Details of Drug-Drug Interaction
| Drug General Information (ID: DDIHE527N3) | |||||||||
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| Drug Name | Milrinone | Drug Info | Amifostine | Drug Info | |||||
| Drug Type | Small molecule | Small molecule | |||||||
| Therapeutic Class | Cardiotonic Agents | Cytoprotective Agent | |||||||
| Structure | |||||||||
| Mechanism of Milrinone-Amifostine Interaction (Severity Level: Moderate) | |||||||||
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| Additive hypotensive effects Click to Show/Hide Mechanism Graph | |||||||||
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| Drug Name | Milrinone | Amifostine | |||||||
| Mechanism 1 |
Hypotensive effects Phosphodiesterase 3 Inhibitor |
Antihypertensive agent | |||||||
| Key Mechanism Factor 1 | |||||||||
| Factor Name | Phosphodiesterase 3 | Structure Sequence | |||||||
| Protein Family | Cyclic nucleotide phosphodiesterase family | ||||||||
| Protein Function |
Cyclic nucleotide phosphodiesterase with specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (PubMed:1315035, PubMed:8695850, PubMed:8155697, PubMed:25961942). Has also activity toward cUMP (PubMed:27975297). Independently of its catalytic activity it is part of an E2/17beta-estradiol-induced pro-apoptotic signaling pathway. E2 stabilizes the PDE3A/SLFN12 complex in the cytosol, promoting the dephosphorylation of SLFN12 and activating its pro-apoptotic ribosomal RNA/rRNA ribonuclease activity. This apoptotic pathway might be relevant in tissues with high concentration of E2 and be for instance involved in placenta remodeling (PubMed:31420216, PubMed:34707099).
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| Mechanism Description |
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| Mechanism 2 |
Hypotensive effects Phosphodiesterase 3 Inhibitor |
Hypotensive effects | |||||||
| Key Mechanism Factor 2 | |||||||||
| Factor Name | Phosphodiesterase 3 | Structure Sequence | |||||||
| Protein Family | Cyclic nucleotide phosphodiesterase family | ||||||||
| Protein Function |
Cyclic nucleotide phosphodiesterase with specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (PubMed:1315035, PubMed:8695850, PubMed:8155697, PubMed:25961942). Has also activity toward cUMP (PubMed:27975297). Independently of its catalytic activity it is part of an E2/17beta-estradiol-induced pro-apoptotic signaling pathway. E2 stabilizes the PDE3A/SLFN12 complex in the cytosol, promoting the dephosphorylation of SLFN12 and activating its pro-apoptotic ribosomal RNA/rRNA ribonuclease activity. This apoptotic pathway might be relevant in tissues with high concentration of E2 and be for instance involved in placenta remodeling (PubMed:31420216, PubMed:34707099).
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| Mechanism Description |
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| Recommended Action | |||||||||
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| Management | If medically feasible, antihypertensive medications should be interrupted 24 hours prior to amifostine administration. Blood pressure should be closely monitored during and after treatment. In addition to hypotension, transient hypertension or exacerbation of preexisting hypertension may occur from intravenous hydration, discontinuation of antihypertensive medications, or other causes. Patients who continue their hypotensive medication(s) during amifostine therapy should be carefully monitored for the development of hypotension. | ||||||||