Buy Alfusin-D (Alfuzosin / Dutasteride) for the treatment of BPH in men
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PHARMACODYNAMICS OF ALFUSIN-D
Mechanism of action
Alfuzosin is a selective antagonist of post-synaptic alpha1-adrenoreceptors, which are located in the prostate, bladder base, bladder neck, prostatic capsule, and prostatic urethra.
Alfuzosin HCl exhibits selectivity for alpha adrenergic receptors in the lower urinary tract. Blockade of these adrenoreceptors can cause smooth muscle in the bladder neck and prostate to relax, resulting in an improvement in urine flow and a reduction in symptoms of BPH.
The effect of 10 mg and 40 mg alfuzosin on QT interval was evaluated in a double-blind, randomized, placebo and active-controlled (moxifloxacin 400 mg), 4-way crossover single dose study in 45 healthy white male subjects aged 19 to 45 years. The QT interval was measured at the time of peak alfuzosin plasma concentrations. The 40 mg dose of alfuzosin was chosen because this dose achieves higher blood levels than those achieved with the co-administration of alfuzosin and ketoconazole 400 mg.
Mechanism of action
Dutasteride is a synthetic 4-azasteroid compound that is a competitive and specific inhibitor of both the type I and type II isoforms of steroid 5 alpha-reductase (5AR). Testosterone is converted to DHT by the enzyme 5 alpha-reductase, which exists as 2 isoforms, type I and type II. The type II isoenzyme is primarily active in the reproductive tissues, while the type I isoenzyme is also responsible for testosterone conversion in the skin and liver. Dutasteride inhibits the conversion of testosterone to 5-alpha-dihydrotestosterone (DHT). DHT is the androgen primarily responsible for the initial development and subsequent enlargement of the prostate gland.
Effect on 5 Alpha-Dihydrotestosterone and Testosterone
The maximum effect of daily doses of dutasteride on the reduction of DHT is dose-dependent and is observed within 1-2 weeks. After 1 and 2 weeks of daily dosing with dutasteride 0.5 mg, median serum DHT concentrations were reduced by 85% and 90%, respectively. In patients with BPH treated with dutasteride 0.5 mg / day for 4 years, the median decrease in serum DHT was 94% at 1 year, 93% at 2 years and 95% at both 3 and 4 years. The median increase in serum testosterone was 19% at both 1 and 2 years, 26% at 3 years and 22% at 4 years, but the mean and median levels remained within the physiologic range.
In patients with BPH treated with 5 mg/day of dutasteride or placebo for up to 12 weeks prior to transurethral resection of the prostate, mean DHT concentrations in prostatic tissue were significantly lower in the dutasteride group compared with placebo (784 and 5,793 pg/g, respectively; (p < 0.001).
Adult males with genetically inherited type II 5 alpha-reductase deficiency also have decreased DHT levels. These 5 alpha-reductase deficient males have a small prostate gland throughout life and do not develop BPH. Except for the associated urogenital defects present at birth, no other clinical abnormalities related to 5 alpha-reductase deficiency have been observed in these individuals.
Effects on other hormones
In healthy volunteers, 52 weeks of treatment with dutasteride 0.5 mg/day (n=26) resulted in no clinically significant change, compared with placebo (n=23), in sex hormone-binding globulin, oestradiol, luteinizing hormone, follicle-stimulating hormone, thyroxine (free T4) anddehydroepiandrosterone. Statistically significant, baseline-adjusted mean increases compared with placebo were observed for total testosterone at 8 weeks (97.1 ng / dL, (p < 0.001).
Plasma lipid panel and bone mineral density were evaluated following 52 weeks of dutasteride 0.5 mg once daily in healthy volunteers. There was no change in bone mineral density as measured by dual energy X-ray absorptiometry (DEXA) compared with either placebo or baseline. In addition, the plasma lipid profile (i.e., total cholesterol, low-density lipoproteins, high-density lipoproteins and triglycerides) was unaffected by dutasteride. No clinically significant changes in adrenal hormone responses to ACTH stimulation were observed in a subset population (n=13) of the 1-year healthy volunteer study.
Alfuzosin with Dutasteride related pharmaceutical drugs and medications
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|Jalyn pharmacodynamics - Dutasteride; Tamsulosin Hydrochloride
||Capsules; Oral; Dutasteride 0.5 mg; Tamsulosin Hydrochloride 0.4 mg
||Afluprost-MR - Alfuzosin Hydrochloride
||Tablets, Modified Release; Oral; Alfuzosin Hydrochloride 10 mg
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