474
P A R T 5
Drugs acting on the autonomic nervous system
NON-SELECTIVE ALPHA-ADRENERGIC
BLOCKING AGENTS
Some adrenergic blocking agents have a specific affinity
for alpha-receptor sites. Their use is somewhat limited
because of the development of even more specific and
safer drugs. Only one of this type of drug, phentolamine
(
Regitine
), is still used (Table 31.2).
Therapeutic actions and indications
Phentolamine blocks the postsynaptic alpha
1
-adrenergic
receptors, decreasing sympathetic tone in the vascula-
ture and causing vasodilation, which leads to a lowering
of blood pressure. It also blocks presynaptic alpha
2
-
receptors, preventing the feedback control of noradrena-
line release. The result is an increase in reflex tachycardia
that occurs when blood pressure is lowered. Phentola-
mine is most frequently used to prevent cell death and
tissue sloughing after extravasation of intravenous
noradrenaline or dopamine, causing a local vasodilation
and a return of blood flow to the area. Table 31.2 shows
usual indications for this agent.
Pharmacokinetics
Phentolamine is rapidly absorbed after IV or IM injec-
tion and is excreted in the urine. There are few data on
its metabolism and distribution.
Contraindications and cautions
Phentolamine is contraindicated in the presence of
allergy to this or similar drugs and in the presence
of coronary artery disease or MI
because of the poten
tial exacerbation of these conditions
; it should be used
cautiously in pregnancy or breastfeeding
because of the
potential adverse effects on the fetus or neonate.
Adverse effects
Individuals receiving phentolamine often experi-
ence extensions of the therapeutic effects, including
hypotension, orthostatic hypotension, angina, MI,
cerebrovascular accident, flushing, tachycardia and
arrhythmia—
all of which are related to vasodilation
and decreased blood pressure.
Headache, weakness
and dizziness often occur
in response to hypotension.
Nausea, vomiting and diarrhoea may also occur.
Clinically important drug–drug interactions
Adrenaline may have decreased hypertensive and
vasoconstrictive effects if taken concomitantly with phen-
tolamine because these agents work in opposing ways in
the body. Increased hypotension may occur if this drug is
combined with alcohol, which is also a vasodilator.
TABLE 31.2
DRUGS IN FOCUS Non-selective alpha-adrenergic blocking agent
Drug name
Dosage/route
Usual indications
phentolamine
(Regitine)
Adult: 5 mg IV or IM 1–2 hours before surgery;
5–10 mg in 10 mL of saline injected into
area of extravasation within 12 hours after
extravasation
Paediatric: 1 mg IM or IV 1–2 hours before
surgery; treat extravasation as in the adult
Prevention of cell death and tissue
sloughing after extravasation
of intravenous noradrenaline or
dopamine, and severe hypertension
reactions caused by manipulation
of the phaeochromocytoma before
and during surgery; diagnosis of
phaeochromocytoma
Prototype summary: Phentolamine
Indications:
Prevention or control of hypertensive
episodes associated with phaeochromocytoma; test
for diagnosis of phaeochromocytoma; prevention
and treatment of dermal necrosis and sloughing
associated with IV extravasation of noradrenaline
or dopamine.
Actions:
Competitively blocks postsynaptic
alpha
1
- and presynaptic alpha
2
-receptors, causing
a vasodilation and lowering of blood pressure,
accompanied by increased reflex tachycardia.
Pharmacokinetics:
Route
Onset
Peak Duration
Intramuscular Rapid
20 mins 30–45 mins
IV
Immediate 2 mins 15–30 mins
T
1/2
:
Metabolism and excretion are unknown.
Adverse effects:
Acute and prolonged hypotensive
episodes, MI, tachycardia, arrhythmias, nausea,
flushing.
Care considerations for people receiving
non-selective alpha-adrenergic blocking
agents
Assessment: History and examination
■
■
Assess for contraindications or cautions:
any known allergies to these drugs
to avoid
