1. PHOSPHODIESTERASES AS DRUG TARGETS K. Upendra Reddy 2010H146037H

5. Max frequency is once per day

9. The figure below shows the mechanism of action of Viagra, and the other PDE5 inhibitors, on the nitric oxide cycle.

10. Side Effects Sildenafil: Headache and flushing Dyspepsia Nasal congestion Abnormal vision (blue halo around lights)

11. Side Effects Vardenafil: Headache and flushing Rhinitis Dyspepsia Tadalafil: Headache and flushing Dyspepsia Nasal congestion Back pain--unique to Cialis Myalgia

12. Drug-Drug Interactions for the PDE 5 Inhibitors

13. Contraindications for PDE 5 Therapy Nitrates: Patients using nitrates regularly or intermittently should not use any of the PDE-5 Inhibitors. Applies for any form of nitrates (sublingual, transdermal, etc) Patients can get extreme hypotension Hypersensitivity to any of the components of the tablet.

14. Use with Caution: Alpha-Blockers: In the past these drugs were contraindications, but recent evidence suggests that they can be used together Patients should be stabilized on either the alpha-blocker or the PDE-5 inhibitor first before the other is added on at the lowest possible dose.

15. Sildenafil: Drug-Drug Interactions: Amiodarone Amlopdipine Aspirin Atazanavir Bosentan Cimetidine Ciprofloxacin Clarithromycin Darunavir/ritonavir Delavirdine Erythromycin Fluvoxamine Grapefruit juice Indinavir Nelfinavir Ritonavir (initially) S-warfarin Saquinavir Saquinavir/ritonavir tacrolimus

16. Tadalafil: Drug-Drug Interactions: Amlodipine Aspirin Atazanavir Bendrofluazide Darunavir/ritonavir Doxazosin Enalapril Ethanol-acute Ketoconazole Lovastatin Midazolam Rifampin S-warfarin Tamsulosin Theophylline

17. Treatment of CHF: PDE-III inhibitors are useful for the treatment of CHF. Increases the myocardial cAMP and transmembrane influx of calcium. Decreases the peripheral vascular resistance. Example: Amrinone Milrinone

19. Due to the broad immuno modulatory action, it has been proposed that efficacious for skin disorders such as dermatitis & psoriasis.

20. Highly selective PDE4 inhibitors are currently under evaluation for the asthma & Chronic Obstructive Pulmonary Disease.

22. Nausea ,emesis, gastric acid production associated with PDE4

25. Kalsi JS, Kell PD. Update on the oral treatments for male erectile dysfunction. EurAcadDermatolVenereol2004;18:267–74.

26. Conti, M., and Jin, S.-L. C. (1999) The molecular biology of cyclic nucleotide phosphodiesterases. Prog. Nucleic Acid Res. Mol. Biol.63, 1-38

27. J Nandhakumar, et al.,Characterization of the Effects of Phosphodiesterases(PDEs) IsozymeInhibitors in Animal Models. Life Sciences and Me.dicineResearch, Volume 2010: LSMR-7.Conti, M. & Beavo, J. Annu. Rev. Biochem. 76, 481–511(2007).