In The Name of Allah

1. In The Name of Allah

2. Renal Disorders Dr. Ghafghazi,Professor of Pharmacology .Isfahan University of Medical sciences and a member of R&D department of Goldaru Pharmaceutical Company

3. Urinary Tract • System that removes waste products from body • Regulates acid/base; fluid balance • Kidneys produce erythropoietin to stimulate red blood cell production. • Kidneys produce renin for angiotensin cyclevasoconstriction & fluid retention through aldosterone secretionblood pressure. • Activate vitamin D (necessary for calcium absorption from GI tract)

4. Filtration • Glomerular filtrate = 125 ml/min or 180 liters/day. • Urine is only 1-2 liters/day so 178 liters are resorbed.

5. Prostate Gland LOCATION: • Surrounds urethra at base of bladder. STRUCTURE: • Grows at puberty from peanut to walnut size under influence of androgen. • Composed of stromal/fibromuscular and epithelial/glandular cells. • Cancer = stromal cells; benign = epithelial

6. Prostate Gland FUNCTION: • Alkalinizes urine so sperm can survive. Secretes acid phosphatase (important to document rape) & prostatic specific antigen (PSA )(marker for cancer) POTENTIALPROBLEM: • Enlarges with older age causing urethra obstruction. • Active cell growth can lead to cancer.

7. Benign Prostatic Hypertrophy • Benign enlargement of prostate gland • As androgen falls, estrogen may stimulate growth. RISK: • Genetics • Older men (50% of men over 50; 80% of men over 70. ASSESSMENT: • Frequency of urination; difficulty beginning urination; bladder hypertrophy; incontinence (from full bladder); nocturia

8. BPH represents an androgen-dependent disorder of metabolism reflecting the many significant changes in steroid levels decrease with age after the fifth decade. Prolactin, estradiol, sex hormone binding ligand, luteinizing hormone (LH), and follicle stimulating hormone (FSH)levels are all increaesed.

9. The ultimate effect of these changes is an increased intraprostatic concentration of dihydrotestosterone (DHT), the potent androgen derived from testosterone.

10. This increase is largely due to a decreased rate of removal combined with an increase in the activity of the enzyme 5-alpha-reductase, the enzyme that coverts T to DHT T and DHT are extensively metabolized by hydroxylation, which decreases the cytosolic receptor proteins for these hormones, thereby allowing their excretion. Estrogen inhibits hydroxylation

11. The PSA test is a highly accurate and sensitive marker for prostate cancer . The normal value for PSA is less than 4 ng/ml. An elevation above 10 is highly indicative of prostate cancer.

12. In the past medical treatment involved a procedure known as a TURP ( trans – urethral resection of the prostate ). Because this surgery is associated with a high rate of morbidity and will often make matters worse, it should be avoided unless absolutely necessary .

13. Nutritional factors Diet appears to play a critical role in the health of the prostate. It is particularly important to avoid pesticides, increase the intake of zinc and essential fatty acids, and keep cholesterol levels below 200 mg/dl .

14. Zinc Paramount to an effective BPH treatment plan is adequate zinc intake and absorption. Zinc supplementation has been shown to reduce the size of the prostate – as determined by rectal palpation, X-ray, and endoscopy and to reduce symptomatology in the majority of patients in studies conducted in the 1970s.

15. The clinical efficacy of zinc is probably due to its critical involvement in many aspects of androgen metabolism. Intestinal uptake of zinc is impaired by estrogens, but enhanced by androgens. Since estrogen levels are increased in men with BPH, zinc uptake may by low.

16. Although zinc levels and 5-alpha -reducates activity do not consistently correlate in hyperplastic tissue , zinc has been shown to inhibit the activity of 5- alpha – reductase , the enzyme that irreversibly converts T to DHT . Zinc also inhibits specific binding of androgens to the cytosol and nuclear androgen receptors .

17. Zinc has also been shown to inhibit prolactin secretion . Prolactin has been shown to increase the uptake of testosterone by the prostate , thereby leading to increased levels of DHT by providing more substrate .

18. Alcohol While only beer raises prolactin levels , higher alcohol intake is definitely associated with BPH . In a 17 study of 6,581 men in Hawaii , it was noted that an alcohol intake of at least 25 ounces / month was directly correlated with the diagnosis of BPH . The association was most significant for beer , wine , and sake , and less for distilled spirits.

19. Cholesterol Cholesterol metabolites are cytotoxic and carcinogenic and have been shown to accumulate in the hyperplastic or cancerous of epithelial cells, leading to the increased regeneration seen in BPH.

20. Hypocholesterolemic drugs have been shown to have a favorable influence on BPH, preventing the accumulation of cholesterol in the prostatic cells and limiting subsequent formation of epoxy cholesterols.

21. Phytosterols have also been shown to improve BPH. The latest double-blind study consisted of 200 men receiving beta- sitosterol (20mg) or placebo three times daily.

22. The beta- sitosterol produced an increase in maximum urine flow rate from a baseline of 9.9ml/s to 15.2ml/s, and a decrease in mean residual urinary volume of 30.4 ml from 65.8ml. No changes were observed in the placebo group .

23. An increased consumption of soy and soyfoods is associated with a decrease in the risk of prostate cancer. Much of this protection is due to the isoflavonoids genistein and daidzein, the so- called phytoestrogens of soy.

24. However , in addition to acting on estrogen receptors, these compounds inhibit 5- alpha- reductase .

25. Botanical medicines According to a recent review article published in the British Journal of Urology, plant- based medicines are much more popular prescriptions in Europe than their synthetic counterparts.

26. Specifically in Germany and Austria botanical medicines are considered “first – line” treatments for BPH and account for greater than 90% of all drugs in the medical management of BPH. In Italy, plant extracts account for roughly 50% of all medications prescribed for BPH, while alpha- blockers and 5- alpha- reductase inhibitors account for only 5.1 and 4.8% respectively.

27. There are about 30 different plant- based compounds currently available in Europe for the treatment of BPH. At least 15 of them contain Serenoa repens (saw palmetto) extract.

28. Other popular botanical medicines include pygeum africanum, Urtica dioica (stinging nettles), and Cernilton(rye-grass pollen ), a special flower pollen extract.

29. Serenoarepens (saw palmetto) The liposterolic extract of the fruit of this palm tree (also known as sabalserrulata), native to Florida, has been shown to significantly improve the signs and symptoms of BPH in numerous clinical studies.

30. The mechanism of action is related to inhibition of DHT binding to both the cytosolic and nuclear androgen receptors, inhibition of 5- alpha – reductase and interference with intraprostatic estrogen receptors .

31. As a result of these multitude of effects, excellent results have been produced in numerous double- blind clinical studies . In summary , it can be stated that roughly 90% of men with mild to moderate BPH experience some improvement in symptoms during the first 4-6 weeks of therapy. All major symptoms of BPH are improved, especially nocturia.

32. Urticadioica (stinging nettles) Extracts of Urticadioica have also been shown to be effective in the treatment of BPH. Fewer studies have been done with urtica extract compared with the other botanical medicines discussed.

33. THERAPEUTIC APPROACH Therapeutic goals for BPH are to : • Normalize prostate nutrient levels • Restore steroid hormones to normal levels • Inhibit excessive conversion of T to DHT • Inhibit DHT receptor binding • Limit promoters of the hyperplastic process, e.g. prolactin .

34. کپسول پروسکورProscur Cap • درمان هیپرپلازی پروستات تکرر و سوزش ادرار اجزا فراورده هر کپسول محتوی 160 میلیگرم عصاره سبل(Saw pallmeto) یا نخل اره ای همراه عصاره زنجبیل چای سبز گزنه رزماری و روغن تخم کدو • مکانیسم اثر انتی اندروژنیک مهار ایزوانزیم های تیپI وII 5-الفاردوکتاز

35. قرص و قطره پروستاتان شکل داروئي : قرص و قطره گياهی خوراکی موارد مصرف : برطرف کننده علائم ناشی از بزرگ شدن پروستات مانند تکرر ادرار, سوزش ودرد هنگام دفع ادرار

36. جزاء فرآورده : قطره پروستاتان از عصاره هيدروالکلی گياهان زير تهيه شده است : • ريشه و برگ گزنه9 ميلی ليترUrticadioica • تخم کدوی بدون پوست 6 ميلی ليتر Cucurbitapepo • گل بابونه 6 ميلی ليترMatricariachamomilla • ميوه خارخاسک6 ميلی ليتر Tribulusterrestris • ميوه انيسون 3 ميلی ليتر Pimpinellaanisum

37. مطالعاتجديد بر روی خواصفارماکولوژيکتخم کدو نشان داده است که دراين ويوو و اينويترو عصارهتخم کدو قادر به مهار آنزيم آلفاردوکتاز می باشد ودارای خاصيت ضد اندروژنی و ضد التهاب است . کميسيونE در کشور آلمانروغن تخم کدو را در درمان اختلالات مثانه و مشکلات دفع ادرار ناشی از هيپرپلازی پروستات توصيه نموده است . روغن تخم کدو دارای موادآنتی اکسيدان بوده و درموش صحرائیاثر ضد التهابی آن به اثبات رسيده است . زينکموجود در تخم کدو دارای نقش مهمی روی تعادلهورمونی بودهو مهار کنندهآلفاردوکتاز است .

38. 28 مطالعه مقدماتی نشان دهندهاين موضوعهستند که زينک موجب بر طرف شدناختلالات ادراری ميشود. بدين جهتمجموعهگزنهو تخم کدو در قطره و قرص پروستاتانبطور سينرژيستيک اعمال پروستات را دربيماران مبتلا به هيپرپلازی خوش خيمآن بهبود می بخشد .

39. خارخاسکدارای خاصيتپيشاب آور و تقويت کننده قوه باء است .و نقش آن در اثر بخشی قطره پروستاتانيک اثر مکمل و تقويت کننده است .گل بابونهکه دارای اثر ضد التهاب و ضد اسپاسم است درشرايط التهاب مخاط پروستات بسيار موثر بوده و التهاب را برطرف می کند . نحوه اثر آن مربوط به مهار آنزيم پروستاگلاندين سنتتازوليپواکسی ژناز است . روغن فرار انيسون دارایاثر شديد ضد اسپاسم و ضدميکروب است . مجموعه مواد موثره گياهانموجود در قطره پروستاتان موجب برطرف شدن التهاب و اسپاسم پروستاتشده و بدين ترتيب علائم ادراری ناشی از هيپرپلازی پروستات را برطرف ساخته و دفع ادرار را بهتر می کند .

40. Erectile Dysfunction داروهاي گياهي موثر دردرمان اختلالات جنسي

41. Male Sexuality

42. Female Sexuality

43. SEXUAL FUNCTION • Sexual function may be divided in to three categories reflecting the sexual response cycle : (1) libido or sexual desire; (2) arousal , including erectile function in men and lubrication in women; and (3) release (orgasm in women and ejaculation in men ) . Drugs can affect one or more areas of the response cycle .

44. SEX . F . CONTINUED • Understanding of the sexual response remains incomplete but there is evidence of dopaminergic , adrenergic , muscarinic and serotonergic involvement . In general , dopamine increases sexual behaviour and serotonin inhibits it .

45. Libido is influenced by reproductive hormones and the emotional and physical health of the individual . Testosterone is necessary for normal sexual arousal , probably in both men and women , and in men testosterone deficiency is associated with impotence .

46. ED CONTINUED • Male sexual function depends on The coordination of neurogenic , hormonal and psychological mechanisms and disruption of one or more of these may result in erectile dysfunction . The penile blood vessels and smooth muscle receive both sympathetic and parasympathetic innervation and erction is primarily a parasympathetic function .

47. In the flaccid state the smooth muscle is contracted , preventing inflow of blood . Parasympathetic nerve stimuli , mediated by nitric oxide , relax the smooth muscle of the arterioles in the corpora cavernosa , allowing blood to flow rapidly in to the penis . Venous outflow from the penis is reduced , blood is trapped within the corpora cavernosa , and rigid erection ensues

48. Mechanism of Erection Dorsal vein Dorsal artery Dorsal nerve Corpora cavernosa Tunica albuginea Cavernosal artery Corpus spongiosum Urethra Flaccid Penis Erect Penis National Erectile Dysfunction Foundation. Understanding Erectile Dysfunction. 1998.

49. The Central Mechanisms of Sexual Function Until relatively recently, most research in ED focused on peripheral neurophysiology and on the local tissues of the penis, leading to the development of highly effective treatments such as penile injections and sildenafil. There has, however, been growing interest in the role of the central nervous system (CNS) in the control of erectile function, and researchers have begun to develop medications that target these central mechanisms.

50. Central mechanism continued • An erection is a carefully orchestrated series of events controlled by the CNS. We now know that the penis is under the complete control of the CNS, both during sexual arousal and at rest. It has been noted, any disturbance in the network of nerve pathways that connects the penis and the CNS can lead to problems with erections.