Dutasteride

Posts Tagged ‘Dutasteride’

Pharmacotherapy in the Management of Prostate Cancer

Posted by admin on October 28th, 2011 No Comments

Prostate cancer is now the second leading cause of death due to cancer in men. Prostate cancer is usually classified as being early/localized (organ confined), locally advanced, metastatic or hormone-relapsed. The management of prostate cancer depends largely upon the stage and the Gleason grade of the tumour, as well as the patient's general medical condition and treatment preference. Surgical intervention is usually reserved for (early) localized prostate cancer, which is deemed to be confined to the prostate capsule. In the more advanced cases surgery is only used for performing channel transurethral resection of prostateto relieve severe lower urinary tract symptoms. The management of prostate cancer is sometimes controversial, not least as the diagnosis of localized or locally advanced prostate cancer is often difficult to establish precisely. Current modalities for diagnosing prostate cancer include prostate-specific antigen (PSA), digital rectal examination, trans-rectal rectal ultrasound scan and computerized tomography / magnetic resonance imaging. Often tumours thought to be localized Read more [...]

Posted in Urological Oncology

Benign Prostatic Hyperplasia

Posted by admin on July 11th, 2011 No Comments

Definition Benign prostatic hyperplasia, a nearly ubiquitous condition, is the most common benign neoplasm of American men and occurs as a result of hormone-driven prostate growth. Pathophysiology The prostate gland comprises three types of tissue: epithelial or glandular, stromal or smooth muscle, and capsule. Both stromal tissue and capsule are embedded with О±1-adrenergic receptors. The precise pathophysiologic mechanisms that cause Benign prostatic hyperplasia are not clear. However, both intraprostatic dihydrotestosterone and type II 5 О±-reductase are thought to be involved. Benign prostatic hyperplasia commonly results from both static (gradual enlargement of the prostate) and dynamic (agents or situations that increase О±-adrenergic tone and constrict the gland's smooth muscle) factors. Examples of drugs that can exacerbate symptoms include testosterone, О±-adrenergic agonists (e.g., decongestants), anticholinergics (e.g., antihistamines, phenothiazines, tricyclic antidepressants, anticholinergic antispasmodics, Read more [...]

Posted in Benign Prostatic Hyperplasia

Gonadotropin Modulators

Posted by admin on May 10th, 2011 No Comments

Overview Chlormadinone acetate (Teikoku's Prostal/Prostal L) is the only gonadotropin modulator available for treating benign prostatic hyperplasia. It is used only in Japan, where finasteride and dutasteride are not approved. Potentially serious side effects (e.g., diarrhea, sexual dysfunction, liver toxicity) make agents in this class less desirable than less-toxic therapies, such as the 5-ARIs. However, new agents in development may offer effective therapeutic relief and an improved side-effect profile. Because of their mechanism of action, these agents could have a greater effect on disease symptoms and progression. Mechanism Of Action Current understanding of the etiology of benign prostatic hyperplasia has established hormonal changes as a major contributor to the enlargement of prostate tissue around the urethra. The control of androgen production in the testes is directly mediated by hypothalamic/pituitary hormones. Gonadotropin-releasing hormone (Gonadotropin-releasing hormone), also known as luteinizing hormone-releasing hormone (luteinizing hormone-releasing hormone), is secreted Read more [...]

Posted in Benign Prostatic Hyperplasia

5-Alpha-Reductase Inhibitors

Posted by admin on May 10th, 2011 No Comments

Overview The basis for using 5-alpha-reductase inhibitors (5-ARIs) to treat benign prostatic hyperplasia stems from the observation that men with congenital 5-alpha-reductase deficiency have abnormally small prostates. Because 5-ARIs reduce prostate size, they are useful in treating patients with enlarged prostates — the subset of patients with static benign prostatic hyperplasia. The goal in the development of new alpha-reductase inhibitors is to generate compounds that are more potent inhibitors of the enzyme but more tolerable to patients. Mechanism Of Action 5-Alpha-reductase converts testosterone within the prostate to the androgen dihydrotestosterone (dihydrotestosterone). Researchers believe that dihydrotestosterone stimulates cell growth via paracrine and autocrine stimulation of prostatic stromal and epithelial tissue. As discussed in the "Etiology and Pathophysiology" section, 5-alpha-reductase isoenzymes can be type 1 or type 2. The role that either type plays in the pathophysiology of androgen-dependent benign prostatic hyperplasia is unclear. However, the currently marketed Read more [...]

Posted in Benign Prostatic Hyperplasia

Benign Prostatic Hyperplasia:Emerging Therapies

Posted by admin on May 10th, 2011 No Comments

The ultimate goal of treatment of benign prostatic hyperplasia and its associated comorbidities is to alleviate clinical symptoms that affect quality of life, eliminate the need for surgery, and prevent chronic and acute urinary retention. The challenge to drug developers is to create agents that have an acceptable onset of action, show a measurable level of efficacy, and induce no significant adverse events. The pipeline of agents in development for treatment of benign prostatic hyperplasia is relatively sparse. Most of the drugs currently under investigation are in early-stage development. Because benign prostatic hyperplasia is not a life-threatening disease, safety is a primary area of product improvement for new therapies. Physicians are not willing to accept drugs with frequent or significant side effects because benign prostatic hyperplasia is not life-threatening. Currently, the majority of pharmaceutical research for benign prostatic hyperplasia is focused on hormone therapy, as opposed to the established alpha-blocker and 5-alpha-reductase inhibitor (5-ARI) classes. The new gonadotropin Read more [...]

Posted in Benign Prostatic Hyperplasia

Gonadotropin Modulators

Posted by admin on May 10th, 2011 No Comments

Overview Gonadotropin modulators, also known as steroid androgen antagonists (e.g., chlormadinone acetate [Teikoku's Prostal/Prostal L]), are specifically labeled for treating benign prostatic hyperplasia, and their use is especially high in Japan, where finasteride and dutasteride are not approved. Potentially serious side effects (e.g., diarrhea, sexual dysfunction, liver toxicity) make agents in this class less desirable than less-toxic therapies such as the 5-ARIs. Because these agents are marketed primarily for prostate cancer, they are not discussed in detail here, with the exception of chlormadinone, which is often prescribed in Japan. Mechanism Of Action The control of androgen production in the testes is directly mediated by hypothalamic/pituitary hormones. Gonadotropin-releasing hormone, also known as luteinizing hormone-releasing hormone, is secreted by neurons in the hypothalamus, and it subsequently stimulates the release of both luteinizing hormone and follicle-stimulating hormone in the anterior pituitary. In the testes, luteinizing hormone interacts with specific cell-surface Read more [...]

Posted in Benign Prostatic Hyperplasia

5-Alpha-Reductase Inhibitors

Posted by admin on May 10th, 2011 No Comments

Overview Because inhibition of the enzyme 5-alpha-reductase is known to reduce prostate size, patients with an enlarged prostate (greater than 40 g) are often prescribed a 5-alpha-reductase inhibitor (5-ARI). Along with alpha Mockers, 5-ARIs dominate the benign prostatic hyperplasia drug market. The agents currently available are finasteride (Merck's Proscar) and dutasteride (GlaxoSmithKline/Astellas's Avodart). These drugs are effective in preventing further prostatic growth and in reducing prostate size, but they have a slow onset of action and cause sexual side effects. Despite these disadvantages, new data on combination therapy with alpha blockers and 5-ARIs have increased 5-ARI use. Mechanism Of Action Research has substantiated the role of 5-alpha-reductase in the pathophysiology of benign prostatic hyperplasia. The fact that men who have undergone castration before puberty or have genetic androgen deficiency are not afflicted by the disease is evidence of the vital role that androgens play in normal male development and in the progression of static benign prostatic hyperplasia. 5-ARIs Read more [...]

Posted in Benign Prostatic Hyperplasia

Posted by admin on May 10th, 2011 No Comments

Dutasteride (GlaxoSmithKline/Astellas's Avodart) was the first marketed dual 5-ARI. In 1999, Glaxo Wellcome (now GlaxoSmithKline [GSK]) entered an agreement with Yamanouchi for this drug's copromotion for benign prostatic hyperplasia in the United Kingdom. Approval in the United States was granted for the treatment of symptomatic benign prostatic hyperplasia in November 2001. In October 2002, the FDA approved a supplemental NDA for dutasteride for the treatment of symptomatic benign prostatic hyperplasia in men with an enlarged prostate. Subsequently, it was launched in the United States in January 2003 and in the United Kingdom in February 2003. In March 2003, GSK announced the launch of dutasteride in all major European markets. As an inhibitor of both types 1 and 2 isoenzymes of 5-alpha-reductase, dutasteride is unique; finasteride inhibits only type 2. However, the type 2 isoenzyme is the dominant form; type 1 accounts for only 15% of the prostatic enzyme. The dual inhibition of the enzyme reduces dihydrotestosterone serum levels to less than 10% of normal, but there is no evidence that inhibition Read more [...]

Posted in Benign Prostatic Hyperplasia

Benign Prostatic Hyperplasia:Current Therapies

Posted by admin on May 10th, 2011 No Comments

Treatment of benign prostatic hyperplasia (benign prostatic hyperplasia) is directed primarily toward managing symptoms and improving patients' quality of life (QoL). The two dominating classes of pharmacological agents used to treat benign prostatic hyperplasia are alpha Mockers and 5-alpha-reductase inhibitors (5-ARIs). Both drug classes are effective in alleviating lower urinary tract symptoms (lower urinary tract symptoms ) associated with benign prostatic hyperplasia, thereby improving patients' comfort level. Alpha blockers are most useful in alleviating symptoms related to dynamic benign prostatic hyperplasia; 5-ARIs are used for the treatment of static benign prostatic hyperplasia. The dynamic and static forms of benign prostatic hyperplasia are discussed in the "Etiology and Pathophysiology" section. Alpha blockers work by relaxing prostatic muscle involved in dynamic benign prostatic hyperplasia; they cannot stop further growth of the prostate. 5-ARIs and gonadotropin modulators (used only in Japan) reduce the cellular growth seen in static benign prostatic hyperplasia. lower Read more [...]

Posted in Benign Prostatic Hyperplasia

Dutasteride

Posted by admin on August 25th, 2010 No Comments

Drug Approvals (British Approved Name, US Adopted Name, rINN) Synonyms: Dutasterida; GG-745; GI-198745; GI-198745X BAN: Dutasteride USAN: Dutasteride INN: Dutasteride [rINN (en)] INN: Dutasterida [rINN (es)] INN: Dutastéride [rINN (fr)] INN: Dutasteridum [rINN (la)] INN: Дутастерид [rINN (ru)] Chemical name: α,α,α,α´,α´,α´-Hexafluoro-3-oxo-4-aza-5α-androst-1-ene-17β-carboxy-2´,5´-xylidide; 3-Oxo-2´,5´-bis(trifluoromethyl)-4-aza-5α-androst-1-ene-17β-carboxanilide Molecular formula: C27H30F6N2O2 =528.5 CAS: 164656-23-9 ATC code: G04CB02 Adverse Effects and Precautions As for Finasteride. Pharmacokinetics Dutasteride is absorbed from the gastrointestinal tract, reaching a peak serum concentration in 1 to 3 hours, with a bioavailability of about 60%. It is highly bound to plasma proteins. Dutasteride is metabolised by the cytochrome P450 isoenzymes CYP3A4 and CYP3A5, and most of a dose is excreted as metabolites in the faeces. At steady state the elimination half-life is about 3 to 5 weeks. Uses and Administration Dutasteride, like finasteride, is an Read more [...]

Posted in Drugs

Posts Tagged ‘Dutasteride’

Symptoms and Treatment

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