Five classes of drugs have now been recognized as first line therapy in hypertension. Better reduction of blood pressure is associated with lesser target organ damage. In ALLHAT trial, the incidence of new onset diabetes was higher in those on diuretic, compared to calcium channel blockers and ACE inhibitors. The harmful effects of antihypertensive therapy are on glucose metabolism, lipid metabolism and electrolyte balance. Hypokalemia confers a higher risk of development of diabetes mellitus. Ramipril has been shown to reduce the risk of new onset diabetes. The same has been demonstrated with losartan and valsartan.
Higher doses of diuretics increase LDL and triglyceride. Indapamide is a metabolically neutral diuretic. Electrolyte abnormalities are common with diuretics. In the MRC trial, hypokalemia caused higher incidence of sudden cardiac death due to cardiac arrhythmias. Elderly women are more prone to electrolyte imbalance with diuretics. Effect of diuretics on urate metabolism cause elevation of serum uric acid levels and cause withdrawl of the drug sometimes, though it may not cause clinical gout. Harmful effects of beta blockers by way of increased insulin resistance are less with the newer vasodilatory betablockers. Betablocker-diuretic combination is quite metabolically unfriendly.