Myelodysplasia and Neurogenic Bladder Dysfunction Medication

Updated: Jul 09, 2019
  • Author: Terry F Favazza, MD; Chief Editor: Marc Cendron, MD  more...
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Medication

Medication Summary

Pharmacologic therapy plays an integral role in the treatment of patients with neurogenic bladder dysfunction. Treatment usually centers around 3 major elements: the use of antibiotics to prevent infection, the use of anticholinergic medications to relax the bladder and (hopefully) to increase storage capacity, and the use of alpha agonists to attempt to improve continence.

Antibiotics are used when indicated to treat acute infections and, in vesicoureteral reflux, are used as prophylaxis to prevent UTIs, pyelonephritis, and renal damage. Anticholinergic medications help suppress involuntary and uninhibited bladder contractions. This decreases urgency and incontinence and increases the bladder's functional storage capacity.

The role of alpha agonists is to increase smooth muscle tone at the bladder neck, initiating a state of urinary retention in an effort to alleviate incontinence. Thus far, the use of alpha agonists has had limited use and limited success in patients with myelodysplasia.

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Anticholinergic Agents

Class Summary

The major stimulus for bladder contraction is activation of the detrusor muscle via muscarinic cholinergic neuronal connections. Anticholinergic medications help suppress bladder contractions, especially involuntary and uninhibited contractions. This serves to decrease urgency and incontinence and to potentially increase the bladder's functional storage capacity.

Oxybutynin (Ditropan)

Synthetic tertiary amine that, similar to atropine, antagonizes the muscarinic actions of acetylcholine. Also has a direct spasmolytic effect on the detrusor muscle and the small intestine, as well as local anesthetic action. Reduces the incidence of uninhibited bladder contractions.

Tolterodine (Detrol)

Competitive muscarinic receptor antagonist for overactive bladder. Differs from other anticholinergic types because it is selective for the urinary bladder over salivary glands. Exhibits a high specificity for muscarinic receptors, and has minimal activity or affinity for other neurotransmitter receptors and other potential targets (eg, calcium channels).

Solifenacin succinate (VESIcare)

Elicits competitive muscarinic receptor antagonist activity, which results in anticholinergic effect and inhibition of bladder smooth muscle contraction. Indicated for overactive bladder with symptoms of urgency, frequency, and urge incontinence.

Darifenacin (Enablex)

Extended-release product eliciting competitive muscarinic receptor antagonistic activity. Reduces bladder smooth muscle contractions. Has high affinity for M3 receptors involved in bladder and GI smooth muscle contraction, saliva production, and iris sphincter function. Indicated for overactive bladder with symptoms of urge incontinence, urgency and frequency. Swallow whole; do not chew, divide, or crush.

Fesoterodine (Toviaz)

Competitive muscarinic receptor antagonist. Antagonistic effect results in decreased bladder smooth muscle contractions. Indicated for symptoms of overactive bladder (eg, urinary urge incontinence, urgency, and frequency). Available as 4- or 8-mg extended-release tab.

Trospium (Sanctura)

Quaternary ammonium compound that elicits antispasmodic and antimuscarinic effects. Antagonizes acetylcholine effect on muscarinic receptors. Parasympathetic effect reduces smooth muscle tone in the bladder. Indicated to treat symptoms of overactive bladder (eg, urinary incontinence, urgency, frequency).

Hyoscyamine (Levbid, Levsin)

Blocks action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands, and the CNS, which, in turn, has antispasmodic effects.

Propantheline (Pro-Banthine)

Blocks action of acetylcholine at postganglionic parasympathetic receptor sites.

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Anticholinergic Agent, Transdermal

Class Summary

The major stimulus for bladder contraction is activation of the detrusor muscle via muscarinic cholinergic neuronal connections. Anticholinergic medications help suppress bladder contractions, especially involuntary and uninhibited contractions. This serves to decrease urgency and incontinence and to potentially increase the bladder's functional storage capacity.

Oxybutynin chloride 10% gel (Gelnique)

Oxybutynin chloride is a synthetic tertiary amine that, similar to atropine, antagonizes the muscarinic actions of acetylcholine. It also has a direct spasmolytic effect on the detrusor muscle and the small intestine, as well as local anesthetic action. Oxybutynin chloride reduces the incidence of uninhibited bladder contractions.

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Neuromuscular Blocker Agent, Toxin

Class Summary

BOTOX blocks neuromuscular transmission by binding to acceptor sites on motor or sympathetic nerve terminals, entering the nerve terminals, and inhibiting the release of acetylcholine. This inhibition occurs as the neurotoxin cleaves SNAP-25, a protein integral to the successful docking and release of acetylcholine from vesicles situated within nerve endings. When injected intramuscularly at therapeutic doses, BOTOX produces partial chemical denervation of the muscle, resulting in a localized reduction in muscle activity. In addition, the muscle may atrophy, axonal sprouting may occur, and extrajunctional acetylcholine receptors may develop. There is evidence that reinnervation of the muscle may occur, thus slowly reversing muscle denervation produced by BOTOX.

Following intradetrusor injection, BOTOX affects the efferent pathways of detrusor activity via inhibition of acetylcholine release. In addition, BOTOX is believed to inhibit afferent neurotransmitters and sensory pathways.

Botulinum toxin type A

BOTOX blocks neuromuscular transmission by binding to acceptor sites on motor or sympathetic nerve terminals, entering the nerve terminals, and inhibiting the release of acetylcholine. When injected intramuscularly at therapeutic doses, BOTOX produces partial chemical denervation of the muscle, resulting in a localized reduction in muscle activity.

Following intradetrusor injection, BOTOX affects the efferent pathways of detrusor activity via inhibition of acetylcholine release. In addition, BOTOX is believed to inhibit afferent neurotransmitters and sensory pathways. It is typically effective for 6-12 months.

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Alpha agonists

Class Summary

The tone of the musculature at the bladder neck is mitigated by alpha-adrenergic stimulation. The role of alpha agonists is to increase tone at the bladder neck, initiating a state of urinary retention, in an effort to decrease incontinence. However, these therapies are often not very effective.

Pseudoephedrine (Sudafed)

Stimulates vasoconstriction by directly activating alpha-adrenergic receptors of the respiratory mucosa. Induces bronchial relaxation and increases heart rate and contractility by stimulating beta-adrenergic receptors.

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BPH, Alpha Blockers

Class Summary

These agents may decrease outlet resistance and reduce leak point pressures in patients with neurogenic bladder.

Tamsulosin (Flomax)

Tamsulosin is a selective alpha1-antagonist for the treatment of BPH. It has been used off-label on a study basis in an attempt to decrease outlet resistance and reduce leak point pressures in patients with neurogenic bladder.

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Tricyclic antidepressants

Class Summary

These medications work by directly inhibiting bladder contractions through a mechanism unrelated to anticholinergic effects. They act to decrease bladder spasms and increase storage capacity.

Imipramine (Tofranil)

Facilitates urine storage by decreasing bladder contractility and increasing outlet resistance. Inhibits reuptake of norepinephrine or serotonin (5-hydroxytryptamine [5-HT]) at presynaptic neurons.

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Antibiotics

Class Summary

These agents are used when indicated to treat acute infections. In patients with vesicoureteral reflux, they are often used as prophylaxis to prevent UTIs, which can potentially lead to pyelonephritis and renal damage.

Of the many antibiotics, 4 agents commonly used in the pediatric population are discussed below.

Trimethoprim and sulfamethoxazole (Bactrim, Septra)

Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. Antibacterial activity includes common urinary tract pathogens except Pseudomonas aeruginosa.

Amoxicillin (Trimox, Amoxil)

Interferes with synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria.

Nitrofurantoin (Furadantin, Macrodantin)

Synthetic nitrofuran that interferes with bacterial carbohydrate metabolism by inhibiting acetylcoenzyme A. Bacteriostatic at low concentrations (5-10 mcg/mL) and bactericidal at higher concentrations.

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Antibiotic, Quinolone

Class Summary

UTIs are common in myelodysplasia and may require antibiotic treatment.

Ciprofloxacin (Cipro, Cipro XR, ProQuin XR)

Ciprofloxacin is a fluoroquinolone that inhibits bacterial DNA synthesis and, consequently, growth, by inhibiting DNA gyrase and topoisomerases, which are required for replication, transcription, and translation of genetic material. Quinolones have broad activity against gram-positive and gram-negative aerobic organisms. Ciprofloxacin has no activity against anaerobes. Continue treatment for at least 2 days (7-14 d typical) after signs and symptoms have disappeared.

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