Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDICGWI3DA)
  Drug Name Verapamil Drug Info Guanethidine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Analgesics Antihypertensive Agents
  Structure

 Mechanism of Verapamil-Guanethidine Interaction (Severity Level: Moderate)
     Additive hypotensive effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Verapamil Guanethidine
      Mechanism Antihypertensive agent
Voltage-gated calcium channel  Blocker 		Antihypertensive agent
Noradrenaline transporter  Inducer
      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).
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      Key Mechanism Factor 2
Factor Name Norepinephrine transporter
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Structure Sequence
MLLARMNPQVQPENNGADTGPEQPLRARKTAELLVVKERNGVQCLLAPRDGDAQPRETWGKKIDFLLSVVGFAVDLANVWRFPYLCYKNGGGAFLIPYTLFLIIAGMPLFYMELALGQYNREGAATVWKICPFFKGVGYAVILIALYVGFYYNVIIAWSLYYLFSSFTLNLPWTDCGHTWNSPNCTDPKLLNGSVLGNHTKYSKYKFTPAAEFYERGVLHLHESSGIHDIGLPQWQLLLCLMVVVIVLYFSLWKGVKTSGKVVWITATLPYFVLFVLLVHGVTLPGASNGINAYLHIDFYRLKEATVWIDAATQIFFSLGAGFGVLIAFASYNKFDNNCYRDALLTSSINCITSFVSGFAIFSILGYMAHEHKVNIEDVATEGAGLVFILYPEAISTLSGSTFWAVVFFVMLLALGLDSSMGGMEAVITGLADDFQVLKRHRKLFTFGVTFSTFLLALFCITKGGIYVLTLLDTFAAGTSILFAVLMEAIGVSWFYGVDRFSNDIQQMMGFRPGLYWRLCWKFVSPAFLLFVVVVSIINFKPLTYDDYIFPPWANWVGWGIALSSMVLVPIYVIYKFLSTQGSLWERLAYGITPENEHHLVAQRDIRQFQLQHWLAI
Gene Name SLC6A2
Uniprot ID SC6A2_HUMAN
KEGG Pathway hsa:6530
Protein Family Sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family
Protein Function
Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
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      Mechanism Description
  • Additive hypotensive effects by the combination of Verapamil and Guanethidine 

Recommended Action
      Management Hemodynamic responses should be monitored during coadministration, especially during the first few weeks of therapy. Patients should be advised to take the alpha-blocker at bedtime and to notify their physician if they experience dizziness or syncope while awake.

References
1 McTavish D, Sorkin EM "Verapamil: an updated review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension." Drugs 38 (1989): 19-76. [PMID: 2670511]
2 Pasanisi F, Elliot HL, Meredith PA, McSharry DR, Reid JL "Combined alpha adrenoceptor antagonism and calcium channel blockage in normal subjects." Clin Pharmacol Ther 36 (1984): 716-23
3 Kiss I, Farsang C "Nifedipine-prazosin interaction in patients with essential hypertension." Cardiovasc Drugs Ther 3 (1989): 413-5