Disease Information

General Information of the Disease (ID: DIS00339)

• Name: Dysmenorrhea
• ICD: ICD-11: GA34

Type(s) of Resistant Mechanism of This Disease

  ADTT: Aberration of the Drug's Therapeutic Target

  DISM: Drug Inactivation by Structure Modification

Drug Resistance Data Categorized by Drug

Approved Drug(s) 4 drug(s) in total

Aspirin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Prostaglandin G/H synthase 2 (PTGS2) [1]

• Resistant Disease: Dysmenorrhea [ICD-11: GA34.3]
• Molecule Alteration: SNP; rs20417
• Resistant Drug: Aspirin
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Notably, rs20417 is a SNP in the promoter region of COX-2 associated with aspirin resistance. Further research is needed to determine if the identified SNP have a transcriptional effect contributing to NSAID-resistant dysmenorrhea.

Key Molecule: Prostaglandin-endoperoxide synthase 1 (PTGS1) [1]

• Resistant Disease: Dysmenorrhea [ICD-11: GA34.3]
• Molecule Alteration: SNP; rs10306114
• Resistant Drug: Aspirin
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Genetic polymorphisms have been shown to disrupt COX-1 inhibition with aspirin. For example, Ulehlova et al demonstrated that COX-1 polymorphism rs10306114 was correlated with high platelet aggregation in aspirin-resistant individuals.

Celecoxib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Cytochrome P450 family 2 subfamily C member 9 (CYP2C9) [1]

• Resistant Disease: Dysmenorrhea [ICD-11: GA34.3]
• Molecule Alteration: SNP; CYP2C9*2/*2
• Resistant Drug: Celecoxib
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: For example, the CYP2C9*2/*2 polymorphism was associated with increased total clearance of celecoxib and diclofenac.48 More research is necessary to determine if other gain-of-function variants exist and alter NSAID metabolism.

Diclofenac

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Cytochrome P450 family 2 subfamily C member 9 (CYP2C9) [1]

• Resistant Disease: Dysmenorrhea [ICD-11: GA34.3]
• Molecule Alteration: SNP; CYP2C9*2/*2
• Resistant Drug: Diclofenac
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: For example, the CYP2C9*2/*2 polymorphism was associated with increased total clearance of celecoxib and diclofenac.48 More research is necessary to determine if other gain-of-function variants exist and alter NSAID metabolism.

Valdecoxib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Prostaglandin G/H synthase 2 (Cox-2) [2]

• Resistant Disease: Dysmenorrhea [ICD-11: GA34.3]
• Molecule Alteration: Function; Inhibition
• Resistant Drug: Valdecoxib
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• In Vivo Model: Standard diet fed male C57BL/6J (B6) mouse model; HFD fed male C57BL/6J (B6) mouse model; Mus musculus
• Experiment for Molecule Alteration: Enzyme linked immunosorbent assay; Western blotting analysis
• Mechanism Description: Valdecoxib improves lipid-induced skeletal muscle insulin resistance via simultaneous suppression of inflammation and endoplasmic reticulum stress.

References

• Ref 1: Nonsteroidal antiinflammatory drug resistance in dysmenorrhea: epidemiology, causes, and treatment .Am J Obstet Gynecol. 2018 Apr;218(4):390-400. doi: 10.1016/j.ajog.2017.08.108. Epub 2017 Sep 6. 10.1016/j.ajog.2017.08.108
• Ref 2: Valdecoxib improves lipid-induced skeletal muscle insulin resistance via simultaneous suppression of inflammation and endoplasmic reticulum stress .Biochem Pharmacol. 2021 Jun;188:114557. doi: 10.1016/j.bcp.2021.114557. Epub 2021 Apr 18. 10.1016/j.bcp.2021.114557