Details of the Drug Combination

General Information of Drug Combination (ID: DC612YU)

• Drug Combination Name: Epinephrine + Tranexamic Acid
• Indication: Pain, Postoperative; Status: Phase 4 [1]
• Component Drugs:
  Epinephrine (DM3KJBC): Small molecular drug
  Tranexamic Acid (DMFI8A7): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Epinephrine

Disease Entry	ICD 11	Status	REF
Acute asthma	CA23	Approved	[2]
Allergy	4A80-4A85	Approved	[3]
Anaphylaxis	N.A.	Approved	[2]
Bronchiectasis	CA24	Approved	[2]
Bronchitis	CA20	Approved	[2]
Periodontitis	DA0C	Approved	[2]
Pulmonary emphysema	CA21.Z	Approved	[2]
Severe asthma	CA23	Approved	[2]
Asthma	CA23	Investigative	[2]

Epinephrine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adrenergic receptor beta-1 (ADRB1)	TTR6W5O	ADRB1_HUMAN	Agonist	[7]

Epinephrine Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic cation transporter 3 (SLC22A3)	DT6201N	S22A3_HUMAN	Substrate	[8]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[9]

Epinephrine Interacts with 5 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[10]
Sulfotransferase 1A1 (SULT1A1)	DEYWLRK	ST1A1_HUMAN	Metabolism	[11]
Thiopurine methyltransferase (TPMT)	DEFQ8VO	TPMT_HUMAN	Metabolism	[12]
Catechol O-methyltransferase (COMT)	DEV3T4A	COMT_HUMAN	Metabolism	[13]
Monoamine oxidase type A (MAO-A)	DERE4TU	AOFA_HUMAN	Metabolism	[14]

Epinephrine Interacts with 33 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Catechol O-methyltransferase (COMT)	OTPWKTQG	COMT_HUMAN	Increases Methylation	[15]
Solute carrier family 22 member 3 (SLC22A3)	OTQYGVXX	S22A3_HUMAN	Increases Uptake	[16]
Superoxide dismutase (SOD1)	OT39TA1L	SODC_HUMAN	Increases Expression	[17]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Expression	[17]
Carbonic anhydrase 2 (CA2)	OTJRMUAG	CAH2_HUMAN	Increases Expression	[18]
Integrin alpha-V (ITGAV)	OTAM7JTR	ITAV_HUMAN	Increases Expression	[18]
Cathepsin K (CTSK)	OTT3YX5O	CATK_HUMAN	Increases Expression	[18]
Renin (REN)	OT52GZR2	RENI_HUMAN	Increases Activity	[19]
Insulin (INS)	OTZ85PDU	INS_HUMAN	Decreases Expression	[20]
Beta-2 adrenergic receptor (ADRB2)	OTSDOX4Q	ADRB2_HUMAN	Increases Activity	[21]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Decreases Cleavage	[22]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Increases Expression	[22]
Proliferating cell nuclear antigen (PCNA)	OTHZ1RIA	PCNA_HUMAN	Increases Expression	[22]
Pyruvate kinase PKM (PKM)	OTLHHMC2	KPYM_HUMAN	Increases Expression	[22]
Alpha-1D adrenergic receptor (ADRA1D)	OTW2CD1O	ADA1D_HUMAN	Increases Activity	[23]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Increases Expression	[24]
Alpha-1A adrenergic receptor (ADRA1A)	OTUIWCL5	ADA1A_HUMAN	Increases Activity	[23]
Alpha-1B adrenergic receptor (ADRA1B)	OTSAYAFD	ADA1B_HUMAN	Increases Activity	[23]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[24]
Tumor necrosis factor ligand superfamily member 6 (FASLG)	OTZARCHH	TNFL6_HUMAN	Increases Expression	[24]
Hexokinase-2 (HK2)	OTC0GCQO	HXK2_HUMAN	Increases Expression	[22]
Ephrin type-A receptor 4 (EPHA4)	OT3AMK0C	EPHA4_HUMAN	Increases Phosphorylation	[25]
Hormone-sensitive lipase (LIPE)	OTMMVJ8A	LIPS_HUMAN	Increases Activity	[26]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Expression	[22]
P2X purinoceptor 7 (P2RX7)	OTNJ9XPL	P2RX7_HUMAN	Decreases Activity	[27]
Leptin (LEP)	OT5Q7ODW	LEP_HUMAN	Increases ADR	[28]
Catalase (CAT)	OTHEBX9R	CATA_HUMAN	Decreases Response To Substance	[29]
Sulfotransferase 1A3 (SULT1A4)	OTHJ8WWV	ST1A3_HUMAN	Increases Sulfation	[30]
Glutathione reductase, mitochondrial (GSR)	OTM2TUYM	GSHR_HUMAN	Increases ADR	[28]
Neuron-specific vesicular protein calcyon (CALY)	OTQ7EMPU	CALY_HUMAN	Decreases Secretion	[31]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases ADR	[28]
Equilibrative nucleoside transporter 4 (SLC29A4)	OTWTZXMX	S29A4_HUMAN	Increases Uptake	[16]
Alpha-2A adrenergic receptor (ADRA2A)	OTZFGOTP	ADA2A_HUMAN	Increases ADR	[28]

Indication(s) of Tranexamic Acid

Disease Entry	ICD 11	Status	REF
Excessive bleeding	GA30.02	Approved	[4]
Menorrhagia	GA20.50	Approved	[5]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[6]
Endometriosis	GA10	Investigative	[5]

Tranexamic Acid Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Plasminogen (PLG)	TTP86E2	PLMN_HUMAN	Inhibitor	[32]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Knee Prosthesis	DCUJ71Z	N. A.	Phase 1	[33]

References

• [1] ClinicalTrials.gov (NCT01964781) The Effect of Topical Administration of Common Drugs on Postoperative Bleeding and Pain
• [2] Epinephrine FDA Label
• [3] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 509).
• [4] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6573).
• [5] Tranexamic acid FDA Label
• [6] Tranexamic Acid (TXA) and Corona Virus 2019 (COVID19) in Inpatients (TCInpatient)
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• [9] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
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• [13] Different metabolism of norepinephrine and epinephrine by catechol-O-methyltransferase and monoamine oxidase in rats. J Pharmacol Exp Ther. 1994 Mar;268(3):1242-51.
• [14] Role of monoamine-oxidase-A-gene variation in the development of glioblastoma in males: a case control study. J Neurooncol. 2019 Nov;145(2):287-294.
• [15] Molecular mechanisms controlling the rate and specificity of catechol O-methylation by human soluble catechol O-methyltransferase. Mol Pharmacol. 2001 Feb;59(2):393-402. doi: 10.1124/mol.59.2.393.
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• [21] Myocardial ischaemia and ventricular arrhthymias precipitated by physiological concentrations of adrenaline in patients with coronary artery disease. Br Heart J. 1992 May;67(5):419-20. doi: 10.1136/hrt.67.5.419-b.
• [22] Epinephrine facilitates the growth of T cell lymphoma by altering cell proliferation, apoptosis, and glucose metabolism. Chem Biol Interact. 2023 Jan 5;369:110278. doi: 10.1016/j.cbi.2022.110278. Epub 2022 Nov 22.
• [23] Carvedilol selectively inhibits oscillatory intracellular calcium changes evoked by human alpha1D- and alpha1B-adrenergic receptors. Cardiovasc Res. 2004 Sep 1;63(4):662-72. doi: 10.1016/j.cardiores.2004.05.014.
• [24] Carvedilol prevents epinephrine-induced apoptosis in human coronary artery endothelial cells: modulation of Fas/Fas ligand and caspase-3 pathway. Cardiovasc Res. 2000 Feb;45(3):788-94. doi: 10.1016/s0008-6363(99)00369-7.
• [25] The platelet P2Y12 receptor contributes to granule secretion through Ephrin A4 receptor. Platelets. 2012;23(8):617-25. doi: 10.3109/09537104.2011.645924. Epub 2012 Jan 24.
• [26] Hormone-sensitive lipase in human adipose tissue, isolated adipocytes, and cultured adipocytes. Pediatr Res. 1982 Dec;16(12):982-8. doi: 10.1203/00006450-198212000-00002.
• [27] Epidermal growth factor facilitates epinephrine inhibition of P2X7-receptor-mediated pore formation and apoptosis: a novel signaling network. Endocrinology. 2005 Jan;146(1):164-74. doi: 10.1210/en.2004-1026. Epub 2004 Sep 30.
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• [31] Increased arterial pressure in mice with overexpression of the ADHD candidate gene calcyon in forebrain. PLoS One. 2019 Feb 12;14(2):e0211903. doi: 10.1371/journal.pone.0211903. eCollection 2019.
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• [33] ClinicalTrials.gov (NCT02319915) Evaluation of the Pharmacokinetic Profile of Tranexamic Acid, After Injection in a Knee Neo-articulation.