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Benign prostatic hyperplasia (BPH) is a benign disease characterized in a high percentage by cervico-urethral disorders. With regard to the obstructive aspect, this is the result of two components: mechanic and dynamic. The mechanic component is a direct consequence of the obstruction caused by enlargement of the prostate gland and the urethral deformation. The dynamic, on the other hand, is derived from the increase in tone of the smooth muscle following stimulation by adrenoreceptor alpha, localized at the level of the bladder neck, prostatic urethra and prostatic capsule. The use of alpha blockers in the treatment of BPH has the goal of intervening in the effects of the obstruction acting on the dynamic components. The use of alpha-blockers drugs, as explained in published literature, shows more or less satisfactorily, a significant symptomatic improvement and consequently an improvement in the quality of life. But the use of alpha blocker presently available may be considered as an unspecific or primitive, strictly symptomatic treatment for irritative symptoms for those who desire to postpone surgery, or in the cases in which surgery is not recommended or refused by the patient, and finally, to prevent acute urinary retention while the patient is waiting for surgery.

Thirty-two patients with voiding dysfunction attributable to symptomatic benign prostatic hyperplasia were treated with naftopidil, an alpha 1-blocker, at doses of 25-75 mg/day for 4-6 weeks. The efficacy of the drug was assessed from the changes in urinary symptoms and urodynamic data. Total symptom scores were significantly reduced after treatment (P < 0.001). Average flow rate and maximum flow rate were significantly increased (P < 0.001 and P < 0.001, respectively), and residual urine volume, residual urine rate (ratio of residual urine volume/sum of voided volume and residual urine volume), and maximum urethral closure pressure were significantly (P < 0.05, P < 0.01, and P < 0.05, respectively) reduced, and at bladder capacity, the first desire to void was significantly (P < 0.05) increased. The pressure/flow study demonstrated no changes in intravesical pressure at maximum flow, but a significant (P < 0.05) reduction in minimum urethral resistance. A mild side effect (dizziness) was noted in one patient (3.3%), which soon disappeared after the dose was decreased. The efficacy was good or excellent in 21 of 30 patients (70.0%). The drug was evaluated to be promising in the treatment of bladder outlet obstruction due to benign prostatic hyperplasia.

Benign prostatic hyperplasia occurs in the majority of men past middle age. Transurethral prostatectomy has stood the test of time, but it may not be suitable for some men by virtue of concurrent medical problems or because patients prefer to avoid the risks and complications associated with surgery. This article outlines some of the alternative therapeutic options that are available.

Urodynamic studies were conducted in 80 incontinent elderly patients (27 men and 53 women; mean age, 77 years) and repeated 2-4 weeks later after patients had been subject to interventions. Interpretable voiding studies were performed in 84% of sessions. Interpretable initial and repeat studies were performed in 74% of patients. For detrusor pressure at maximum flow the intra-individual, between-sessions variability was +/- 11.7 cm H2O (SD) and the initial-repeat correlation coefficient was 0.61. For maximum flow rate the corresponding figures were +/- 4.7 ml/s and 0.44. Mean residual urine volume was 195 ml, with a between-sessions variability of +/- 113 ml (SD). These results suggest that there is substantial long-term variability in voiding function, including urethral resistance. Of the mean, 5% showed a change in obstruction classification (unobstructed/obstructed) between sessions. This variability and the modest proportion of interpretable studies should be taken into account when assessing urethral obstruction and designing clinical trials.

A case of acute urinary obstruction due to early lichen sclerosus disease is described. In this case both histological corroboration and efficacy of potent topical steroid have been beneficial.

The effects of i.v. administration of different drugs utilized in the therapy of detrusor instability have been studied in conscious catheterized female rats with infravesical outflow obstruction induced by partial urethral ligature, in comparison to normal animals. The effects of oxybutynin (1 mg/kg), terodiline (10 mg/kg), and nifedipine (1 mg/kg), were evaluated with regard to bladder capacity (BVC) and micturition pressure (MP) both in normal and obstructed rats. The effects on micturition and residual volume, as well as on spontaneous contractile activity representative of bladder instability, were also observed in obstructed rats. In normal animals, terodiline and oxybutynin induced a significant decrease in micturition pressure without changes in BVC. In obstructed rats, these drugs administered at the same doses did not induce any significant change in all the observed parameters. Nifedipine that in normal rats also reduced the MP, in obstructed animals induced an inhibition of bladder instability (about 50%) with no effects on the other cystometrographic parameters.

The efficacy and safety of YM617, a new alpha 1-blocker, were evaluated in 121 patients with urinary obstruction of the lower urinary tract in the long-term administration study for 1 year. A total of 121 patients, i.e., 111 with benign prostatic hypertrophy (BPH), 6 with bladder neck sclerosis (BNS), 3 with BPH with BNS and 1 with female urinary obstruction, were orally administered 0.1 to 0.4 mg of YM617 once daily. Patients showing improvement of patient's impression and of subjective symptoms judged by the physician were increased until the 16th to 20th week, and it had been maintained there after. Objective findings were improved to a constant level after the 4th week. Patient's impression and subjective symptoms were improved in a certain dose-response relationship Side effects were observed in 3 patients but none were serious. YM617 proved to be useful in the treatment of patients with urinary obstruction of the lower urinary tract like BPH because it maintained the efficacy and safety in the long-term administration.

Fifty-eight normotensive patients with benign prostatic hyperplasia and maximum urinary flow rates of less than 15 ml/s were randomly assigned to receive a 12-week course of treatment with prazosin or placebo in a double-blind parallel group trial. Prazosin was administered orally in doses of 0.5 mg and then 1 mg twice daily for 4 days each and 2 mg twice daily for the remainder of the trial. Patients on treatment with prazosin had an increased urinary flow rate as compared to placebo with a significant reduction in maximum voiding detrusor pressure and maximum detrusor pressure at peak urinary flow. Although a significant effect on frequency was not demonstrated, standard parameters of detrusor instability were reduced. Investigators' double-blind overall assessment of efficacy significantly favoured the prazosin treatment. Twelve patients were excluded from the final analysis, 8 being withdrawn because of adverse effects, 5 on treatment with prazosin and 3 in the placebo group. Oral prazosin appears to be safe and effective in the long-term treatment of patients with benign prostatic hyperplasia.

Prazosin HCl was administered to 20 patients with urinary obstructions associated with prostatic hypertrophy. Significant reductions were recorded in the nighttime and the mean 24-hour urination frequencies. Patient-assessed symptoms diminished significantly, and uroflowmetry revealed significant increases in average and maximum urine flow rates. Residual urine volume decreased, the residual urine ratio declined, and bladder compliance tended to increase. The prazosin HCl therapy produced no significant effects on blood pressure or pulse rate, and no side effects appeared. The therapy was judged to be 'extremely beneficial' in 10%, 'beneficial' or better in 50%, and 'marginally beneficial' or better in 85% of all the patients.

Prazosin, a selective alpha 1-adrenoceptor blocker, was compared with Paraprost in a double-blind, multi-institutional study in patients with benign prostatic hyperplasia. The trial encompassed 77 evaluable patients in the prazosin group and 79 in the Paraprost group. Both drugs significantly improved obstructive and irritative symptoms. Residual urine (volume or percentage of total urine) was reduced by both prazosin and Paraprost. Average and maximum flow rates increased significantly in the prazosin group while those were unchanged in the Paraprost group. Side effects occurred in 1 patient treated with prazosin (1.1%) and 3 patients with Paraprost (3.3%). Thus, we confirm the clinical value and minimal side effects of prazosin in the treatment of bladder outflow obstruction resulting from benign prostatic hyperplasia.

74 patients diagnosed as suffering from benign prostatic hypertrophy (BPH) were treated with prazosin for 8 weeks. We look at the evolution of the symptomatology and the urodynamic and morphologic parameters during the treatment and they are compared with the basal ones. The irritative symptoms (nocturia, pollakiuria, imperiosity and dysuria), evaluated by means of a quantitative scale, undergo significant statistical improvement. The same occurred with the obstructive symptoms. Urodynamically, an increase took place in total vesical capacity, maximum, and mean flow, as well as a drop or reduction in non-inhibited contractions. 27 patients suffered adverse effects, which obliged 8 of them to abandon the treatment. Global efficacy was excellent in 20% and good in 52%, whilst it was fair and ineffective in 19 and 9%, respectively.

The effects of prazosin HCl on the urethral pressure profile (UPP) were studied in 14 patients with benign prostatic hyperplasia. Urethral pressure profilometry was performed 1 h after oral administration of 1 or 2 mg prazosin HCl. Functional profile and continence zone lengths were significantly reduced following administration of 1 or 2 mg prazosin HCl, as compared with the pretreatment lengths. The administration of 2 mg prazosin HCl resulted in a significant decrease in prostatic peak pressure, whereas the maximum urethral closure pressure exhibited an insignificant decrease. The results suggest that the effects of prazosin HCl on UPP were dose dependent within the range from 1 to 2 mg.

Prazosin HCl was administered in dosages of 1.5-4.5 mg/day for 4 weeks to 40 patients suffering from dysuria accompanying prostatic hyperplasia. Significant reductions were observed in the mean frequency of night-time and 24-hour urination. Additionally, significant improvements were recorded for the time for start of urination, time from start to finish of urination and related variables. The improvements correlated with dosage levels. Objective variables measured by urine flow rates also exhibited significant improvement. A statistically significant decrease in systolic without a decline in diastolic blood pressure was observed. Slight dizziness was observed in 1 patient and elevated laboratory test values in another, but neither warranted discontinuation of the medication; however, 1 patient did have two doses of medication held. Overall, the drug was judged beneficial to some degree in 95% of the patients.

The effects of prazosin HCl treatment on several variables were determined in 16 patients suffering from micturition disturbances associated with benign prostatic hypertrophy. After administration of the drug in doses of 1-2 mg/day, subjective symptoms improved in 11 patients (68.8%). Urine retention rate, maximum urine flow rate, and average urine flow rate exhibited statistically significant improvement, but voided urine volume did not. Urethral pressures declined significantly in the bladder neck and prostatic urethra but not in the pressure at the external sphincter. The results suggest prazosin HCl may be effective in small doses in symptomatic treatment of benign prostatic hypertrophy.

The effects of alpha 1-adrenergic blockade with prazosin HCl were examined in 28 patients with benign prostatic hypertrophy and bladder neck contracture. The patients received 2-3 mg of prazosin HCl daily administered orally. Improvement in subjective symptoms was observed in 75% of the patients. We evaluated clinical effects as the minimum time of micturition (calculated as the ratio of voided volume/maximum flow rate) for voided volumes less than 200 ml and the maximum flow rates and average flow rates for voided volumes over 200 ml. Evaluation of the findings on a flow rate nomogram revealed improvement in maximum flow rates and average flow rates in 41% of the patients. Side effects such as dizziness developed in only 1 patient.

Beta-adrenergic activity of the proximal urethra was studied in 11 patients. Maximum urethral pressure was recorded before, and 20 and 60 minutes after the intravenous administration of 0.5 mg. orciprenaline sulfate. There was a 40 per cent or more decrease in the maximum urethral pressure in 6 of the 11 patients. Beta-adrenoreceptor agonists could prove useful in facilitating vesical emptying by reducing urethral resistance in patients with neurogenic bladder dysfunction.

Lower urinary tract obstruction in patients with neurological lesions can be due to "sympathetic dyssynergia". The obstruction can be at the level of the external sphincter. Phentolamine (i.v.) used during the voiding cystourethrogram helps to make the diagnosis. Phenoxybenzamine therapy produced improvement in 10 of 18 patients. As a rule, patients had to continue on the drug to maintain their response.

E-643, a newly developed alpha 1-adrenergic blocker with a postsynaptic action, was tried on 17 subjects, 10 patients with neurogenic bladder and 7 patients with lower urethral obstruction. The results of treatment were excellent in 5, good in 7, and poor in 5 of them, the rate of effectiveness therefore being 70.6%. The inhibitory effect of E-643 on the contractility of the detrusor was no stronger than that of other alpha-blockers. The rate of effectiveness for neurogenic bladders was as high as 80% whereas that for lower urethral obstruction was much lower: 57%. Concerning benign prostatic hyperplasia (B.P.H.) alone, this agent was markedly beneficial. In the case of B.P.H the urethra pressure in the prostatic urethra tends to drop and urination is facilitated even without a change in maximum urethral closure pressure, which reduces the amount of residual urine, this sequence of events taking place on condition that the contractility of the detrusor is adequate. According to urodynamic criteria, the underlying causes of the so-called bladder neck contracture can be classified into organic and functional obstruction, but it is mistaken to use this term for functional disturbance of the bladder neck. It seems worthwhile to determine the clinical effect of alpha-blockers on functional urethral obstruction. E-643 produced few if any appreciable signs or symptoms of side effects either subjectively or objectively.

The use of pharmacologic agents in treating disorders of the bladder and proximal urethra has expanded because of new knowledge gained in the past few years. A better understanding of the properties of these organs as they relate to drugs has contributed to this expansion. The authors present their experience with a number of drugs in treating disorders of the detrusor muscle and proximal urethra, and they briefly review the literature.