title: Combined use of alpha-adrenergic and muscarinic antagonists for the treatment of voiding dysfunction.
abstract: OBJECTIVE
  We provide an overview of the medical literature supporting the combined use of muscarinic and alpha-adrenergic antagonist therapy for the treatment of voiding dysfunction.
  
  
  METHODS
  The MEDLINE database (1966 to 2004) of the United States National Library of Medicine was searched for pertinent studies.
  
  
  RESULTS
  Although the mechanism of action of alpha-adrenergic antagonist therapy for voiding dysfunction has traditionally been assumed to be relaxation of the periurethral, prostatic and bladder neck smooth muscle, substantial evidence supports action at extraprostatic sites involved in micturition, including the bladder dome smooth muscle, peripheral ganglia, spinal cord and brain. Likewise the mechanism of action of anticholinergic therapy has been traditionally assumed to be inhibition of the M3 muscarinic receptor subtypes that mediate normal bladder contractions. However, M2 receptor mediates hypertrophied bladder contractions and there is evidence for an M2 component to the suprasacral control of voiding.
  
  
  CONCLUSIONS
  Based on the physiology of alpha-adrenergic and muscarinic receptors the inhibition of each one would be expected to be more beneficial than that of either alone because they would work on 2 components of detrusor function. Patients who would likely benefit from this combination therapy are men with lower urinary tract symptoms, women with urgency/frequency syndrome (overactive bladder), patients with uninhibited bladder contractions due to neurogenic bladder, and patients with pelvic pain and voiding symptoms, ie interstitial cystitis and chronic prostatitis/chronic pelvic pain syndrome.
authors.affiliation: Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140-5104, USA. rugg1@msn.com
authors.forename: Michael R
authors.initials: MR
authors.lastname: Ruggieri
authors.forename: Alan S
authors.initials: AS
authors.lastname: Braverman
authors.forename: Michel A
authors.initials: MA
authors.lastname: Pontari
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000627:therapeutic use*; D011470:Prostatic Hyperplasia / Q000150:complications / Q000175:diagnosis; D011788:Quality of Life; D020127:Recovery of Function; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome; D016482:Urinalysis; D014549:Urinary Incontinence / Q000175:diagnosis / Q000188:drug therapy; D014552:Urinary Tract Infections / Q000150:complications / Q000175:diagnosis; D014555:Urination Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D014563:Urodynamics
chemical_list: D000317:Adrenergic alpha-Antagonists; D018727:Muscarinic Antagonists