A-adrenergic receptor agonist

SECTION 16 Urologic Disorders a-Adrenergic Receptor Agonists... 

Many open trials support the use of a variety of a-adrenergic receptor agonists in SUI. Combining an a-adrenergic receptor agonist with an estrogen yields somewhat superior clinical and urodynamic responses compared with monotherapy. 

Tizanidine is an a -adrenergic receptor agonist at supraspinal and spinal levels. This effect results in inhibition of spinal polysynaptic reflex activity. It presumably reduces spasticity by increasing presynaptic inhibition of motor neurons. Tizanidine has no direct effect on skeletal muscle, the neuromuscular junction or on monosynaptic reflex activity. 

Hwa J, Perez DM. The unique nature of the serine interactions for a,-adrenergic receptor agonist binding and activation. J Biol Chem 1996 271 6322-6327. 

FIGURE 23-2. Adrenoceptor-G protein interaction. AC = adenylate cyclase a-agonist = a-adrenergic receptor agonist ATP = adenosine triphosphate agonist = jS-adrenergic receptor agonist cAMP = cyclic adenosine monophosphate Gs = G stimulatory protein Gi = G inhibitory protein. (Adapted with permission from ref. 106.)... 

Duloxetine (when approved for treatment of urinary in- continence), a-adrenergic receptor agonists, and topical (vaginal) estrogens (alone or together) are the therapies of choice in urethral underactivity (stress incontinence). 

Several studies have evaluated whether the clinical and urodynamic effects of a combination of estrogen and an a-adrenergic receptor agonist exceed those of the individual therapies in SUI. In general, combination therapy has resulted in somewhat superior clinical and urodynamic responses compared with monotherapy, including severity of complaints, amount of urine lost per episode, number of daily voluntary micturitions, number of leakage episodes per day, patient preference, pad use, maximum urethral closure pressure, functional urethral length, and pressure transmission ratio. 

The optimal approach to the pharmacotherapy of SUI, is unclear. Although not supported by evidence-based medicine, many clinicians will initiate a trial of topical estrogen initially, followed by addition of an a-adrenergic receptor agonist in estrogen nonresponders unless contraindicated. Once duloxetine is approved, it will probably be the drug of choice in SUI, providing that it is tolerated. 

LOCAL VASCULAR EFFECTS OF a ADRENERGIC RECEPTOR AGONISTS... 

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