Midodrine, a
prodrug, is converted after
oral administration into its active drug,
desglymidodrine, which acts as an alpha(1)-adrenoceptor stimulant.
Midodrine is prescribed for the treatment of neurogenic
orthostatic hypotension in patients with
spinal cord injury. By virtue of its alpha(1)-adrenergic effects,
midodrine causes an increase in the tone of the vesical sphincter, which may silently lead to progressive retention of urine, particularly in patients with
spinal cord injury who void urine spontaneously. Further,
midodrine may aggravate detrusor-sphincter
dyssynergia, which can lead to hydroureteronephrosis. A 68-year-old man with C-4
tetraplegia was voiding urine satisfactorily through reflex detrusor contractions. He was prescribed
midodrine (5 mg at 8:00 AM, 5 mg at 1:00 PM, and 2.5 mg
at 10:00 PM) for
postural hypotension. During the next 7 wk, this patient experienced severe leg
spasms while passing urine, and the flow of urine became very slow. Intravenous urography showed bilateral hydroureteronephrosis, although an earlier study had revealed normal kidneys.
Midodrine therapy was stopped, and intermittent catheterization 4 times a day, along with oral
oxybutynin, was started. After
midodrine was discontinued, the leg
spasms during passage of urine and slowing of the urine stream coincident with the
spasms disappeared completely. The patient was able to pursue
activities of daily living without taking
midodrine. A 40-year-old man with C-7
tetraplegia was passing urine spontaneously with no problem. For
postural hypotension, he was prescribed
midodrine (5 mg in the morning and 2.5 mg at lunchtime),
fludrocortisone (100 microg daily), and
ephedrine (15 mg by mouth, taken 10 min before getting up in the morning). Three months later, the patient presented with sweating. During the day, he would pass only small amounts of urine, but from evening onward, he would void large volumes of urine, and the sweating would diminish. Intravenous urography showed vesical
diverticula; a postmicturition film revealed moderate residual urine. This patient was able to stop taking the second dose of
midodrine, but he required
midodrine and
ephedrine in the morning to enable him to get up without feeling dizzy. After the noon
midodrine dose was stopped, the patient's sweating diminished by late afternoon. During the morning hours, however, he continued to sweat and had difficulty passing urine. Intermittent catheterization was not possible in the community setting, and the patient remains under close follow-up. These cases illustrate that patients with cervical spinal cord injury who void spontaneously may develop insidious urologic adverse effects after taking
midodrine for
postural hypotension. When patients with
spinal cord injury develop urologic adverse effects while taking
midodrine, the drug should be stopped, and other pharmacologic agents (eg,
fludrocortisone) and nonpharmacologic methods should be prescribed for management of
orthostatic hypotension. If a patient continues to require
midodrine to control postural
hypotension, intermittent catheterization combined with
antimuscarinic therapy (eg,
oxybutynin) should be recommended instead of spontaneous voiding.