Table 3 Summary of findings
Drug | High sodium diet | Pharmacokinetics | Pharmacodynamics |
|---|---|---|---|
Ca-blockers | 1) Lower clearance nifedipine with African ancestry [46] | 1) Ancestry/age profiling superior to renin in predictingdrug response [38] | |
2) CYP3A4 genotypes sooner at BPgoal†‡ | 2) Ca-blockers effectively block enhanced Ca-dependentvascular contractility, potentially mediated by high CK/lowNO with African ancestry (Figure 2) [11, 12, 72] | ||
3) CYP3A5 genotypes not associated with BP response [17, 24] | 3) Pharmacogenomics: ACE G12269A, C17888T, andG20037A, and variants in the promoter region of theangiotensinogen gene (−217G = > A and–20A = > C), were not associated withBP response to respectively amlodipine and nifidipine [23, 26] | ||
Diuretics | No effect on BP lowering efficacy [70] | No differences found between ancestry groups [33] | 1) No association with plasma renin levels [57, 63, 65, 66], or ancestry/age better predictor of responsethan renin [15, 38] |
2) Diuretics effectively block enhanced sodium retention [86], potentially mediated by high CK in persons ofAfrican ancestry (Figure 3) [11, 12, 73, 87] | |||
3) Pharmacogenomics: greater BP response with AGT 6Aand AT1R 1166A alleles (only women); [30]GNB3T allele associated with greater BP response toHCT (only men); [32]ACE I/D, CYP11B2 C-344 T, RENA7174G [30], STK39[76], α-adducin Gly460Trp, ADRBK1, andGRK5 Gln41Leu [77] not associated with BP response | |||
ACE-i | Lower efficacy with high salt [41] | No association of BP response with CYP3A4 A392G,T16090C, or CYP3A5 A6986G genotypes [17] | 1) Ancestry/age profiling superior to renin in predictingdrug response [38] |
2) Low NO bioavailability may attenuate response(Figure 2) [10, 12, 36, 37, 72, 79–81] | |||
3) Pharmacogenomics: ACE DD poorer response to lisinopril;[28]§ Homozygous ACE G12269A andC17888T faster on BP goal with ramipril than heterozygousgenotypes; [23] AA genotype 217G = > A and–20A= > C, promoter region of theangiotensinogen gene: no significant BP decrease withenalapril or lisinopril [26]. | |||
β-Blockers | No effect on BP lowering efficacy [70] | No consistent differences between persons of African vsEuropean ancestry [44, 45, 52, 55, 56, 59, 61, 64],[67] | 1) Ancestry/age profiling superior to renin in predictingdrug response [15, 38, 53] |
2) High vascular contractility may promote peripheralvasoconstriction with β-adrenergic blockers(Figure 2) [3, 11, 12, 72, 88–92] | |||
3) Pharmacogenomics: ADRB1 Arg 389/Ser 49 associateswith greater, or attenuated BP lowering; [14, 20, 74]GRK4 Ala142Val faster on BP goal with metoprolol(only men); [19]GRK4 Arg65Leu and Ala486Val, GRK5 andGRK2 genotypes not associated with BP response [18, 77] |