Detrusor

Genitourinary—urinary urgency and difficulty with urination, caused by spasms of the ureter. Urinary urgency also may occur because of the action of the drugs on the detrusor muscle of the bladder. Some patients may experience difficulty voiding because of contraction of the bladder sphincter. 

Urinary fracf-d Natation of smooth muscles of the ureters and kidney pelvis, contraction of the detrusor muscle of the bladder... 

This chapter discusses drug s used to treat urinary tract infections (UTIs) and certain miscellaneous drag > used to relieve the symptoms associated with an overactive bladder (involuntary contractions of the detrusor or bladder muscle). Structures of the urinary system that may be affected include the bladder (cystitis), prostate gland (prostatitis), the kidney, or the urethra (see Pig. 47-1). These drug s also help control the discomfort associated with irritation of the lower urinary tract mucosa caused by infection, trauma, surgery, and endoscopic procedures. 

The miscellaneous drugp are used to relieve the symptoms associated with an overactive bladder (involuntary contractions of the detrusor or bladder muscle)... 

The expression of TRPVl in the bladder is, however, not restricted to afferent nerves urothelium, detrusor muscle and fibroblasts also express TRPVl in the human bladder [140]. The implication of these findings for intravesical vanilloid therapy is unclear [141], but the increase in TRPVl immunoreactivity in the urothelium in patients with neurogenic detrusor overactivity (that occurs in concert with increased TRPVl in bladder af-ferents) is a very intriguing finding [142]. In the male urogenital system, TRPVl is also present in testicles, prostate and scrotal skin [143], and it was postulated that TRPVl ligands may be beneficial in the treatment of benign prostatic hyperplasia [144]. 

Two types of urinary tract symptoms are commonly seen in MS incomplete bladder emptying and incontinence. Incomplete bladder emptying is due to dyscoordination of the external urethral sphincter and detrusor activity.14 Most patients who develop this condition require intermittent or permanent uri-I nary catheterization.14 Incontinence in most MS patients is... 

O The lower urinary tract symptoms and signs of benign prostatic hyperplasia are due to static, dynamic, or detrusor factors. The static factor refers to anatomic obstruction of the bladder neck caused by an enlarged prostate gland. The dynamic factor refers to excessive stimulation of a-adrenergic receptors in the smooth muscle of the prostate, urethra, and bladder neck. The detrusor factor refers to irritability of hypertrophied detrusor muscle as a result of long-standing bladder outlet obstruction. 

Filling cystometry provides information on bladder capacity, detrusor contractility, and the presence of uninhibited bladder contractions, which could also cause LUTS... 

In UUI, the detrusor (bladder) muscle is overactive and contracts inappropriately during the filling phase. The amount of urine lost per episode can be as large as the entire contents of the bladder may empty. Sleep may be disrupted by nocturia and enuresis. 

DHIC detrusor hyperactivity with impaired contractility... 

Detrusor muscle Smooth muscle of the bladder body. When the detrusor muscle contracts, the bladder is emptied of urine. 

Peak urinary flow rate <10 mL/s Postvoid residual urine volume >25-50 mL Increased BUN and serum creatinine All of the above signs plus obstructive voiding symptoms and irritative voiding symptoms (signs of detrusor instability)... 

Ratz PH, MacCammon KA, Altstatt D, Blackmore PF, Shenfeld OZ, Schlossberg SM (1999) Differential effects of sex hormones and phystoestrogens on peak and steady state contractions in isolated rabbit detrusor. J Urol 162 1821-1828... 

Babiychuk EB, Draeger A 2000 Annexins in cell membrane dynamics. Ca2+-regulated association of lipid microdomains. J Cell Biol 150 1113-1124 Ber DM 2001 Excitation-contraction coupling and cardiac contractile force, 2nd edn. Kluwer Academic Publishers, Dordrecht/Boston/London Blaustein MP, Golovina VA 2001 Structural complexity and functional diversity of endoplasmic reticulum Ca2+ stores. Trends Neurosci 24 602—608 Flynn ER, Bradley KN, Muir TC, McCarron JG 2001 Functionally separate intracellular Ca2+ stores in smooth muscle. J Biol Chem 276 36411-36418 Fry CH, WuCl 997 Initiation of contraction in detrusor smooth muscle. Scand J Urol Nephrol Suppl 184 7-14... 

Brading The appearance of spontaneous contractile activity in detrusor strips depends very much on their thickness. 

Zderic SA, Rohrmann D, Gong C et al 1996 The decompensated detrusor II evidence for loss of sarcoplasmic reticulum function after bladder outlet obstruction in the rabbit. J Urol 156 587-592... 

HT4 receptors are also present in the pig and human hearts, primarily located in the atrium [9]. Experiments showed that stimulation of these receptors can result in tachycardia and can trigger positive inotropic effects. Moreover, it has been demonstrated that the 5-HT4 receptor is present in the human detrusor muscle and facilitates a cholinergic mechanism which may lead to increased bladder contractions [10]. Finally, acute (but not repeated) stimulation of 5-HT4 receptors present on the human adrenal cortex has been reported to trigger the release of corticosterone and aldosterone [11]. 

Responses to activation of the parasympathetic system. Parasympathetic nerves regulate processes connected with energy assimilation (food intake, digestion, absorption) and storage. These processes operate when the body is at rest, allowing a decreased tidal volume (increased bronchomotor tone) and decreased cardiac activity. Secretion of saliva and intestinal fluids promotes the digestion of foodstuffs transport of intestinal contents is speeded up because of enhanced peristaltic activity and lowered tone of sphincteric muscles. To empty the urinary bladder (micturition), wall tension is increased by detrusor activation with a concurrent relaxation of sphincter tonus. 

Prostatic hypertrophy with impaired micturition loss of parasympathetic control of the detrusor muscle exacerbates difficulties in voiding urine. 

In patients with conditions characterized by involuntary bladder contractions, oxybutynin increases vesical capacity, diminishes frequency of uninhibited contractions of the detrusor muscle, and delays initial desire to void. Oxybutynin thus decreases urgency and the frequency of incontinent episodes and voluntary urination. 

Tolterodine has a pronounced effect on bladder function in healthy volunteers. The main effects following a 6.4 mg single dose of tolterodine were an increase in residual urine, reflecting an incomplete emptying of the bladder, and a decrease in detrusor pressure. 

Pharmacology Trospium is an antispasmodic, antimuscarinic agent. Trospium antagonizes the effect of acetylcholine on muscarinic receptors in cholinergically innervated organs. Its parasympatholytic action reduces the tonus of smooth muscle in the bladder. Trospium increases maximum cystometric bladder capacity and volume at first detrusor contraction. 

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