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Chapter: Clinical Pharmacology: Autonomic nervous system drugs

Noncatecholamines

Noncatecholamine adrenergic drugs have a variety of therapeuticuses because of the many effects they can have on the body.

Noncatecholamines

 

Noncatecholamine adrenergic drugs have a variety of therapeuticuses because of the many effects they can have on the body, in-cluding:

 

·                 local or systemic constriction of blood vessels (phenylephrine)

 

·                 nasal and eye decongestion and dilation of the bronchioles (al-buterol, bitolterol, ephedrine, formoterol, isoetharine hydrochlo-ride, isoproterenol, levalbuterol, metaproterenol, pirbuterol, sal-meterol, and terbutaline)

·                 smooth-muscle relaxation (terbutaline).

 

Pharmacokinetics

 

Although these drugs are all excreted in urine, they’re absorbed in different ways.

 

Absorption and distribution

 

Absorption of the noncatecholamines depends on the administra-tion route:

 

·                 Inhaled drugs, such as albuterol, are absorbed gradually from the bronchi and result in lower drug levels in the body.

·                 Oral drugs are absorbed well from the GI tract and are distrib-uted widely in body fluids and tissues.

 

·                 Some noncatecholamines, such as ephedrine, cross the blood-brain barrier and can be found in high concentrations in the brain and cerebrospinal fluid (fluid that moves through and protects the brain and spinal canal).

 

Metabolism

 

Noncatecholamines are metabolized and inactivated primarily in the liver but also in the lungs, GI tract, and other tissues.

Excretion

 

Noncatecholamines and their metabolites are excreted primarily in urine. Some, such as inhaled albuterol, are excreted within 24 hours; others, such as oral albuterol, within 3 days. Acidic urine increases excretion of many noncatecholamines; alkaline urine slows excretion.

 

Pharmacodynamics

 

Noncatecholamines can be direct-acting, indirect-acting, or dual-acting (unlike catecholamines, which are primarily direct-acting).

 

·                 Direct-acting noncatecholamines that stimulate alpha receptors include phenylephrine. Those that selectively stimulate beta2 re-ceptors include albuterol, isoetharine, metaproterenol, and terbu-taline.

·                 Dual-acting noncatecholamines include ephedrine.

 

Pharmacotherapeutics

 

Noncatecholamines stimulate the sympathetic nervous system, producing a variety of effects in the body. Phenylephrine, for ex-ample, causes vasoconstriction and is used to treat hypotension in cases of severe shock. Terbutaline is used to stop preterm labor.


Drug interactions

Here are a few examples of drugs that interact with noncatechol-amines:

 

·                 Anesthetics (general), cyclopropane, and halogenated hydrocar-bons can cause arrhythmias. Hypotension can also occur if these drugs are taken with noncatecholamines that exert predominantly beta2 activity, such as terbutaline.

 

·                 Monoamine oxidase inhibitors can cause severe hypertension and even death.

 

·                 Oxytocic drugs that stimulate the uterus to contract can be in-hibited when taken with terbutaline. When taken with other non-catecholamines, oxytocic drugs can cause hypertensive crisis or a stroke.

 

·                 Tricyclic antidepressants can cause hypertension and arrhyth-mias.

 

·                 Urine alkalizers, such as acetazolamide and sodium bicarbon-ate, slow excretion of noncatecholamines, prolonging their dura-tion of action. (See Adverse reactions to noncatecholamines.)

 

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