Parasympathetic pathways promote detrusor contraction and voiding
- All muscarinic receptors found in detrusor – M2 most prevalent, but M3 seems to provide most of the detrusor contraction
- Anti-cholinergic drugs as per OAB treatments
Sympathetic pathways promote storage and filling
- Alpha 1 receptors at bladder neck, prostatic and urethral smooth muscle – contraction promotes continence and storage, with closed outlet
- Alpha blockers as per BPH treatments
- Beta 3 receptors in detrusor – promotes relaxation of detrusor
- Beta-3 agonists as per OAB treatments.
Other potential pharmacological targets for the lower urinary tract include:
- PDE5 inhibitors
- Increase intracellular cGMP (cGMP normally broken down by PDE5), relaxing smooth muscle. May also alter reflex pathways and neurotransmission, and over long term increase blood perfusion and oxygenation to lower tract.
- Doesn’t seem entirely related to smooth muscle relaxation, as flow rate doesn’t improve but IPSS does
- Oestrogens
- Reverse atrophic tissue changes, improve blood flow and improve tissue and epithelial thickness of female genital and urethral tissues
- Desmopressin
- Synthetic analogue of ADH – reduces urine production by increasing reabsorption
- Tricyclic antidepressants
- Imipramine is a tricyclic antidepressant – thought to be helpful with some anticholinergic properties – significant cardiac risks however
- Beneficial for nocturnal enuresis in children but limited by cardiac and neural risks
- Doxepin is another TCA occasionally seen with anticholinergic properties
- Duloxetine
- SNRI – inhibits the presynaptic reuptake of serotonin and noradrenaline, with increased concentrations of these neurotransmitters increasing pudendal nerve stimulation and increasing resting urethral sphincter tone.
- May improve SUI but adverse effects common
- Alpha agonists
- g. pseudoephedrine to try and increase sympathetic effects at bladder neck in SUI – weak evidence only
- Herbal extracts