Antihypertensives are a class of

drugs A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via inhalation, injection, smoking, ingestio ...

that are used to treat

hypertension Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...

(high blood pressure). Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as

stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

, heart failure, kidney failure and

myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...

. Evidence suggests that a reduction of

blood pressure Blood pressure (BP) is the pressure of Circulatory system, circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term ...

by 5 mmHg can decrease the risk of stroke by 34% and of ischaemic heart disease by 21%. It can reduce the likelihood of

dementia Dementia is a syndrome associated with many neurodegenerative diseases, characterized by a general decline in cognitive abilities that affects a person's ability to perform activities of daily living, everyday activities. This typically invo ...

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF ...

, and mortality from

cardiovascular disease Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina, heart attack), heart failure, hypertensive heart disease, rheumati ...

. There are many classes of antihypertensives, which lower blood pressure by different means. Among the most important and most widely used medications are thiazide diuretics,

calcium channel blocker Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as ...

s, angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin II receptor blockers or antagonists (ARBs), and

beta blocker Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms ( arrhythmia), and to protect the heart from a second heart attack after a first heart attack ( secondary prevention ...

s. Which type of medication to use initially for hypertension has been the subject of several large studies and resulting national guidelines. The fundamental goal of treatment should be the prevention of the important endpoints of hypertension, such as heart attack, stroke and heart failure. Patient age, associated clinical conditions and end-organ damage also play a part in determining dosage and type of medication administered. The several classes of antihypertensives differ in side effect profiles, ability to prevent endpoints, and cost. The choice of more expensive agents, where cheaper ones would be equally effective, may have negative impacts on national healthcare budgets. As of 2018, the best available

evidence Evidence for a proposition is what supports the proposition. It is usually understood as an indication that the proposition is truth, true. The exact definition and role of evidence vary across different fields. In epistemology, evidence is what J ...

favors low-dose thiazide diuretics as the first-line treatment of choice for high blood pressure when drugs are necessary. 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 Nice ( ; ) is a city in and the prefecture of the Alpes-Maritimes department in France. The Nice agglomeration extends far beyond the administrative city limits, with a population of nearly one million

Diuretic A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics ...

s help the kidneys eliminate excess salt and water from the body's tissues and blood. *

Loop diuretic Loop diuretics are pharmacological agents that primarily inhibit the Na-K-Cl cotransporter located on the luminal membrane of cells along the thick ascending limb of the loop of Henle. They are often used for the treatment of hypertension and e ...

s: ** bumetanide ** ethacrynic acid **

furosemide Furosemide, sold under the brand name Lasix among others, is a loop diuretic medication used to treat edema due to heart failure, liver scarring, or kidney disease. Furosemide may also be used for the treatment of high blood pressure. It can ...

** torsemide *

Thiazide Thiazide () refers to both a class of sulfur-containing organic molecules and a class of diuretics based on the chemical structure of benzothiadiazine. The thiazide drug class was discovered and developed at Merck and Co. in the 1950s. The firs ...

diuretics: ** epitizide **

hydrochlorothiazide Hydrochlorothiazide, sold under the brand name Hydrodiuril among others, is a diuretic medication used to treat hypertension and swelling due to fluid build-up. Other uses include treating diabetes insipidus and renal tubular acidosis and t ...

and chlorothiazide ** bendroflumethiazide ** methyclothiazide ** polythiazide * Thiazide-like diuretics: ** indapamide ** chlorthalidone ** metolazone ** xipamide ** clopamide * Potassium-sparing diuretics: ** amiloride ** triamterene **

spironolactone Spironolactone, sold under the brand name Aldactone among others, is classed as a diuretic medication. It can be used to treat edema, fluid build-up due to hepatic cirrhosis, liver disease or kidney disease. It is also used to reduce risk o ...

** eplerenone In the United States, the JNC8 (Eighth Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) recommends thiazide-type diuretics to be one of the first-line drug treatments for hypertension, either as monotherapy or in combination with calcium channel blockers, ACEis, or ARBs. There are fixed-dose

combination drugs A combination drug is a combination of two or more pharmaceutical drugs as active ingredients combined into a single dosage form, typically as a ''fixed-dose combination'', with each constituent standardized to specifications of a fixed dose. F ...

, such as ACE inhibitor and thiazide combinations. Despite thiazides being cheap and effective, they are not prescribed as often as some newer drugs. This is because they have been associated with increased risk of new-onset diabetes and as such are recommended for use in patients over 65, for whom the risk of new-onset diabetes is outweighed by the benefits of controlling systolic blood pressure. Another theory is that they are off-patent and thus rarely promoted by the drug industry. 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. ENaC blocker medications need stronger public evidence for their blood pressure reducing effect.

Calcium channel blockers

Calcium channel blocker Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as ...

s block the entry of calcium into muscle cells in artery walls, resulting in the relaxation of muscle cells and vasodilation. * dihydropyridines: **

amlodipine Amlodipine, sold under the brand name Norvasc among others, is a calcium channel blocker medication used to treat hypertension, high blood pressure, coronary artery disease (CAD) and variant angina (also called Prinzmetal angina or coronary ar ...

** barnidipine ** cilnidipine ** clevidipine ** felodipine ** isradipine ** lercanidipine ** levamlodipine ** nicardipine ** nifedipine ** nimodipine **

nisoldipine Nisoldipine is a pharmaceutical drug used for the treatment of chronic angina pectoris and hypertension. It is a calcium channel blocker of the dihydropyridine class. It is sold in the United States under the proprietary name Sular. Nisoldipine h ...

** nitrendipine * non-dihydropyridines: **

diltiazem Diltiazem, sold under the brand name Cardizem among others, is a nondihydropyridine calcium channel blocker medication used to treat high blood pressure, angina, and certain heart arrhythmias. It may also be used in hyperthyroidism if beta b ...

** verapamil 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 Thiazide () refers to both a class of sulfur-containing organic molecules and a class of diuretics based on the chemical structure of benzothiadiazine. The thiazide drug class was discovered and developed at Merck and Co. in the 1950s. The firs ...

-type diuretics, ACEis, or ARBs for all patients regardless of age or race. The ratio of CCBs' anti-

proteinuria Proteinuria is the presence of excess proteins in the urine. In healthy persons, urine contains very little protein, less than 150 mg/day; an excess is suggestive of illness. Excess protein in the urine often causes the urine to become fo ...

effect, non-dihydropyridine to dihydropyridine was 30 to −2. The anti-proteinuria effect of non-dihydropyridine is due to better selectivity during glomerular filtration and/or a lower perfusion rate through the renal system. Notable side effects of CCBs include edema, flushing in the face, headache, drowsiness, and dizziness.

ACEis

ACEis inhibit the activity of

angiotensin-converting enzyme Angiotensin-converting enzyme (), or ACE, is a central component of the renin–angiotensin system (RAS), which controls blood pressure by regulating the volume of fluids in the body. It converts the hormone angiotensin I to the active vasocon ...

(ACE), an enzyme responsible for the conversion of angiotensin I into

angiotensin Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adr ...

II, a potent vasoconstrictor. *

captopril Captopril, sold under the brand name Capoten among others, is an ACE inhibitor, angiotensin-converting enzyme (ACE) inhibitor used for the treatment of hypertension and some types of congestive heart failure. Captopril was the first oral ACE inh ...

enalapril Enalapril, sold under the brand name Vasotec among others, is an ACE inhibitor medication used to treat high blood pressure, diabetic kidney disease, and heart failure. For heart failure, it is generally used with a diuretic, such as furosem ...

* fosinopril * lisinopril * moexipril * perindopril * quinapril * ramipril * trandolapril * benazepril A systematic review of 63 trials with over 35,000 participants indicated ACEis significantly reduced doubling of serum creatinine levels compared to other drugs (ARBs, α blockers, β blockers, etc.), and the authors suggested this as a first line of defense. The AASK trial showed that ACEis are more effective at slowing down the decline of

kidney function Assessment of kidney function occurs in different ways, using the presence of symptoms and medical sign, signs, as well as measurements using urine tests, blood tests, and medical imaging. Renal physiology, Functions of a healthy kidney include ...

compared to calcium channel blockers and beta blockers. As such, ACEis should be the drug treatment of choice for patients with

chronic kidney disease Chronic kidney disease (CKD) is a type of long-term kidney disease, defined by the sustained presence of abnormal kidney function and/or abnormal kidney structure. To meet criteria for CKD, the abnormalities must be present for at least three mo ...

regardless of race or diabetic status. However, ACEis (and ARBs) should not be a first-line treatment for black hypertensives without

. Results from the ALLHAT trial showed that

-type diuretics and calcium channel blockers were both more effective as monotherapy in improving cardiovascular outcomes compared to ACEis for this subgroup. 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. There are fixed-dose

, such as ACE inhibitor and thiazide combinations. Notable side effects of ACEis include dry cough, high blood levels of potassium, fatigue, dizziness, headaches, loss of taste and a risk for

angioedema Angioedema is an area of swelling (edema) of the lower layer of skin and tissue just under the skin or mucous membranes. The swelling may occur in the face, tongue, larynx, abdomen, or arms and legs. Often it is associated with hives, which are ...

ARBs

ARBs work by antagonizing the activation of angiotensin receptors. * azilsartan * candesartan *

eprosartan Eprosartan, sold under the brand name Teveten among others, is an angiotensin II receptor antagonist used for the treatment of hypertension, high blood pressure. Eprosartan is sometimes paired with hydrochlorothiazide. As with other angiotensin ...

* irbesartan * losartan * olmesartan * telmisartan * valsartan * fimasartan In 2004, an article in the BMJ examined the evidence for and against the suggestion that ARBs may increase the risk of

(heart attack). The matter was debated in 2006 in the medical journal of the

American Heart Association The American Heart Association (AHA) is a nonprofit organization in the United States that funds cardiovascular medical research, educates consumers on healthy living and fosters appropriate Heart, cardiac care in an effort to reduce disability ...

. There is no consensus on whether ARBs have a tendency to increase MI, but there is also no substantive evidence to indicate that ARBs are able to reduce MI. 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

. 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. As a consequence of AT1 blockade, ARBs increase angiotensin II levels several-fold above baseline by uncoupling a negative-feedback loop. Increased levels of circulating angiotensin II result in unopposed stimulation of the AT2 receptors, which are, in addition upregulated. 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. An ARB happens to be the favorable alternative to an ACEi if a hypertensive patient with the heart-failure type of reduced ejection fraction treated with an ACEi (or ACEis) was intolerant of cough,

other than

hyperkalemia Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0 mmol/L (3.5 and 5.0 mEq/L) with levels above 5.5mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Oc ...

Adrenergic receptor antagonists

Beta-blockers can block beta-1 adrenergic receptors and/or beta-2 adrenergic receptors. 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. Those that block beta-2-adrenergic receptors reduce blood pressure through increased relaxation of smooth muscle. Alpha-blockers can block alpha-1 adrenergic receptors and/or alpha-2 adrenergic receptors. Those that block alpha-1-adrenergic receptors on vascular smooth muscle cells prevent vasoconstriction. Blockade of alpha-2-adrenergic receptors prevents the negative feedback mechanism of norepinephrine (NE). Non-selective alpha-blockers generate a balance whereby alpha-2-blockers release NE to reduce the vasodilation effects induced by alpha-1-blockers. *

Beta blocker Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms ( arrhythmia), and to protect the heart from a second heart attack after a first heart attack ( secondary prevention ...

s ** acebutolol **

atenolol Atenolol is a beta blocker medication primarily used to treat high blood pressure and angina, heart-associated chest pain. Although used to treat high blood pressure, it does not seem to improve mortality rate, mortality in those with the condi ...

** bisoprolol ** betaxolol ** carteolol ** carvedilol ** labetalol ** metoprolol ** nadolol ** nebivolol ** oxprenolol ** penbutolol ** pindolol **

propranolol Propranolol is a medication of the beta blocker class. It is used to treat hypertension, high blood pressure, some types of cardiac dysrhythmia, irregular heart rate, thyrotoxicosis, capillary hemangiomas, akathisia, performance anxiety, and ...

timolol Timolol is a beta blocker medication used either by mouth or as eye drops. As eye drops it is used to treat increased pressure inside the eye such as in ocular hypertension and glaucoma. By mouth it is used for high blood pressure, chest ...

* Alpha blockers: **

doxazosin Doxazosin, sold under the brand name Cardura among others, is a medication used to treat symptoms of benign prostatic hyperplasia (enlarged prostate), hypertension (high blood pressure), and post-traumatic stress disorder (PTSD). For high bloo ...

chlorpromazine Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar d ...

phentolamine Phentolamine, sold under the brand name Regitine among others, is a reversible nonselective α- adrenergic antagonist. Mechanism Its primary action is vasodilation due to α1 blockade. Non-selective α-blockers can cause a much more pronounced ...

** indoramin ** phenoxybenzamine **

prazosin Prazosin, sold under the brand name Minipress among others, is a medication used to treat high blood pressure, symptoms of an enlarged prostate, and nightmares related to post-traumatic stress disorder (PTSD). It is an α1 blocker. It is a les ...

** terazosin **

tolazoline Tolazoline is a non-selective Competitive antagonist, competitive Alpha blocker#Classification, α-adrenergic receptor antagonist. It is a vasodilator that is used to treat spasms of peripheral blood vessels (as in acrocyanosis). It has also been ...

** urapidil * Mixed Alpha + Beta blockers: ** bucindolol ** carvedilol ** labetalol ** clonidine (indirectly) Although

s lower blood pressure, they do not have a positive benefit on endpoints as some other antihypertensives do. In particular, beta-blockers are no longer recommended as first-line treatment due to relative adverse risk of stroke and new-onset of type 2 diabetes when compared to other medications, while certain specific beta-blockers such as

appear to be less useful in overall treatment of hypertension than several other agents. A systematic review of 63 trials with over 35,000 participants indicated β-blockers increased the risk of mortality, compared to other antihypertensive therapies. They do, however, have an important role in the prevention of heart attacks in people who have already had a heart attack. In the United Kingdom, the June 2006 "Hypertension: Management of Hypertension in Adults in Primary Care" guideline of the National Institute for Health and Clinical Excellence, downgraded the role of beta-blockers due to their risk of provoking

type 2 diabetes Type 2 diabetes (T2D), formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent ...

. 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. However, they may be useful for some men with symptoms of prostate disease.

Vasodilators

Vasodilator Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel wal ...

s act directly on the

smooth muscle Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called bec ...

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. 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). Hydralazine and its derivatives are also used in the treatment of severe hypertension, although they should be avoided in emergencies. 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 Gestational hypertension or pregnancy-induced hypertension (PIH) is the development of new hypertension in a pregnant woman after 20 weeks of gestation without the presence of protein in the urine or other signs of pre-eclampsia. Gestational hype ...

Renin inhibitors

Renin comes one level higher than ACE in the

renin–angiotensin system The renin–angiotensin system (RAS), or renin–angiotensin–aldosterone system (RAAS), is a hormone system that regulates blood pressure, fluid, and electrolyte balance, and systemic vascular resistance. When renal blood flow is reduced, ...

. Renin inhibitors can therefore effectively reduce hypertension. Aliskiren (developed by Novartis) is a renin inhibitor which has been approved by the U.S. FDA for the treatment of hypertension.

Aldosterone receptor antagonist

Aldosterone Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays ...

receptor antagonists, also known as mineralocorticoid receptor antagonist (MRA) can lower blood pressure by blocking the binding of aldosterone to the mineralocorticoid receptor. Spironolactone and eplerenone are MRAs that causes a block in the reabsorption of sodium, resulting in a decrease in blood pressure. * eplerenone *

Aldosterone receptor antagonists are not recommended as first-line agents for blood pressure, but spironolactone and eplerenone are both used in the treatment of

and resistant hypertension.

Alpha-2 adrenergic receptor agonists

Central alpha agonists lower blood pressure by stimulating alpha-receptors in the brain which open peripheral arteries easing blood flow. These alpha 2 receptors are known as autoreceptors which provide

negative feedback Negative feedback (or balancing feedback) occurs when some function (Mathematics), function of the output of a system, process, or mechanism is feedback, fed back in a manner that tends to reduce the fluctuations in the output, whether caused ...

in neurotransmission (in this case, the vasoconstriction effects of adrenaline). Central alpha agonists, such as clonidine, are usually prescribed when all other anti-hypertensive medications have failed. For treating hypertension, these drugs are usually administered in combination with a diuretic. * clonidine * guanabenz * guanfacine * methyldopa * moxonidine Adverse effects of this class of drugs include sedation, drying of the nasal mucosa and rebound hypertension upon discontinuation. Some indirect anti-adrenergics are rarely used in treatment-resistant hypertension: * guanethidine replaces norepinephrine in vesicles, decreasing its tonic release * mecamylamine antinicotinic and ganglion blocker *

reserpine Reserpine is a drug that is used for the treatment of hypertension, high blood pressure, usually in combination with a thiazide diuretic or vasodilator. Large clinical trials have shown that combined treatment with reserpine plus a thiazide diur ...

indirect via irreversible VMAT inhibition

Endothelium receptor blockers

Bosentan belongs to a new class of drugs and works by blocking endothelin receptors. It is specifically indicated only for the treatment of

pulmonary artery A pulmonary artery is an artery in the pulmonary circulation that carries deoxygenated blood from the right side of the heart to the lungs. The largest pulmonary artery is the ''main pulmonary artery'' or ''pulmonary trunk'' from the heart, and ...

hypertension in patients with moderate to severe heart failure.

Choice of initial medication

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. 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:

-type diuretics, calcium channel blockers, ACEis, or ARBs. The first large study to show a mortality benefit from antihypertensive treatment was the VA-NHLBI study, which found that chlorthalidone was effective. 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 Hypercholesterolemia, also called high cholesterol, is the presence of high levels of cholesterol in the blood. It is a form of hyperlipidemia (high levels of lipids in the blood), hyperlipoproteinemia (high levels of lipoproteins in the blood), ...

, 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 group An ethnicity or ethnic group is a group of people with shared attributes, which they collectively believe to have, and long-term endogamy. Ethnicities share attributes like language, culture, common sets of ancestry, traditions, society, re ...

s 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.

), 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 Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...

may be improved with the use of beta blockers. *

Asthma Asthma is a common long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wh ...

tics have been reported to have worsening symptoms when using

s. * Beta blockers can trigger or worsen

psoriasis Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by patches of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small localized patches to complete b ...

psoriatic arthritis Psoriatic arthritis (PsA) is a long-term inflammatory arthritis that may occur in some people affected by the autoimmune disease psoriasis. The classic features of psoriatic arthritis include dactylitis (sausage-like swelling of the fingers ...

, and

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...

. *

Benign prostatic hyperplasia Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. Symptoms may include frequent urination, trouble starting to urinate, weak stream, urinary retention, inability t ...

may be improved with the use of an alpha blocker. *

Chronic kidney disease Chronic kidney disease (CKD) is a type of long-term kidney disease, defined by the sustained presence of abnormal kidney function and/or abnormal kidney structure. To meet criteria for CKD, the abnormalities must be present for at least three mo ...

. ACEis 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 Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained hyperglycemia, high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or th ...

. The ACEis and ARBs have been shown to prevent the

kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

and

retina The retina (; or retinas) is the innermost, photosensitivity, light-sensitive layer of tissue (biology), tissue of the eye of most vertebrates and some Mollusca, molluscs. The optics of the eye create a focus (optics), focused two-dimensional ...

l complications of diabetes mellitus. *

Gout Gout ( ) is a form of inflammatory arthritis characterized by recurrent attacks of pain in a red, tender, hot, and Joint effusion, swollen joint, caused by the deposition of needle-like crystals of uric acid known as monosodium urate crysta ...

may be worsened by thiazide diuretics, while losartan reduces serum urate. *

Kidney stone Kidney stone disease (known as nephrolithiasis, renal calculus disease, or urolithiasis) is a crystallopathy and occurs when there are too many minerals in the urine and not enough liquid or hydration. This imbalance causes tiny pieces of cr ...

s 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 Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF ...

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 Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

. 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. * 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, ACEis, or ARBs. *

Tremor A tremor is an involuntary, somewhat rhythmic muscle contraction and relaxation involving neural oscillations, oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the h ...

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

History of Thiazides Chlorothiazide was discovered in 1957, but the first known instance of an effective antihypertensive treatment was in 1947 using primaquine, an antimalarial. History of Calcium Channel Blockers In 1883, Ringer discovered the involvement of calcium for cellular activity on isolated heart. Later in 1901, Stiles reported the same activity in muscle contraction. In the early 1940s, Kamada (from Japan) and Heilbrunn (from the United States) noted how calcium was involved with muscle contractions. In 1964, calcium channel blockers were discovered in Godfraind's laboratory through the screening of coronary dilators, which showed how calcium was blocked from entering artery cells, resulting in vasorelaxation.

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. 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.

References

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