Details of the Drug Combination

General Information of Drug Combination (ID: DCDTSG1)

• Drug Combination Name: Heparin + Tramadol
• Indication: Second Degree Burns; Status: Phase 1 [1]
• Component Drugs:
  Heparin (DM4ZP3W): Small molecular drug
  Tramadol (DMRQD04): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Heparin

Disease Entry	ICD 11	Status	REF
Aplastic anemia	3A70	Approved	[2]
Bacteremia	1A73	Approved	[2]
Burns	N.A.	Approved	[2]
Coronary heart disease	BA80.Z	Approved	[2]
Deep vein thrombosis	BD71	Approved	[2]
Disseminated intravascular coagulation	3B20	Approved	[2]
Metabolic disorder	5C50-5D2Z	Approved	[2]
Pneumonia	CA40	Approved	[2]
Pulmonary embolism	BB00	Approved	[2]
Venous thrombosis	BA43	Approved	[3]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[4]
Diabetic angiopathy	BD53.Y	Investigative	[2]

Indication(s) of Tramadol

Disease Entry	ICD 11	Status	REF
Osteoarthritis	FA00-FA05	Approved	[5]
Pain	MG30-MG3Z	Approved	[6]
Chronic pain	MG30	Investigative	[5]
Premature ejaculation	HA03.0Z	Investigative	[5]

Tramadol Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
5-HT 2C receptor (HTR2C)	TTWJBZ5	5HT2C_HUMAN	Modulator	[7]

Tramadol Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[8]

Tramadol Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[9]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[10]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[9]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[9]

Tramadol Interacts with 6 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Steroid 17-alpha-hydroxylase/17,20 lyase (CYP17A1)	OTZKVLVJ	CP17A_HUMAN	Decreases Activity	[11]
L-lactate dehydrogenase A chain (LDHA)	OTN7K4XB	LDHA_HUMAN	Decreases Expression	[12]
Creatine kinase B-type (CKB)	OTUCKOTT	KCRB_HUMAN	Decreases Expression	[12]
NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial (NDUFS1)	OTTIZDFR	NDUS1_HUMAN	Decreases Expression	[12]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Affects Activity	[12]
kinase isozyme 3, mitochondrial (PDK3)	OTCPSTID	PDK3_HUMAN	Increases Expression	[12]

References

• [1] ClinicalTrials.gov (NCT02497326) Heparin for the Treatment of Burn Wound Pain
• [2] Heparin FDA Label
• [3] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 090809.
• [4] Hypothesis for potential pathogenesis of SARS-CoV-2 infection-a review of immune changes in patients with viral pneumonia. Emerg Microbes Infect. 2020 Dec;9(1):727-732.
• [5] Tramadol FDA Label
• [6] 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: 8286).
• [7] The inhibitory effects of tramadol on 5-hydroxytryptamine type 2C receptors expressed in Xenopus oocytes. Anesth Analg. 2004 May;98(5):1401-6, table of contents.
• [8] Tramadol hydrochloride: pharmacokinetics, pharmacodynamics, adverse side effects, co-administration of drugs and new drug delivery systems. Biomed Pharmacother. 2015 Mar;70:234-8.
• [9] Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004;43(13):879-923.
• [10] Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.
• [11] Steroidogenic disruptive effects of the serotonin-noradrenaline reuptake inhibitors duloxetine, venlafaxine and tramadol in the H295R cell assay and in a recombinant CYP17 assay. Toxicol In Vitro. 2018 Mar;47:63-71.
• [12] Comparative study of the neurotoxicological effects of tramadol and tapentadol in SH-SY5Y cells. Toxicology. 2016 Jun 1;359-360:1-10. doi: 10.1016/j.tox.2016.06.010. Epub 2016 Jun 15.