MINOXIDIL
Minoxidilworks via a sulphate metabolite which activates K
channels. This relaxes vascular smooth muscle, reducing
peripheral vascular resistance and lowering blood pressure.
It is a powerful vasodilator and is used in very severe hyper-
tension unresponsive to other drugs, combined with a
β-adrenoceptor antagonist to block reflex tachycardia and a
loop diuretic because of the severe fluid retention it causes. It
increases hair growth (indeed the sulphate metabolite is
licensed as a topical cream for male baldness) and coarsens
facial features, so is unacceptable to most women.
HYDRALAZINE
Hydralazinehas a direct vasodilator action that is not fully
understood. It used to be widely used as part of ‘triple ther-
apy’ with a β-adrenoceptor antagonist and a diuretic in
patients with severe hypertension, but has been rendered
largely obsolete by better tolerated drugs such as Ca^2 antag-
onists (see above). Large doses are associated with a lupus-
like syndrome with positive antinuclear antibodies. It has
been widely and safely used in pregnancy and retains a use
for severe hypertension in this setting although nifedipineis
now preferred by many obstetric physicians.
NITROPRUSSIDE
Nitroprussideis given by intravenous infusion in hyperten-
sive emergencies (e.g. hypertensive encephalopathy), in an
intensive care unit. It is a rapid acting inorganic nitrate which
degrades to NO. Co-administration of a β-adrenoceptor
antagonist is usually required. Prolonged use is precluded
by the development of cyanide toxicity and its use requires
specialist expertise.CENTRALLY ACTING DRUGS
α-Methyldopahas been extensively used in pregnancy and is
a preferred agent when drug treatment is needed in this set-
ting. Drowsiness is common, but often wears off. A positive
Coombs’ test is also not uncommon: rarely this is associated
with haemolytic anaemia. Other immune effects include drug
fever and hepatitis. Its mechanism is uptake into central neu-
rones and metabolism to false transmitter (α-methylnor-
adrenaline) which is an α 2 -adrenoceptor agonist. Activating
centralα 2 -adrenoceptors inhibits sympathetic outflow from
the CNS. Moxonidineis another centrally acting drug: it acts
on imidazoline receptors and is said to be better tolerated than
methyldopa.194 HYPERTENSION
Table 28.3:Additional antihypertensive drugs used in special situations
Drug Mechanism of action Uses Side-effects/limitations
Minoxidil Minoxidil sulphate (active Very severe hypertension Fluid retention; reflex tachycardia;
metabolite) is a K-channel that is resistant to hirsutism; coarsening of facial
activator other drugs appearance. Must be used in
combination with other drugs (usually a
loop diuretic and β-antagonist)Nitroprusside Breaks down chemically to NO, Given by intravenous Short term IV use only: prolonged use
which activates guanylyl cyclase infusion in intensive care causes cyanide toxicity (monitor plasma
in vascular smooth muscle unit for control of thiocyanate); sensitive to light;
malignant hypertension close monitoring to avoid hypotension
is essentialHydralazine Direct action on vascular smooth Previously used in Headache; flushing; tachycardia; fluid
muscle; biochemical mechanism ‘stepped-care’ approach retention. Long-term high-dose use
not understood to severe hypertension: causes systemic lupus-like syndrome in
β-antagonist in combination susceptible individuals
with diuretic. Retains a
place in severe hypertension
during pregnancyα-Methyldopa Taken up by noradrenergic Hypertension during Drowsiness (common); depression;
nerve terminals and converted pregnancy. Occasionally hepatitis; immune haemolytic anaemia;
toα-methylnoradrenaline, useful in patients who drug fever
which is released as a false cannot tolerate other drugs
transmitter. This acts centrally
as an α 2 -agonist and reduces
sympathetic outflow