|
|
RESEARCH ARTICLE |
|
|
|
| Year : 2003 | Volume
: 19
| Issue : 2 | Page : 113-116 |
| |
Doxazocin in management of benign prostatic hyperplasia
NK Mohanty, RP Arora, AK Jha, S Singh Pal
Department of Urology, Safdarjang Hospital, New Delhi, India
Correspondence Address:
N K Mohanty
D-11/87, West Kidwai Nagar, New Delhi - 110 023
India
 Source of Support: None, Conflict of Interest: None  | Check |
 Abstract | | |
A total 220 patients with benign prostatic hyperplasia (BPH) but not having absolute indication for surgery were enrolled for 8 weeks single label study, using doxazocin (Doxacard) 4 mg daily for their features of prostatism, with a six month follow up. The study revealed an improvement of 90% in their symptoms at the end of the study with an increase of maximum flow rate (MFR) by 5-5.5 ml/sec and average flow rate (AFR) 2.5-3 ml/sec. Adverse effects were minimum and patient compliance was very good with good drug tolerability. Our study strongly supports the use of doxazocin as an alternative in the management of uncomplicated BPH with hypertension.
Keywords: α - alderneric, doxazocin, Doxacard.
How to cite this article:
Mohanty N K, Arora R P, Jha A K, Pal S S. Doxazocin in management of benign prostatic hyperplasia. Indian J Urol 2003;19:113-6 |
| Introduction | |  |
Benign prostatic hyperplasia (BPH) occurs in approximately 50% of men in 5th decade and in 90% at the 9th decade of life. [1] BPH causing bladder outlet obstruction has two components - the static factor due to enlarged adenoma and the dynamic factor due to contraction of smooth muscles in the prostate, prostatic capsule, bladder neck and prostatic urethra. The hyperplasia in BPH is predominantly stromal of which smooth muscle constitutes 40% (Bartsch). [2] The degree of muscle tone in these areas are regulated by α-adrenergic receptors, as this gland is mainly innervated by adrenergic sympathetic nerves, α-adrenergic blockers have been shown to improve urinary flow and the irritative symptoms. [3] Caine [4],[5] first demonstrated the presence of these receptors in prostatic tissue while Furuga, [6] and Christensen [7] demonstrated the use of α-adrenergic antagonist in relieving outflow obstruction due to BPH. From 1976, α-adrenergic blockers are in use (Cain) [8] . Since then many α-adrenergic blockers are in use. The recent discovery of highly selective αl-a blockers and its use in management of BPH has greatly improved the efficacy of medical management of BPH. [9] Studies have shown that αl-a receptors are predominant in human prostate (Lepor). [10]
Doxazocin, a 3rd generation α-blocker is one such highly selective drug now in use in BPH. It has a half life of 22 hours and has a relatively slow onset of action with peak plasma concentration being achieved in 2-6 hours after dosing (Rudi). [11] Plasma elimination of doxazocin is biphasic, the 1 st elimination phase occurring between 3 and 12 hours after administration, the 2 nd phase occurring after 20 hours after administration.
As a result of these features, doxazocin has a smooth onset of action when given once daily, [12] resulting in good patients compliance and not influenced by age or renal function. [13] Recent studies [14] have shown it to be safe, and effective drug in management of BPH, particularly in patients with hypertension in whom it also greatly reduces the risk of coronary heart disease (CHD).
In our present open label study, we determine the safety and efficacy of doxazocin in management of BPH among patients not having absolute indication for surgery.
| Patients and Methods | | |
240 consecutive patients having features of prostatism but not having absolute indication for surgery were in cluded in our studies with a 6-month follow up.
- Patients suspected of having malignancy of prostate, chronic renal failure, neurogenic bladder, stricture urethra with significant hepatic and cardiovascular dysfunction were excluded from this study.
- Previous history of taking drugs for BPH were also not included.
- All the patients included in the study had a detailed history, clinical examination including per rectal examination; and symptoms score following international prostate symptoms score (IPSS) pattern. This was followed by ultrasound estimation of weight of prostate in grams, postmicturation urine volume and uroflowmetry. The baseline maximum flow rate (MFR) was less than 12 ml/sec, average flow rate (AFR) less than 5 ml/sec, post micturating urine volume more than 100 ml in our study.
- A baseline blood biochemistry including liver function test (LFT), kidney function test (KFT), lipid profile and serum PSA was done in all our patients.
- Blood pressure record was done before and during therapy regularly.
- A written informed consent was obtained from all the patients before starting the therapy.
- 4 mg of doxazocin (Doxacard), once a day for 2 months was given to all our patients in a graduated manner.
- During the 2-months' therapy all patients were asked to record their blood pressure (BP) regularly. Any adverse effects were also recorded during the treatment.
- The patients were then followed up at 2-monthly intervals for next 6 months with records of their symptomtaology as per IPSS pattern. At the end of 8 months from starting the therapy, ultrasound of prostate weight, postmicturating urine volume, uroflowmetry, LFT, KFT, PSA and lipid profile was obtained and analysed.
| Results | | |
Out of a total number of 240 patients there were 20 dropouts leaving a total 220 patients for analysis. The average age of our patients was 67 years varying from 40 to 88 years. For uniformity of therapy, only I brand of doxazocin (Doxacard - Cipla) was used.
Symptom Score
Improvement in the symptoms was observed within 2 weeks of starting the therapy. At the end of the therapy 90% improvement in the obstructive and irritative symptoms was observed. From the average initial IPSS of 17 the score fell to 6. At the end of 8th month a 75% improvement in the subjective symptomatology was achieved [Table - 1].
Flow Rates
At the end of the therapy, the average maximum flow rate showed improvement by 5-5.5 ml/sec from baseline value of 10 ± 2 ml/sec reaching a good MFR of 15 ± 0.5 ml/sec, while the average mean flow rate showed improvement by 2.5-3 ml/sec from the baseline value of 4.5 ± 0.5 ml/sec reaching a good AFR of 7 ± 0.5 ml/sec. At the end of 8th month, on follow up MFR was 13 ± 0.5 ml/sec and AFR was 5.5 ± 0.5 ml/sec [Table - 2].
Residual Urine Volume
At the end of the therapy, there was a significant reduction in the postmicturating urine volume by 36% while at the end of 8th month on follow-up there was a 26% reduction in volume. No significant change in prostate size was observed; rather in a good number of patients, size of prostate showed increase in weight.
Adverse Events
Most of the adverse events were either mild to moderate in severity. The most common adverse effect was dizziness followed by vertigo, asthenia, headache, hypotension and dryness of mouth and skin [Table - 3].
Blood Pressure
Out of a total number of 220 patients, 99 patients (45%) were normotensive and 121 patients (55%) were hypertensive before therapy. The average fall in systolic/diastolic pressure was 20/10 mmHg among all hypertensive patients, while the fall was within a range of 8/4 mmHg among normotensive patients respectively. None of the patients discontinued the therapy due to hypotension. There was moderate degree in fall of total serum cholesterol and low density lipoprotein but LFT and KFT did not show significant changes. Though the serum PSA level showed a fall, it was not of much clinical significance.
| Discussion | | |
The standard treatment for BPH is surgery, making prostatectomy the 2nd most common surgical procedure in men aged over 50 years of age. Although the majority of the patients experience symptomatic improvement following prostatic surgery, several published studies have indicated that the long-term outcome is not as favorable as previously assumed. [15],[16],[17] Again an increasing elderly population and escalating healthcare cost have motivated the search for non-surgical therapies for BPH. Different studies have shown doxazocin improved MFR, which is regarded as the most important objective efficacy parameter for BPH. In our study, similar observations were made. Significant subjective improvement in nocturia, hesitancy, urgency, intermittency and weak stream was achieved by doxazocin in our study as compared to others. We followed the IPSS pattern for clinical evaluation of our patients. The IPSS is based on the AUA scale with an additional question about impact of symptoms on quality of life. This score pattern is nowadays internationally accepted and widely followed.
The once daily dose schedule makes doxazocin administration convenient especially in elderly males who are under other medications due to their other geriatric problems, resulting in a good patient compliance.
Since more than 50% of patients of BPH have concomittant hypertension, doxazocin is very useful in reducing their blood pressure alongwith alleviating their prostatism symptoms. Among normotensive patients blood pressure change due to doxazocin is insignificant.
The moderate fall in serum triglycerides and cholesterol level in our study is similar to those reported by other authors. [18] Doxazocin has also other beneficial effects:
i) moderate decrease in total cholesterol, low density lipoprotein (LDL) and triglycerides' thereby reducing CHD risk factors;
ii) increased platelet activation;
iii) improved tissue plasminogen activator activity;
iv) decreased left ventricular hypertrophy;
Taken together, the above beneficial effects of doxazocin can significantly reduce the calculated risk of CHD,[19] which is a unique aspect of doxazocin.
| Conclusions | | |
Medical management of BPH has a valuable role to play in patients with mild to moderate prostatism. Our study has shown that a daily dose of 4 mg of doxazocin (Doxacard), a 3rd generation α-adrenergic antagonist is not only well tolerated and safe but also greatly improves the urine flow rate and symptoms of prostatism apart from having beneficial effects like reducing the risk of CHD with a very low adverse effect.
| References | | |
| 1. | Walsh PC. Benign prostatic hyperplasia. In Campbell's Urology 6ih ed. 1992; chapt. 25(1): 1009-1029.  |
| 2. | Bartsch G, Muller HJ et al. Light microscopic sterological analysis of the normal human prostate and BPH. |
| 3. | Hedlund H, Anderson KE. Alpha adrenoreceptors and muscarine receptors in the isolated human prostate. J Urol 1985; 134: 1291-1298. |
| 4. | Caine M, Raz Si et al. Adrenergic and cholinergic receptors in the human prostate, prostatic capsule and bladder neck. Br J Urol 1975; 47: 193. |
| 5. | Caine M, Schuger L. The capsule in benign prostatic hypertrophy. Dept of Health & Human Services, National Inst of Health Publication 1987; No. 87-2881, 221. |
| 6. | Furuya S, Abiko et al. Alpha adrenergic activity and urethral pressure in prostatic zone in benign prostatic hypertrophy. J Urol 1982; 128: 836. |
| 7. | Christensen M, Bruskewitz RC. Clinical manifestation of benign prostatic hyperplasia and indication for therapeutic intervention. Urol Clin N Am 1990; 17: 509. |
| 8. | Caine M, Perlberg S. The use of alpha adrenergic blockers in benign prostatic obstruction. Br J Urol 1976; 48: 225. |
| 9. | Pool SL. Role of the sympathetic nervous system in hypertension and BPH. Br J Clin Pract 1994; 74: 13. |
| 10. | Leper H, Machi G. Relative efficacy of terazocin vs terazocin and flutamide for the treatment of symptomatic BPH. Prostate 1992; 20: 89. |
| 11. | Rudi A, Janknegt. Profile of doxazocin in patients with BPH. Scand J Urol Neph 1995; 29: 21-27. |
| 12. | Elliott HL, Mededitti. Pharmacokinetic overview of doxazocin. Am J Cardiol 1987; 59: 78G. |
| 13. | Young RA, Brogday RN. Doxazocin - A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in mild to moderate hypertension. Drugs 1988; 35: 525-541. |
| 14. | Janknegt RA, Chapple CR. Efficacy and safety of the al-blocker doxazocin in the treatment of benign prostatic hyperplasia. Analysis of 5 studies - doxazocin study group. Eur Urol 1993; 24: 319. |
| 15. | Barry MJ, Mulley AG et al. Watchful waiting vs immediate transurethral resection for symptomatic prostatism. The importance of patients' preferences. JAMA 1988; 259: 3010-17. |
| 16. | Fawler FJ Jr; Wennberg JE et al. Symptoms status and quality of life following prostatectomy. JAMA 1988; 259: 3018-22. |
| 17. | Roos NP, Wennberg JE et al. Mortality and reoperation after open and transurethral resection of prostate for BPH. N Eng J Med 1989; 320: 1120-24. |
| 18. | Pool J. Effects of doxazocin in serum lipids - A review of the clinical data and molecular basis for altered lipid metabolism. Am Heart J 1991; 121: 251. |
| 19. | Levy D, Wilson PWF et al. Stratifying patients at risk from coronary disease, new insight from the Framingham heart study. Am Heart J 1990; 119: 712-17. |
[Table - 1], [Table - 2], [Table - 3]
|
