470
P A R T 5
Drugs acting on the autonomic nervous system
A
drenergic blocking agents are also called
sympatho
lytic
drugs because they lyse, or block, the effects of the
sympathetic nervous system (SNS). The therapeutic and
adverse effects associated with these drugs are related
to their
adrenergic-receptor-site specificity
, that is, the
ability to react with specific adrenergic receptor sites
without activating them, thus preventing the typical
manifestations of SNS activation. By occupying the
adrenergic receptor site, they prevent noradrenaline
release from the nerve terminal or from the adrenal
medulla from activating the receptor, thus blocking the
SNS effects.
The adrenergic blockers have varying degrees of
specificity for the adrenergic receptor sites. For example,
some can interact with both alpha- and beta-recep-
tors. Some are specific to alpha-receptors, with some
being even more specific to just alpha
1
-receptors. Other
adrenergic blockers interact with both beta
1
- and
beta
2
-receptors, whereas others interact with just either
beta
1
- or beta
2
-receptors. This specificity allows the
clinician to select a drug that will have the desired thera
peutic effects without the undesired effects that occur
when the entire SNS is blocked. In general, however, the
specificity of adrenergic blocking agents depends on the
concentration of the drug in the body. Most specificity is
lost with higher serum drug levels (see Figure 31.1).
The effects of the adrenergic blocking agents vary
with the age of the person (see Box 31.1). Various alter-
native and herbal remedies can also affect these drugs
(see Box 31.2).
NON-SELECTIVE ADRENERGIC BLOCKING
AGENTS
Drugs that block both alpha- and beta-adrenergic
receptors are primarily used to treat cardiac-related
conditions. These drugs include amiodarone (
Cordar
one X
), carvedilol (
Dilatrend
) and labetalol (
Presolol
,
Trandate
) (see Table 31.1).
Therapeutic actions and indications
Adrenergic blocking agents competitively block the
effects of noradrenaline at alpha- and beta-receptors
throughout the SNS. Subsequently, this results in lower
blood pressure, slower pulse rate and increased renal
perfusion with decreased renin levels. Most of these
drugs are indicated to treat essential hypertension, alone
or in combination with diuretics.
Labetalol is a newer drug that is used orally to
treat hypertension. It can also be used with diuret-
ics and has been used to treat hypertension associated
with
phaeochromocytoma
(tumour of the chromaffin
cells of the adrenal medulla, which periodically releases
large amounts of noradrenaline and adrenaline into the
system) and clonidine withdrawal. Amiodarone, which
is available in oral and IV forms, is saved for serious
emergencies and only used as an antiarrhythmic (see
Chapter 45). Carvedilol is only available orally and is
used to treat hypertension, as well as heart failure and
left ventricular dysfunction after myocardial infarction
Pupils do not dilate
Increased GI secretions
Increased GI activity
Lowered blood pressure
Decreased venous return
related to vasodilation
Decreased glucose
regulation
Relaxed sphincters to
increase urine flow
Relaxed sphincters to
increase GI excretions
Decreased sexual
response
Loss of bronchodilation
Effects of adrenergic blockade
Pharmacodynamics of
adrenergic blockers
Noradrenaline
Norepinephrine
Dopamine
Noradrenaline
Tyramine (from diet)
Dopa
Adrenergic
receptor
α
1
,
β
1
or
β
2
Adrenergic receptor
α
2
Ca
+
Ca
+
Beta
1-
, Beta
2-
and Alpha
1-
,
adrenergic
blockers
work here
α
2
adrenergic
blockers work
here
cAMP
FIGURE 31.1
Site of action of adrenergic receptors and resultant physiological responses. These responses are blocked by adrenergic blockers.
