Adrenergic antagonist drug

 

Urinary incontinence definition

The complaint of any involuntary leakage of urine and which is a social or hygienic problem.

Urinary incontinence classification

Acute incontinence:

Usually associated with acute medical condition such as; cystitis, vaginitis, urethritis, acute confusional state or drug induced ( eg; prazocin ).

Persistent incontinence:

It classified into 3 classes; urge incontinence, stress incontinence and overflow incontinence.

Persistent urinary incontinence classification

1. Urge urinary incontinence.
2. Stress urinary incontinence.
3. Overflow urinary incontinence.

Urge urinary incontinence 

This type of incontinence is caused by detrusor muscle instability.

Urge urinary incontinence risk factors

•  Aging
•  neurological disorders
•  recurrent UTIs
• less likely due to stones or tumor.

Urge urinary incontinence diagnosis

Clinical picture (symptoms ).

urge urinary incontinence symptoms

• Frequency of urination.
• Involuntary voiding that is preceding by a warning of few seconds to a few minutes.
• Nocturia and enuresis.
• Urodynamic tests are considered the gold standards for diagnosis of urge urinary incontinence.
• urinalysis and urine culture should be negative ( to rule out UTIs as a cause of frequency ).

Stress urinary incontinence 

• This type is the most common type of urinary incontinence.
• The involuntary leakage occurs only during stress ( increased intra-abdominal pressure ).
• Most commonly caused by urethral underactivity associated with weakness of pelvic floor muscles.
• The patient usually notices the urinary incontinence during activities like exercise, running, lifting, coughing or sneezing.
• This type of urinary incontinence is more common in females ( seen in males only with lower urinary tract surgery or injury compromising the sphincters ).

Stress urinary incontinence risk factors

• Age
• Female gender
• Pregnancy
• Vaginal delivery
• Obesity
• Surgery (radical prostatectomy , transurethral resection ).

Stress urinary incontinence diagnosis

Mainly diagnosed by clinical picture ( symptoms).

Stress urinary incontinence symptoms 

Leakage of urine during activities like exercise, running, lifting, coughing or sneezing.

Overflow urinary incontinence

• Overflow urinary incontinence is a consequence of urinary bladder underactivity or internal sphincter overactivity.
• Overflow urinary incontinence occur when the bladder is filled to capacity at all times but is unable to empty, causing urine to leak from the distended bladder past a normal or even overactive outlet and sphincter.
• In this type usually there is an increase in post void residual urine volume.
• This type is more common in men because of prostate abnormalities.

Overflow urinary incontinence risk factors

• Urethral overactivity risk factors:
• Gender ( more common in males ).
• Benign prostatic hyperplasia ( BPH ).
• Prostate cancer.
• Abdominal pelvic surgeries.
• Bladder underactivity risk factors:
• Diabetes mellitus.
• Lower spinal injury.
• Multiple sclerosis.
• Radical pelvic surgery.

Overflow urinary incontinence diagnosis

Overflow urinary incontinence is mainly diagnosed by clinical picture ( symptoms ).

Overflow urinary incontinence symptoms and signs

• Lower abdominal fullness.
• Straining of void.
• Decreased force of stream.
• Interrupted stream.
• Sense of incomplete emptying.
• Increased post void residual urine volume.

 

Investigations for diagnosis of urinary incontinence

1. Complete medical and medication history.
2. Physical examination: abdominal, pelvic, genital, prostate examination.
3. Neurological examination.
4. Urinalysis ( to rule out UTIs ).
5. Urodynamic studies such as; post void urine volume, cystometry, urethral pressure profilometry and uroflometry. 

Urinary incontinence treatment and management

Goals of therapy:

• Restoration of continence.
• Reduction of urinary incontinence episodes.
• Prevent complications (skin breakdown ).
• Minimize adverse events of treatment.

Non-pharmacological treatment

1. Life style modifications: decrease fluid intake , decrease caffeine intake , weight reduction and smoking cessation ).
2. Bladder training ( scheduled voiding and urge suppressing techniques ).
3. Pelvic floor muscle rehabilitation ( kegel exercise ).
4. Anti-continence devices.
5. Surgery for stress urinary incontinence ( by narrowing the urethra ).

Pharmacological treatment

Urge urinary incontinence treatment 

Anticholinergic drugs have approved to be the most effective agents in reliving urge urinary incontinence symptom due to:

• Suppression of premature detrusor muscle contractions.
• Enhancing bladder storage.

 

Anticholinergic drugs used in urge urinary incontinence:

• Oxybutynin:

• Oxybutynin is most common anticholinergic used for treatment of urge urinary incontinence; because it is not expensive as comparing with other anticholinergic drugs used for this purpose.
• It is associated with major adverse effect ( dry mouth ), which is related to its metabolite N-desethyloxybutynin.

How can be dry mouth managed in those patients?

1. The use of candies or artificial saliva.
2. Start oxybutynin at low doses and titrate very slowly.
3. The use of extended release formula of oxybutynin.

• Tolterodine:

• Tolterodine has a comparable efficacy to oxybutynin, but tolterodine has better tolerability.

• Major problem of this agent:

It is suggested to CYP2D6 polymorphism, tolterodine is metabolized at a slower rate in poor metabolizers than in extensive metabolizers; this results in significantly higher serum concentrations of tolterodine and in negligible concentrations of the 5-hydroxymethyl metabolite.

 

• Trospium chloride:
• Antimuscrinic agent acts only on urinary bladder and gastrointestinal tract.
• It is quaternary ammonium salt, so cannot cross blood brain barrier, so it has less neurotoxicity.

• Solifenacin and darifenacin:

• They are uroselective agents ( act only on urinary bladder ).
• Solifenacin is associated with lowest rate of discontinuation at low doses.

• Other drugs used in urge urinary incontinence:

• Tricyclic antidepressants ( TCAs ):

It facilitates urine storage by decreasing bladder contractility and increasing outlet resistance. It has an alpha-adrenergic effect on the bladder neck, an anticholinergic effect on the detrusor muscle, and a local anesthetic effect on the bladder mucosa.

• Botulinum toxin:

It is reserved for refractory urge urinary incontinence which is not responding to other therapies).

Stress urinary incontinence treatment

• Duloxetine:

• Serotonin and norepinephrine are involved in the control of internal and external sphincters, these neurotransmitters increase the tone of internal and external sphincter during storage phase.
• Duloxetine is a dual inhibitor of serotonin and norepinephrine reuptake which leads to the concentration of those neurotransmitters in the internal and external sphincters.
• Duloxetine was shown to be effective in reducing incontinence episodes.
• Duloxetine has a high rate of discontinuation because of its adverse effects ( nausea , headache and constipation ).
• Consider gradual titration and tapering upon discontinuation.
• Duloxetine is not used with SSRIs, because of high risk of serotonin syndrome ).

• Estrogens:

• Used in women especially with estrogen deficiency related urethritis and vaginitis.
• Only topical preparations of estrogen vaginal creams and vaginal suppositories ) should be used.
• Beneficial effects of estrogen in stress urinary incontinence:
• Enhance the proliferation of urethral epithelium.
• Increase the numbers and sensitivity of urogenital alpha adrenergic receptors.

• Alpha adrenergic receptor agonists:

• Ephedrine, pseudoephedrine and phenylephrine are the used drugs from this class in stress urinary incontinence.
• Generally they are not recommended choices.
• Combining these drugs with estrogen therapy was superior to monotherapy in women with stress urinary incontinence (combine with estrogen to decrease the dose of alpha 1 blocker dose ).
• Adverse effects of these drugs include: hypertension, headache, dry mouth, nausea, insomnia and restlessness.
• These drugs are contraindicated in the presence of hypertension, tachyarrhythmia, coronary artery disease or myocardial infarction.
• Combining these drugs with estrogen therapy was superior to monotherapy in women with stress urinary incontinence (combine with estrogen to decrease the dose of alpha 1 blocker dose ).

References

• Pharmacotherapy principles and practice 4 edition.

• Pubmed.

• Medscape.