Benign Prostatic Hyperplasia PDF

Benign prostatic hyperplasia By Dr.karar hasan ali  Pathophysiology  The prostate is a part glandular, part fibromuscular structure about the size of a walnut that surrounds the first part of the male urethra at the base of the bladder. In simple terms, the prostate can be divide...

Benign prostatic hyperplasia By Dr.karar hasan ali  Pathophysiology  The prostate is a part glandular, part fibromuscular structure about the size of a walnut that surrounds the first part of the male urethra at the base of the bladder. In simple terms, the prostate can be divided into a lobular inner zone encapsulated by an external layer. The inner zone is where benign hypertrophic changes are generally found, whereas most malignant changes originate in the peripheral zone.  Prostatic hypertrophy is directly related to the ageing process and to hormone activity. Within the prostate, testosterone is converted by 5α-reductase to dihydrotestosterone (DHT). DHT is five times more potent than testosterone and is responsible for stimulating growth factors that influence cell division leading to prostatic hyperplasia and enlargement.  As the prostate enlarges, it can compress the urethra and this, together with increased adrenergic tone, can lead to bladder outflow obstruction (BOO) and lower urinary tract symptoms (LUTSs). Therefore, the term BPH includes benign prostatic enlargement (BPE), the clinical features associated with urinary obstruction and LUTSs. Symptoms  Men with BPH can develop bothersome LUTSs that can impact negatively on their quality of life. It is important to emphasise that not all men who experience LUTSs have BPH.  LUTSs can have different aetiologies including bladder cancer or stones, urinary tract infection (UTI) or urethral stricture. Furthermore, a histological diagnosis of BPH does not mean the patient will suffer from LUTSs.  LUTSs can be divided into symptoms of failure of urine storage (irritative) and those caused by failure to empty the bladder (obstructive or voiding).  Irritative symptoms  Frequency  Nocturia  Urgency and urge incontinence  Obstructive symptoms  Poor urinary flow  Hesitancy in initiation of micturition  Post-micturition dribble  Sensation of incomplete emptying  Occasional acute retention of urine requiring emergency treatment  Treatment  Most men over the age of 50 years exhibit some of the symptoms of BPH. The range of treatment options for the management of BPH includes watchful waiting, medical therapies and surgical interventions. The key issue, therefore, is deciding who should be treated and when.  Therapeutic management  The principal treatment options are α-adrenoceptor blocking drugs, 5α-reductase inhibitors and combination therapy. Phytotherapy is also used in the management of BPH, although the benefits remain unproven.  α-Adrenoceptor blocking drugs  In the prostate, α1 -receptors predominate and mediate the contraction of the gland's smooth muscle. At least three subtypes of this receptor exist (α1A, α1B and α1D). The α1A is thought to be the dominant receptor in the prostate, although its role clinically has still to be confirmed. This increase in sympathetic tone is potentially reversible by α- adrenoceptor antagonists.  In general, all the agents are considered to produce similar clinical improvements of LUTSs and urinary flow.  Benefits can be seen usually within the first few days of therapy and can be maintained in the long-term.  α-Adrenoceptor antagonists also have a comparable side-effect profile, which includes postural hypotension, dizziness, fatigue, headache, drowsiness, nasal congestion and ejaculatory dysfunction.  Patients with BPH frequently experience erectile and ejaculatory dysfunction.  The treatment of BPH should also aim to improve sexual function. However, the effect of α1 - adrenoceptor antagonists on male sexual function is variable and influenced by the choice of agent and patient characteristics  Prazosin.  Prazosin was the first α1 -blocker used to relieve the symptoms of BPH but it lacks relative selectivity for α1A receptors and has been associated with many adverse affects such as drowsiness, weakness, headache and postural hypotension (especially after the first dose).  Terazosin.  Terazosin was the first in the category to appear in controlled trials aimed at evaluating the efficacy and safety profile of long acting α1 -blockers in the management of BPH.  Efficacy is dose dependant and dose titration is necessary, as terazosin can cause postural hypotension. Adverse effects, although generally mild, occur more frequently than with other α1 -adrenoceptor antagonists, resulting in up to a fourfold increase in treatment discontinuation.  Doxazosin.  Doxazosin has a long half-life of about 22h, which allows for once-daily dosing. When starting treatment, dose titration is recommended to limit postural hypotension. There would appear to be no significant difference in symptom score regardless of whether the standard or controlledrelease preparation is used.  Tamsulosin.  Tamsulosin is a selective inhibitor of the α1Aand α1B-adrenoceptor. It has an elimination half-life of about 13h and is available as a prolonged release formulation that allows once-daily dosing. There is no requirement to titrate the dose upward when initiating treatment. Although the side effect profile of tamsulosin is similar to other α1 -adrenoceptor antagonists, it is normally well tolerated.  Intraoperative floppy iris syndrome (IFIS) has been reported during cataract surgery in men treated with tamsulosin, as it is highly selective to iris dilator muscle. IFIS can lead to complications and poor outcomes during cataract surgery. As a result, it is essential that patients inform their cataract surgeon that they are taking tamsulosin during the pre-operative assessment. It has been recommended to avoid starting treatment and to discontinue treatment with tamsulosin 1–2 weeks before cataract surgery.  Alfuzosin.  Alfuzosin displays a higher selectivity for the prostate compared with tamsulosin or doxazosin. It has a half-life of 5h, but it is available as a once-daily formulation. It has a rapid onset of action and good tolerability. It reduces the overall clinical progression of BPH and it appears to have a sustained beneficial effect on quality of life.  Alfuzosin has the least effect on ejaculatory function. Alfuzosin should not be co- administered with potent inhibitors of cytochrome P450 3A4 such as itraconazole, ketoconazole and ritonavir, since this can lead to a several fold increase to exposure in alfuzosin.  5α-Reductase inhibitors  The primary androgen responsible for the development and progression of BPH is DHT. There are two isoenzymes of 5α- reductase: type 1 is found in most 5α-reductase producing tissues such as the liver, skin and hair; type 2 is predominant in genital tissue, including the prostate.  5α-Reductase inhibitors down regulate prostate growth by blocking the conversion of testosterone to the more potent DHT.  The two agents currently available in this group are finasteride and dutasteride.  Both have been shown to reduce prostate volume, to improve symptom scores and flow rates, and reduce the incidence of complications such as acute urinary retention (AUR) and the need for surgical intervention to treat BPH.  Improvements in LUTSs are normally seen after the first 6 months of treatment and are sustained during continuous treatment Finasteride.  Finasteride is a type 2, 5α-reductase inhibitor that can reduce prostate size by about 30%, improve symptom scores and increase urinary flow.  Those most likely to benefit are men with a prostate larger than 40mL.  Side effects include decreased libido, impotence, reduced ejaculatory volume and, less commonly, gynaecomastia and breast tenderness. Combination therapy  It is well established that α-adrenoceptor antagonists are best for managing acute symptoms but have no impact on reducing the risk of complications such as AUR or progression to prostate surgery.  In contrast, 5α-reducatase inhibitors have little impact on short-term acute symptoms but reduce prostate size, improve urinary flow and obstructive symptoms in the long-term.  Furthermore, α-adrenoceptor antagonists are effective regardless of prostate volume, whereas the 5α-reductase inhibitors are more suited for the management of LUTSs in men with large prostates.  In terms of long-term benefits, continued treatment with 5α-reductase inhibitors decreases the risk of AUR and BPH-related surgery.  Therefore, it appears logical to use a combination of an α- adrenoceptor antagonist and a 5α-reductase inhibitor to manage acute symptoms and reduce progression of BPH.  The combination was also found to reduce AUR and progression to BPH-related surgery and, although superior to tamsulosin with respect to these complications, combination therapy was not better than dutasteride.  Overall, the adverse events associated with combination therapy were few and treatment was well tolerated.  Combination therapy with an α-adrenoceptor antagonist and a 5α-reductase inhibitor has now been adopted widely into routine practice for the early management of LUTSs and to reduce progression of BPH.   Surgical treatments  Surgical interventions are commonly performed in men with LUTSs caused by BPH that have failed to respond to medical treatment.  Surgery is also indicated in patients who develop complications such as intractable or recurrent urinary retention, renal impairment, persistent haematuria, recurrent UTIs or bladder stones THANK YOU