1.) The efficacy and tolerability of vardenafil, a new, oral, selective phosphodiesterase type 5 inhibitor, in patients with erectile dysfunction: the first at-home clinical trial

2.) B O S T O N. Dos nuevos fármacos, Cialis (tadalafil) de Lilly y Vardenafil de Bayer, pronto aparecerán en la arena de la disfunción sexual.

3.) Two Companies to Seek Psoriasis Drug Approval

4.) Humoral immune response to a therapeutic polyvalent cancer vaccine after complete resection of thick primary melanoma and sentinel lymphadenectomy.

5.) A granuloma annulare-like eruption associated with the use of amlodipine(Norvasc).

6.) [A case of acute cholestatic hepatitis associated with orlistat] XENICAL

7.) Slimming product Reductil has been linked to 34 deaths.

8.) The BEST study: results according to prior treatment. (ACNÉ)

9.) Treatment of cutaneous calcinosis in limited systemic sclerosis with minocycline.

10.) 5 Alpha-reductase inhibitors: what's new? DUTASTERIDE

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1.) The efficacy and tolerability of vardenafil, a new, oral, selective phosphodiesterase type 5 inhibitor, in patients with erectile dysfunction: the first at-home clinical trial

Source: http://www.biopsychiatry.com/vardenafil.html

by

Porst H, Rosen R, Padma-Nathan H,

Goldstein I, Giuliano F, Ulbrich E, Bandel T.

Urological Practice, Hamburg, Germany.

porst20354@aol.com

Int J Impot Res2001 Aug;13(4):192-9

ABSTRACT

Vardenafil, a novel selective phosphodiesterase type 5 inhibitor, was evaluated in its first large-scale at-home trial. A total of 601 men with mild to severe erectile dysfunction (ED) were enrolled in this multi-centre, randomized, double-blind, placebo-controlled trial of 12 weeks of treatment with either placebo or 5, 10 and 20 mg of vardenafil. Primary endpoints were Q3 (vaginal penetration) and Q4 (maintenance of erection) of the International Index of Erectile Function (IIEF). In the intent-to-treat population (n=580), the changes from baseline for 5, 10 and 20 mg vardenafil (1.2, 1.3 and 1.5, respectively) were all improved (P<0.001) over placebo (0.2) for Q3 and were similarly improved for Q4 (1.4, 1.5 and 1.7) compared to placebo (0.5) (P<0.001). All vardenafil doses improved all IIEF domains compared to placebo (P<0.001). The percentage of successful intercourses was between 71 and 75% for the three vardenafil doses. For the 20 mg dose, 80% of the patients experienced improved erections (GAQ) compared to 30% for placebo. Most frequent treatment-emergent adverse events were headache (7-15%), flushing (10-11%) and up to 7% for dyspepsia or rhinitis. Vardenafil treatment resulted in a high efficacy and low adverse-event profile in a population with mixed ED etiologies.

Que viene después del Viagra?

2.) B O S T O N. Dos nuevos fármacos, Cialis (tadalafil) de Lilly y Vardenafil de Bayer, pronto aparecerán en la arena de la disfunción sexual.

Source: http://www.galenored.com/vsaludable/noticias/otras/postviagra.htm

Como el Viagra (Sildenafil), las otras drogas hacen más fácil la erección en hombres con disfunción eréctil (ED) luego del estímulo sexual. Pero, las nuevas drogas parecen trabajar más rápidamente, duran más mucho tiempo y tienen menos efectos colaterales.

Una erección sólo ocurre cuando el flujo de sangre genital se desvía a los cilindros esponjosos centrales (cuerpos cavernosos) del pene de un hombre, un proceso que se pone más difícil a medida que el hombre envejece.

La excitación sexual activa una ola de GMP cíclico, el activador natural de flujo de sangre del pene que gobierna el vigor de la erección en un hombre durante el coito. Después del orgasmo—bajo la influencia de una enzima los phosphoediesterasa-5 (PDE-5), el GMP cíclico desciende y la erección termina. El Viagra, Cialis y Vardenafil son todos inhibidores de PDE-5 y trabajan para sostener los niveles de GMP cíclico logrando que un hombre pueda tener una erección más firme y más rígida durante el sexo.

Pero, hay una diferencia entre las drogas:

Los diseñadores de Cialis y Vardenafil han pensaron en incrementar las ventajas del fármaco a partir de la molécula original.

Facilidad de Uso: El Viagra no trabaja bien cuando es tomado con la comida o después del alcohol. Cialis trabaja bien con o sin comida e incluso es eficaz después de una succión moderada de alcohol.

Comienzo de acción: Se dice a los pacientes que toman Viagra, que esperen 1 hora por lo menos antes de intentar tener sexo. Cialis es eficaz dentro de 15-20 minutos.

La duración de acción: Después de una dosis de Viagra, los niveles de GMP cíclicos permanecen elevados durante varias horas, lo que le permite al paciente tener amplio sexo. El efecto de Cialis y posiblemente Vardenafil parece ser más prolongado. Después de una dosis de Cialis son posibles episodios sexuales múltiples.

Los europeos han apodado al Cialis "Le Weekend" ("la semanal") y han alardeado de que una píldora tomada con el vino y cena un viernes es todo lo que un hombre necesita para manetnerse sexualmente potente el sábado y el domingo. Pero, para el hombre mortal una nueva píldora para cada día que él planea tener el sexo parece más realista.

Los efectos colaterales: Las enzimas similares a PDE-5 reaccionan inhibiendo la PDE-6. Por ejemplo, el Viagra que interrumpe la producción de Phosphodiesterasa 6 (PDE-6), una enzima importante en la visión colorida, puede causar visión azulada en algunos pacientes. Cialis se ha diseñado para evitar interacción con PDE-6 y no causa la visión azul.

Los nuevos inhibidores de PDE-5 fortalecen las erecciones aumentando el flujo de sangre al pene, pero también ensanchan los vasos en otra parte en el cuerpo, lo que provoca que un porcentaje pequeño de hombres experimenten dolor de cabeza, congestión nasal o estómago agitado. Estos efectos generalmente disminuyen con el uso continuado.

Conclusión: El Viagra no fue sólo la primera píldora para disfunción eréctil, tambien hizo más fácil hablar de sexo para nosotros. Más aun con Cialis y Vardenafil las opciones estarán una vez más abiertas a los hombres con ED luego que reciban la aprobación por parte de la FDA. Otros productos están en el desarrollo y hay un progreso significativo en otro largo problema largamente discutido: la disfunción sexual femenina.

Referencia:

Dr. Richard F. Spark, M.D.

Comments to ABC NEWS. 2002, January 3

Dr. Richard F. Spark, M.D., is a Senior Attending Physician at Beth Israel Deaconess Medical Center and is an Associate Clinical Professor of Medicine at Harvard Medical School. Dr. Spark is the author of Sexual Health for Men: The Complete Guide. He is also a consultant for Pfizer and Lilly ICOS.

3.) Two Companies to Seek Psoriasis Drug Approval

New York Times Syndicate

Source: http://www.psoriasis-help.org.uk/html/news2.htm

 

By Ronald Rosenberg

Friday, June 22, 2001

Genentech Inc. and Biogen Inc. said Thursday they will each seek regulatory approval to market their drugs to treat psoriasis, setting up a race between the two biotech giants for leadership in this $2 billion market.

The two companies are scrambling to become the first to market a psoriasis treatment that addresses the underlying causes of the disease and is much safer than current medications, such as cyclosporine and a series of ointments and creams.

``These drugs make what we do now look like the Stone Age,'' said Dr. Craig Leonardi, a dermatologist and clinical associate professor at St. Louis University, who has tested both company's drugs and several others. ``This is a huge week for psoriasis patients who will soon have some very good treatment options.''

About seven million people have psoriasis, a chronic skin condition in which red scaly patches develop. Both companies are proposing drugs of similar efficacy to address the 2.1 million patients with the moderate-to-severe form of the disease. There is no cure for it and the company that gains marketing approval first could have a major advantage, according to some Wall Street analysts.

Genentech, its partner Xoma Ltd., and Biogen are furthest along in developing psoriasis drugs. They presented their latest clinical studies at the International Psoriasis Symposium in San Francisco this week.

Biogen revealed that its phase 3 results for Amevive showed 71 percent of patients saw at least a 50 percent easing of the disease, with far less scaling and itchiness after two separate 12-week treatment periods. About 40 percent of these patients experienced a reduction in lesions of 75 percent or more.

The drug, tested in 1,500 people, remained effective for about 10 months after patients stopped taking it. Moreover, the drug did not damage the body's ability to fight infection, the Cambridge company said, citing a series of recent studies that looked at this issue.

Genentech, based in San Francisco, and partner Xoma of Berkeley, Calif., said their drug, called Xanelim, had comparable efficacy and safety results. About 39 percent of patients in its phase 3 trials who received the most effective dose over a 12-week period had a 75 percent or better improvement in their symptoms with a weekly under-the-skin injection.

However, there are some differences: Xanelim reportedly acts slightly faster in clearing psoriasis symptoms during the first two weeks of treatment while Amevive has longer staying power, as patients do not relapse as quickly when they stop taking the medication.

And while both companies maintain their drugs do not interfere with the immune system, Amevive is considered the stronger of the two.

If patient convenience is a key yardstick, Xanelim has an edge as an under-the-skin injection, which is considered better because it can be self-administered, much like an insulin shot.

Amevive has been tested in two versions: injected into a muscle or into the blood stream - the latter in a much larger dose.

``I think the convenience of Xanelim is a huge advantage,'' said Dr. Leonardi, who had 140 patients taking Xanelim and about 27 on Amevive. However, he concedes getting patients to self-inject themselves is new to dermatologists.

Biogen, which plans to offer both the intramuscular and intravenous forms, noted that a significant number of multiple sclerosis patients give themselves the once-a-week intramuscular injection of Avonex, the company's very successful drug treatment for that disease.

``We have a drug (Amevive) that has no risk of increased infection and we found some patients who responded very quickly,'' said Gunther Winkler, Biogen's program executive on Amevive.

He said the company discovered its drug in the late 1980s and began testing it in people starting in 1995.

``It is an amazing feeling to develop a drug from the start and see it through to submission to the FDA probably by the end of the year, and ultimately change how psoriasis is treated,'' said Winkler.

4.) Humoral immune response to a therapeutic polyvalent cancer vaccine after complete resection of thick primary melanoma and sentinel lymphadenectomy.

J Clin Oncol 2003 Jan 15;21(2):313-9

Chung MH, Gupta RK, Hsueh E, Essner R, Ye W, Yee R, Morton DL.

Sonya Valley Ghidossi Vaccine Laboratory of the Roy E. Coats Research Laboratories of the John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, CA 90404, USA.

PURPOSE: A therapeutic polyvalent cancer vaccine (Canvaxin vaccine; CancerVax Corp, Carlsbad, CA) induces antibodies to a glycoprotein tumor-associated antigen (TA90). However, endogenous immune responses to TA90 have also been reported. This study examined anti-TA90 antibody responses with respect to the survival of patients who received adjuvant vaccine immunotherapy after resection of thick (> or = 4 mm) primary cutaneous melanoma. PATIENTS AND METHODS: Serum specimens were obtained from 54 patients immediately before and then 1, 2, 4, and 6 months after wide local excision of thick primary cutaneous melanoma and sentinel lymphadenectomy. All patients were offered adjuvant therapies with the vaccine, high-dose interferon, or other agents. An enzyme-linked immunosorbent assay was used to determine serial serum titers of immunoglobulin G (IgG) and IgM antibodies against TA90. These titers were correlated with clinical course. RESULTS: Forty-three patients chose vaccine therapy, and 11 patients chose postoperative observation. Preoperative anti-TA90 IgG and IgM titers were similar for vaccine and observation groups (P =.184). At a median follow-up of 26 months, univariate analysis of Cox regression showed that disease-free survival and overall survival of vaccine patients were significantly correlated with maximal IgM response (P =.0006 and.006, respectively) but not with maximal IgG response (P =.73 and.95, respectively). Neither response predicted survival in the observation group. CONCLUSION: Postoperative vaccine therapy may enhance IgG and IgM immune responses to TA90 after surgical resection, but only the IgM response is correlated with improved survival. These findings may become useful to guide selection of patients for postoperative adjuvant therapy of high-risk melanoma.

5.) A granuloma annulare-like eruption associated with the use of amlodipine(Norvasc).

Australas J Dermatol 2002 Feb;43(1):24-7

Lim AC, Hart K, Murrell D.

Department of Dermatology, St George Hospital Clinical School, University of New South Wales, Sydney, New South Wales, Australia.

A granuloma annulare-like drug reaction is a rarely encountered clinical entity. A 64-year-old Caucasian female developed a granuloma annulare-like reaction 13 days after starting amlodipine and cleared within 3 months after drug cessation. The eruption consisted of multiple erythematous pruritic papules, distributed symmetrically over the lateral aspects of the legs and thighs, as well as on both palms. Histology showed focal collagen degeneration and significant interstitial histiocytic dermal infiltrate suggestive of granuloma annulare. We review previously reported cases of granuloma annulare-like drug reactions, in the context of a recently proposed classification for drug-induced interstitial granulomatous reactions.

 

6.) [A case of acute cholestatic hepatitis associated with orlistat] XENICAL

Taehan Kan Hakhoe Chi 2002 Sep;8(3):317-20

[Article in Korean]

Kim DH, Lee EH, Hwang JC, Jeung JH, Kim do H, Cheong JY, Cho SW, Kim YB.

Department of Gastroenterology, Ajou University College of Medicine, Suwon, Korea. sung-woncho@hotmail.com

Orlistat(Xenical(R), Roche) is considered a safe and effective drug to treat obesity by reduced absorption of 30% digested fat. To date, no serious adverse effects affecting the liver have been published except a case of subacute hepatic failure leading to liver transplantation in a young women with moderate obesity treated with orlistat. We report a case of acute cholestatic hepatitis in a young woman with moderate obesity treated with orlistat: a 33-year-old female admitted for the evaluation of jaundice. Abdominal ultrasonography, ERCP, routine chemistry, viral markers, and a fine needle biopsy of liver were performed. Microscopic findings of the liver biopsy specimen were compatible with acute cholestatic hepatitis. After steroid therapy, liver function was improved.

 

7.) Reconocen que el adelgazante Reductil fue relacionado con 34 muertes

Source: http://www.healthig.com

Un despacho periodístico fechado en Londres, el 18 de marzo pasado, comunica que un total de 34 pacientes han muerto tras tomar el medicamento antiobesidad Reductil, perteneciente a Laboratorios Abbott. Eugene Sun, vicepresidente de desarrollos farmacéuticos de la compañía, hizo pública la cifra de fallecidos después de que el Departamento de Salud británico informara de la muerte de dos pacientes en ese país e indicara que en más de 200 personas se han observado reacciones adversas al fármaco en el Reino Unido.

Sun dijo que la empresa tiene información de 28 muertes en Estados unidos, dos en Italia, dos en el Reino unido, una en Sudáfrica y una en Suiza. Italia suspendió la venta de Reductil (sibutramina) la semana pasada tras recibir 50 informes sobre reacciones adversas en pacientes, incluidos los dos fallecimientos. En España se vende el medicamento desde el año pasado.

Abbot señaló que la tasa de muerte relacionada con Reductil es inferior a un 1% de la mortalidad relacionada con la obesidad, que a menudo sufren afecciones como diabetes y enfermedades cardiovasculares.

Casi nueve millones de personas han tomado la droga en el mundo, aclaró Sun. Los 34 fallecimientos suponen una incidencia de dos muertos por cada 100.000 personas tratadas anualmente con este fármaco, señaló el vicepresidente de Abbot. Los estudios sobre la obesidad indican que 400 personas por cada 100.000 mueren cada año por esta causa.

Reductil salió al mercado en 1997, después de varios años en ensayos en humanos. Tras la suspensión de la venta del fármaco en Italia, Abbot repasó los datos relacionados con la sibutramina en todo el mundo y envió toda la información sobre las reacciones adversas a las autoridades reguladoras.

Los dos fallecidos en el Reino Unido, según indicó el laboratorio, sufrían complicaciones cardíacas graves. Uno de ellos, además, padecía diabetes y un problema de tiroides; murió a los dos días de ser tratado con sibutramina. El otro había estado en tratamiento con este fármaco cuatro meses pero dejó de tomarlo cinco días antes de morir por un fallo en el corazón.

El Departamento de Salud británico declaró: 'Hasta el 13 de marzo de 2002 se han recibido 212 informes de lo que se sospecha son reacciones adversas, relacionadas con la sibutramina'. De estos informes, 93 fueron considerados graves. La declaración oficial indica que los pacientes que actualmente están siendo tratados con Reductil pueden continuar haciéndolo, 'pero si se sienten mal deben hablar con su médico'.

En otros países las autoridades están estudiando la documentación sobre reacciones adversas del fármaco para preparar un informe de la Agencia Europea de Evaluación de Medicamentos.

8.) The BEST study: results according to prior treatment. (ACNE)

Cutis 2003 Feb;71(2 Suppl):27-34

Rodriguez D, Davis MW.

Dadeland Dermatology Group, Miami, Florida, USA.

Combination topical products may provide the best available treatment option to patients with acne because the majority of these products not only combine drugs with 2 distinct mechanisms of action but also avoid systemic adverse events that may be associated with oral therapies. Recently, the BenzaClin (benzoyl peroxide/ clindamycin topical gel) Efficacy and Satisfaction Trial (BEST) was conducted. This large, open-label, multicenter study assessed patient satisfaction, treatment efficacy, and quality of life (QOL) in response to 8 weeks of treatment with benzoyl peroxide/clindamycin topical gel. Patients who were previously dissatisfied with their current acne therapy were enrolled in the study. This paper presents results stratified by prior treatment in patients who were receiving benzoyl peroxide, clindamycin, other topical antibiotics, or retinoids prior to study enrollment. Mean patient satisfaction scores were significantly increased regardless of which prior treatments were used (P < or = .0001 for all groups). Furthermore, acne severity was significantly improved among all groups (P < or = .0001), with more than 90% of most groups experiencing marked, moderate, or mild improvements in their acne by the end of the study. Patient satisfaction is an important element in the experience of acne because it is usually linked to improved efficacy; therefore, assurance of patient satisfaction with therapy is a significant consideration in the treatment of this illness.

9.) Treatment of cutaneous calcinosis in limited systemic sclerosis with minocycline.

Ann Rheum Dis 2003 Mar;62(3):267-9

Robertson LP, Marshall RW, Hickling P.

Department of Rheumatology, Royal Cornwall Hospital, Truro, UK. Academic Rheumatology, University of Bristol, UK. Department of Rheumatology, Derriford Hospital, UK.

OBJECTIVES: To evaluate the effect of minocycline as treatment for cutaneous calcinosis in limited cutaneous systemic sclerosis (lcSSc). METHODS: Patients with lcSSc who had cutaneous calcinosis causing pain or ulceration, or both, were prescribed minocycline 50 or 100 mg daily regularly in an open label manner between November 1994 and April 2000. At routine clinical follow up the appearance of the calcinosis deposits was assessed clinically and radiographically, and the patients' assessment of the degree of discomfort, size, and frequency of ulceration was recorded. Demographic data, including disease duration, clinical features, and antinuclear antibody (ANA) titres, were also recorded. RESULTS: Nine patients have been treated to date. Eight of the nine patients were ANA positive, five of whom were positive for anticentromere antibodies. Eight patients have shown definite improvement and seven patients continue to receive treatment. The frequency of ulceration and inflammation associated with the calcinosis deposits decreased with treatment. The size of the calcinosis deposits also decreased but was less dramatic than expected. Improvement occurred at the earliest after one month of treatment with a mean (SD) of 4.8 (3.8) months. The mean (SD) length of treatment was 3.5 (1.9) years. An unexpected effect was the darkening of the calcinosis deposits to a blue/black colour. CONCLUSIONS: Minocycline may be effective in the control of calcinosis in systemic sclerosis. A low dose only is required and appears to be generally well tolerated. The mechanism of action may be mainly through inhibition of matrix metalloproteinases and anti-inflammatory effects. Calcium binding properties and antibacterial actions may also have a role.

 

10.) 5 Alpha-reductase inhibitors: what's new? DUTASTERIDE

Curr Opin Urol 2003 Jan;13(1):31-7

Foley CL, Kirby RS.

PURPOSE OF REVIEW Medical therapy is now the first-line treatment for most men with symptomatic benign prostatic hyperplasia. This review aims to highlight the recent contributions to our understanding of 5 alpha-reductase inhibitor usage.RECENT FINDINGS For the last decade, finasteride has been the only available 5 alpha-reductase inhibitor, acting upon the type 2 isoenzyme of 5-alpha reductase. Dutasteride is the first drug that can inhibit both isoenzymes and is soon to be available. Biochemically it achieves greater and more rapid dihydrotestosterone suppression compared with finasteride. Clinically, it appears to be at least as good in terms of improving symptoms and flow rates, and reducing the risk of acute urinary retention or the requirement for benign prostatic hyperplasia-related surgery. However, until these two drugs are formally compared, the true benefits of additional type 1 isoenzyme inhibition are unknown. The recently reported Medical Therapy of Prostatic Symptoms trial has convincingly demonstrated superior outcomes with combination therapy compared with monotherapy, unlike previous trials of shorter duration. The ability of 5 alpha-reductase inhibitors to prevent disease progression was also confirmed. Newer roles for 5 alpha-reductase inhibitors are also being defined. Finasteride has been shown to reduce and control benign prostatic hyperplasia-related haematuria, although its value in controlling perioperative bleeding is less clear. Their role as chemopreventive agents for prostate cancer is also under investigation.SUMMARY Recent studies have both clarified and extended the roles of 5 alpha-reductase inhibitors in benign prostatic hyperplasia, and these may expand further if chemopreventive abilities are proved. In addition, dual isoenzyme inhibition will soon be available.

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DATA-MEDICOS /DERMAGIC-EXPRESS /JANUARY JOURNAL 2..003/ DR. JOSE LAPENTA R.  DERMATOLOGIST

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