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P A R T 5
Drugs acting on the autonomic nervous system
Therapeutic actions and indications
The therapeutic effects of the alpha
1
-selective adren-
ergic blocking agents come from their ability to block
the postsynaptic alpha
1
-receptor sites. This causes a
decrease in vascular tone and vasodilation, which leads
to a fall in blood pressure. Because these drugs do not
block the presynaptic alpha
2
-receptor sites, the reflex
tachycardia that accompanies a fall in blood pressure
does not occur. They also block smooth muscle recep-
tors in the prostate, prostatic capsule, prostatic urethra
and urinary bladder neck, which leads to a relaxation of
the bladder and prostate, and improved flow of urine in
males. These drugs are available in oral form and can
be used to treat benign prostatic hypertrophy (BPH) (see
Chapter 52 for further discussion on BPH) and hyper-
tension. The drugs may be used alone or as part of a
combination therapy. Table 31.3 shows usual indica-
tions for each of these agents.
Pharmacokinetics
The alpha
1
-selective adrenergic blocking agents are well
absorbed after oral administration and undergo extens
ive hepatic metabolism. They are excreted in the urine.
Contraindications and cautions
The alpha
1
-selective adrenergic blocking agents are
contraindicated in the presence of allergy to any of these
drugs
to avoid hypersensitivity reactions
and also with
breastfeeding
because the drugs cross into breast milk
and could have adverse effects on the neonate.
They
should be used cautiously in the presence of HF or renal
failure
because their blood pressure–lowering effects
could exacerbate these conditions
and with hepatic
impairment,
which could alter the metabolism of these
drugs.
Caution also should be used during pregnancy
because of the potential for adverse effects on the fetus.
Adverse effects
The adverse effects associated with the use of these drugs
are usually related to their effects of SNS blockage.
CNS effects include headache, dizziness, weakness,
fatigue, drowsiness and depression. Nausea, vomiting,
abdominal pain and diarrhoea may occur
as a result of
direct effects on the GI tract and sympathetic blocking.
Anticipated cardiovascular effects include arrhythmias,
hypotension, oedema, HF and angina. The vasodilation
caused by these drugs can also cause flushing, rhinitis,
reddened eyes, nasal congestion and priapism.
Clinically important drug–drug interactions
Increased hypotensive effects may occur if these drugs are
combined with any other vasodilating or antihypertens
ive drugs, such as nitrates, calcium-channel blockers and
angiotensin-converting enzyme (ACE) inhibitors.
Prototype summary: Doxazosin
Indications:
Treatment of mild to moderate
hypertension as monotherapy or in combination
with other antihypertensives; treatment of BPH.
Actions:
Reduces total peripheral resistance through
alpha blockade; does not affect heart rate or
cardiac output; increases high-density lipoproteins
while lowering total cholesterol levels.
Pharmacokinetics:
Route Onset
Peak
Duration
Oral
Varies
2–3 hours
Not known
T
1/2
:
22 hours, with hepatic metabolism and
excretion in the bile, faeces and urine.
Adverse effects:
Headache, fatigue, dizziness,
postural dizziness, vertigo, tachycardia, oedema,
nausea, dyspepsia, diarrhoea, sexual dysfunction.
Care considerations for people receiving
alpha
1
-selective adrenergic blocking agents
Assessment: History and examination
■
■
Assess for contraindications or cautions:
any known allergies to either drug t
o avoid
hypersensitivity reactions
; HF or renal failure,
which could be exacerbated by drug use
; hepatic
dysfunction,
which could alter the drug’s
metabolism
; and current status of pregnancy or
breastfeeding
because of unknown or adverse
effects to the fetus or neonate.
■
■
Perform a physical assessment
to establish baseline
data for determining the effectiveness of drug
therapy and the occurrence of any adverse effects.
■
■
Monitor the level of orientation, affect and reflexes
to monitor for CNS changes related to drug
therapy.
■
■
Monitor vital signs and assess cardiovascular
status, including pulse, blood pressure, peripheral
perfusion and cardiac output,
to evaluate for
possible cardiac effects
; obtain an ECG as ordered
to assess for possible irregularities in rate or
rhythm.
■
■
Assess renal function, including urinary output,
to evaluate effects on the renal system and assess
BPH and its effects on urinary output.
■
■
Monitor renal and hepatic function tests
to
evaluate potential need for dose adjustment.
Implementation with rationale
■
■
Monitor blood pressure, pulse, rhythm and cardiac
output regularly
to evaluate for changes that may
