Details of Drug-Drug Interaction
| Drug General Information (ID: DDISU7GACL) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Drug Name | Sildenafil | Drug Info | Phentolamine | Drug Info | |||||
| Drug Type | Small molecule | Small molecule | |||||||
| Therapeutic Class | Impotence Agents/Agents For Pulmonary Hypertension | Antihypertensive Agents | |||||||
| Structure | |||||||||
| Mechanism of Sildenafil-Phentolamine Interaction (Severity Level: Moderate) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Additive hypotensive effects Click to Show/Hide Mechanism Graph | |||||||||
 |
|||||||||
| Drug Name | Sildenafil | Phentolamine | |||||||
| Mechanism |
Hypotensive effects Prostacyclin receptor Agonist |
Antihypertensive agent Alpha-1 adrenergic receptor Antagonist |
|||||||
| Key Mechanism Factor 1 | |||||||||
| Factor Name | Prostacyclin receptor |
×
Structure
Sequence
MADSCRNLTYVRGSVGPATSTLMFVAGVVGNGLALGILSARRPARPSAFAVLVTGLAATDLLGTSFLSPAVFVAYARNSSLLGLARGGPALCDAFAFAMTFFGLASMLILFAMAVERCLALSHPYLYAQLDGPRCARLALPAIYAFCVLFCALPLLGLGQHQQYCPGSWCFLRMRWAQPGGAAFSLAYAGLVALLVAAIFLCNGSVTLSLCRMYRQQKRHQGSLGPRPRTGEDEVDHLILLALMTVVMAVCSLPLTIRCFTQAVAPDSSSEMGDLLAFRFYAFNPILDPWVFILFRKAVFQRLKLWVCCLCLGPAHGDSQTPLSQLASGRRDPRAPSAPVGKEGSCVPLSAWGEGQVEPLPPTQQSSGSAVGTSSKAEASVACSLC
|
|||||||
| Gene Name | PTGIR | ||||||||
| Uniprot ID | PI2R_HUMAN | ||||||||
| KEGG Pathway | hsa:5739 | ||||||||
| Protein Family | G-protein coupled receptor 1 family | ||||||||
| Protein Function |
Receptor for prostacyclin (prostaglandin I2 or PGI2). The activity of this receptor is mediated by G(s) proteins which activate adenylate cyclase.
Click to Show/Hide
|
||||||||
| Key Mechanism Factor 2 | |||||||||
| Factor Name | Adrenergic receptor alpha-1 | Structure Sequence | |||||||
| Protein Family | G-protein coupled receptor 1 family | ||||||||
| Protein Function |
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
Click to Show/Hide
|
||||||||
| Mechanism Description |
|
||||||||
| Recommended Action | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Management | Caution is advised if sildenafil is used in combination with alpha blockers. Patients who demonstrate hemodynamic instability on alpha blocker therapy alone are at increased risk of symptomatic hypotension with concomitant use of sildenafil. Therefore, patients should be stable on alpha blocker therapy prior to initiating sildenafil, and sildenafil should be initiated at the lowest recommended dosage when used for erectile dysfunction (i.e., 25 mg). No dosage adjustment is necessary if used in the treatment of pulmonary arterial hypertension. In those patients already on an optimized dosage of sildenafil, alpha blocker therapy should be initiated at the lowest dosage. The safety of sildenafil in combination with alpha blockers may be affected by other variables such as intravascular volume depletion and use of other antihypertensive medications. | ||||||||