toxina botulínica na bexiga hiperativa - 15/13h10... · comportamento vesical semelhante à hd...

Toxina Botulnica na Bexiga Hiperativa II Encontro de Urologia do Sudeste Ricardo Castellani de Mattos TiSBU

Mecanismos de Ao. Diferenas entre as formulaes. Histrico. Aspectos Tcnicos

Profundidade da injeo; Nmero de injees; Injeo trigonal;

Eficcia e Segurana Presena de HD; Doses

Neurognica; Idioptica;

Durao do efeito Eventos Adversos.

Recomendaes.

Toxina Botulnica na Bexiga Hiperativa

Toxina Botulnica - Mecanismo de ao: Internalizao por

endocitose; Liberao da cadeia

leve no citoplasma; Quebra das protenas

SNAP 25 do complexo SNARE;

Impedimento da liberao da Ach das vesculas.

Rowland, 2002.

Toxina Botulnica - Mecanismos de ao vesical complexos: Hipteses etiolgicas da SBH, Drake 2008:

Hiptese Neurognica atividade reflexa anormal (SNC...); Hiptese Miognica maior predisposio s contraes

espontneas e propagao do estmulo entre as fibras detrusoras, denervao - aumento de receptores de membrana (pode haver comportamento vesical semelhante HD na ausncia de eferncia);

Hiptese Integrativa (Atividade Autonmica Perifrica) aumento da atividade entre os mdulos atravs do plexo miovesical, papel das clulas intersticiais (camadas suburotelial e muscular).

Toxina Botulnica - Mecanismos de ao vesical complexos, Drake, 2008: Bloqueio eferente Ach; Interferncia na liberao de outros transmissores neuronais ou

no-neuronais; Interferncia em mecanismos aferentes, afetando o volume da

primeira contrao involuntria; Interferncia em mecanismos interneuronais.

Diferenas entre as formulaes: Clostridium botulinum subtipos mais relevantes: A e B; No h intercambialidade de doses entre as drogas;

Botox onabotulinotoxina A - cadeia leve: 50 kD, cadeia pesada: 100kD, demais protenas: 750 kD - 900 kD (total)

Maior peso molecular: menor disperso nos tecidos e sistmica Tang-Liu, 2003, Aoki, 2006

Dysport abobotulinotoxina A - > 300 kD; Xeomin incobotulinotoxina A 150 kD, isenta de complexos

proticos.

Histrico Fenol subtrigonal, Ewing, 1982; Capsaicina, Fowler, 1994; Resiniferatoxina, Craft, 1993, Lazzeri, 1997; Dissinergia detrusor-esfincteriana, Dykstra, 1990, Schurch, 1996;

11 paraplegics and 13 tetraplegics Transurethral versus transperineal botulinum-A toxin injections Botulinum-A toxin has no effect on the detrusor, since it interferes

much less with the parasympathetic system than the D type toxin.

Toxina Botulnica detrusora, Schurch, 2000; Prospectivo, no randomizado, 2 centros; 31 pacientes, TRM, cat. int., hiperreflexia e incontinncia; Anticolinrgicos em altas doses; 200-300 U, 20-30 punes, poupando o trgono.

Continncia, reduo/retirada do anticolinrgico, volume reflexo, capacidade cistomtrica mxima, presso mxima de mico do detrusor, volume residual ps miccional, disreflexia autonmica.

Toxina Botulnica detrusora, Schurch, 2000;

Tcnica nvel intramural das injees: injeo detrusora x injeo suburotelial, Krhurt 2012;

32 spinal cord injury patients detrusor compliance was better in the intradetrusor group; Results in both groups were comparable.

injeo detrusora, suburotelial e na base vesical, Kuo, 2007; total of 45 patients with idiopathic detrusor overactivity; all 3 methods had a therapeutic effect on

idiopathic detrusor overactivity; injection relieved urgency sensation but did not increase bladder

capacity.

Tcnica nmero de injees

Neurognica - mais comum: 20 injees, 20 mL Idioptica mais comum: 30 injees, 30 mL (EAU Guidelines,

2013/Mangera, 2011); Injeo trigonal resultados conflitantes

Khuo, 2011 idiopathic detrusor overactivity refractory to antimuscarinics; bladder body x bladder body/trigone x bladderbase/trigone ; no significant differences in success rates; incidence of adverse events was similar among three groups;

Mangera, 2011 Neurognica - Trigonal injections may possibly improve daily incontinence

and lead to better continence rates; Idioptica - greater reductions in Overactive Bladder Symptom Score

lasting for a longer period of time with trigonal injections.

Eficcia Presena de HD Avaliao Urodinmica Kanagarajah, 2012;

27 women and 5 men; 19 pacientes OAB-dry, 13 pacientes OAB-wet; Refractory idiopathic OAB patients without DOA on urodynamics

may benefit from intradetrusor BTX-A. Dmochowski, 2010;

SBH idioptica; 76.0% (238 of 313) of patients had DO at baseline; In a subgroup analysis the efficacy of onabotulinumtoxinA was

similar in patients with and without DO.

Eficcia doses Idioptica, Dmochowski, 2010

Durable efficacy was observed for all onabotulinumtoxinA dose groups of 100 U or greater;

doses greater than 150 U contributed minimal additional or clinically relevant improvement in symptoms.

Eficcia doses Neurognica, Cruz, 2011

275 pacientes, EM ou TRM; Patients received 30 intradetrusor injections of onabotulinumtoxinA

200 U (n = 92), 300 U (n = 91), or placebo (n = 92), avoiding the trigone.

Both doses were well tolerated with no clinically relevant differences in efficacy or duration of effect between the two doses;

Efeito dose-teto: 200 U.

Eficcia durao do efeito Cochrane, 2011: The duration of effect of botulinum toxin type A

may range from three to twelve months. The effect of botulinum toxin type B seems to be limited to less than ten weeks.

Mangera, 2011: time interval between injections; the range for onabotulinumtoxinA was 616 mo, and the range for abobotulinumtoxinA was 512 mo.

Cruz, 2011: time to patient-requested retreatment 42,1 semanas (cerca de 290 dias, 9-10 meses).

Segurana - eventos adversos Idioptica, Dmochowski, 2010

Dose dependent changes in post-void residual urine clean intermittent catheterization was also dose dependent significantly greater with onabotulinumtoxinA than with placebo were urinary

tract infection and urinary retention.

Segurana - eventos adversos Idioptica, Dmochowski, 2010

Segurana - eventos adversos Neurognica, Cruz, 2011

Segurana - eventos adversos Chapple, 2012 (ICS Abstracts)

ONABOTULINUMTOXINA SIGNIFICANTLY DECREASES URINARY INCONTINENCE AND PROVIDES TREATMENT BENEFIT IN PATIENTS WITH IDIOPATHIC OVERACTIVE BLADDER

548 patients

Recomendaes AUA, Guidelines

SBH no-neurognica 2012 Terceira linha no aprovada pelo FDA Clinicians may offer intradetrusor onabotulinumtoxinA as third-line

treatment in the carefully-selected and thoroughly-counseled patient who has been refractory to first- and second-line OAB treatments. The patient must be able and willing to return for frequent post-void residual evaluation and able and willing to perform self-catheterization if necessary. Option (Evidence Strength Grade C)

Eventos adversos com prejuzo da QoL.

Recomendaes Aprovao pelo FDA

Disfuno Neurognica, agosto 2011.

Recomendaes Aprovao pelo FDA

Bexiga Hiperativa refratria a anticolinrgicos, janeiro 2013.

Recomendaes EUA, Guidelines

Disfuno Neurognica do Trato Urinrio Inferior, 2011 Botulinum toxin injection in the detrusor is the most effective minimally

invasive treatment to reduce neurogenic detrusor overactivity. GR A

Incontinncia Urinria, 2013 Offer botulinum toxin A intravesical injections to patients with urge urinary

incontinence refractory to antimuscarinic therapy. Offer onabotulinumtoxinA 100 U as initial dose to minimise the risk of

urinary retention and urinary tract infection.

Recomendaes SBU, Diretrizes TRATAMENTO DE SEGUNDA LINHA DA BEXIGA HIPERATIVA

Existem duas alternativas para o tratamento destes pacientes com eficcia comprovada: a neuromodulao e a aplicao da toxina botulnica diretamento no detrussor. (...) A dose empregada varia de 100 a 300 U, diludas em 30 ml de soluo salina, aplicando 1 ml da diluio em 30 pontos diferentes da musculatura detrussora, geralmente poupando-se o trgono vesical.

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