View source for Antihypertensive

{{Short description|Class of drugs used to treat high blood pressure}}
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'''Antihypertensives''' are a class of [[medication|drugs]] that are used to treat [[hypertension]] (high blood pressure).<ref>{{MeshName|Antihypertensive+Agents}}</ref> Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as [[stroke]], heart failure, kidney failure and [[myocardial infarction]]. Evidence suggests that a reduction of [[blood pressure]] by 5&nbsp;mmHg can decrease the risk of stroke by 34% and of [[ischaemic heart disease]] by 21%. It can reduce the likelihood of [[dementia]], [[heart failure]], and [[death|mortality]] from [[cardiovascular disease]].<ref>{{cite journal | vauthors = Law M, Wald N, Morris J | title = Lowering blood pressure to prevent myocardial infarction and stroke: a new preventive strategy | journal = Health Technology Assessment | volume = 7 | issue = 31 | pages = 1–94 | year = 2003 | pmid = 14604498 | doi = 10.3310/hta7310 | doi-access = free }}</ref> There are many classes of antihypertensives, which lower blood pressure by different means. Among the most important and most widely used medications are [[thiazide diuretic]]s, [[calcium channel blocker]]s, [[angiotensin-converting enzyme inhibitor]]s (ACE inhibitors), [[Angiotensin II receptor blocker|angiotensin II receptor blockers or antagonists]] (ARBs), and [[beta blocker]]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 [[clinical endpoint|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.<ref name=nps02>{{cite journal|url=http://www.australianprescriber.com/magazine/33/4/108/12 |title=Drug treatment of elevated blood pressure | vauthors = Nelson M |journal=Australian Prescriber |issue=33 |pages=108–112 |access-date=August 11, 2010 |archive-url=https://web.archive.org/web/20100826074015/http://www.australianprescriber.com/magazine/33/4/108/12 |archive-date=26 August 2010 |url-status=usurped }}</ref> 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.<ref name="budget">{{cite journal | vauthors = Nelson MR, McNeil JJ, Peeters A, Reid CM, Krum H | title = PBS/RPBS cost implications of trends and guideline recommendations in the pharmacological management of hypertension in Australia, 1994-1998 | journal = The Medical Journal of Australia | volume = 174 | issue = 11 | pages = 565–8 | date = June 2001 | pmid = 11453328 | doi = 10.5694/j.1326-5377.2001.tb143436.x | s2cid = 204078909 }}</ref> As of 2018, the best available [[evidence-based medicine|evidence]] favors low-dose thiazide diuretics as the [[first-line treatment]] of choice for high blood pressure when drugs are necessary.<ref name=Cochrane>{{cite journal | vauthors = Wright JM, Musini VM, Gill R | title = First-line drugs for hypertension | journal = The Cochrane Database of Systematic Reviews | volume = 2018 | article-number = CD001841 | date = April 2018 | issue = 4 | pmid = 29667175 | doi = 10.1002/14651858.CD001841.pub3 | veditors = Wright JM | pmc = 6513559 }}</ref> 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.<ref>{{cite web |url=http://www.nice.org.uk/nicemedia/pdf/CG034NICEguideline.pdf |title=Hypertension: Management of hypertension in adults in primary care &#124; Guidance &#124; NICE |date=28 June 2006 |access-date=2012-01-09 |url-status=live |archive-url=https://web.archive.org/web/20120107063630/http://www.nice.org.uk/nicemedia/pdf/CG034NICEguideline.pdf |archive-date=2012-01-07 }}, p19</ref>

==Diuretics==
[[File:Hydrochlorothiazide.png|thumb|[[Hydrochlorothiazide]], a popular [[thiazide]] diuretic]]
[[Diuretic]]s help the kidneys eliminate excess salt and water from the body's tissues and blood.
* [[Loop diuretic]]s:
** [[bumetanide]]
** [[ethacrynic acid]]
** [[furosemide]]
** [[torsemide]]
* [[Thiazide]] diuretics:
** [[epitizide]]
** [[hydrochlorothiazide]] and [[chlorothiazide]]
** [[bendroflumethiazide]]
** [[methyclothiazide]]
** [[polythiazide]]
* [[Thiazide-like diuretic]]s:
** [[indapamide]]
** [[chlorthalidone]]
** [[metolazone]]
** [[xipamide]]
** [[clopamide]]
* [[Potassium-sparing diuretics]]:
** [[amiloride]]
** [[triamterene]]
** [[spironolactone]]
** [[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.<ref name=JNC8 /> There are fixed-dose [[combination drugs]], such as [[ACE inhibitor and thiazide combination]]s. 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.<ref name="ahg2008">{{cite journal | vauthors = Zillich AJ, Garg J, Basu S, Bakris GL, Carter BL | title = Thiazide diuretics, potassium, and the development of diabetes: a quantitative review | journal = Hypertension | volume = 48 | issue = 2 | pages = 219–24 | date = August 2006 | pmid = 16801488 | doi = 10.1161/01.HYP.0000231552.10054.aa | doi-access = free }}</ref> Another theory is that they are off-patent and thus rarely promoted by the drug industry.<ref name="promotion">{{cite journal | vauthors = Wang TJ, Ausiello JC, Stafford RS | title = Trends in antihypertensive drug advertising, 1985-1996 | journal = Circulation | volume = 99 | issue = 15 | pages = 2055–7 | date = April 1999 | pmid = 10209012 | doi = 10.1161/01.CIR.99.15.2055 | doi-access = free }}</ref> 

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.<ref>{{cite journal | vauthors = Heran BS, Chen JM, Wang JJ, Wright JM | title = Blood pressure lowering efficacy of potassium-sparing diuretics (that block the epithelial sodium channel) for primary hypertension | journal = The Cochrane Database of Systematic Reviews | volume = 2012 | article-number = CD008167 | date = November 2012 | issue = 11 | pmid = 23152254 | doi = 10.1002/14651858.CD008167.pub3 | collaboration = Cochrane Hypertension Group | pmc = 11380160 }}</ref>

==Calcium channel blockers==
[[Calcium channel blocker]]s block the entry of calcium into muscle cells in artery walls, resulting in the relaxation of muscle cells and vasodilation.<ref name="Elliott_2011">{{cite journal | vauthors = Elliott WJ, Ram CV | title = Calcium channel blockers | journal = Journal of Clinical Hypertension | volume = 13 | issue = 9 | pages = 687–689 | date = September 2011 | pmid = 21896151 | pmc = 8108866 | doi = 10.1111/j.1751-7176.2011.00513.x }}</ref><ref>{{cite book | chapter = Calcium Channel Blockers |date=2012 | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK548577/ | title = LiverTox: Clinical and Research Information on Drug-Induced Liver Injury |access-date=2023-12-22 |place=Bethesda (MD) |publisher=National Institute of Diabetes and Digestive and Kidney Diseases |pmid=31643892}}</ref>
* [[dihydropyridine]]s:
** [[amlodipine]]
** [[barnidipine]]
** [[cilnidipine]]
** [[clevidipine]]
** [[felodipine]]
** [[isradipine]]
** [[lercanidipine]]
** [[levamlodipine]]
** [[nicardipine]]
** [[nifedipine]]
** [[nimodipine]]
** [[nisoldipine]]
** [[nitrendipine]]
* non-dihydropyridines:
** [[diltiazem]]
** [[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]]-type diuretics, ACEis, or ARBs for all patients regardless of age or race.<ref name=JNC8>{{cite journal | vauthors = James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, Lackland DT, LeFevre ML, MacKenzie TD, Ogedegbe O, Smith SC, Svetkey LP, Taler SJ, Townsend RR, Wright JT, Narva AS, Ortiz E | title = 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8) | journal = JAMA | volume = 311 | issue = 5 | pages = 507–20 | date = February 2014 | pmid = 24352797 | doi = 10.1001/jama.2013.284427 | doi-access = free }}</ref>

The ratio of CCBs' anti-[[proteinuria]] effect, non-dihydropyridine to dihydropyridine was 30 to −2.<ref name="Bakris Weir Secic Campbell 2004 pp. 1991–2002">{{cite journal | vauthors = Bakris GL, Weir MR, Secic M, Campbell B, Weis-McNulty A | title = Differential effects of calcium antagonist subclasses on markers of nephropathy progression | journal = Kidney International | volume = 65 | issue = 6 | pages = 1991–2002 | date = June 2004 | pmid = 15149313 | doi = 10.1111/j.1523-1755.2004.00620.x | doi-access = free }}</ref> 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.<ref name="Elliott_2011" />

Notable side effects of CCBs include edema, flushing in the face, headache, drowsiness, and dizziness.<ref name="Elliott_2011" />

==ACEis==
[[File:Captopril skeletal.svg|thumb|[[Captopril]], the prototypical ACEi]]
ACEis inhibit the activity of [[angiotensin-converting enzyme]] (ACE), an enzyme responsible for the conversion of angiotensin I into [[angiotensin]] II, a potent [[vasoconstrictor]].<ref>{{cite book | vauthors = Spiller HA | chapter = ACE Inhibitors |date= January 2005 | title = Encyclopedia of Toxicology |pages=9–11 | edition = Second | veditors = Wexler P | chapter-url = https://www.sciencedirect.com/science/article/pii/B0123694000000065 |access-date=2024-03-13 |place=New York |publisher=Elsevier |doi=10.1016/b0-12-369400-0/00006-5 |isbn=978-0-12-369400-3}}</ref>
* [[captopril]]
* [[enalapril]]
* [[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.<ref name = "wu" /> The AASK trial showed that ACEis are more effective at slowing down the decline of [[kidney function]] compared to [[calcium channel blockers]] and [[beta blockers]].<ref name="AASK">{{cite journal | vauthors = Wright JT, Bakris G, Greene T, Agodoa LY, Appel LJ, Charleston J, Cheek D, Douglas-Baltimore JG, Gassman J, Glassock R, Hebert L, Jamerson K, Lewis J, Phillips RA, Toto RD, Middleton JP, Rostand SG | title = Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial | journal = JAMA | volume = 288 | issue = 19 | pages = 2421–31 | date = November 2002 | pmid = 12435255 | doi = 10.1001/jama.288.19.2421 | doi-access = free }}</ref> As such, ACEis should be the drug treatment of choice for patients with [[chronic kidney disease]] regardless of race or diabetic status.<ref name=JNC8 />

However, ACEis (and ARBs) should not be a first-line treatment for black hypertensives without [[chronic kidney disease]].<ref name=JNC8 /> Results from the [[Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial|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.<ref name=allhat /> 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.<ref>{{cite journal|author5-link=Barry R. Davis | vauthors = Leenen FH, Nwachuku CE, Black HR, Cushman WC, Davis BR, Simpson LM, Alderman MH, Atlas SA, Basile JN, Cuyjet AB, Dart R, Felicetta JV, Grimm RH, Haywood LJ, Jafri SZ, Proschan MA, Thadani U, Whelton PK, Wright JT | title = Clinical events in high-risk hypertensive patients randomly assigned to calcium channel blocker versus ACEi in the antihypertensive and lipid-lowering treatment to prevent heart attack trial | journal = Hypertension | volume = 48 | issue = 3 | pages = 374–84 | date = September 2006 | pmid = 16864749 | doi = 10.1161/01.HYP.0000231662.77359.de | doi-access = free }}</ref> There are fixed-dose [[combination drugs]], such as [[ACE inhibitor and thiazide combination]]s.<ref>{{cite journal | vauthors = Borghi C, Soldati M, Bragagni A, Cicero AF | title = Safety implications of combining ACEis with thiazides for the treatment of hypertensive patients | journal = Expert Opinion on Drug Safety | volume = 19 | issue = 12 | pages = 1577–1583 | date = December 2020 | pmid = 33047990 | doi = 10.1080/14740338.2020.1836151 | s2cid = 222320206 }}</ref>

Notable side effects of ACEis include [[dry cough]], [[hyperkalemia|high blood levels of potassium]], fatigue, dizziness, headaches, loss of taste and a risk for [[angioedema]].<ref>{{cite web|url=http://www.mayoclinic.org/diseases-conditions/high-blood-pressure/in-depth/ace-inhibitors/art-20047480?pg=2|title=High blood pressure (hypertension) - Uses for ACE inhibitors|website=[[Mayo Clinic]]|access-date=2016-07-27|url-status=live|archive-url=https://web.archive.org/web/20160801120145/http://www.mayoclinic.org/diseases-conditions/high-blood-pressure/in-depth/ace-inhibitors/art-20047480?pg=2|archive-date=2016-08-01}} Page updated: June 29, 2016</ref>

==ARBs==
[[File:Valsartan.svg|thumb|[[Valsartan]], an ARB]]
ARBs work by [[receptor antagonist|antagonizing]] the activation of [[angiotensin receptor]]s.<ref>{{cite journal | vauthors = Barreras A, Gurk-Turner C | title = Angiotensin II receptor blockers | journal = Proceedings | volume = 16 | issue = 1 | pages = 123–126 | date = January 2003 | pmid = 16278727 | pmc = 1200815 | doi = 10.1080/08998280.2003.11927893 }}</ref>
* [[azilsartan]]
* [[candesartan]]
* [[eprosartan]]
* [[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 [[myocardial infarction]] (heart attack).<ref name="BMJ1">{{cite journal | vauthors = Verma S, Strauss M | title = Angiotensin receptor blockers and myocardial infarction | journal = BMJ | volume = 329 | issue = 7477 | pages = 1248–9 | date = November 2004 | pmid = 15564232 | pmc = 534428 | doi = 10.1136/bmj.329.7477.1248 }}</ref> The matter was debated in 2006 in the medical journal of the [[American Heart Association]]. 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.<ref name="Circ1">{{cite journal | vauthors = Strauss MH, Hall AS | title = Angiotensin receptor blockers may increase risk of myocardial infarction: unraveling the ARB-MI paradox | journal = Circulation | volume = 114 | issue = 8 | pages = 838–54 | date = August 2006 | pmid = 16923768 | doi = 10.1161/CIRCULATIONAHA.105.594986 | doi-access = free }}</ref><ref name="Circ2">{{cite journal | vauthors = Tsuyuki RT, McDonald MA | title = Angiotensin receptor blockers do not increase risk of myocardial infarction | journal = Circulation | volume = 114 | issue = 8 | pages = 855–60 | date = August 2006 | pmid = 16923769 | doi = 10.1161/CIRCULATIONAHA.105.594978 | doi-access = free }}</ref>

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]].<ref name="Lancet1">
{{cite journal | vauthors = Julius S, Kjeldsen SE, Weber M, Brunner HR, Ekman S, Hansson L, Hua T, Laragh J, McInnes GT, Mitchell L, Plat F, Schork A, Smith B, Zanchetti A | title = Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial | journal = Lancet | volume = 363 | issue = 9426 | pages = 2022–31 | date = June 2004 | pmid = 15207952 | doi = 10.1016/S0140-6736(04)16451-9 | s2cid = 19111421 | hdl = 11392/462725 | hdl-access = free }}</ref>

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.<ref name="Lancet2">
{{cite journal | vauthors = Granger CB, McMurray JJ, Yusuf S, Held P, Michelson EL, Olofsson B, Ostergren J, Pfeffer MA, Swedberg K | title = Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial | journal = Lancet | volume = 362 | issue = 9386 | pages = 772–6 | date = September 2003 | pmid = 13678870 | doi = 10.1016/S0140-6736(03)14284-5 | s2cid = 5650345 }}</ref>

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.<ref name="AJH1">
{{cite journal | vauthors = Levy BI | title = How to explain the differences between renin angiotensin system modulators | journal = American Journal of Hypertension | volume = 18 | issue = 9 Pt 2 | pages = 134S–141S | date = September 2005 | pmid = 16125050 | doi = 10.1016/j.amjhyper.2005.05.005 | doi-access = free }}</ref><ref name="Circ23">
{{cite journal | vauthors = Lévy BI | title = Can angiotensin II type 2 receptors have deleterious effects in cardiovascular disease? Implications for therapeutic blockade of the renin-angiotensin system | journal = Circulation | volume = 109 | issue = 1 | pages = 8–13 | date = January 2004 | pmid = 14707017 | doi = 10.1161/01.CIR.0000096609.73772.C5 | doi-access = free }}</ref><ref name="CircHyp43">
{{cite journal | vauthors = Reudelhuber TL | title = The continuing saga of the AT2 receptor: a case of the good, the bad, and the innocuous | journal = Hypertension | volume = 46 | issue = 6 | pages = 1261–2 | date = December 2005 | pmid = 16286568 | doi = 10.1161/01.HYP.0000193498.07087.83 | doi-access = free }}</ref>

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, [[angioedema]] other than [[hyperkalemia]] or [[chronic kidney disease]].<ref name="Yusuf Pitt Davis Hood 1991 pp. 293–302">{{cite journal | vauthors = Yusuf S, Pitt B, Davis CE, Hood WB, Cohn JN | title = Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure | journal = The New England Journal of Medicine | volume = 325 | issue = 5 | pages = 293–302 | date = August 1991 | pmid = 2057034 | doi = 10.1056/nejm199108013250501 | doi-access = free }}</ref><ref name="ACC/AHA/HFSA 2016">{{cite journal | vauthors = Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Colvin MM, Drazner MH, Filippatos G, Fonarow GC, Givertz MM, Hollenberg SM, Lindenfeld J, Masoudi FA, McBride PE, Peterson PN, Stevenson LW, Westlake C | title = 2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America | journal = Circulation | volume = 134 | issue = 13 | pages = e282-93 | date = September 2016 | pmid = 27208050 | doi = 10.1161/CIR.0000000000000435 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Li EC, Heran BS, Wright JM | title = Angiotensin converting enzyme (ACE) inhibitors versus angiotensin receptor blockers for primary hypertension | journal = The Cochrane Database of Systematic Reviews | volume = 2014 | issue = 8 | article-number = CD009096 | date = August 2014 | pmid = 25148386 | pmc = 6486121 | doi = 10.1002/14651858.CD009096.pub2 }}</ref>

==Adrenergic receptor antagonists==
[[File:Propranolol.svg|thumb|[[Propranolol]], the first beta-blocker to be successfully developed]]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.<ref>{{Citation | vauthors = Farzam K, Jan A |title=Beta Blockers |date=2023 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK532906/ |access-date=2024-01-21 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30422501 }}</ref>

Alpha-blockers can block alpha-1 adrenergic receptors and/or alpha-2 adrenergic receptors.<ref name="Nachawati_2023">{{cite book | vauthors = Nachawati D, Patel JB | chapter = Alpha-Blockers |date=2023 | title = StatPearls | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK556066/ |access-date=2024-01-21 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=32310526 }}</ref>  Those that block alpha-1-adrenergic receptors on vascular smooth muscle cells prevent vasoconstriction.<ref name="Nachawati_2023" />  Blockade of alpha-2-adrenergic receptors prevents the negative feedback mechanism of norepinephrine (NE).<ref name="Nachawati_2023" />  Non-selective alpha-blockers generate a balance whereby alpha-2-blockers release NE to reduce the vasodilation effects induced by alpha-1-blockers.<ref name="Nachawati_2023" />
* [[Beta blocker]]s
** [[acebutolol]]
** [[atenolol]]
** [[bisoprolol]]
** [[betaxolol]]
** [[carteolol]]
** [[carvedilol]]
** [[labetalol]]
** [[metoprolol]]
** [[nadolol]]
** [[nebivolol]]
** [[oxprenolol]]
** [[penbutolol]]
** [[pindolol]]
** [[propranolol]]
** [[timolol]]
* [[Alpha blocker]]s:
** [[doxazosin]]
** [[chlorpromazine]]
** [[phentolamine]]
** [[indoramin]]
** [[phenoxybenzamine]]
** [[prazosin]]
** [[terazosin]]
** [[tolazoline]]
** [[urapidil]]
* Mixed Alpha + Beta blockers:
** [[bucindolol]]
** [[carvedilol]]
** [[labetalol]]
** [[clonidine]] (indirectly)

Although [[beta blocker]]s lower blood pressure, they do not have a positive benefit on endpoints as some other antihypertensives do.<ref name="betablockers">{{cite journal | vauthors = Lindholm LH, Carlberg B, Samuelsson O | title = Should beta blockers remain first choice in the treatment of primary hypertension? A meta-analysis | journal = Lancet | volume = 366 | issue = 9496 | pages = 1545–53 | date = 29 Oct – 4 Nov 2005 | pmid = 16257341 | doi = 10.1016/S0140-6736(05)67573-3 | s2cid = 34364430 }}</ref> 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,<ref name=nps02 /> while certain specific beta-blockers such as [[atenolol]] appear to be less useful in overall treatment of hypertension than several other agents.<ref name="atenolol">{{cite journal | vauthors = Carlberg B, Samuelsson O, Lindholm LH | title = Atenolol in hypertension: is it a wise choice? | journal = Lancet | volume = 364 | issue = 9446 | pages = 1684–9 | date = 6–12 Nov 2004 | pmid = 15530629 | doi = 10.1016/S0140-6736(04)17355-8 | s2cid = 23759357 }}</ref> A systematic review of 63 trials with over 35,000 participants indicated β-blockers increased the risk of mortality, compared to other antihypertensive therapies.<ref name=wu>{{cite journal | vauthors = Wu HY, Huang JW, Lin HJ, Liao WC, Peng YS, Hung KY, Wu KD, Tu YK, Chien KL | title = Comparative effectiveness of renin-angiotensin system blockers and other antihypertensive drugs in patients with diabetes: systematic review and bayesian network meta-analysis | journal = BMJ | volume = 347 | article-number = f6008 | date = October 2013 | pmid = 24157497 | pmc = 3807847 | doi = 10.1136/bmj.f6008 }}</ref> They do, however, have an important role in the prevention of heart attacks in people who have already had a heart attack.<ref name="bbmi">{{cite journal | vauthors = Freemantle N, Cleland J, Young P, Mason J, Harrison J | title = beta Blockade after myocardial infarction: systematic review and meta regression analysis | journal = BMJ | volume = 318 | issue = 7200 | pages = 1730–7 | date = June 1999 | pmid = 10381708 | pmc = 31101 | doi = 10.1136/bmj.318.7200.1730 }}</ref> In the United Kingdom, the June 2006 "Hypertension: Management of Hypertension in Adults in Primary Care"<ref>{{cite web|title=Hypertension: management of hypertension in adults in primary care |url=http://www.nice.org.uk/download.aspx?o=CG034quickrefguide |format=PDF |publisher=[[National Institute for Health and Clinical Excellence]] |access-date=2006-09-30 |archive-url=https://web.archive.org/web/20070216204848/http://www.nice.org.uk/download.aspx?o=CG034quickrefguide |archive-date=2007-02-16 }}</ref> 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]].<ref>{{cite web | vauthors = Ladva S | title=NICE and BHS launch updated hypertension guideline | url=http://www.nelm.nhs.uk/Record%20Viewing/viewRecord.aspx?id=567178 | archive-url=https://web.archive.org/web/20070929210400/http://www.nelm.nhs.uk/Record%20Viewing/viewRecord.aspx?id=567178 | archive-date=2007-09-29 | date=2006-06-28 | publisher=[[National Institute for Health and Clinical Excellence]] | access-date=2006-09-30 }}</ref>

Despite lowering blood pressure, [[alpha blocker]]s have significantly poorer endpoint outcomes than other antihypertensives, and are no longer recommended as a first-line choice in the treatment of hypertension.<ref name="alpha">{{cite journal | author = ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group | title = Diuretic versus alpha-blocker as first-step antihypertensive therapy: final results from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) | journal = Hypertension | volume = 42 | issue = 3 | pages = 239–46 | date = September 2003 | pmid = 12925554 | doi = 10.1161/01.HYP.0000086521.95630.5A | doi-access = free }}</ref>
However, they may be useful for some men with symptoms of [[benign prostatic hyperplasia|prostate disease]].

==Vasodilators==
[[Vasodilator]]s 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 emergency|hypertensive emergencies]] or when other drugs have failed, and even so are rarely given alone.<ref>{{cite book | vauthors = Hariri L, Patel JB | chapter = Vasodilators |date=2024 | title = StatPearls | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK554423/ |access-date=2024-03-16 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=32119310 }}</ref>

[[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]]).<ref name=Brunton>{{cite book |vauthors=Brunton L, Parker K, Blumenthal D, Buxton I |title=Goodman & Gilman's Manual of Pharmacology and Therapeutics |year=2007 |publisher=[[McGraw-Hill]] |location=New York |isbn=978-0-07-144343-2 |pages=544–60 |chapter=Therapy of hypertension}}</ref><ref name=Varon>{{cite journal | vauthors = Varon J, Marik PE | title = The diagnosis and management of hypertensive crises | journal = Chest | volume = 118 | issue = 1 | pages = 214–27 | date = July 2000 | pmid = 10893382 | doi = 10.1378/chest.118.1.214}}</ref> [[Hydralazine]] and its derivatives are also used in the treatment of severe hypertension, although they should be avoided in emergencies.<ref name=Varon/> 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]].<ref name=Brunton/>

==Renin inhibitors==
[[Renin]] comes one level higher than ACE in the [[renin–angiotensin system]]. [[Renin inhibitor]]s 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.<ref>{{cite web| vauthors = Mehta A |title=Direct Renin Inhibitors as Antihypertensive Drugs|url=http://pharmaxchange.info/press/2011/01/direct-renin-inhibitors-as-antihypertensive-drugs/|access-date=6 February 2014|date=January 1, 2011|url-status=live|archive-url=https://web.archive.org/web/20140221232314/http://pharmaxchange.info/press/2011/01/direct-renin-inhibitors-as-antihypertensive-drugs/|archive-date=21 February 2014}}</ref>

==Aldosterone receptor antagonist==
[[Aldosterone]] 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.<ref>{{cite journal | vauthors = Craft J | title = Eplerenone (Inspra), a new aldosterone antagonist for the treatment of systemic hypertension and heart failure | journal = Proceedings | volume = 17 | issue = 2 | pages = 217–220 | date = April 2004 | pmid = 16200104 | pmc = 1200656 | doi = 10.1080/08998280.2004.11927973 }}</ref><ref>{{cite book | vauthors = Patibandla S, Heaton J, Kyaw H | chapter = Spironolactone |date=2024 | title = StatPearls | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK554421/ |access-date=2024-03-16 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=32119308 }}</ref>
* [[eplerenone]]
* [[spironolactone]]

Aldosterone receptor antagonists are not recommended as first-line agents for blood pressure,<ref name="jnc7">{{cite journal | vauthors = Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jones DW, Materson BJ, Oparil S, Wright JT, Roccella EJ | title = The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report | journal = JAMA | volume = 289 | issue = 19 | pages = 2560–72 | date = May 2003 | pmid = 12748199 | doi = 10.1001/jama.289.19.2560 }}</ref> but spironolactone and eplerenone are both used in the treatment of [[heart failure]] 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 adrenergic receptor|alpha 2 receptors]] are known as [[autoreceptors]] which provide [[negative feedback]] 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.<ref>{{cite journal | vauthors = Giovannitti JA, Thoms SM, Crawford JJ | title = Alpha-2 adrenergic receptor agonists: a review of current clinical applications | journal = Anesthesia Progress | volume = 62 | issue = 1 | pages = 31–39 | date = 2015 | pmid = 25849473 | pmc = 4389556 | doi = 10.2344/0003-3006-62.1.31 }}</ref>

Some indirect anti-adrenergics are rarely used in treatment-resistant hypertension:
* [[guanethidine]]{{snd}} replaces norepinephrine in vesicles, decreasing its [[Tonic (physiology)|tonic]] release
* [[mecamylamine]]{{snd}} [[antinicotinic]] and ganglion blocker
* [[reserpine]]{{snd}} 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]] hypertension in patients with moderate to severe heart failure.<ref>{{cite journal | vauthors = Valerio CJ, Coghlan JG | title = Bosentan in the treatment of pulmonary arterial hypertension with the focus on the mildly symptomatic patient | journal = Vascular Health and Risk Management | volume = 5 | pages = 607–619 | date = August 2009 | pmid = 19688101 | pmc = 2725793 | doi = 10.2147/VHRM.S4713 | doi-access = free }}</ref>

==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.<ref name="jnc7" /> 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.<ref name=JNC8 />

The first large study to show a mortality benefit from antihypertensive treatment was the VA-NHLBI study, which found that chlorthalidone was effective.<ref>{{cite journal | pmid=360921 | date=1978 | title=Evaluation of drug treatment in mild hypertension: VA-NHLBI feasibility trial. Plan and preliminary results of a two-year feasibility trial for a multicenter intervention study to evaluate the benefits versus the disadvantages of treating mild hypertension. | vauthors = Neurath Jr HM, Goldman AI, Lavin MA, Schnaper HW, Fitz AE, Frohlich ED, Steele B, Richman HG | collaboration = Veterans Administration-National Heart, Lung, and Blood Institute Study Group for Evaluating Treatment in Mild Hypertension | journal=Annals of the New York Academy of Sciences | volume=304 | pages=267–292 | doi=10.1111/j.1749-6632.1978.tb25604.x | s2cid=40939559 }}</ref> 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).<ref name="allhat">{{cite journal | vauthors = Furberg CD, Wright Jr JT, Davis BR, Cutler JA, Alderman M, Black H, etal | title = Major outcomes in high-risk hypertensive patients randomized to ACEi or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) | journal = JAMA | volume = 288 | issue = 23 | pages = 2981–97 | date = December 2002 | pmid = 12479763 | doi = 10.1001/jama.288.23.2981 | collaboration = The Allhat Officers And Coordinators For The Allhat Collaborative Research Group | doi-access = free }}</ref> (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.<ref name="anbp2">{{cite journal | vauthors = Wing LM, Reid CM, Ryan P, Beilin LJ, Brown MA, Jennings GL, Johnston CI, McNeil JJ, Macdonald GJ, Marley JE, Morgan TO, West MJ | title = A comparison of outcomes with ACEis and diuretics for hypertension in the elderly | journal = The New England Journal of Medicine | volume = 348 | issue = 7 | pages = 583–92 | date = February 2003 | pmid = 12584366 | doi = 10.1056/NEJMoa021716 | url = http://espace.library.uq.edu.au/view/UQ:67786/UQ67786_OA.pdf | hdl = 2440/4230 | hdl-access = free }}</ref>

Thiazide diuretics are effective, recommended as the best first-line drug for hypertension,<ref>{{cite journal |vauthors=Whelton PK, Williams B |title=The 2018 European Society of Cardiology/European Society of Hypertension and 2017 American College of Cardiology/American Heart Association Blood Pressure Guidelines: More Similar Than Different |journal=JAMA |volume=320 |issue=17 |pages=1749–1750 |date=November 2018 |pmid=30398611 |doi=10.1001/jama.2018.16755 |s2cid=53207044 }}</ref> 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&nbsp;mg was used, with titration up to 25&nbsp;mg for those subjects who did not achieve blood pressure control at 12.5&nbsp;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.<ref>{{cite web | vauthors = Watson K | date = 18 May 2016 | title = Which Thiazide-Type Diuretic Should be First-Line in Patients with Hypertension? | url = https://blogs.pharmacy.umaryland.edu/atrium/2016/05/18/which-thiazide-type-diuretic-should-be-first-line-in-patients-with-hypertension/ | work = University of Maryland School of Pharmacy }}</ref> 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.<ref>{{cite web | veditors = Oiseth S, Jones L, Maza E|url=https://www.lecturio.com/concepts/hyperaldosteronism/| title=Hyperaldosteronism|website=The Lecturio Medical Concept Library |access-date= 25 July 2021}}</ref>

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.<ref>{{cite journal | vauthors = Lewis PJ, Kohner EM, Petrie A, Dollery CT | title = Deterioration of glucose tolerance in hypertensive patients on prolonged diuretic treatment | journal = Lancet | volume = 1 | issue = 7959 | pages = 564–6 | date = March 1976 | pmid = 55840 | doi = 10.1016/S0140-6736(76)90359-7 | s2cid = 20976708 }}</ref><ref>{{cite journal | vauthors = Murphy MB, Lewis PJ, Kohner E, Schumer B, Dollery CT | title = Glucose intolerance in hypertensive patients treated with diuretics; a fourteen-year follow-up | journal = Lancet | volume = 2 | issue = 8311 | pages = 1293–5 | date = December 1982 | pmid = 6128594 | doi = 10.1016/S0140-6736(82)91506-9 | s2cid = 43027989 }}</ref><ref>{{cite journal | vauthors = Messerli FH, Williams B, Ritz E | title = Essential hypertension | journal = Lancet | volume = 370 | issue = 9587 | pages = 591–603 | date = August 2007 | pmid = 17707755 | doi = 10.1016/S0140-6736(07)61299-9 | s2cid = 26414121 }}</ref> However, as the Merck Manual of Geriatrics notes, "thiazide-type diuretics are especially safe and effective in the elderly."<ref>{{cite book |title=Merck Manual of Geriatrics |chapter=Section 11. Cardiovascular Disorders – Chapter 85. Hypertension |chapter-url=http://www.merck.com/mkgr/mmg/sec11/ch85/ch85a.jsp |date=July 2005 |url-status=live |archive-url=https://web.archive.org/web/20090123203540/http://www.merck.com/mkgr/mmg/sec11/ch85/ch85a.jsp |archive-date=2009-01-23 }}</ref>

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]]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. [[spironolactone]] or [[furosemide]]), an alpha-blocker or a beta-blocker.<ref name="NICE-BP">{{cite web|title=CG34 Hypertension – quick reference guide |publisher=[[National Institute for Health and Clinical Excellence]] |date=28 June 2006 |url=http://www.nice.org.uk/nicemedia/pdf/cg034quickrefguide.pdf |access-date=2009-03-04 |archive-url=https://web.archive.org/web/20090313072133/http://www.nice.org.uk/nicemedia/pdf/cg034quickrefguide.pdf |archive-date=13 March 2009 }}</ref> 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".<ref name="NICE-BP"/><ref name="pmid14594956">{{cite journal | vauthors = Williams B | title = Treatment of hypertension in the UK: simple as ABCD? | journal = Journal of the Royal Society of Medicine | volume = 96 | issue = 11 | pages = 521–2 | date = November 2003 | pmid = 14594956 | pmc = 539621 | doi = 10.1177/014107680309601101 }}</ref>

===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 [[Multiple morbidities|multi-morbidity]] can affect the choice of medication, the target blood pressure and even whether to treat or not.<ref>{{cite journal | vauthors = Parekh N, Page A, Ali K, Davies K, Rajkumar C | title = A practical approach to the pharmacological management of hypertension in older people | journal = Therapeutic Advances in Drug Safety | volume = 8 | issue = 4 | pages = 117–132 | date = April 2017 | pmid = 28439398 | pmc = 5394506 | doi = 10.1177/2042098616682721 }}</ref>
* [[Anxiety]] may be improved with the use of beta blockers.
* [[Asthma]]tics have been reported to have worsening symptoms when using [[beta blocker]]s.
* Beta blockers can trigger or worsen [[psoriasis]], [[psoriatic arthritis]], and [[rheumatoid arthritis]].<ref>{{cite journal | vauthors = Tatu AL, Elisei AM, Chioncel V, Miulescu M, Nwabudike LC | title = Immunologic adverse reactions of β-blockers and the skin | journal = Experimental and Therapeutic Medicine | volume = 18 | issue = 2 | pages = 955–959 | date = August 2019 | pmid = 31384329 | doi = 10.3892/etm.2019.7504 | s2cid = 145847997 | doi-access = free | pmc = 6639944 }}</ref>
* [[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.<ref name=JNC8 /><ref name=AASK />
* [[Dementia|Late-stage dementia]] should consider [[deprescribing]] antihypertensives, according to the [[Medication appropriateness tool for co‐morbid health conditions in dementia (MATCH-D) criteria|Medication Appropriateness Tool for Comorbid Health Conditions in Dementia (MATCH-D)]].<ref>{{cite journal | vauthors = Page AT, Potter K, Clifford R, McLachlan AJ, Etherton-Beer C | title = Medication appropriateness tool for co-morbid health conditions in dementia: consensus recommendations from a multidisciplinary expert panel | journal = Internal Medicine Journal | volume = 46 | issue = 10 | pages = 1189–1197 | date = October 2016 | pmid = 27527376 | pmc = 5129475 | doi = 10.1111/imj.13215 }}</ref>
* [[Diabetes mellitus]].  The ACEis and ARBs have been shown to prevent the [[kidney]] and [[retina]]l complications of diabetes mellitus.
* [[Gout]] may be worsened by thiazide diuretics, while losartan reduces serum urate.<ref>{{cite journal | vauthors = Würzner G, Gerster JC, Chiolero A, Maillard M, Fallab-Stubi CL, Brunner HR, Burnier M | title = Comparative effects of losartan and irbesartan on serum uric acid in hypertensive patients with hyperuricaemia and gout | journal = Journal of Hypertension | volume = 19 | issue = 10 | pages = 1855–1860 | date = October 2001 | pmid = 11593107 | doi = 10.1097/00004872-200110000-00021 | s2cid = 20842819 }}</ref>
* [[Kidney stone]]s may be improved with the use of thiazide-type diuretics <ref>Worcester EM, Coe FL: Clinical practice. Calcium kidney stones" ''N Engl J Med'' 2010;363(10) 954-963.  {{cite journal | vauthors = Worcester EM, Coe FL | title = Clinical practice. Calcium kidney stones | journal = The New England Journal of Medicine | volume = 363 | issue = 10 | pages = 954–63 | date = September 2010 | pmid = 20818905 | pmc = 3192488 | doi = 10.1056/NEJMcp1001011 }}</ref>
* [[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.<ref name="pmid12748199">{{cite journal | vauthors = Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jones DW, Materson BJ, Oparil S, Wright JT, Roccella EJ | title = The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report | journal = JAMA | volume = 289 | issue = 19 | pages = 2560–72 | date = May 2003 | pmid = 12748199 | doi = 10.1001/jama.289.19.2560 | url = https://www.nhlbi.nih.gov/files/docs/guidelines/jnc7full.pdf |access-date=2013-02-17 |url-status=live |archive-url=https://web.archive.org/web/20130216133645/http://www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdf |archive-date=2013-02-16 }}</ref>
* [[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.<ref>{{cite journal | vauthors = Rosendorff C, Black HR, Cannon CP, Gersh BJ, Gore J, Izzo JL, Kaplan NM, O'Connor CM, O'Gara PT, Oparil S | title = Treatment of hypertension in the prevention and management of ischemic heart disease: a scientific statement from the American Heart Association Council for High Blood Pressure Research and the Councils on Clinical Cardiology and Epidemiology and Prevention | journal = Circulation | volume = 115 | issue = 21 | pages = 2761–88 | date = May 2007 | pmid = 17502569 | doi = 10.1161/circulationaha.107.183885 | doi-access = free }}</ref>
* [[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.<ref name="jnc7" />
* [[Periodontal disease]] could mitigate the efficacy of antihypertensive drugs.<ref>{{cite journal | vauthors = Pietropaoli D, Del Pinto R, Ferri C, Wright JT, Giannoni M, Ortu E, Monaco A | title = Poor Oral Health and Blood Pressure Control Among US Hypertensive Adults | journal = Hypertension | volume = 72 | issue = 6 | pages = 1365–1373 | date = December 2018 | pmid = 30540406 | doi = 10.1161/HYPERTENSIONAHA.118.11528 | doi-access = free }}</ref>
* 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.<ref name=JNC8 />
* [[Tremor]] may warrant the use of beta blockers.
The JNC8 guidelines indicate reasons to choose one drug over the others for certain individual patients.<ref name=JNC8 />

==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.<ref>{{cite journal | vauthors = Papadopoulou Z, Tsialiou TM, Styanidou FE, Kavvadas D, Papamitsou T | title = In Utero Exposure to Antihypertensive Medication during the First Trimester: Is the Risk Worth Taking? | journal = Acta Medica Academica | volume = 50 | issue = 3 | pages = 372–381 | date = December 2021 | pmid = 35164513 | doi = 10.5644/ama2006-124.356 | s2cid = 246826268 | doi-access = free }}</ref> 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.<ref>{{Cite journal |date=15 February 2023 |title=Decision aid helps pregnant women with high blood pressure |url=https://evidence.nihr.ac.uk/alert/decision-aid-helps-pregnant-women-with-high-blood-pressure/ |journal=NIHR Evidence|doi=10.3310/nihrevidence_56796 |s2cid=257843687 |url-access=subscription }}</ref><ref>{{cite journal | vauthors = Whybrow R, Sandall J, Girling J, Brown H, Seed PT, Green M, Findlay S, Webster L, Chappell LC | title = Implementation of a novel shared decision-making intervention in women with chronic hypertension in pregnancy: multiple-site multiple-method investigation | journal = Pregnancy Hypertension | volume = 30 | pages = 137–144 | date = December 2022 | pmid = 36194966 | doi = 10.1016/j.preghy.2022.09.007 | s2cid = 252414448 | doi-access = free }}</ref>

==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.<ref>{{cite book | vauthors = Freis ED | chapter = Historical Development of Antihypertensive Treatment | title = Hyperlension: Pathophysiology, Diagnosis, and Management. | pages = 2741–5 | edition = Second | veditors = Laragh JM, Brenner BM | publisher = Raven Press, Ltd. | location = New York | date = 1995 | chapter-url = https://profiles.nlm.nih.gov/ps/access/XFBBGL.pdf | archive-url = https://web.archive.org/web/20170222175707/https://profiles.nlm.nih.gov/ps/access/XFBBGL.pdf | archive-date=2017-02-22 }}</ref>

'''History of Calcium Channel Blockers'''

In 1883, Ringer discovered the involvement of calcium for cellular activity on isolated heart.<ref name="Godfraind_2017">{{cite journal | vauthors = Godfraind T | title = Discovery and Development of Calcium Channel Blockers | journal = Frontiers in Pharmacology | volume = 8 | page = 286 | date = 2017-05-29 | pmid = 28611661 | pmc = 5447095 | doi = 10.3389/fphar.2017.00286 | doi-access = free }}</ref> Later in 1901, Stiles reported the same activity in muscle contraction.<ref name="Godfraind_2017" /> In the early 1940s, Kamada (from Japan) and Heilbrunn (from the United States) noted how calcium was involved with muscle contractions.<ref name="Godfraind_2017" /> 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.<ref name="Godfraind_2017" />

==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.<ref>{{cite journal | vauthors = Brown MJ | title = Success and failure of vaccines against renin-angiotensin system components | journal = Nature Reviews. Cardiology | volume = 6 | issue = 10 | pages = 639–47 | date = October 2009 | pmid = 19707182 | doi = 10.1038/nrcardio.2009.156 | s2cid = 15949 }}</ref>

'''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.<ref name=":0">{{Cite journal |last=Gnjidic |first=Danijela |last2=Langford |first2=Aili V. |last3=Jordan |first3=Vanessa |last4=Sawan |first4=Mouna |last5=Sheppard |first5=James P. |last6=Thompson |first6=Wade |last7=Todd |first7=Adam |last8=Hopper |first8=Ingrid |last9=Hilmer |first9=Sarah N. |last10=Reeve |first10=Emily |date=2025-03-31 |title=Withdrawal of antihypertensive drugs in older people |journal=The Cochrane Database of Systematic Reviews |volume=3 |issue=3 |article-number=CD012572 |doi=10.1002/14651858.CD012572.pub3 |issn=1469-493X |pmc=11956142 |pmid=40162571}}</ref> 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.<ref name=":0" />

== References ==
{{reflist|30em}}

{{Major Drug Groups}}
{{Endothelial antihypertensives}}
{{Diuretics}}
{{Agents acting on the renin–angiotensin system}}

{{DEFAULTSORT:Antihypertensive Drug}}
[[Category:Antihypertensive agents]]