Editing Functional: Pharmacological Management of LUTS (section)

===== Mechanisms of action (3): =====
# '''<span style="color:#ff0000">Decrease the activity in AFFARENT nerves (both C and Aδ fibers) from the bladder</span>'''
#* '''<span style="color:#ff0000">Primary mechanism; anti-cholinergics act mainly during the storage phase (rather than the voiding phase)</span>'''
#** '''During the storage phase'''
#*** '''ACh is released''' from both neuronal and non-neuronal sources (e.g., the urothelium and suburothelium) '''and''' '''directly or indirectly''' (by increasing detrusor smooth muscle tone) '''excites afferent nerves in the suburothelium and within the detrusor'''
#*** '''Normally no parasympathetic input to the LUT.'''
#* '''Since they act during the storage phase, they can be safely administered in men with bladder outlet obstruction as they do not alter urinary flow rate, voiding pressure, or incidence of urinary retention.'''
#** '''Caution should be used in large PVRs'''
# '''<span style="color:#ff0000">Blocking the muscarinic receptors on the detrusor muscle,</span>''' which are otherwise stimulated by ACh released from activated cholinergic (parasympathetic) nerves.
#* '''Less significant effect than reducing AFFARENT activity'''
# '''<span style="color:#ff0000">Reduce the micromotions caused by the release of small packets of Ach</span>'''
* '''<span style="color:#ff0000">In patients with involuntary bladder contractions (detrusor overactivity) of any cause, anti-cholinergics (5):</span>'''
*# '''<span style="color:#ff0000">Increase the volume to the first detrusor overactivity</span>''' (affarent)
*# '''<span style="color:#ff0000">Increase the total bladder capacity</span>''' (affarent)
*# '''<span style="color:#ff0000">Increase mean voided volume</span>''' (affarent)
*# '''<span style="color:#ff0000">Decrease urgency</span>''' (affarent)
*# '''<span style="color:#ff0000">Decrease the amplitude of the contraction</span>''' (efferent)
* '''Do not affect detrusor or abdominal leak point pressure'''
* '''Produce only partial inhibition due to secondary release of a transmitter other than Ach'''
** This is known as atropine resistance and is the most common hypothesis explaining the difficulty of curing detrusor overactivity with anti-cholimergic agents alone, and supports the rationale of combined treatment of detrusor overactivity with agents of different mechanisms of action. The importance or unimportance of an atropine-resistant component to detrusor contraction in the treatment of detrusor overactivity in humans remains to be established.