Antihypertensive
Patient age, associated clinical conditions and end-organ damage also play a part in determining dosage and type of medication administered.
[5] Although clinical evidence shows calcium channel blockers and thiazide-type diuretics are preferred first-line treatments for most people (from both efficacy and cost points of view), an ACEi is recommended by NICE in the UK for those under 55 years old.
[9] Medications that are classified as potassium-sparing diuretics which block the epithelial sodium channel (ENaC), such as amiloride and triamterene, are seldom prescribed as monotherapy.
[11][12] The 8th Joint National Committee (JNC-8) recommends calcium channel blockers to be a first-line treatment either as monotherapy or in combination with thiazide-type diuretics, ACEis, or ARBs for all patients regardless of age or race.
[7] Results from the ALLHAT trial showed that thiazide-type diuretics and calcium channel blockers were both more effective as monotherapy in improving cardiovascular outcomes compared to ACEis for this subgroup.
[17] Furthermore, ACEis were less effective in reducing blood pressure and had a 51% higher risk of stroke in black hypertensives when used as initial therapy compared to a calcium channel blocker.
[19] Notable side effects of ACEis include dry cough, high blood levels of potassium, fatigue, dizziness, headaches, loss of taste and a risk for angioedema.
[23][24] In the VALUE trial, the ARB valsartan produced a statistically significant 19% (p=0.02) relative increase in the prespecified secondary end point of myocardial infarction (fatal and non-fatal) compared with amlodipine.
[25] The CHARM-alternative trial showed a significant +52% (p=0.025) increase in myocardial infarction with candesartan (versus placebo) despite a reduction in blood pressure.
Recent data suggest that AT2 receptor stimulation may be less beneficial than previously proposed and may even be harmful under certain circumstances through mediation of growth promotion, fibrosis, and hypertrophy, as well as proatherogenic and proinflammatory effects.
Those that block beta-1-adrenergic receptors prevent the binding of endogenous catecholamines (such as epinephrine and norepinephrine), which ultimately reduces blood pressure through decreasing renin and cardiac output release.
[39] Despite lowering blood pressure, alpha blockers have significantly poorer endpoint outcomes than other antihypertensives, and are no longer recommended as a first-line choice in the treatment of hypertension.
Vasodilators act directly on the smooth muscle of arteries to relax their walls so blood can move more easily through them; they are only used in hypertensive emergencies or when other drugs have failed, and even so are rarely given alone.
[41] Sodium nitroprusside, a very potent, short-acting vasodilator, is most commonly used for the quick, temporary reduction of blood pressure in emergencies (such as malignant hypertension or aortic dissection).
[43] They are no longer indicated as first-line therapy for high blood pressure due to side effects and safety concerns, but hydralazine remains a drug of choice in gestational hypertension.
[45][46] Aldosterone receptor antagonists are not recommended as first-line agents for blood pressure,[47] but spironolactone and eplerenone are both used in the treatment of heart failure and resistant hypertension.
[48] Some indirect anti-adrenergics are rarely used in treatment-resistant hypertension: Bosentan belongs to a new class of drugs and works by blocking endothelin receptors.
[49] 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.
[47] In the United States, JNC8 (2014) recommends any drug from one of the four following classes to be a good choice as either initial therapy or as an add-on treatment: thiazide-type diuretics, calcium channel blockers, ACEis, or ARBs.
[50] 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).
[53] 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.
Adverse effects of thiazide diuretics include hypercholesterolemia, and impaired glucose tolerance with increased risk of developing diabetes mellitus type 2.
[7] Hypertensive disorders during pregnancy constitute a significant risk factor for maternal and fetal outcomes, necessitating antihypertensive treatment.
