Editing Functional: Pharmacological Management of LUTS (section)

==== Toxins ====

===== Botulinum toxin =====
* '''A neurotoxin produced by''' '''gram-positive Clostridium botulinum'''
* '''7 subtypes; subtype A has the longest duration of action, making it the most relevant clinically.'''
** Subtype A is available in different forms''':''' 
***'''OnabotulinumtoxinA''' (onabotA) - '''Botox'''
***'''AbobotulinumtoxinA''' (abobotA) - '''Dysport'''
***IncobotulinumtoxinA (incobotA) - Xeomin
**** Although the toxin is the same, it is wrapped by different proteins that modify the relative potency of each brand.
**** Most of the information available about intravesical application of BoNTA derives from the use of onabotA (Botox).
****Dysport associated with higher rates of need for clean intermittent self-catheterization
** Clinical dose conversion studies for the LUT do not exist.
* '''<span style="color:#ff0000">Mechanisms of action (4):'''
*# '''<span style="color:#ff0000">Inhibits release of acetylcholine from pre-synaptic cholinergic motor nerve endings by cleaving SNAP 25 and rendering the SNARE complex inactive, resulting in muscle paralysis'''
*#* '''Acts on both striated muscle and smooth muscle'''
*#** '''Striated muscle paralysis recovers within 2-4 months'''
*# '''<span style="color:#ff0000">Terminal axonal degeneration due to accumulation of neurotransmitter-containing synaptic vesicles'''
*# '''<span style="color:#ff0000">Inhibits the release of other neurotransmitters including ATP and neuropeptides such as substance P'''
*# '''<span style="color:#ff0000">Reduces afferent activity from bladder'''
* Efficacy
** RCTs have documented the clinical effects of onabotulinumtoxinA both in neurogenic detrusor overactivity and idiopathic detrusor overactivity, wherein the drug decreases incontinence episodes, frequency, and urgency and improves QoL.
** '''Shown to be effective in patients with OAB.'''
*** '''Successful OAB treatment with BoNTA does not appear to be related to the existence of DO.''' No differences in outcomes were found between those with and those without baseline DO
* '''<span style="color:#ff0000">Dosing: FDA-approved dose of 200U for neurogenic OAB</span>[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3649594/ §][https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4739988/ §]'''
**'''<span style="color:#ff0000">Not FDA-approved in non-neurogenic OAB patients, 100U typically used</span>'''
*'''<span style="color:#ff0000">Contraindications (4):</span>'''
*# '''<span style="color:#ff0000">Active urinary tract infection</span>'''
*# '''<span style="color:#ff0000">Acute urinary retention</span>'''
*# '''<span style="color:#ff0000">Unwillingness or inability to self-catheterize</span>'''
*# '''<span style="color:#ff0000">Hypersensitivity</span>'''
* '''<span style="color:#ff0000">Adverse events:</span>'''
**'''<span style="color:#ff0000">Most common (3):</span>'''
**#'''<span style="color:#ff0000">Bladder pain</span>'''
**#'''<span style="color:#ff0000">Gross hematuria (usually mild)</span>'''
**# '''<span style="color:#ff0000">Urinary tract infection</span>'''
**'''<span style="color:#ff0000">Most serious (2):</span>''' 
**#'''<span style="color:#ff0000">Urinary retention and a transient necessity to perform CIC (≈5%)</span>'''
**#*<span style="color:#ff0000">'''Patient must be able and willing to return for frequent post-void residual evaluation and able and willing to perform self-catheterization if necessary'''
**#*'''The proportion of patients who initiate CIC at any time during treatment cycle 1 was 6.1%''' versus none in the placebo group; for over half the patients who initiated CIC, the duration of CIC was 6 weeks or less.
**#'''Paralysis of the striated musculature caused by circulatory leakage of the toxin'''
**#* '''Has never been reported.'''
**#** '''Caution should be used in treating high-risk patients, including:'''
**#**# '''Children'''
**#**# '''Patients with low pulmonary reserve'''
**#**# '''Patients with myasthenia gravis'''
**#* '''Transient muscle weakness''' was reported with abobotA application
**'''<span style="color:#ff0000">Other:</span>''' 
**#'''<span style="color:#ff0000">Dry mouth</span>'''
**#'''<span style="color:#ff0000">Dysphagia</span>'''
**#'''<span style="color:#ff0000">Impaired vision</span>'''
**# '''<span style="color:#ff0000">Eyelid weakness</span>'''
**#'''<span style="color:#ff0000">Arm weakness</span>'''
**#'''<span style="color:#ff0000">Leg weakness</span>'''
**# '''<span style="color:#ff0000">Torso weakness</span>''' 
** '''Aminoglycosides should be avoided during BoNTA treatment because they might block motor plates and therefore enhance BoNTA effect'''

===== Capsaicin and resiniferatozin (vanilloids) =====
* Cause an initial excitation followed by a long-lasting blockade.
* Resiniferatoxin is 1000 times more potent than capsaicin for desensitization and a few hundred times more potent for excitation
* Not commonly used; there have been positive and negative trials with RTX.