The Pharmacology of Antihypertensive Drugs: Genetic Variability and Drug Responses

Abstract

Hypertension is a significant global health challenge, affecting over 1.5 billion individuals worldwide and contributing substantially to cardiovascular disease morbidity and mortality. Despite the availability of various antihypertensive drugs, inter-individual variability in drug responses remains a persistent issue, leading to suboptimal blood pressure control and increased risk of adverse outcomes. Genetic polymorphisms have been identified as key factors influencing the pharmacological efficacy of antihypertensive agents, including calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, and diuretics. Single nucleotide polymorphisms (SNPs) in genes encoding drug targets, metabolizing enzymes, and transporters modulate drug responses through diverse mechanisms, such as altering receptor sensitivity, ion transport, and metabolic pathways. Genome-wide association studies have revealed numerous loci associated with blood pressure responses to specific antihypertensive drugs, highlighting the complex genetic architecture underlying hypertension and its treatment. Notably, ethnic variations in drug responses underscore the need for personalized approaches to hypertension management, as exemplified by the differential efficacy of diuretics and calcium channel blockers in Black populations compared to White populations. While these findings provide valuable insights, further research is necessary to refine clinical guidelines and facilitate the integration of pharmacogenomics into routine practice. Addressing the complexities of genetic variability in antihypertensive drug responses will pave the way for optimized and individualized therapeutic strategies, ultimately reducing the prevalence of uncontrolled hypertension and its associated complications.