Page 167 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 9 Adrenoceptor Agonists & Sympathomimetic Drugs 153

processes underlying anaphylaxis. It is recommended that patients Additional Therapeutic Uses
at risk for anaphylaxis carry epinephrine in an autoinjector
2
(EpiPen, Auvi-Q) for self-administration. Recent price-gouging Although the primary use of the α agonist clonidine is in the treat-
increases in the cost of the EpiPen in the USA have raised fears ment of hypertension (see Chapter 11), the drug has been found to
that high costs will limit access to this drug. have efficacy in the treatment of diarrhea in diabetics with autonomic
neuropathy, perhaps because of its ability to enhance salt and water
Ophthalmic Applications absorption from the intestine. In addition, clonidine has efficacy in
diminishing craving for narcotics and alcohol during withdrawal and
Phenylephrine is an effective mydriatic agent frequently used to may facilitate cessation of cigarette smoking. Clonidine has also been
facilitate examination of the retina. It is also a useful decongestant used to diminish menopausal hot flushes and is being used experi-
for minor allergic hyperemia and itching of the conjunctival mem- mentally to reduce hemodynamic instability during general anes-
branes. Sympathomimetics administered as ophthalmic drops are thesia. Dexmedetomidine is an α agonist used for sedation under
2
also useful in localizing the lesion in Horner’s syndrome. (See Box: intensive care circumstances and during anesthesia (see Chapter 25).
An Application of Basic Pharmacology to a Clinical Problem.) It blunts the sympathetic response to surgery, which may be beneficial
Glaucoma responds to a variety of sympathomimetic and in some situations. It lowers opioid requirements for pain control and
sympathoplegic drugs. (See Box: The Treatment of Glaucoma, does not depress ventilation. Clonidine is also sometimes used as a
in Chapter 10.) Both α -selective agonists (apraclonidine and premedication before anesthesia. Tizanidine is an α agonist closely
2
2
brimonidine) and β-blocking agents (timolol and others) are related to clonidine that is used as a “central muscle relaxant” (see
common topical therapies for glaucoma. Chapter 27), but many physicians are not aware of its cardiovascular
actions, which may lead to unanticipated adverse effects.
Genitourinary Applications
As noted above, β -selective agents (eg, terbutaline) relax the preg-
2
nant uterus. In the past, these agents were used to suppress prema- An Application of Basic Pharmacology
ture labor. However, meta-analysis of older trials and a randomized to a Clinical Problem
study suggest that β-agonist therapy has no significant benefit on
perinatal infant mortality and may increase maternal morbidity.
Horner’s syndrome is a condition—usually unilateral—that
Central Nervous System Applications results from interruption of the sympathetic nerves to the
face. The effects include vasodilation, ptosis, miosis, and
The amphetamines have a mood-elevating (euphoriant) effect; loss of sweating on the affected side. The syndrome can be
this effect is the basis for the widespread abuse of this drug group caused by either a preganglionic or a postganglionic lesion,
(see Chapter 32). The amphetamines also have an alerting, sleep- and knowledge of the location of the lesion (preganglionic
deferring action that is manifested by improved attention to or postganglionic) helps determine the optimal therapy.
repetitive tasks and by acceleration and desynchronization of the A localized lesion in a nerve causes degeneration of the
electroencephalogram. A therapeutic application of this effect is distal portion of that fiber and loss of transmitter contents
in the treatment of narcolepsy. Modafinil, a new amphetamine from the degenerated nerve ending—without affecting
substitute, is approved for use in narcolepsy and is claimed to neurons innervated by the fiber. Therefore, a preganglionic
have fewer disadvantages (excessive mood changes, insomnia, and lesion leaves the postganglionic adrenergic neuron intact,
abuse potential) than amphetamine in this condition. Amphet- whereas a postganglionic lesion results in degeneration of
amines have appetite-suppressing effects, but there is no evidence the adrenergic nerve endings and loss of stored catechol-
that long-term improvement in weight control can be achieved amines from them. Because indirectly acting sympathomi-
with amphetamines alone, especially when administered for a metics require normal stores of catecholamines, such drugs
relatively short course. A final application of the CNS-active can be used to test for the presence of normal adrenergic
sympathomimetics is in the attention deficit hyperactivity nerve endings. The iris, because it is easily visible and
disorder (ADHD), a behavioral syndrome consisting of short responsive to topical sympathomimetics, is a convenient
attention span, hyperkinetic physical behavior, and learning prob- assay tissue in the patient.
lems. Some patients with this syndrome respond well to low doses If the lesion of Horner’s syndrome is postganglionic,
of methylphenidate and related agents. Extended-release formu- indirectly acting sympathomimetics (eg, cocaine, hydroxy-
lations of methylphenidate may simplify dosing regimens and amphetamine) will not dilate the abnormally constricted
increase adherence to therapy, especially in school-age children. pupil because catecholamines have been lost from the
agonists cloni- nerve endings in the iris. In contrast, the pupil dilates in
Slow or continuous-release preparations of the α 2
dine and guanfacine are also effective in children with ADHD. response to phenylephrine, which acts directly on the α
The norepinephrine reuptake inhibitor atomoxetine is sometimes receptors on the smooth muscle of the iris. A patient with
used in ADHD. Clinical trials suggest that modafinil may also be a preganglionic lesion, on the other hand, shows a normal
useful in ADHD, but because the safety profile in children has response to both drugs, since the postganglionic fibers and
not been defined, it has not gained approval by the FDA for this their catecholamine stores remain intact in this situation.
indication.