Details of Drug-Drug Interaction
| Drug General Information (ID: DDIBT6X4VO) | |||||||||
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| Drug Name | Sildenafil | Drug Info | Amyl Nitrite | Drug Info | |||||
| Drug Type | Small molecule | Small molecule | |||||||
| Therapeutic Class | Impotence Agents/Agents For Pulmonary Hypertension | Antidotes | |||||||
| Structure | |||||||||
| Mechanism of Sildenafil-Amyl Nitrite Interaction (Severity Level: Major) | |||||||||
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| Additive hypotensive effects Click to Show/Hide Mechanism Graph | |||||||||
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| Drug Name | Sildenafil | Amyl Nitrite | |||||||
| Mechanism |
Hypotensive effects Phosphodiesterase 5A Inhibitor |
Hypotensive effects Guanylate cyclase Agonist |
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| Key Mechanism Factor 1 | |||||||||
| Factor Name | Phosphodiesterase 5A |
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Structure
Sequence
MERAGPSFGQQRQQQQPQQQKQQQRDQDSVEAWLDDHWDFTFSYFVRKATREMVNAWFAERVHTIPVCKEGIRGHTESCSCPLQQSPRADNSAPGTPTRKISASEFDRPLRPIVVKDSEGTVSFLSDSEKKEQMPLTPPRFDHDEGDQCSRLLELVKDISSHLDVTALCHKIFLHIHGLISADRYSLFLVCEDSSNDKFLISRLFDVAEGSTLEEVSNNCIRLEWNKGIVGHVAALGEPLNIKDAYEDPRFNAEVDQITGYKTQSILCMPIKNHREEVVGVAQAINKKSGNGGTFTEKDEKDFAAYLAFCGIVLHNAQLYETSLLENKRNQVLLDLASLIFEEQQSLEVILKKIAATIISFMQVQKCTIFIVDEDCSDSFSSVFHMECEELEKSSDTLTREHDANKINYMYAQYVKNTMEPLNIPDVSKDKRFPWTTENTGNVNQQCIRSLLCTPIKNGKKNKVIGVCQLVNKMEENTGKVKPFNRNDEQFLEAFVIFCGLGIQNTQMYEAVERAMAKQMVTLEVLSYHASAAEEETRELQSLAAAVVPSAQTLKITDFSFSDFELSDLETALCTIRMFTDLNLVQNFQMKHEVLCRWILSVKKNYRKNVAYHNWRHAFNTAQCMFAALKAGKIQNKLTDLEILALLIAALSHDLDHRGVNNSYIQRSEHPLAQLYCHSIMEHHHFDQCLMILNSPGNQILSGLSIEEYKTTLKIIKQAILATDLALYIKRRGEFFELIRKNQFNLEDPHQKELFLAMLMTACDLSAITKPWPIQQRIAELVATEFFDQGDRERKELNIEPTDLMNREKKNKIPSMQVGFIDAICLQLYEALTHVSEDCFPLLDGCRKNRQKWQALAEQQEKMLINGESGQAKRN
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| Gene Name | PDE5A | ||||||||
| Uniprot ID | PDE5A_HUMAN | ||||||||
| KEGG Pathway | hsa:8654 | ||||||||
| Protein Family | Cyclic nucleotide phosphodiesterase family | ||||||||
| Protein Function |
Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP (PubMed:9714779, PubMed:15489334). Specifically regulates nitric-oxide-generated cGMP (PubMed:15489334).
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| Key Mechanism Factor 2 | |||||||||
| Factor Name | Guanylate cyclase soluble | Structure Sequence | |||||||
| Protein Family | Adenylyl cyclase class-4/guanylyl cyclase family | ||||||||
| Protein Function |
There are two types of guanylate cyclases: soluble forms and membrane-associated receptor forms. Activated by nitric oxide in the presence of magnesium or manganese ions.
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| Mechanism Description |
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| Recommended Action | |||||||||
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| Management | The use of PDE5 inhibitors in patients receiving organic nitrates or other nitric oxide donors, either regularly or intermittently, is considered contraindicated. A suitable time interval following sildenafil or vardenafil use for the safe administration of nitrates has not been determined. For patients treated with avanafil or tadalafil, at least 12 hours after the last dose of avanafil and 48 hours after the last dose of tadalafil are recommended before nitrate administration, should it be deemed medically necessary in a life-threatening situation. Even then, nitrates should only be administered under close medical supervision with appropriate hemodynamic monitoring. Patients should be advised to seek immediate medical attention if they experience anginal chest pain after taking a PDE5 inhibitor. | ||||||||