholamines are potent inotropes’they make the heart contract more forcefully. As a result, the ventricles empty more completely with each heartbeat, increasing the heart’s workload and the amount of oxygen it needs to do this harder work.

Rapid rates

Catecholamines also produce a positive chronotropic effect, which means that they cause the heart to beat faster. That happens because the pacemaker cells in the heart’s sinoatrial (SA) node depolarize at a faster rate. As catecholamines cause blood vessels to constrict and blood pressure to rise, the heart rate can fall as the body tries to compensate for an excessive rise in blood pressure.

Fascinating rhythm

Catecholamines can cause the Purkinje fibers (an intricate web of fibers that carry electrical impulses into the ventricles) to fire spontaneously, possibly producing abnormal heart rhythms, such as premature ventricular contractions and fibrillation. Epinephrine is more likely than norepinephrine to produce this spontaneous firing.

Pharmacotherapeutics

The therapeutic uses of catecholamines depend on the particular receptor that’s activated.

• Norepinephrine stimulates alpha receptors almost exclusively.
• Dobutamine and isoproterenol stimulate only beta receptors.
• Epinephrine stimulates both alpha and beta receptors.
• Dopamine activates primarily dopamine receptors.

Boosting blood pressure

Catecholamines that stimulate alpha receptors are used to treat low blood pressure (hypotension). They generally work best when used to treat hypotension caused by:

• relaxation of the blood vessel (also called a loss of vasomotor tone)
• blood loss (such as from hemorrhage).

Restoring rhythm

Catecholamines that stimulate beta₁ receptors are used to treat:

• bradycardia
• heart block (a delay or interruption in the conduction of electrical impulses between the atria and ventricles)
• low cardiac output.

It’s electric

Because they’re believed to make the heart more responsive to defibrillation (using an electrical current to terminate a deadly arrhythmia), beta₁-adrenergic drugs are used to treat:

• ventricular fibrillation (quivering of the ventricles, resulting in no pulse)
• asystole (no electrical activity in the heart)
• cardiac arrest.

Better breathing

Catecholamines that exert beta₂ activity are used to treat:

• acute or chronic bronchial asthma
• emphysema
• bronchitis
• acute hypersensitivity (allergic) reactions to drugs.

Kind to the kidneys

Dopamine, which stimulates the dopamine receptors, is used in low doses to improve blood flow to the kidneys by dilating the renal blood vessels.

Synthetic vs. natural

The effects of natural catecholamines (those produced by the body) differ somewhat from the effects of manufactured catecholamines. Manufactured catecholamines have a short duration of action, which can limit their therapeutic usefulness.

Drug interactions

Drug interactions involving catecholamines can be serious, resulting in hypotension, hypertension, arrhythmias, seizures, and high blood glucose levels in diabetic patients.

• Alpha-adrenergic blockers, such as phentolamine, can produce hypotension when taken with a catecholamine.
• Beta-adrenergic blockers, such as propranolol, taken with a catecholamine can lead to bronchial constriction.
• Epinephrine may cause hyperglycemia in diabetic patients receiving the drug. These patients may require an increased dose of insulin or oral antidiabetic agents.
• Other adrenergics taken with a catecholamine can produce additive, or double, effects, such as hypertension and arrhythmias, as well as enhance other adverse effects. Increased risk of adverse effects, such as hypertension, may occur when adrenergic drugs are given with other drugs that can cause hypertension.
• Tricyclic antidepressants taken with a catecholamine can lead to hypertension.