For mild blood pressure elevation, consensus guidelines call for medically supervised lifestyle changes and observation before recommending initiation of drug therapy. However, according to the American Hypertension Association, evidence of sustained damage to the body may be present even prior to observed elevation of blood pressure. Therefore, the use of hypertensive medications may be started in individuals with apparent normal blood pressures but who show evidence of hypertension-related nephropathy, proteinuria, atherosclerotic vascular disease, as well as other evidence of hypertension-related organ damage. If lifestyle changes are ineffective, then drug therapy is initiated, often requiring more than one agent to effectively lower hypertension. Which type of many medications should be used initially for hypertension has been the subject of several large studies and various national guidelines. Considerations include factors such as age, race, and other medical conditions. The largest study, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) in 2002, concluded that chlorthalidone (a thiazide-like diuretic) was as effective as lisinopril (an ACEi) or amlodipine (a calcium channel blocker). (ALLHAT showed that doxazosin, an alpha-adrenergic receptor blocker, had a higher incidence of heart failure events, and the doxazosin arm of the study was stopped.) A subsequent smaller study (ANBP2) did not show the slight advantages in thiazide diuretic outcomes observed in the ALLHAT study, and actually showed slightly better outcomes for ACEis in older white male patients. Thiazide diuretics are 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 ACEis. Subsequently, if dual therapy is required to use an ACEi 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. • Beta blockers can trigger or worsen
psoriasis,
psoriatic arthritis, and
rheumatoid arthritis. •
Benign prostatic hyperplasia may be improved with the use of an
alpha blocker. •
Chronic kidney disease. ACEis or ARBs should be included in the treatment plan to improve kidney outcomes regardless of race or diabetic status. •
Diabetes mellitus. The ACEis and ARBs 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, ACEis, ARBs, 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. ACEis and ARBs are contraindicated in women who are or who intend to become pregnant. • 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, ACEis, 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==