Phosphodiesterase Inhibitors
Cyclic-Nucleotide PDE Isoenzymes & Their Selective Inhibitors — Methylxanthines (theophylline, pentoxifylline), PDE3 (milrinone, cilostazol), PDE4 (roflumilast, apremilast), PDE5 (sildenafil, tadalafil, vardenafil): Isoform Distribution, Organ-Selective Effects, Adverse Effects & the Nitrate Contraindication
Introduction & class logic
- Phosphodiesterase (PDE) inhibitors block the cyclic-nucleotide PDE enzymes that hydrolyse the second messengers cyclic AMP (cAMP) and cyclic GMP (cGMP) to their inactive 5′-monophosphates; inhibition therefore raises cellular cAMP and/or cGMP and amplifies their downstream signalling.
- The isoenzyme superfamily — cyclic-nucleotide PDEs form a superfamily of eleven isoenzyme families (PDE1–PDE11) differing in substrate preference (cAMP-specific, cGMP-specific or dual), tissue distribution and regulation.
- Therapeutic logic — because individual PDE isoforms predominate in particular tissues, an inhibitor selective for one isoform produces a relatively organ-specific rise in cyclic nucleotide — e.g. PDE5 in corpus cavernosum & pulmonary vasculature, PDE3 in heart & vessels, PDE4 in inflammatory cells.
- Cross-cutting class — the class spans respiratory (bronchodilation, anti-inflammation), cardiovascular (inotropy, vasodilation, pulmonary hypertension, antiplatelet), urogenital (erectile dysfunction) and dermatological/rheumatological (psoriasis, psoriatic arthritis) systems.
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Phosphodiesterase Inhibitors
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