DDInter1666 DDInter1008
In eliciting its mechanism of action, sildenafil ultimately prevents or minimizes the breakdown of cyclic guanosine monophosphate (cGMP) by inhibiting cGMP specific phosphodiesterase type 5 (PDE5) [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. The result of doing so allows cGMP present in both the penis and pulmonary vasculature to elicit smooth muscle relaxation and vasodilation that subsequently facilitates relief in pulmonary arterial hypertension and the increased flow of blood into the spongy erectile tissue of the penis that consequently allows it to grow in size and become erect and rigid [F3850, F3853, F3856, F3859, F3883, F3886, L5611, L5614]. Interestingly enough, it is precisely via this mechanism why sildenafil was at first researched as a potential treatment
Ketoconazole is an imidazole antifungal agent used in the prevention and treatment of a variety of fungal infections.[FDA Label] It functions by preventing the synthesis of ergosterol, the fungal equivalent of cholesterol, thereby increasing membrane fluidity and preventing growth of the fungus.[A181802,T116] Ketoconazole was first approved in an oral formulation for systemic use by the FDA in 1981. At this time it was considered a significant improvement over previous antifungals, [miconazole] and [clotrimazole], due to its broad spectrum and good absorption. However, it was discovered that ketoconazole produces frequent gastrointestinal side effects and dose-related hepatitis.[A188054,A188057] These effects combined with waning efficacy led to its eventual replacement by triazole agents, [fluconazole], [itraconazole], [voriconazole], and [posaconazole]. Ketoconazole and its predecessor [clotrimazole] continue to be used in topical formulations.
Sildenafil {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Ketoconazole
Sildenafil {u} (Compound) causes {v} (Side Effect) Hypersensitivity
Hypersensitivity {u} (Side Effect) is caused by {v} (Compound) Ketoconazole
Sildenafil {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Itraconazole
Itraconazole {u} (Compound) resembles {v} (Compound) Ketoconazole
Sildenafil {u} (Compound) causes {v} (Side Effect) Hypersensitivity
Hypersensitivity {u} (Side Effect) is caused by {v} (Compound) Itraconazole
Itraconazole {u} (Compound) resembles {v} (Compound) Ketoconazole
Sildenafil {u} (Compound) causes {v} (Side Effect) Eye irritation
Eye irritation {u} (Side Effect) is caused by {v} (Compound) Posaconazole
Posaconazole {u} (Compound) resembles {v} (Compound) Ketoconazole
Sildenafil {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Posaconazole
Posaconazole {u} (Compound) resembles {v} (Compound) Ketoconazole
Sildenafil {u} (Compound) resembles {v} (Compound) Vardenafil
Vardenafil {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Ketoconazole
Sildenafil {u} (Compound) binds {v} (Gene) ABCC5
ABCC5 {u} (Gene) regulates {v} (Gene) ABHD4
ABHD4 {u} (Gene) is upregulated by {v} (Compound) Ketoconazole
Sildenafil {u} (Compound) resembles {v} (Compound) Vardenafil
Vardenafil {u} (Compound) causes {v} (Side Effect) Hypersensitivity
Hypersensitivity {u} (Side Effect) is caused by {v} (Compound) Ketoconazole
Sildenafil {u} (Compound) upregulates {v} (Gene) LPL
LPL {u} (Gene) is regulated by {v} (Gene) ALAS1
ALAS1 {u} (Gene) is upregulated by {v} (Compound) Ketoconazole
Sildenafil (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Ketoconazole (Compound)
Sildenafil (Compound) causes Hypersensitivity (Side Effect) and Hypersensitivity (Side Effect) is caused by Ketoconazole (Compound)
Sildenafil (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Itraconazole (Compound) and Itraconazole (Compound) resembles Ketoconazole (Compound)
Sildenafil (Compound) causes Hypersensitivity (Side Effect) and Hypersensitivity (Side Effect) is caused by Itraconazole (Compound) and Itraconazole (Compound) resembles Ketoconazole (Compound)
Sildenafil (Compound) causes Eye irritation (Side Effect) and Eye irritation (Side Effect) is caused by Posaconazole (Compound) and Posaconazole (Compound) resembles Ketoconazole (Compound)
Sildenafil (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Posaconazole (Compound) and Posaconazole (Compound) resembles Ketoconazole (Compound)
Sildenafil (Compound) resembles Vardenafil (Compound) and Vardenafil (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Ketoconazole (Compound)
Sildenafil (Compound) binds ABCC5 (Gene) and ABCC5 (Gene) regulates ABHD4 (Gene) and ABHD4 (Gene) is upregulated by Ketoconazole (Compound)
Sildenafil (Compound) resembles Vardenafil (Compound) and Vardenafil (Compound) causes Hypersensitivity (Side Effect) and Hypersensitivity (Side Effect) is caused by Ketoconazole (Compound)
Sildenafil (Compound) upregulates LPL (Gene) and LPL (Gene) is regulated by ALAS1 (Gene) and ALAS1 (Gene) is upregulated by Ketoconazole (Compound)