Editing Functional: Pharmacological Management of LUTS (section)

=== Increasing Intravesical Pressure and Bladder Contractility ===
* '''Currently no effective drug for the treatment of detrusor underactivity or underactive bladder'''
* '''Parasympathomimetic agents'''
** ACh, which stimulates bladder contraction, cannot be used for therapeutic purposes because of its action at both muscarinic and nicotinic receptors and it is rapidly hydrolyzed by cholinesterases.
** Many ACh-like drugs exist, but only bethanechol chloride exhibits a relatively selective in vitro action on the urinary bladder and gut with little or no nicotinic action.
*** '''Bethanechol''' 
****'''Cholinesterase resistant'''
****'''Causes an in vitro contraction of smooth muscle from all areas of the bladder.''' 
****'''Little evidence of its efficacy'''
**** At least in a "denervated" bladder, an oral dose of 200 mg is required to produce the same urodynamic effects as a subcutaneous dose of 5 mg.
* Prostaglandins
** Synthesized both locally in bladder muscle and mucosa
*** Synthesis initiated by various physiologic stimuli such as detrusor muscle stretch, mucosal injury, and neural stimulation; directly by adenosine triphosphate; and by mediators of inflammation.
** Have been variably reported to be useful in facilitating bladder emptying with intravesical administration. Possible roles include:
**# Neuromodulators of efferent and afferent transmission
**# Sensitization
**# Activation of certain sensory nerves
**# Potentiation of acetylcholine (but not ATP) release from cholinergic nerve terminals through prejunctional prostanoid receptors.
** Initial reports of the use of intravesical prostanoids producing lasting favorable clinical effects have not been confirmed.