Application of Novel Therapies for Bladder Outlet Obstruction

Introduction

Excretion is one of the most essential parts of human physiology. Toxic byproducts of the human body go out of the through excretion. Urination is one of the key methods of eliminating toxic substances from the body. But, blockage in the renal system may lead to improper voiding. This causes an electrolyte imbalance in the body. At the same time, the accumulation of toxic substances may lead to toxicity in the body. Obstruction in the bladder outlet is one of the main causes of improper urine elimination from the body.

What Is Bladder Outlet Obstruction?

Obstructive uropathy is a condition that is characterized by blockage or hindrance of the urinary flow. This blockage can be caused by structural or can be caused by functional reasons. When the blockage is seen at the neck or the bottom of the urinary bladder, it is called bladder outlet obstruction. This functional obstruction or resistance can be present anywhere from the bladder neck to the urethral meatus. These types of obstruction can be seen in both men and women.

1. Pathophysiology: The pathophysiology of bladder outlet obstruction is based on the causative factors related to it. In men, bladder outlet obstruction is related to prostate complications. Different terminological conditions are used nowadays in defining bladder obstruction. The histological changes in the prostate that lead to obstruction is benign prostatic hyperplasia. Several risk factors like hypertension, obesity, obstructive sleep apnea, and metabolic dysfunctions are responsible for this. These factors cause to the generation of oxidative stress. These cause glandular and stromal hyperplasia. Also, factors like decreasing amount of testosterone and an increasing amount of dihydrotestosterone (DHT) and androgen receptors associated with increasing age are associated with benign prostatic hyperplasia. This hyperplasia causes benign prostatic enlargement. This enlargement causes obstruction in the prostate transition zone that surrounds the urethra. The symptoms of the long-standing disease lead to high-pressure retention and changes in the contractility of the detrusor muscle. The symptom caused by these factors is known as lower urinary tract symptoms. Other than this, conditions like defective valve posterior urethral valve region, posterior carcinoma, and urethral carcinoma are associated with this. Functional disorders like Fowler’s syndrome (a disorder characterized by large bladder capacity, reduced sensations, and detrusor inactivity) and dysfunctional voiding can lead to such complications.

In women, the causative factors for bladder outlet obstruction are more complicated. Stress urinary incontinence surgery (surgery for preventing accidental leakage of urine during physical activity) is one of the main causative factors for bladder obstruction. Anatomic obstructions due to pathological factors like Skene’s gland cyst (cyst in the Skene’s gland which is located at the lower end of the urethra), presence of the Mullerian duct remnants, urethral diverticulum (presence of unwanted sac in the urethra), and ectopic ureterocele (presence of extra tube in the urinary system). Cervical carcinoma, vaginal cancer, and urethral carcinoma are also associated with bladder obstruction. Functional conditions like dysfunctional voiding and external sphincter pseudodyssynergia (unusual contraction of the sphincter during voiding) are also related to this. Neurological disorders like spinal cord injury, multiple sclerosis, and Parkinson’s disease may also cause bladder obstruction.

Symptoms: The symptoms of bladder obstruction are:

• Inability to start urine flow. Patients often complain of the absence of a urine stream.

• The frequent urge to urinate.

• The feeling of full bladder even after urination.

• Decreased amount of urination.

• Decreased urinary output.

• Pain in the lower abdominal region.

• Frequent urination at night time, especially during sleeping.

What Are the Treatment Options?

The treatment option for bladder obstructions is difficult. In elderly patients, the insertion of a Foley catheter can be helpful in removing symptomatic complications. Initially, a 16 or 18 Fr Foley can be used. Such catheters can be helpful in cases of benign prostatic hyperplasia. Cases where urethral catheterization is not suitable can be treated with the help of suprapubic catheterization or cystostomy. Surgical interventions for removing bladder obstructions can also be done. In men, bilateral incisions are made to remove the obstruction from the bladder neck. Retrograde ejaculation is a problem in such cases of surgical interventions. Such types of surgery can also be performed on women also. Alpha-1-adrenergic receptors inhibitors such as Tamsulosin and Terazosin can be useful in such cases. These drugs are responsible for the relaxation of the smooth muscles of the bladder neck and help to reduce the symptoms of bladder obstruction. 5-alpha-reductase inhibitors are one of the potent drugs in such situations. These drugs can be useful in reducing the size of the prostate by inhibiting the conversion of testosterone to dihydrotestosterone in the prostate.

What Are the Novel Therapies in Bladder Outlet Obstruction?

The traditional drugs have several side effects, like ejaculatory dysfunctions, erectile dysfunctions, and abdominal pain. Such complications can be treated using combination therapy. Combination therapy is also helpful in reducing disease progression. Apart from this, several newer drugs are used in such cases. These are:

1. Phosphodiesterase-5 Inhibitors: These drugs are mainly used for the treatment of erectile dysfunctions. These drugs reduce smooth muscle tone by increasing intracellular cyclic guanosine monophosphate. These drugs are sometimes used in cases of both erectile dysfunction and bladder obstructions. Sometimes these drugs are used in combination with Alpha-1-adrenergic receptors inhibitors.

2. Beta-adrenoceptor Agonists: These drugs are responsible for increasing adenylate cyclase activity in the stromal and epithelial tissues.

3. Muscarinic Receptor Antagonists: These drugs are useful for reducing symptoms like voiding difficulties and urinary retention. Drugs like Tolterodine, Solifenacin, Propiverine, Oxybutynin, or Darifenacin are often combined with adrenoceptor antagonists for improved action. The reduction of the size of the proliferating prostate cells, inhibiting detrusor overactivity, and reduction in the tonicity of the prostatic smooth muscle are achieved by the application of these drugs.

4. P2X1-purinoceptor Antagonist: Prosthetic muscle contraction is mediated by P2X-purinoceptor. Specifically, the P2X1-purinoceptor subtype regulates the function of the adenosine triphosphate and induces the contractility of the muscle. Thus inhibition of the P2X1-purinoceptor causes the relaxation of prosthetic smooth muscles.

Conclusion

Bladder outlet obstruction causes retention of urine and improper voiding of the urinary bladder. Such obstructions are mainly caused by anatomical complications. Other than this, functional complications can also lead to bladder obstruction. Prostatic hyperplasia is one of the main reasons for bladder obstruction. Novel drugs reduce bladder voiding and cause relaxation of the smooth muscles. These drugs are also helpful in decreasing the size of the prostatic hyperplasia.