Page 151 - Basic _ Clinical Pharmacology ( PDFDrive )

C H A P T E R

Adrenoceptor Agonists & 9

Sympathomimetic Drugs

*
Italo Biaggioni, MD, & David Robertson, MD

C ASE STUD Y

A 68-year-old man presents with a complaint of light- There was an inadequate compensatory increase in heart
headedness on standing that is worse after meals and in rate (from 84 to 88 bpm), considering the degree of ortho-
hot environments. Symptoms started about 4 years ago and static hypotension. Physical examination is otherwise unre-
have slowly progressed to the point that he is disabled. He markable with no evidence of peripheral neuropathy or
has fainted several times but always recovers conscious- parkinsonian features. Laboratory examinations are negative
ness almost as soon as he falls. Review of symptoms reveals except for plasma norepinephrine, which is low at 98 pg/mL
slight worsening of constipation, urinary retention out of (normal for his age 250–400 pg/mL). A diagnosis of pure
proportion to prostate size, and decreased sweating. He is autonomic failure is made, based on the clinical picture and
otherwise healthy with no history of hypertension, diabetes, the absence of drugs that could induce orthostatic hypoten-
or Parkinson’s disease. Because of urinary retention, he was sion and diseases commonly associated with autonomic
placed on the α antagonist tamsulosin, but the fainting neuropathy (eg, diabetes, Parkinson’s disease). What precau-
1
spells got worse. Physical examination revealed a blood pres- tions should this patient observe in using sympathomimetic
sure of 167/84 mm Hg supine and 106/55 mm Hg standing. drugs? Can such drugs be used in his treatment?

The sympathetic nervous system is an important regulator of Drugs that mimic the actions of epinephrine or norepineph-
virtually all organ systems. This is particularly evident in the rine have traditionally been termed sympathomimetic drugs.
regulation of blood pressure. As illustrated in the case study, the The sympathomimetics can be grouped by mode of action and
autonomic nervous system is crucial for the maintenance of blood by the spectrum of receptors that they activate. Some of these
pressure even under relatively minor situations of stress (eg, the drugs (eg, norepinephrine and epinephrine) are direct agonists;
gravitational stress of standing). they directly interact with and activate adrenoceptors. Others
The ultimate effects of sympathetic stimulation are mediated are indirect agonists because their actions are dependent on their
by release of norepinephrine from nerve terminals, which then ability to enhance the actions of endogenous catecholamines by
activates adrenoceptors on postsynaptic sites (see Chapter 6). (1) inducing the release of catecholamines by displacing them
Also, in response to a variety of stimuli such as stress, the adrenal from adrenergic nerve endings (eg, the mechanism of action of
medulla releases epinephrine, which is transported in the blood tyramine), (2) decreasing the clearance of catecholamines by
to target tissues. In other words, epinephrine acts as a hormone, inhibiting their neuronal reuptake (eg, the mechanism of action
whereas norepinephrine acts as a neurotransmitter. of cocaine and tricyclic antidepressants), or (3) preventing the
enzymatic metabolism of norepinephrine (monoamine oxidase
* and catechol-O-methyltransferase inhibitors). Some drugs have
The authors thank Drs. Vsevolod Gurevich and Aurelio Galli for helpful
comments. both direct and indirect actions.

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