The treatment of ED and the awareness of its frequency and importance stem directly the introduction of the oral phosphodiesterase type 5 (PDE5) inhibitor sildenafil (Viagra avaliable at Canadian Health Care Mall Pinterest) tadalafil (Cialis, Cialis Professional Canada) and vardenafil(Levitra)
Its mechanism of action by blocking PDE5’s degradation of c promotes blood flow into the penis (see Figure 3.2, page 9) and the restoration of er function. Vardenafil and tadalafil have recently been added to this family of drugs. Be their mechanism of action is the same, there is no reason to assume there will b significant differences in ED effectiveness; however, their PDE selectivity and half-life be of clinical importance. Potency is not clinically relevant, because it is a way of expre in vitro concentrations of a drug—in short, given in dose equivalents the clinical end-will be the same.
Haemodynamically, PDE5 inhibitors have mild nitrate-like actions (sildenafil viagra australia originally intended to be a drug for mild angina). As PDE5 is present in smooth m cells throughout the vasculature and the NO/cGMP pathway is involved in the regul of blood pressure, PDE5 inhibitors have a modest hypotensive action. In healthy subj a single dose of 100 mg sildenafil transiently lowered blood pressure by an average o 7 mmHg, with a return to baseline 6 hours post-dose. There was no effect on heart ra
As NO is an important neurotransmitter throughout the vasculature and is involv the regulation of vascular smooth muscle relaxation, a synergistic and clinically impo interaction with oral and sublingual nitrates can occur (Appendix 3). A profound f blood pressure can result. The mechanism involves the combination of nitrates incre cGMP formation by activating guanylate cyclase and PDE5 inhibition decreasing c breakdown by inhibiting PDE5. The concomitant administration of PDE5 inhibitor nitrates is a contraindication to their use and this recommendation also extends to NO donors such as nicorandil. Clinical guidelines regarding timing of nitrate use post-P inhibitor or use of a PDE5 inhibitor after cessation of oral or sublingual nitrates ar available, but recent studies are helpful. In a study involving healthy volunteers at 10 dosage, sildenafil, with its short half-life (see later), did not react with sublingual nit 6 hours post-use. Tadalafil, with it long halflife, did not react at 48 hours. No dat available for vardenafil, but as its half-life is similar to sildenafil, a similar result is expected. Oral nitrates are not prognostically important drugs, so they can be disconti and, if needed, alternative agents substituted. After oral nitrate cessation, and pro there has been no clinical deterioration, PDE5 inhibitors can be used safely. recommended that the time interval prior to PDE5 inhibitor use is 5 half-lives, which e 5 days for the most popular once-daily oral nitrate agents.
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