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Guerra et al. J Transl Genet Genom 2022;6:304-21      https://dx.doi.org/10.20517/jtgg.2022.08                                                                                      Page 314



                          Table 4. Pharmacogenetics of drugs in associated symptoms and neurogenic dysphagia

                          Drug                          Properties                                                                                                      Pharmacogenetics
                                                        Name: Omeprazole                                                                                                Mechanistic genes: ATP4A, AHR, ADH1C, ALDH3A1,
                                                        IUPAC name: 1H-Benzimidazole, 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]                AHR, ATP4A, ATP4B, CASR, CBR1, CFTR, CHRM3,
                                                        Molecular Formula: C H N O S                                                                                    FMO1, HRH2, MMP2, NR1I2, NR1I3, RRAS2, SNAP25,
                                                                           17  19  3  3
                                                        Molecular weight: 345.42 g/mol                                                                                  SSTR2
                                                        Mechanism: Concentrates in acid conditions of parietal cell secretory canaliculi. Forms active sulfenamide metabolite which   Metabolic genes:
                                                        irreversibly binds to and inactivates hydrogen-potassium ATPase (proton or acid pump), blocking final step in secretion of   Substrate: CYP1A1, CYP2C8 (minor), CYP2C9
                                                        hydrochloric acid. Acid secretion is inhibited until additional hydrogen-potassium ATPase is synthesized, resulting in   (minor), CYP2C18 (minor), CYP3A4 (major),
                                                        prolonged duration of action. Suppresses H. pylori in duodenal ulcer and/or reflux esophagitis infected with organism.    CYP2C19 (major), CYP2A6 (minor), CYP2D6 (minor)
                                                        Effect: Antiulcer agents and acid suppressants, proton-pump inhibitors, substituted benzimidazole               Inhibitor: CYP1A2 (moderate), CYP2C9 (moderate),
                                                                                                                                                                        CYP2D6 (moderate), CYP3A4 (moderate), CYP2C19
                                                                                                                                                                        (strong)
                                                                                                                                                                        Inducer: CYP1A1, CYP1A2, CYP1B1, CYP3A4, CYP2B6
                                                                                                                                                                        Transporter genes ABCG2 (inhibitor), ABCC3
                                                                                                                                                                        (inducer), ABCB1, ABCC6 (substrate/inhibitor),
                                                                                                                                                                        ABCC6, UGT1A1

                                                        Name: Pantoprazole                                                                                              Mechanistic genes: ATP4A, DDAH1, ABCC2, CASR,
                                                        IUPAC name: (1) 1H-Benzimidazole, 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl]sulfinyl]           CHRM3, HRH2, IL1B, PPAs, SNAP25, SSTR2
                                                        Molecular Formula: C H F N O S. Molecular weight: 383.37 g/mol                                                  Metabolic genes:
                                                                           16  15 2  3  4
                                                        Action: Suppresses gastric acid secretion by inhibiting parietal cell H+/K+ ATP pump                            Substrate: CYP3A4 (major), CYP2C19, CYP2C19
                                                        Effect: Antiulcer agents and acid suppressants, proton-pump inhibitors, substituted benzimidazole               (major), CYP2D6 (minor), SULTs, UGTs
                                                                                                                                                                        Inhibitor: CYP2C19 (strong),CYP1A2 (weak), CYP2C9
                                                                                                                                                                        (moderate), CYP2D6 (weak), CYP3A4 (moderate)
                                                                                                                                                                        Inducer: CYP1A2, CYP3A4
                                                                                                                                                                        Transporter genes: ABCB1 (substrate/inhibitor),
                                                                                                                                                                        ABCG2 (substrate/Inhibitor), SLC22A8 (inhibitor)

                                                        Name: Lansoprazole                                                                                              Mechanistic genes: ATP4A; CASR, MAPT, CYP1A1,
                                                        IUPAC name: 1H-Benzimidazole, 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfinyl]-             CYP1B1, HRH2, SNAP25, SSTR2
                                                        Molecular Formula: C H F N O S                                                                                  Metabolic genes:
                                                                           16  14 3  3  2
                                                        Molecular Weight: 369.36 g/mol                                                                                  Substrate: CYP2C8 (major), CYP2C9 (major),
                                                        Mechanism: Decreases acid secretion in gastric parietal cells through inhibition of (H +, K +)-ATPase enzyme system, blocking  CYP2C18 (major), CYP2C19 (major), CYP3A4/5
                                                        final step in gastric acid production                                                                           (major); POR
                                                        Effect: Antiulcer agents and acid suppressants, proton-pump inhibitors, substituted benzimidazole               Inhibitor: CYP2C9, (moderate), CYP2C19 (strong),
                                                                                                                                                                        CYP3A4 CYP2D6 (moderate), CYP2E1 (moderate),
                                                                                                                                                                        CYP3A4 (moderate), PPA1
                                                                                                                                                                        Inducer: CYP1A2, CYP1A1, CYP1B1, CYP2C9, CYP3A4
                                                                                                                                                                        Transporter genes: ABCG2 (inhibitor), ABCB1
                                                                                                                                                                        (substrate/inhibitor), SLC22A8 (inhibitor), SLC22A1,
                                                                                                                                                                        SLC22A2, SLC22A3
                                                        Name: Rabeprazole                                                                                               Mechanistic genes: ATP4A, DDAH1, ATP4B, CASR,
                                                        IUPAC name: 1H-Benzimidazole, 2-[[[4-(3-methoxypropoxy)-3-methyl-2-pyridinyl]methyl]sulfinyl]                   CHRM3, HRH2, HTR1D, NR1I2, SNAP25, SSTR2
                                                        Molecular Formula: C H N NaO S                                                                                  Metabolic genes:
                                                                           18  20  3  3
                                                        Molecular weight: 381.42 g/mol                                                                                  Substrate: CYP3A4 (major), CYP2C19 (major),
                                                        Action: Suppresses gastric acid secretion by inhibiting parietal cell H+/K+ ATP pump                            CYP2D6 (major)
                                                        Effect: Antiulcer agents and acid suppressants, proton-pump inhibitors, substituted benzimidazole               Inhibitor: CYP2C9 (moderate), CYP2C8 (moderate),
                                                                                                                                                                        CYP2C19 (strong), CYP2D6 (moderate)
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