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 Alexandros Lekas, MD, PhD, FEBU

 Urologist Surgeon Andrologist
 Doctor of Medicine, University of Athens
 Fellow of the European Board of Urology
 Postgraduate in Germany, Ammerland Klinik
 University of Gottingen

 

 

 

 

 

 

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Benign Prostate Hyperplasia - pharmaceutical treatment

alpha-adrenergic competitors

Sympathetic nervous system plays an important role in the function of the lower urinary tract by noradrenaline, adrenergic receptors and adrenaline.

Adrenergic receptors (AR) are classified into a-a and b-AR are classified in a1-and a2-adrenergic receptors. The alpha1-adrenergic receptors (a1-AR) are classified into 3 categories and classified according to A1a-AR, a1b a1d-AR and-AR.

Prostate, excel-A1a and a1b-ARs. The A1a-AR constitute 60-85% of a1-Ars in the gland and shown that the percentage increase in hyperplastic tissue. a1-AR are found in abundance than the prostate, bladder and bladder triangle but also in other organs such as the spinal cord, blood vessels, liver and central nervous system.

This distribution justifies the adverse reactions may occur after administration of alpha-adrenergic blockers.

Due to the high concentration of a1-AR in the prostate and bladder neck, use of alpha-adrenergic blockers (a-blockers) seems logical addition and promising for the treatment of LUTS through relaxation of smooth muscle which can to bring.

Phenoxybenzamine, a nonselective alpha-antagonist, was the first a-blocker described and who seemed to have a selective action on the lower urinary tract. Despite the initial enthusiasm was soon abandoned because of the many serious side effects caused.

Prazosin consists early a1-blockers and with other alpha1-adrenergic blockers used for the treatment of BPH. The drawbacks of these substances was that because of the short half-life that had had to be given twice daily.
Terazosin (Hytrin) has been studied more than most, in large multicenter double-blind randomized studies which investigated both the action and the safety of doses 2, 5 and 10mg, with very good results.

Another inhibitor that has been widely studied is doxazosin. Doxazosis unlike terazosin has a longer half-life which allows us to be administered once a day.

The most potent inhibitor alpha1-adrenoceptor is tamsulosin, which exhibits selectivity in A1a-AR. The drug offers improvement in symptoms of men with BPH and can be administered at doses 0,4 mg/24h without showing any serious side effects.

Another alpha adrenergic blocker used to treat BPH is alfuzosin.

When administered formulations of this category should always keep in mind the fact that patients with BPH are usually older with attendant problems, such as hypertension, diabetes and coronary artery disease, for which it is likely to take medication . Thus, administration of alpha-blockers should in most cases be done in conjunction with other drugs the patient is taking and for this reason it is appropriate to calculate the possible side effects of the synergistic action of these.
In conclusion, alpha-blockers are drugs that can lead to remission of symptoms by 20-50% and increase urine flow by 20-30%. The effect is immediate, an improvement from the first 48 hours and the objective improvement requires at least one month treatment, and if after receiving eight weeks have brought about improvement, recommended discontinuation.

5a-reductase inhibitors

The rationale for the use of antiandrogens in BPH treatment, is based on the finding that in order to maintain hyperplastic tissue, androgen levels are required. At the same time androgen reduction will entail a reduction in the volume of the gland and thus urine resistance at urination process.
Inhibitors of 5a-reductase that are known today are: finasteride and dutasteride. 

1. Finasteride

Finasteride is an inhibitor of the enzyme 5a-R type II. Finasteride administration results in reduction of DHT, but not to castrate levels, since T is converted to DHT by the action of isozyme I.
Regarding the effect of finasteride on PSA, the urological community has concluded that after one year of treatment, prostate antigen decrease is around 50%. Thus, in clinical practice, we estimate that the "correct" value of PSA in men treated with finasteride annually is equal to the value found by 2. Finasteride has been shown that in addition to reducing the size of the prostate, may also reduce the risk of hematuria and intraoperative blood loss.

2. Dutasteride

Dutasteride is an inhibitor of both types (I and II) of 5a-R and its administration results in decreased plasma DHT by 90%. However, this does not cause any reduction in endoprostate levels of DHT, a rate greater than that of finasteride .
Adverse reactions seen after drug administration do not differ from those of finasteride and include erectile dysfunction, ejaculation disorders, decreased libido, and gynecomastia.
In conclusion, we can say that inhibitors of 5a-reductase activity after 6 months of treatment lead to a prostate volume reduction and symptoms / flow rate improvement.

Phytotherapeutic substances

These substances derive from plants and are very popular in Europe and America. Due to the numerous individual components, it is difficult to prove which of them can be active.
In some studies it has been found that some of them have the same clinical benefit with finasteride and alpha-adrenergic blockers, with far fewer side effects.
The lack of existing studies and updated experiences regarding phyto-therapeutic substances' value, lead us to be cautious in recommending this treatment in patients with BPH.


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