Overactive Bladder (OAB) Content of the lecture

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1 Overactive bladder (OAB) : Introduction and Medical Management R.J. Opsomer Cliniques St Luc, labo d urodynamique, UCL - Bruxelles Overactive Bladder (OAB) Content of the lecture The syndrome of Overactive bladder : definition Epidemiology and Diagnosis Treatment options of OAB Pharmacotherapy Clinical cases What is Overactive Bladder (OAB)? Overactive Bladder (OAB) is a symptom or syndrome suggestive of lower urinary tract dysfunction It is specifically defined as a syndrome with: Urgency, with or without urge incontinence, usually with frequency and nocturia Standardisation Subcommittee of the International Continence Society (ICS) Abrams P, Cardozo L, Fall M et al Neurourol Urodyn 2002;21:

2 International Continence Society (ICS) definition of symptoms Urgency Incontinence a sudden compelling desire to pass urine, which is difficult to defer any involuntary leakage of urine Frequency Nocturia Abrams P, Cardozo L, Fall M et al Neurourol Urodyn 2002;21: voiding too often usually defined as : 8 or more micturitions in 24 hours waking more than once at night to void The Urge Continuum A Flowchart OAB dry Increased Micturition Frequency +/- +/- Nocturia Urgency Warning time reduced OAB wet Incontinence Reduced Volume Voided/Micturition Data on File: Personal communication Mr Chris Chapple Prevalence of OAB in Europe Overall, 16% of the population aged >40 years in 6 European countries have symptoms of OAB Prevalence of OAB increases with age Prevalence (%) Men Women N = 16, Chapple ICS Age (years) Milsom I et al. BJU Int. 2001;87:

3 Garage Door Syndrome OAB: Detrusor overactivity or not? OAB is usually suggestive of detrusor overactivity Detrusor overactivity: A urodynamic observation characterised by involuntary detrusor contractions during the filling phase Neurogenic Idiopathic Caused by a relevant No defined cause neurological condition Abrams P, Cardozo L, Fall M et al Neurourol Urodyn 2002;21: urological 3

4 urological I. Supraspinal disorders II. Spinal disorders (suprasacral) Neuro-urological urological pathologies with OAB symptoms 4

5 Urgency due to BPH? or a neurological disorder? or both?? Nocturia?? according to Magritte a urological? neuro-urological? nephrological?. symptom.. 5

6 Diagnosis and treatment options of OAB History Physical exam Electrophysiologic Diagnosis Lab tests tests Urodynamic tests Imaging Diagnosis of OAB medical / surgical / obstetrical history diabetes, neurological disorders, previous operations,... physical examination rectal examination, vaginal examination,... (minimal) diagnostic tests : Voiding diary: patient monitors fluid intake and urine output Urine tests rule out infection Urodynamics : flowmetry + residual urine Imaging : ultrasound 6

7 Physical exam Rectal exam: - sphincteric tonus - voluntary control Neurological testing: - Genital sensitivity -Perinealmotricity - Local reflectivity Diagnosis of OAB (invasive) diagnostic tests : - video-urodynamics - cystoscopy (+ cytology) stable bladder = normal test unstable bladder (hyperactive) 7

8 Principle of video-urodynamics UCL St Luc Brussels Treatment modalities for OAB Behavioural techniques: fluid intake schedule scheduled toileting bladder retraining pelvic muscles exercises Bladder biofeedback (during video-urodynamics) Pharmacology - anticholinergic / antimuscarinic or antispasmodic drugs Electrostimulation - Tibial nerve stim / neuromodulation Surgery Pharmacological options for OAB 8

9 Antimuscarinic drugs Parasympathetic (cholinergic) nerves release acetylcholine : activation of muscarinic receptors (M2-M3) contraction of detrusor muscle Antimuscarinic drugs block muscarinic receptors : inhibit involuntary contractions of the bladder increase capacity of the bladder delay the initial urge to void Efficacy of antimuscarinic drugs in OAB Urgency episodes Incontinence episodes Frequency Volume voided / micturition Nocturia Anti-muscarinic drugs Oxybutynine hydrochloride Ditropan - Sanofi-Synthelabo (5mg, 2-4x/day) Driptane - Fournier Pharma (5mg, 2-4x/day) antimuscarinic, antispasmodic and local anaesthetic properties some degree of selectivity for M3 and M1 receptors higher affinity for receptors in parotid gland than in the bladder 9

10 Antimuscarinic drugs Tolterodine tartrate Detrusitol - Pfizer (2mg, 2x/day) Detrusitol Retard (4mg, 1x/day) selectivity for bladder muscarinic receptors over those in salivary glands as effective as oxybutynin, but with fewer adverse effects Antimuscarinic drugs Solifenacin : Vesicare - Astellas (5mg, 1x/day) (10mg 1x/day) Fesoterodin : Toviaz -Pfizer Antimuscarinic drugs Flavoxate hydrochloride Urispas - Altana Pharma (200mg, 3-4x/day) antispasmodic, anaesthetic and analgesic effect less side-effects, but considered less effective (Propiverine hydrochloride) anticholinergic and calcium antagonistic properties (Trospium chloride) licensed for the treatment of detrusor instability or hyperreflexia no central anticholinergic effects 10

11 ANTIMUSCARINICS: Balance to find between Efficacy and Tolerability Efficacy Urge Urinary Incontinence Episodes Frequency Tolerability Effects on Other Organs Receptor Profile Bladder Selectivity PK/PD 11

12 Distribution of muscarinic receptors. Antimuscarinic Adverse Events: Dry mouth %Dry Mouth , Solifenacin 5mg Solifenacin 10mg Tolterodine Retard Tolterodine IR Oxybutynin IR SmPC Vesicare, Detrusitol Retard, Detrusitol, Abrams et al., Br. J.; Urol. (1998) 81: Transdermal Oxybutynin «patchs» 12

13 Transdermal patches side effects Contra indications for anticholinergics Glaucoma Infravesical obstruction Alzheimer s disease Parkinson s disease 13

14 5-HMT (metabolite of Fesoterodin) Is less lipophilic than tolterodine 41 Lipophilicity is an important predictor of the ability of a drug to cross the blood-brain barrier Octanol/water distribution coefficient (logd) is a standard measure of lipophilicity Lower logd of 5-HMT makes crossing of bloodbrain barrier less likely logd (octanol/water ratio) trospium 5-HMT solifenacin tolterodine darifenacin* oxybutynin *Darifenacin was not included in the same study as the other agents. The lipophilicity was obtained from a separate trial done on darifenacin alone. Malhotra B et al. Presented at Br Pharmacol Soc Winter Meeting Chapple C. Expert Opin Investig Drugs. 2004;13:

15 43 Uncovering Toviaz : (fesoterodine fumarate) A New Option in the Management of OAB Conversion into the active metabolite 44 15

16 Clinical case n 1 G.F. 73 yo History: - hip surgery in 2001 complaints: - urgency (incontinence), weak flow - nocturia Physical exam: - BPH 16

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18 Clinical case n 1 G.F., 73 yo Conclusion of urodynamic testing bladder instability Infravesical obstruction Small residual urine Treatment? drugs physiotherapy surgery Treatment? Drugs: - alpha blockers - alpha blockers + anti-muscarinic physiotherapy surgery 18

19 The three fundamental aspects of BPH Who will benefit from surgery? Prostatism and neurological disorders Micturition Filling phase Normal subject Parkinson s disease: small amplitude unstable bladder contractions Filling phase micturition 19

20 A parkinson-like syndrome: Shy Drager syndrome - MSA Ordre de mict Abaque d Abrams alternative to surgery? Prostatic spiral 20

21 cystometry Instability (phasic activity) Hypertonia (tonic activity) 21