History of Sildenafil, post-approval experience and upcoming developments
clinical development; Pfizer incorporation In the mid-1980’s, scientists at Pfizer Research co-administration of the two types of agents is Headquarters, Sandwich, UK, decided to work on contra-indicated due to the potential synergistic a new approach to treating cardiovascular dis- ease by trying to create novel compounds which VIAGRA™ has now been on the market for over would selectively block phosphodiesterase iso- 4 years and numerous Phase IV studies and in- enzymes and thereby raise levels of cyclic-GMP.
dependent studies have confirmed its efficacy The hope was that if such a molecule could be and safety profile in a wide range of patients in developed, it would have all the beneficial vaso- all parts of the world. In the first year of the dilatory properties of nitrates but without the launch there was some concern that sildenafil tachyphylaxis which is a problem with the long and/or sexual activity might be provoking serious term clinical use of nitrates. In 1989, UK-92,480, cardiovascular events in susceptible individuals.
now known as sildenafil citrate (VIAGRA™ ) was However, all subsequent studies have failed to first synthesised and profiling showed it to be a demonstrate any signal of such a problem. Most highly potent selective inhibitor of phosphodi- recently, the results of a prescription event esterase 5. It first entered clinical development monitoring study in over 20,000 men followed for in 1991 as a potential treatment for angina. In an average of 18 months revealed that the car- 1992 erections were reported by some volun- diovascular mortality in men prescribed sildenafil teers in a multiple dose pharmacokinetic study.
was numerically lower than that of an age- At a similar time, there were scientific publica- tions suggesting that nitric oxide may have been Sildenafil remains under investigation for a vari- involved in the erectile process. The focus of ety of other indications. Results of clinical trials in patients with female sexual dysfunction have switched from angina to erectile dysfunction, and provided conflicting results but there are indica- clinical profiling revealed the potential of this new tions that, with further refinement of clinical trial agent as on-demand therapy for erectile dys- methodology and selection of subjects, a thera- function. Subsequently, Sandwich scientists peutic role for sildenafil in certain types of female confirmed the presence of PDE5 in the smooth sexual dysfunction will be confirmed.
muscle of the human corpus cavernosum.
Sildenafil started life as a potential cardiovascu- In 1997 a registration dossier was compiled lar agent, and as knowledge of its clinical effects which included results of 21 double blind placebo increases, there is more and more focus on its controlled trials, all of which demonstrated the potential to treat certain cardiovascular disor- efficacy of the compound to treat patients with ders. A number of studies and clinical observa- ED of various aetiologies. The main side effects tions indicate an exciting potential for this com- were related to the smooth muscle relaxant pound to treat patients with pulmonary arterial properties of the compound and included tran- hypertension. There is a prospect that this could sient headache, flushing, dyspepsia and nasal lead to a breakthrough in the treatment of this congestion. A minority of patients experienced life-restricting illness (analagous to the break- transient visual symptoms. Since sildenafil and through that sildenafil achieved in the field of nitrates both work on the NO c-GMP pathway,

Source: http://www.winterworkshop.de/archiv/abstracts2003/osterloh.pdf

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SkylineDental Leland L. Yee, DDS NOMBRE DEL PACIENTE:______________________________________________ DECLARACIÓN DE LA HISTORIA MÉDICA Y CONSENTIMIENTO PARA PROCEDER: Yo certifico que las respuestas al cuestionario médico son correctas y veridicas a mi conocimento. Porque un cambio en la historia médica ó medicamentos puede afectar mi tratamiento dental, yo comprendo la importan

Microsoft word - effects of smoking and methods of cessation

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