Diazoxide (Hyperstat) is chemically similar to the
thi-azide diuretics. It is devoid of diuretic activity and causes NA+
and water retention. Diazoxide is a very po-tent vasodilator and is available
only for intravenous use in the treatment of hypertensive emergencies. The
mechanism by which diazoxide relaxes vascular smooth muscle is related to its
ability to activate potassium channels and produce a hyperpolarization of the
Diazoxide lowers blood
pressure within 3 to 5 minutes after rapid intravenous injection, and its duration
of ac-tion may be 4 to 12 hours. Interestingly, if diazoxide is either injected
slowly or infused its hypotensive action is quite modest. This is believed to
be due to a rapid and extensive binding of the drug to plasma proteins. Both
the liver and kidney contribute to its metabolism and excretion. The plasma
half-life is therefore prolonged in patients with chronic renal failure.
The hemodynamic effects of
diazoxide are similar to those of hydralazine and minoxidil. It produces direct
relaxation of arteriolar smooth muscle with little effect on capacitance beds.
Since it does not impair cardiovas-cular reflexes, orthostasis is not a
problem. Its adminis-tration is, however, associated with a reflex increase in
cardiac output that partially counters its antihyperten-sive effects.
Propranolol and other β-blockers potenti-ate the vasodilating properties of the
drug. Diazoxide has no direct action on the heart. Although renal blood flow
and glomerular filtration may fall transiently, they generally return to
predrug levels within an hour.
Diazoxide is administered
intravenously for the treat-ment of hypertensive
emergencies, particularly malig-nant hypertension, hypertensive
encephalopathy, and eclampsia. It is effective in 75 to 85% of the patients to
whom it is administered and rarely reduces blood pres-sure below the
In patients with coronary
insufficiency, a β-blocker can be given in conjunction with diazoxide to
decrease the cardiac work associated with reflex increases in sym-pathetic
stimulation of the heart. However, β-blockers potentiate the hypotensive effect
of diazoxide, and therefore, the dose of the vasodilator should be low-ered.
The dose of diazoxide should also be lowered if the patient has recently been
treated with guanethidine or another drug that depresses the action of the
sympa-thetic nervous system. Such drugs permit a greater hy-potensive effect
because they reduce the increase in cardiac output that normally partially
counteracts the fall in pressure.
Diazoxide appears to have a
direct antinatriuretic action. This direct action, coupled with the
neuroen-docrine reflexes that are activated by a decrease in pe- ripheral
vascular resistance, leads to severe retention of NA+ and water.
Since tolerance to diazoxide can de-velop rapidly, it is frequently
administered in conjunc-tion with a diuretic.
Since diazoxide is not often
used for long-term treat-ment, toxicities associated with chronic use are
rare.The chief concern is the side effects associated with the in-creased
workload on the heart, which may precipitate myocardial ischemia and NA+
and water retention. These undesirable effects can be controlled by concur-rent
therapy with a β-blocker and a diuretic.
Diazoxide may cause
hyperglycemia, especially in diabetics, so if the drug is used for several
days, blood glucose levels should be measured.
When used in the treatment of
toxemia, diazoxide may stop labor, because it relaxes uterine smooth muscle.