Details of Drug-Drug Interaction
| Drug General Information (ID: DDI42AY3NW) | |||||||||
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| Drug Name | Labetalol | Drug Info | Guanethidine | Drug Info | |||||
| Drug Type | Small molecule | Small molecule | |||||||
| Therapeutic Class | Antihypertensive Agents | Antihypertensive Agents | |||||||
| Structure | |||||||||
| Mechanism of Labetalol-Guanethidine Interaction (Severity Level: Moderate) | |||||||||
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| Additive hypotensive effects Click to Show/Hide Mechanism Graph | |||||||||
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| Drug Name | Labetalol | Guanethidine | |||||||
| Mechanism 1 |
Antihypertensive agent Alpha-1 adrenergic receptor Antagonist |
Antihypertensive agent Noradrenaline transporter Inducer |
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| Key Mechanism Factor 1 | |||||||||
| 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.
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| Key Mechanism Factor 2 | |||||||||
| Factor Name | Norepinephrine transporter |
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Structure
Sequence
MLLARMNPQVQPENNGADTGPEQPLRARKTAELLVVKERNGVQCLLAPRDGDAQPRETWGKKIDFLLSVVGFAVDLANVWRFPYLCYKNGGGAFLIPYTLFLIIAGMPLFYMELALGQYNREGAATVWKICPFFKGVGYAVILIALYVGFYYNVIIAWSLYYLFSSFTLNLPWTDCGHTWNSPNCTDPKLLNGSVLGNHTKYSKYKFTPAAEFYERGVLHLHESSGIHDIGLPQWQLLLCLMVVVIVLYFSLWKGVKTSGKVVWITATLPYFVLFVLLVHGVTLPGASNGINAYLHIDFYRLKEATVWIDAATQIFFSLGAGFGVLIAFASYNKFDNNCYRDALLTSSINCITSFVSGFAIFSILGYMAHEHKVNIEDVATEGAGLVFILYPEAISTLSGSTFWAVVFFVMLLALGLDSSMGGMEAVITGLADDFQVLKRHRKLFTFGVTFSTFLLALFCITKGGIYVLTLLDTFAAGTSILFAVLMEAIGVSWFYGVDRFSNDIQQMMGFRPGLYWRLCWKFVSPAFLLFVVVVSIINFKPLTYDDYIFPPWANWVGWGIALSSMVLVPIYVIYKFLSTQGSLWERLAYGITPENEHHLVAQRDIRQFQLQHWLAI
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| 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 |
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| Increased risk of bradycardia Click to Show/Hide Mechanism Graph | |||||||||
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| Drug Name | Labetalol | Guanethidine | |||||||
| Mechanism 2 |
Bradycardia Beta adrenergic receptor Antagonist |
Potentiate the bradycardia effect of beta blocker | |||||||
| Key Mechanism Factor 3 | |||||||||
| Factor Name | Adrenergic receptor beta | Structure Sequence | |||||||
| Protein Family | G-protein coupled receptor 1 family | ||||||||
| Protein Function |
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity. Mediates Ras activation through G(s)-alpha- and cAMP-mediated signaling. Involved in the regulation of sleep/wake behaviors (PubMed:31473062).
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| Mechanism Description |
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| Mechanism 3 |
Bradycardia Beta-1 adrenergic receptor Antagonist |
Potentiate the bradycardia effect of beta blocker | |||||||
| Key Mechanism Factor 4 | |||||||||
| Factor Name | Adrenergic receptor beta-1 |
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Structure
Sequence
MGAGVLVLGASEPGNLSSAAPLPDGAATAARLLVPASPPASLLPPASESPEPLSQQWTAGMGLLMALIVLLIVAGNVLVIVAIAKTPRLQTLTNLFIMSLASADLVMGLLVVPFGATIVVWGRWEYGSFFCELWTSVDVLCVTASIETLCVIALDRYLAITSPFRYQSLLTRARARGLVCTVWAISALVSFLPILMHWWRAESDEARRCYNDPKCCDFVTNRAYAIASSVVSFYVPLCIMAFVYLRVFREAQKQVKKIDSCERRFLGGPARPPSPSPSPVPAPAPPPGPPRPAAAAATAPLANGRAGKRRPSRLVALREQKALKTLGIIMGVFTLCWLPFFLANVVKAFHRELVPDRLFVFFNWLGYANSAFNPIIYCRSPDFRKAFQRLLCCARRAARRRHATHGDRPRASGCLARPGPPPSPGAASDDDDDDVVGATPPARLLEPWAGCNGGAAADSDSSLDEPCRPGFASESKV
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| Gene Name | ADRB1 | ||||||||
| Uniprot ID | ADRB1_HUMAN | ||||||||
| KEGG Pathway | hsa:153 | ||||||||
| Protein Family | G-protein coupled receptor 1 family | ||||||||
| Protein Function |
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity. Mediates Ras activation through G(s)-alpha- and cAMP-mediated signaling. Involved in the regulation of sleep/wake behaviors (PubMed:31473062).
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| Mechanism Description |
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| Recommended Action | |||||||||
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| Management | Caution is advised if beta-blockers, including ophthalmic formulations, are prescribed in combination with sympathetic ganglion-blocking or catecholamine-depleting agents. Patients should contact their doctor if they experience dizziness, lightheadedness, syncope, bradycardia, shortness of breath, difficulty breathing, edema, and/or chest pain. | ||||||||