Table 3

Summary of findings
Drug High sodium diet Pharmacokinetics Pharmacodynamics
Ca-blockers No effect* on BP lowering efficacy [34,40,41,43] 1) Lower clearance nifedipine with African ancestry [46] 1) Ancestry/age profiling superior to renin in predicting drug response [38]
2) CYP3A4 genotypes sooner at BP goal†‡ 2) Ca-blockers effectively block enhanced Ca-dependent vascular contractility, potentially mediated by high CK/low NO with African ancestry (Figure 2) [11,12,72]
3) CYP3A5 genotypes not associated with BP response [17,24] 3) Pharmacogenomics: ACE G12269A, C17888T, and G20037A, and variants in the promoter region of the angiotensinogen gene (−217G = > A and –20A = > C), were not associated with BP 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 response than renin [15,38]
2) Diuretics effectively block enhanced sodium retention [86], potentially mediated by high CK in persons of African ancestry (Figure 3) [11,12,73,87]
3) Pharmacogenomics: greater BP response with AGT 6A and AT1R 1166A alleles (only women); [30]GNB3T allele associated with greater BP response to HCT (only men); [32]ACE I/D, CYP11B2 C-344 T, REN A7174G [30], STK39[76], α-adducin Gly460Trp, ADRBK1, and GRK5 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 predicting drug 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 and C17888T faster on BP goal with ramipril than heterozygous genotypes; [23] AA genotype 217G = > A and –20A= > C, promoter region of the angiotensinogen gene: no significant BP decrease with enalapril or lisinopril [26].
β-Blockers No effect on BP lowering efficacy [70] No consistent differences between persons of African vs European ancestry [44,45,52,55,56,59,61,64],[67] 1) Ancestry/age profiling superior to renin in predicting drug response [15,38,53]
2) High vascular contractility may promote peripheral vasoconstriction with β-adrenergic blockers (Figure 2) [3,11,12,72,88-92]
3) Pharmacogenomics: ADRB1 Arg 389/Ser 49 associates with greater, or attenuated BP lowering; [14,20,74]GRK4 Ala142Val faster on BP goal with metoprolol (only men); [19]GRK4 Arg65Leu and Ala486Val, GRK5 and GRK2 genotypes not associated with BP response [18,77]

Legend: Diuretics, hydrochlorothiazide (HCT), or other diuretic drug; ACE-i, ACE inhibitors; β-blockers, β-adrenergi c blockers; BP, blood pressure; Ca-blockers, calcium channel blockers; CK, creatine kinase. *At higher drug dose; Pharmacodynamics unclear; Only women/usual BP goal with CYP3A4 A392; or low BP goal with CYP3A4 16090C. §Very modest effect, −0.85 mm Hg systolic (SE 0.51) and −0.50 mm Hg diastolic (SE 0.28).

Brewster and Seedat

Brewster and Seedat BMC Medicine 2013 11:141   doi:10.1186/1741-7015-11-141

Open Data