Which of the following is the most predominant muscarinic receptor in the bladder?
Post-ganglionic parasympathetic nerves release acetylcholine which binds to muscarinic receptors leading to detrusor contraction. There are five types of muscarinic receptors described (M1-5). M1-3 receptors are found in the bladder. Two thirds of receptors are M2 and one-third are M3. Functionally the most important muscarinic receptor is the M3 receptor, which induce entry of calcium into the cell leading to detrusor contraction even though the M2 receptor is the most commonly found one.
Which of the following antimuscarinics has the least central nervous system side effects?
Whilst antimuscarinic agents are the mainstay of pharmacological treatment of overactive bladder syndrome, their use can be limited by side effects. Central nervous system effects are particularly important in the elderly population as the structure of the blood brain barrier may be impaired due to stroke, Alzheimer’s disease or diabetes. Central nervous system side effects include headache, dizziness or tiredness. These may be determined by the ability of the antimuscarinic agent to cross the blood brain barrier, the specificity for muscarinic receptors or actions of metabolites. Antimuscarinics are described as tertiary (e.g., oxybutynin) or quaternary amines (e.g., trospium chloride). Tertiary amines are lipophilic and are more likely to cross the blood brain barrier compared with quaternary amines which are, in theory, associated with fewer central nervous system side effects. All the tertiary amines (darifenacin, tolterodine and solifenacin) may cause cognitive side effects and exacerbating the anticholinergic burden but oxybutynin seems to be the one with the most negative effect on cognitive function. All five muscarinic receptors are found in the brain. M1 and M2 receptors are associated with memory and cognition whereas M3 receptors (which are clinically significant for detrusor contraction) have a low expression in the brain. Antimuscarinics, which have receptor specificity for M3 receptors, in theory, should have a lower risk of cognitive side effects.
Which of the following is not a contraindication for antimuscarinic use?
The use of anticholinergics is contraindicated in closed-angle glaucoma, toxic megacolon and ulcerative colitis. Myasthenia gravis is an autoimmune neurological disorder characterised by antibodies against the acetylcholine receptor. Whilst the British National Formulary describes significant bladder outflow obstruction and urinary retention as contraindications to antimuscarinic use, there is evidence that the use of antimuscarinics in patients with bladder outflow obstruction does not lead to significant adverse events. In a randomised, placebo-controlled trial, Abrams et al. investigated the safely of tolterodine in men with a urodynamic diagnosis of bladder outflow obstruction and overactive bladder syndrome. Whilst the increase in post-void residual urine was statistically higher in patients treated with tolterodine compared with placebo, this was not clinically meaningful; the rate of adverse events (including urinary retention) was not significantly higher in those taking antimuscarinic therapy, as long as post-void residuals are less than 200 mL.
Abrams P, Kaplan S, De Koning Gans HJ. Millard Safety and tolerability of tolterodine for the treatment of overactive bladder in men with bladder outlet obstruction. J Urol, 2006 Mar; 175(3 Pt 1): 999–1004.
Which of the following is the commonest side effect of duloxetine?
Duloxetine is a serotonin and noradrenaline reuptake inhibitor. Inhibition of serotonin and noradrenaline reuptake is thought to improve stress incontinence by increasing tone in the pudendal nerve, thereby increasing tone in the rhabdosphincter during bladder filling. A Cochrane Review in 2009 evaluated the use of serotonin and noradrenaline reuptake inhibitors in ten randomised controlled trials, showing a significant improvement in quality of life and reduction in incontinence episode frequency by 50% compared with placebo. Objective cure (as measured by pad test) however failed to demonstrate a benefit over placebo. Amongst the trials in this review, approximately one in three participants experienced adverse events. Side effects of duloxetine include hot flushes, anorexia, dry mouth and constipation but the commonest is nausea.
Mariappan P, Alhasso AA, Grant A, N’Dow JMO. Serotonin and noradrenaline reuptake inhibitors (SNRI) for stress urinary incontinence in adults (review). Cochrane Database of Systematic Reviews 2005; Issue 3. Art. No.: CD004742. doi:10.1002/14651858.CD004742.pub2.
What filling speed is used during cystometry in neurogenic patients?
The filling rate during filling cystometry is important and determined by the patient undergoing urodynamic assessment (e.g., neuropathic versus non-neuropathic). Medium to fast fill during filling cystometry is described as 50–100 mL/min. In neuropathic bladders a slower fill of <20 mL/min is used. Fast filling in a neuropathic patient may lead to ‘artefactual’ detrusor contractions and reduced compliance.
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