Question

1. Describe MOA for PDEi's in context of pathophysiology of ED?

2. SAR of PDEi's. Describe the effect of functional groups highlighted in colors ( red and blue) on activity of PDEi shown in figure below. $//img.homeworklib.com/questions/1f056260-c7c3-11eb-88c5-ab66a6064cdb.png?x-oss-process=image/resize,w_560$

3. Why tadalafil half-life ( 18 hrs) is much longer than sildenafil (6 hrs)?

4. Are the PDEi's lipophilic or hydrophilic? Explain the effect of cLogP. What is the one implication of cLogP from the patients education point of view?

5. How PDEi's used for ED differ from Alprostadil?

Answer 1

1. PDEi's Are phosphodiesterase 4 inhibitors.PDE4Is inhibit the degradation of cAMP to 5'-AMP. This leads to increased level of cAMP And relaxes smooth muscle.

MOA for PDei's in pathophysiology of Es CNS stimulation NANC triggering enos actively is endothelium enos Nitrite • SGC stimulator Synergy • SGC activator soluble guanylyl cyclase activation PDE5 Increase in a GMP) concentration PDES cahibitors Smooth muscle cell relaxation & dilation of arterioles.

2.question is incomplete..need full expansion of SAR.

3. Tadalafil has longer half life because it has long elimination half life than sildenafil.

4.PDEi's are lipophilic.low hydrophilic have high cLogP.

5. PDEi's action is through competitive inhibition of PDE- 5 and requires endogenous nitrous oxide production.while alpostradil Doesnot depend on nitous oxide.PDEi's are oral drug therapy while alpostradil are non oral therapy.