Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIULMDTNQ)
  Drug Name Verapamil Drug Info Isoflurane Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Analgesics Anesthetics
  Structure

 Mechanism of Verapamil-Isoflurane Interaction (Severity Level: Moderate)
     Additive hypotensive effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Verapamil Isoflurane
      Mechanism 1 Antihypertensive agent
Voltage-gated calcium channel  Blocker 		Antihypertensive agent
      Key Mechanism Factor 1
Factor Name Voltage-dependent L-type calcium channel Structure Sequence
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 Verapamil and Isoflurane 
      Mechanism 2 Antihypertensive agent
Voltage-gated calcium channel  Blocker 		Hypotensive effects
      Key Mechanism Factor 2
Factor Name Voltage-dependent L-type calcium channel Structure Sequence
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 Verapamil and Isoflurane 
     Increased risk of cardiac depression Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Verapamil Isoflurane
      Mechanism 3 Cardiac depressant effects Cardiac depressant effects
      Key Mechanism Factor 3
Factor Name Cardiac depression
Factor Description Cardiac depression may manifest as negative heart rate, negative conduction, and negative contractility. Symptoms include: excessive or more than normal sleep, irritability, loss of interest in activities, and fatigue.
      Mechanism Description
  • Increased risk of cardiac depression by the combination of Verapamil and Isoflurane 

Recommended Action
      Management Discontinuation of calcium channel blockers prior to surgery is generally not recommended because of the rebound effect in patients with coronary heart disease or arterial hypertension. However, extreme care must be taken when administering halogenated anesthetics to patients under treatment with calcium channel blockers. Hemodynamic and electrocardiographic monitoring are recommended during the operation and postoperatively, and the dosage of one or both drugs adjusted as necessary.

References
1 Product Information. Cardizem (diltiazem). Hoechst Marion-Roussel Inc, Kansas City, MO.
2 Product Information. Covera-HS (verapamil). Searle, Skokie, IL.
3 Hantler CB, Wilton N, Learned DM, et al "Impaired myocardial conduction in patients receiving diltiazem therapy during enflurane anesthesia." Anesthesiology 67 (1987): 94-6