effective, recommended as the best first-line drug for hypertension, and are much more affordable than other therapies, yet they are not prescribed as often as some newer drugs. chlorthalidone is the thiazide drug that is most strongly supported by the evidence as providing a mortality benefit; in the allhat study, a chlorthalidone dose of 12.5 mg was used, with titration up to 25 mg for those subjects who did not achieve blood pressure control at 12.5 mg. chlorthalidone has repeatedly been found to have a stronger effect on lowering blood pressure than hydrochlorothiazide, and hydrochlorothiazide and chlorthalidone have a similar risk of hypokalemia and other adverse effects at the usual doses prescribed in routine clinical practice. patients with an exaggerated hypokalemic response to a low dose of a thiazide diuretic should be suspected to have hyperaldosteronism, a common cause of secondary hypertension. other medications have a role in treating hypertension. adverse effects of thiazide diuretics include hypercholesterolemia, and impaired glucose tolerance with increased risk of developing diabetes mellitus type 2. the thiazide diuretics also deplete circulating potassium unless combined with a potassium-sparing diuretic or supplemental potassium. some authors have challenged thiazides as first line treatment. however, as the merck manual of geriatrics notes, "thiazide-type diuretics are especially safe and effective in the elderly." current uk guidelines suggest starting patients over the age of 55 years and all those of african/afrocaribbean ethnicity firstly on calcium channel blockers or thiazide diuretics, whilst younger patients of other ethnic groups should be started on ace-inhibitors. subsequently, if dual therapy is required to use ace-inhibitor in combination with either a calcium channel blocker or a (thiazide) diuretic. triple therapy is then of all three groups and should the need arise then to add in a fourth agent, to consider either a further diuretic (e.g. spironolactone or furosemide), an alpha-blocker or a beta-blocker. prior to the demotion of beta-blockers as first line agents, the uk sequence of combination therapy used the first letter of the drug classes and was known as the "abcd rule". patient factors the choice between the drugs is to a large degree determined by the characteristics of the patient being prescribed for, the drugs' side effects, and cost. most drugs have other uses; sometimes the presence of other symptoms can warrant the use of one particular antihypertensive. examples include: age can affect the choice of medications. current uk guidelines suggest starting patients over the age of 55 years first on calcium channel blockers or thiazide diuretics. age and multi-morbidity can affect the choice of medication, the target blood pressure and even whether to treat or not. anxiety may be improved with the use of beta blockers. asthmatics have been reported to have worsening symptoms when using beta blockers. benign prostatic hyperplasia may be improved with the use of an alpha blocker. chronic kidney disease. ace inhibitors or arbs should be included in the treatment plan to improve kidney outcomes regardless of race or diabetic status. late-stage dementia should consider deprescribing antihypertensives, according to the medication appropriateness tool for comorbid health conditions in dementia (match-d) diabetes mellitus. the ace inhibitors and angiotensin receptor blockers have been shown to prevent the kidney and retinal complications of diabetes mellitus. gout may be worsened by thiazide diuretics, while losartan reduces serum urate. kidney stones may be improved with the use of thiazide-type diuretics heart block. β-blockers and nondihydropyridine calcium channel blockers should not be used in patients with heart block greater than first degree. jnc8 does not recommend β-blockers as initial therapy for hypertension heart failure may be worsened with nondihydropyridine calcium channel blockers, the alpha blocker doxazosin, and the alpha-2 agonists moxonidine and clonidine. on the other hand, β-blockers, diuretics, ace inhibitors, angiotensin receptor blockers, and aldosterone receptor antagonists have been shown to improve outcome. pregnancy. although α-methyldopa is generally regarded as a first-line agent, labetalol and metoprolol are also acceptable. atenolol has been associated with intrauterine growth retardation, as well as decreased placental growth and weight when prescribed during pregnancy. ace inhibitors and angiotensin ii receptor blockers (arbs) are contraindicated in women who are or who intend to become pregnant. periodontal disease could mitigate the efficacy of antihypertensive drugs. race. jnc8 guidelines particularly point out that when used as monotherapy, thiazide diuretics, and calcium channel blockers have been found to be more effective in reducing blood pressure in black hypertensives than β-blockers, ace inhibitors, or arbs. tremor may warrant the use of beta blockers. the jnc8 guidelines indicate reasons to choose one drug over the others for certain individual patients. antihypertensive medication during the first trimester of pregnancy hypertensive disorders during pregnancy constitute a significant risk factor for maternal and fetal outcomes, necessitating antihypertensive treatment. however, current data concerning the safety of in utero exposure to antihypertensive medication are controversial. while some studies recommend the administration of certain agents, others underline the possible adverse effects on fetal development. in general, a-methyldopa, β-blockers and calcium channel blockers are the first or second treatment line for hypertension during pregnancy. however, aceis, arbs and diuretics are mostly contraindicated, as the potential risk outweighs the benefits of their administration. additionally, several drugs should be avoided, due to the lack of data regarding their safety. women are often concerned about the safety of antihypertensives and as a result, many do not take their treatment as prescribed. shared decision-making aids have been shown to reduce women's uncertainty about taking antihypertensives and increase the number of women taking them as prescribed. history chlorothiazide was discovered in 1957, but the first known instance of an effective antihypertensive treatment was in 1947 using primaquine, an antimalarial. research blood pressure vaccines vaccinations are being trialed and may become a treatment option for high blood pressure in the future. cyt006-angqb was only moderately successful in studies, but similar vaccines are being investigated. withdrawal of anti-hypertensive drugs in older people the latest evidence does not have evidence of an effect due to discontinuing vs continuing medications used for treating elevated blood pressure or prevention of heart disease in older adults on all-case mortality and incidence of heart attack. the findings are based on low quality evidence suggesting it may be safe to stop anti-hypertensive medications. however, older adults should not stop any of their medications without talking to a healthcare professional.