4 However urodynamic evaluation is the gold standard: “Urodynamic evaluation is still considered to be the gold standard for quantitating the degree of obstruction, related detrusor contractile dysfunction, and simultaneous pressure/ow analysis”. Roger R. Treatment First-Line Treatment Behavioural therapies are recommended as rst-line treatment. This includes bladder training, bladder control strategies, pelvic oor muscle training and uid management. In OAB patients, pelvic oor muscle training is primarily used as an urgency suppression technique, aimed at inuencing, and minimizing the “urge” symptoms of OAB, which is usually more sudden, intense, and unpleasant than the normal sensation to void. Patients are taught to contract their pelvic muscle oor (PMF) rapidly, and in some instances also to contract for prolonged durations (where there is also stress incontinence) to help inhibit urgency producing detrusor (bladder contractions. Other urgency suppression techniques that share dermatomal and myotome distribution with S2-4 (for e.g. heel raises, adductor squeezes, rubbing inner thighs and direct penile/perineal manual compression) may be used in combination with the quick re PMF contractions to suppress the urge”. Second-Line Treatment (Pharmacological Management) The best outcomes are achieved through a combination of pharmacological interventions and behavioural modications. Antimuscarinics are the pharmacological treatment of choice for overactive bladder. These include: propiverine, darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine, and trospium chloride. Propiverine, oxybutynin, tolterodine, and trospium are available in both immediate-release (IR) and extended-release (ER) formulations, while oxybutynin is also available in a sustained-release patch form for transdermal administration). The anticholinergics block the parasympathetic acetylcholine pathway and thereby reduce the intensity of detrusor muscle contractions. However, they are not specic to the muscarinic receptors in the bladder. Blockade of M2 causes side effects such as inhibition of salivary secretion (dry mouth), dry eye causing blurred vision for near objects, tachycardia, drowsiness, decreased cognitive function, and inhibition of gut motility resulting in constipation. propiverine has been shown to have a lower afnity for M2 receptors, which are effective in cardiac functions, compared to tolterodine, oxybutynin, darifenacin, and trospium. A comparison of binding afnity (pKi) of antimuscarinic compounds for the human recombinant receptor subtype M2 Mode of action Propiverine and oxybutynin are the only two antimuscarinics agents that have a dual mode of action. In addition to its antimuscarinic effects, propiverine can also inhibit the purinergic mechanism, which is another factor responsible for detrusor contraction. Potential Drug Drug Interactions Propiverine can be considered a weak inhibitor of cytochrome P450 (CYP3A4) and signicant increases in the concentrations of other drugs metabolised by this pathway are therefore not expected. Pharmacokinetics The pharmacokinetics are not altered in patients with severe renal impairment (CC<30 mL/min) or mild to moderate liver failure from fatty liver disease, and in elderly patients (60–85 years) compared to young healthy adults. No dose adjustment is required with propiverine in patients with mild to moderate renal impairment. No dose adjustment is recommended in patients with severe renal impairment unless the dose exceeds 30mg/day. No dose adjustment is required in patients with mild liver failure. Efcacy The efcacy of propiverine is well documented in numerous clinical studies. In a metanalysis by Huang W et al. “Propiverine was effective for urgency, frequency, and urgency incontinence, suggesting that it contributes to improving overall OAB symptoms, especially by improving urgency and urgency incontinence episodes; propiverine may have improved the daily living activities impaired by OAB”. In dose determination studies done by Mazur D et al, there was a 50% improvement observed in the efcacy parameters in the group given 15 mg/day, while the efcacy reached 80% in the group given 30 mg/day. In a study done by Thuroff JW et al, the subjective improvement in OAB patients with the use of propiverine was shown to be 77%. In addition, a decrease in max detrusor pressure and an increase in max bladder capacity were observed compared to placebo. Propiverine Tolterodine Oxybutynin Darifenacin Trospium 5.4 8 7.8 7.4 9.2 UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE
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