Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIYSTJ4RD)
  Drug Name Magnesium sulfate Drug Info Nifedipine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Analgesics Analgesics
  Structure

 Mechanism of Magnesium sulfate-Nifedipine Interaction (Severity Level: Moderate)
     Additive hypotensive effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Magnesium sulfate Nifedipine
      Mechanism 1 Hypotensive effects
N-methyl-D-aspartate receptor  Antagonist 		Hypotensive effects
Voltage-gated L-type calcium channel  Blocker
      Key Mechanism Factor 1
Factor Name Glutamate receptor ionotropic NMDA 1
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Structure Sequence
MSTMRLLTLALLFSCSVARAACDPKIVNIGAVLSTRKHEQMFREAVNQANKRHGSWKIQLNATSVTHKPNAIQMALSVCEDLISSQVYAILVSHPPTPNDHFTPTPVSYTAGFYRIPVLGLTTRMSIYSDKSIHLSFLRTVPPYSHQSSVWFEMMRVYSWNHIILLVSDDHEGRAAQKRLETLLEERESKAEKVLQFDPGTKNVTALLMEAKELEARVIILSASEDDAATVYRAAAMLNMTGSGYVWLVGEREISGNALRYAPDGILGLQLINGKNESAHISDAVGVVAQAVHELLEKENITDPPRGCVGNTNIWKTGPLFKRVLMSSKYADGVTGRVEFNEDGDRKFANYSIMNLQNRKLVQVGIYNGTHVIPNDRKIIWPGGETEKPRGYQMSTRLKIVTIHQEPFVYVKPTLSDGTCKEEFTVNGDPVKKVICTGPNDTSPGSPRHTVPQCCYGFCIDLLIKLARTMNFTYEVHLVADGKFGTQERVNNSNKKEWNGMMGELLSGQADMIVAPLTINNERAQYIEFSKPFKYQGLTILVKKEIPRSTLDSFMQPFQSTLWLLVGLSVHVVAVMLYLLDRFSPFGRFKVNSEEEEEDALTLSSAMWFSWGVLLNSGIGEGAPRSFSARILGMVWAGFAMIIVASYTANLAAFLVLDRPEERITGINDPRLRNPSDKFIYATVKQSSVDIYFRRQVELSTMYRHMEKHNYESAAEAIQAVRDNKLHAFIWDSAVLEFEASQKCDLVTTGELFFRSGFGIGMRKDSPWKQNVSLSILKSHENGFMEDLDKTWVRYQECDSRSNAPATLTFENMAGVFMLVAGGIVAGIFLIFIEIAYKRHKDARRKQMQLAFAAVNVWRKNLQDRKSGRAEPDPKKKATFRAITSTLASSFKRRRSSKDTSTGGGRGALQNQKDTVLPRRAIEREEGQLQLCSRHRES
Gene Name GRIN1
Uniprot ID NMDZ1_HUMAN
KEGG Pathway hsa:2902
Protein Family Glutamate-gated ion channel (TC 1.A.10.1) family
Protein Function
Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:7685113, PubMed:28126851, PubMed:26919761, PubMed:26875626, PubMed:28105280). Sensitivity to glutamate and channel kinetics depend on the subunit composition (PubMed:26919761).
    Click to Show/Hide
      Key Mechanism Factor 2
Factor Name Voltage-dependent L-type calcium channel subunit beta-1
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Structure Sequence
MVQKTSMSRGPYPPSQEIPMEVFDPSPQGKYSKRKGRFKRSDGSTSSDTTSNSFVRQGSAESYTSRPSDSDVSLEEDREALRKEAERQALAQLEKAKTKPVAFAVRTNVGYNPSPGDEVPVQGVAITFEPKDFLHIKEKYNNDWWIGRLVKEGCEVGFIPSPVKLDSLRLLQEQKLRQNRLGSSKSGDNSSSSLGDVVTGTRRPTPPASAKQKQKSTEHVPPYDVVPSMRPIILVGPSLKGYEVTDMMQKALFDFLKHRFDGRISITRVTADISLAKRSVLNNPSKHIIIERSNTRSSLAEVQSEIERIFELARTLQLVALDADTINHPAQLSKTSLAPIIVYIKITSPKVLQRLIKSRGKSQSKHLNVQIAASEKLAQCPPEMFDIILDENQLEDACEHLAEYLEAYWKATHPPSSTPPNPLLNRTMATAALAASPAPVSNLQGPYLASGDQPLERATGEHASMHEYPGELGQPPGLYPSSHPPGRAGTLRALSRQDTFDADTPGSRNSAYTELGDSCVDMETDPSEGPGLGDPAGGGTPPARQGSWEDEEEDYEEELTDNRNRGRNKARYCAEGGGPVLGRNKNELEGWGRGVYIR
Gene Name CACNB1
Uniprot ID CACB1_HUMAN
KEGG Pathway hsa:782
Protein Family Calcium channel beta subunit family
Protein Function
Regulatory subunit of L-type calcium channels (PubMed:1309651, PubMed:8107964, PubMed:15615847). Regulates the activity of L-type calcium channels that contain CACNA1A as pore-forming subunit (By similarity). Regulates the activity of L-type calcium channels that contain CACNA1C as pore-forming subunit and increases the presence of the channel complex at the cell membrane (PubMed:15615847). Required for functional expression L-type calcium channels that contain CACNA1D as pore-forming subunit (PubMed:1309651). Regulates the activity of L-type calcium channels that contain CACNA1B as pore-forming subunit (PubMed:8107964).
    Click to Show/Hide
      Mechanism Description
  • Additive hypotensive effects by the combination of Magnesium sulfate and Nifedipine 
     Additive neuromuscular blocking effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Magnesium sulfate Nifedipine
      Mechanism 2 Neuromuscular blocking effects Neuromuscular blocking effects
      Key Mechanism Factor 3
Factor Name Neuromuscular blocking effects
Factor Description Neuromuscular blocking agents cause paralysis of affected skeletal muscles by blocking postsynaptic acetylcholine (Nm) receptors, thereby blocking neuromuscular signaling at the neuromuscular junction. Neuromuscular blocking agents can cause the following side effects: muscle paralysis, jaw stiffness, and shortness of breath. Concomitant use of drugs with neuromuscular blocking activity may result in severe and/or prolonged respiratory depression.
      Mechanism Description
  • Additive neuromuscular blocking effects by the combination of Magnesium sulfate and Nifedipine 

Recommended Action
      Management The cardiovascular, respiratory, and neurologic status of patients should be closely monitored if these drugs must be given concurrently.

References
1 Benami M, Giladi Y, Shalev E "The combination of magnesium sulphate and nifedipine - a cause of neuromuscular blockade." Br J Obstet Gynaecol 101 (1994): 262-3. [PMID: 8193107]
2 DiMagno MJ, DiMagno EP. Chronic pancreatitis.?Curr Opin Gastroenterol. 2012;28(5):523-531. [PMID: 22782018]
3 Canadian Pharmacists Association.
4 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
5 Product Information. Adalat (nifedipine). Bayer, West Haven, CT.
6 Snyder SW, Cardwell MS "Neuromuscular blockade with magnesium sulfate and nifedipine." Am J Obstet Gynecol 161 (1989): 35-6. [PMID: 2750819]
7 Waisman GD, Mayorga LM, Camera MI, Vignolo CA, Martinotti A "Magnesium plus nifedipine: potentiation of hypotensive effect in preeclampsia?" Am J Obstet Gynecol 159 (1988): 308-9. [PMID: 3407684]