BENIGN PROSTATIC HYPERTROPHY PDF

‫‪BENIGN PROSTATIC HYPERTROPHY‬‬ ‫تعتبر هذه الملزمة بمثابة نموذج مرتب وملخص من الملزمة األصلية‪ ،‬حيث تم تنظيم المعلومات بطريقة مبسطة وفعّالة في جدول‬ ‫‪.‬مقارنة بين األمراض‪.‬يمكن االعتماد عليها بديالً عن الملزمة األصلية‬ ‫نسأل هللا أن يرحم...

‫‪BENIGN PROSTATIC HYPERTROPHY‬‬ ‫تعتبر هذه الملزمة بمثابة نموذج مرتب وملخص من الملزمة األصلية‪ ،‬حيث تم تنظيم المعلومات بطريقة مبسطة وفعّالة في جدول‬ ‫‪.‬مقارنة بين األمراض‪.‬يمكن االعتماد عليها بديالً عن الملزمة األصلية‬ ‫نسأل هللا أن يرحم جدتي ويغفر لها‪ ،‬وندعو بقراءة سورة الفاتحة على روحها الطاهرة‪ ،‬سائلين هللا أن يجعل هذا العمل في ميزان‬ ‫حسناتها اخوكم حسين الغانمي‬ ‫‪https://t.me/hhssda2‬‬  The prostate is an organ, that encircles the portion of the proximal posterior urethra that is located at the base of the urinary bladder. The prostate produces secretions, which are part of the ejaculate Benign prostatic hypertrophy (BPH) is the most common benign neoplasm in men who are at least 40 years of age. BPH can produce lower urinary tract symptoms (LUTS), a collection of obstructive and irritative voiding symptoms that are consistent with impaired emptying of urine from and defective storage of urine in the bladder EPIDEMIOLOGY AND ETIOLOGY BPH first presents as benign prostatic hyperplasia, a histologic disease in many elderly men which increases in prevalence with advancing patient age. Patients with histologic disease, only about 50% of patients develop an enlarged prostate on digital palpation and 25% of patients exhibit clinical voiding symptoms Two chief etiologic factors for BPH include advanced patient age and the stimulatory effect of androgens. Prior to 40 years of age, the prostate in the adult male is approximately 15 to 20 g. The testes and adrenal glands produce 90% and 10%, respectively, of circulating testosterone. 1- Testosterone enters prostate cells, where predominantly Type II 5α-reductase converts testosterone to dihydrotestosterone, which combines with a cytoplasmic receptor 2- The complex enters the nucleus and induces changes in protein synthesis that promote glandular tissue growth of the prostate 3- Thus 5α-reductase inhibitors (eg, finasteride and dutasteride) directly interfere with one of the major etiologic factors of BPH The prostate is composed of two types of tissue: (a) Glandular or epithelial tissue, which produces prostate-specific antigen (PSA). (b) Muscle or stromal tissue, which can contract around the urethra and bladder outlet when stimulated. Whereas androgens stimulate glandular tissue growth, they have no direct effect on stromal tissue Stromal tissue growth may be stimulated by estrogen Because testosterone is converted to estrogen in peripheral tissues in males, testosterone may be associated indirectly with stromal hyperplasia. PATHOPHYSIOLOGY LUTS and signs of BPH are due to 1-The static anatomic obstruction of the bladder neck caused by an enlarged prostate gland. 2-The dynamic factor refers to excessive stimulation of α 1A-adrenergic receptors in the smooth muscle of the prostate, urethra, and bladder neck, which results in smooth muscle contraction. 3-The detrusor factor refers to bladder detrusor muscle hypertrophy in response to prolonged bladder outlet obstruction detrusor muscle fibers undergo hypertrophy so that the bladder can generate higher pressure to overcome bladder outlet obstruction The hypertrophic detrusor muscle becomes irritable, contracting abnormally in response to small amounts of urine in the bladder This causes storage voiding symptoms (urinary frequency, nocturia, urgency, or urinary incontinence). If obstruction is not treated, the bladder muscle will decompensate and be unable to empty completely; post void residual urine volume (PVR) will increase androgen antagonism does not induce a complete reduction in prostate size to normal. This explains one of the limitations of 5α-reductase inhibitors Stromal tissue is the primary locus of α1-adrenergic receptor. in the prostate. An estimated 98% of the α adrenergic receptors in the prostate are found in prostatic stromal tissue This explains why α1-adrenergic antagonists are effective for managing symptoms of BPH independent of prostate size atherosclerosis of the pelvic vascular supply to the prostate and bladder has been linked to BPH Predictors of disease progression include an enlarged prostate of at least 30 g (1.05 oz) or PSA of 1.4 ng/mL (1.4 mcg/L) or greater. TREATMENT Desired Outcomes 1- Reducing or eliminating obstructive and irritative voiding symptoms. 2- Slowing disease progression. 3- Preventing disease complications and reducing the need for surgical intervention 4- Avoiding or minimizing adverse treatment effects. 5- Providing economical therapy 6- Maintaining or improving quality of life.  A digital rectal examination (DRE) is repeated annually. If the patient’s symptoms worsen, specific treatment is initiated. Watchful waiting is effective in approximately 65% of patients with mild LUTS after 5 years. 1- α 1-Adrenergic antagonists are preferred over 5α-reductase inhibitors because the former have a faster onset of action (days to a few weeks) and improve symptoms independent of prostate size 2- α1-Adrenergic antagonists are preferred for patients with LUTS, who also have a small prostate (< 30 cm3 approximately 30 g 5α-Reductase inhibitors have a delayed onset of peak clinical effect of 6 months and are most effective in patients with moderate to severe LUTS and larger size prostate glands > 30 g Surgery is indicated for patients 1-Who are at risk of disease progression those with large prostates [> 30 g 2-Patients with moderate-severe symptoms. 3-Patients are unresponsive to or intolerant of drug treatment 4- Patients have complications of BPH disease  Surgery can result in significant morbidity, including erectile dysfunction, retrograde ejaculation, urethral stricture, urinary incontinence, bleeding, or urinary tract infection The gold standard is prostatectomy, which can be performed transurethrally using electrocautery for intermediate prostate size or as an open surgical procedure for very large prostate more than 80mg or associated with urologic disorder The outcomes of prostatectomy include an almost immediate improvement of LUTS, an increase of peak urinary flow rate by 6 to 15 mL/s, and a PVR decrease of 30 to 80 mL. Symptoms Patients may complain of obstructive voiding symptoms (eg, urinary hesitancy, decreased force of urinary stream, straining to void, incomplete bladder emptying, and intermittency) and/or irritative voiding symptoms (eg, urinary frequency, nocturia, and urgency with or without incontinence). It should be noted that LUTS is not specific for BPH. LUTS may be due to other urologic disorders including prostate cancer, prostatitis, or neurogenic bladder. Signs Enlarged prostate on DRE; Upper and lower urinary tract infection, Urosepsis, Urinary incontinence refractory urinary retention, Chronic renal failure, Bladder diverticula, Bladder stones, Recurrent gross hematuria. Laboratory Tests Serum PSA: The combination of PSA and DRE of the prostate can be used to screen for prostate cancer, which could also cause an enlarged prostate. PSA is a surrogate marker for an enlarged prostate due to BPH Urinalysis to rule out infection as a cause of the patient’s voiding symptoms; also check urinalysis for microscopic hematuria, which typically accompanies BPH. Plasma BUN and serum creatinine may be increased as a result of long-standing bladder outlet obstruction. are reserved for those patients in whom renal dysfunction is suspected. Other Diagnostic Tests Decreased peak and mean urinary flow rate (< 10–15 mL/s) is not specific for BPH; it can also be due to other urologic disorders (eg, urethral stricture, meatal stenosis, or bladder hypotonicity) Increased PVR (post voiding residual) greater than 50 Ml DRE to check for an enlarged prostate > 15–20 g A focused neurological examination to check the integrity of innervation to the urinary bladder (that is responsible for bladder emptying). Transurethral cystoscopy reveals an enlarged prostate Transrectal ultrasound of the prostate; to evaluate prostate size and best surgical approach. Transrectal prostate needle biopsy to be done to document the presence of prostate cancer. Computerized tomography of the urinary tract (CT urogram) with contrast if the patient has chronic bladder outlet obstruction; Filling cystometry provides information on bladder capacity, detrusor contractility, and the presence of uninhibited bladder contractions, which could also cause LUTS. Nonpharmacologic Therapy (Behavioral Modification) 1-To reduce nocturia, patients should be instructed to stop drinking fluids 3 or 4 hours before going to bed and then void before going to sleep. 2-Patients should avoid excessive intake of caffeine-containing beverages, sugar-sweetened drinks, and alcohol because these may cause urinary frequency. 3-Patients should avoid taking nonprescription medications that can worsen obstructive voiding symptoms (eg, antihistamines or decongestants). 4-Patients who take a diuretic should avoid taking it in the evening. 5-Patients are also advised to stop smoking and lose excessive weight.  Pharmacologic Therapy ▶ α1-Adrenergic Antagonist Monotherapy Causing relaxation of the bladder neck, prostatic urethra, and prostate smooth muscle. A secondary mechanism of action may be that α1-adrenergic antagonists induce prostatic apoptosis. All α 1-adrenergic antagonists are considered equally effective in relieving symptoms. In various clinical trials, 1- 30% to 80% of patients experience improvement in the AUA Symptom Score by 30% to 45%. 2- 20% to 40% of patients experience urinary flow rate increases of 2 to 3 mL/s. The onset of action is days to weeks, with peak clinical effects observed in several weeks. Therefore, in patients with significant hepatic dysfunction, these drugs should be used in the lowest possible dose because are hepatically metabolized With the exception of silodosin, these drugs do not require dosage modification in patients with renal dysfunction. tamsulosin and silodosin, have the potential to produce less hypotension Silodosin has significantly greater α1A-adrenergic selectivity than tamsulosin and is preferred when a patient has minimal tolerance for any blood pressure–lowering adverse effects. alfuzosin, a functionally uroselective α1-adrenergic antagonist, produce effective relaxation of prostatic smooth muscle with minimal vascular vasodilation. Agents appear to be clinically uroselective, are preferred in patients who usually have low blood pressure or those taking multiple antihypertensives Pharmacologic and functional uroselectivity are dose related phenomena. Large daily doses of tamsulosin, silodosin, or alfuzosin may cause loss of uroselectivity, with resultant hypotension and dizziness in some patients. In patients with both hypertension and moderate to severe LUTS, it is recommended that an appropriate antihypertensive be added to an α 1-adrenergic antagonist. Need for up-titration of daily dose. Up-titration is required for immediate-release terazosin and doxazosin It is minimally required for extended-release doxazosin and tamsulosin. Plasma half-life. α1-Adrenergic antagonists with short plasma half-lives (eg, prazosin, which is a first generation α 1-adrenergic antagonist) require multiple doses during the day. Dosage formulation. Immediate-release formulations of terazosin and doxazosin are quickly absorbed and produce high peak plasma levels. Adverse effects. 1-Hypotensive is less commonly associated with extended release alfuzosin and extended-release doxazosin; and least commonly associated with tamsulosin and silodosin 2-Nasal congestion and malaise 3-Floppy iris or small pupil syndrome 2-Reversible delayed Hypotensive adverse effects of terazosin and doxazosin can be additive with those of diuretics, antihypertensives, and phosphodiesterase type 5 inhibitors (eg, sildenafil). ▶ 5α-Reductase Inhibitor Monotherapy 5α-Reductase inhibitors which result in shrinkage of an enlarged prostate by approximately 15% to 25% after 6 months of continuous treatment They inhibit 5α-reductase, which is responsible for intra-prostatic conversion of testosterone to dihydrotestosterone, the active androgen that stimulates prostate tissue growth. Two subtypes of 5α-reductase, Type I and II, are present in the prostate; the majority is the Type II isoenzyme. Finasteride is a selective Type II isoenzyme inhibitor, whereas dutasteride is a nonselective inhibitor of both isoenzymes When compared with finasteride, dutasteride produces a faster and more complete inhibition of 5α reductase in prostate cells 5α-reductase inhibitors may also cause apoptosis of prostate cells Finasteride and dutasteride are considered equally effective in relieving LUTS by 15% to 30% in 30% to 70% of patients Increasing the urinary flow rate by 1 to 2 mL/s, Decreasing PVR by 18% to 28%, which is less improvement than that seen with α 1-adrenergic antagonists A minimum of 6 months is required to evaluate the full clinical effectiveness of treatment. Unlike α1- adrenergic antagonists, long-term use of 5α-reductase inhibitors is used to prevent BPH-related complications and disease progression 5-α-Reductase inhibitors have been shown significantly enlarged prostate glands (> 40 g [1.4 oz]) when used continuously for at least four consecutive years. These agents are hepatically metabolized. No specific recommendations for dosage modification are available in patients with significant hepatic dysfunction No dosage adjustment is needed in patients with renal impairment Sexual dysfunction, including decreased libido, erectile dysfunction, ejaculation disorders, and gynecomastia, occurs in 5% to 15% of treated patients The frequency of sexual dysfunction peaks generally 1 year after the start of treatment, and the incidence of such adverse effects tends to be higher for dutasteride than for finasteride. post-finasteride syndrome of persistent sexual dysfunction even after discontinuation of finasteride has been described. Dutasteride has been shown to increase insulin resistance in adipose tissue, and may be associated with an increased risk of congestive heart failure 5α-reductase inhibitors are associated with a dose-related increased risk of osteoporosis. agents reduce the incidence of prostate cancer by 25%, but are suspected to increase the risk of developing moderate to high grade cancer, if prostate cancer does develop. Exposure to 5α-reductase inhibitors is contraindicated in pregnant females as the drugs may cause feminization of a male fetus. Pregnant females should not handle these drugs unless they are wearing gloves.  During continuing treatment of BPH, the patient should undergo an annual repeat PSA and DRE. These agents decrease PSA by a mean of 50% after 6 months of continuous use. A rising PSA level suggests that the patient has worsening BPH, new onset prostate cancer, or that the patient is noncompliant with his regimen of 5α-reductase inhibitor. ▶ Tadalafil Tadalafil is expensive; therefore, the best candidates for treatment are those with BPH and erectile dysfunction, or those patients with LUTS that is not responsive to α-adrenergic antagonists. Tadalafil may be prescribed alone, or along with an α1-adrenergic antagonist or 5α-reductase inhibitor. Tadalafil is comparable to α1-adrenergic antagonists in relieving LUTS and decreasing the AUA Symptom Score by 3.8 points after 12 weeks ,it does not produce a clinically significant increase in urinary flow rate or reduce PVR. Tadalafil should be avoided if the creatinine clearance is less than 30 mL/min (0.50 mL/s). Tadalafil is contraindicated in patients on nitrates by any route of administration. If the patient is sexually active, tadalafil should not be used in patients with unstable angina, uncontrolled or high-risk arrhythmias, persistent hypotension, poorly controlled hypertension, or New York Heart Association Classification IV congestive heart failure; or patients who have had a myocardial infarction within the past 2 weeks. ▶ Anticholinergic Agents The detrusor muscle is innervated with muscarinic receptors. M3 receptor stimulation is associated with abnormal detrusor contractions, which can cause irritative voiding symptoms Anticholinergic agents are indicated when a patient has bothersome irritative voiding symptoms despite treatment with an α 1-adrenergic antagonist. Typically, an anticholinergic agent is added sequentially to an established α1-adrenergic antagonist regimen. The ideal patient for the combination has a urinary flow rate of at least 10 mL/s and a PVR less than 50 mL. Many anticholinergic agents are available. Darifenacin is the only M3 uroselective anticholinergic agent. If irritative symptoms do not improve after starting an anticholinergic agent, up-titrating the dose or switching to another anticholinergic agent may be helpful. ▶ Mirabegron In the urinary bladder, 95% of all β-adrenergic receptors are of the β3 type. Receptor stimulation relaxes the detrusor muscle, but does not interfere with the bladder’s contractility. Mirabegron is a β3-adrenergic agonist. It causes release of norepinephrine which stimulates β3-adrenergic receptors. The detrusor muscle relaxes and urine storage in the bladder is improved. mirabegron reduces irritative voiding symptoms. Although not Food and Drug Administration (FDA)-approved for this indication, mirabegron is an alternative to an anticholinergic agent in patients who poorly tolerate or are at high risk of anticholinergic adverse effects, or when irritative voiding symptoms do not respond to an anticholinergic agent A combination of an α1-adrenergic antagonist and 5α-reductase inhibitor may be considered in symptomatic patients who do not respond to an adequate trial of monotherapy or in symptomatic patients at high risk of BPH complications, that is, those with an enlarged prostate of at least 30 g A recent study suggests that initiating a combination regimen in patients with moderate LUTS due to BPH may produce persistent improvements in AUA Symptom Score and urinary flow rate and may reduce the risk of clinical progression after 1 year than treatment with an α1-adrenergic antagonist alone