Antihypertensive
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2008-07-15T19:27:15Z
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'''Antihypertensives''' are a class of [[medication|drugs]] that are used in [[medicine]] and [[pharmacology]] to treat [[hypertension]] (high blood pressure). There are many classes of antihypertensives, which—by varying means—act by lowering blood pressure. Evidence suggests that reduction of the [[blood pressure]] by 5-6 mmHg can decrease the risk of stroke by 40%, of [[coronary heart disease]] by 15-20%, and reduces the likelihood of [[dementia]], [[heart failure]], and [[death|mortality]] from [[cardiovascular disease]].
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. Several classes of medications are effective in reducing blood pressure. However, these classes 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 | author=Nelson MR, McNeil JJ, Peeters A et al | journal=Med J Aust | title=PBS/RPBS cost implications of trends and guideline recommendations in the pharmacological management of hypertension in Australia, 1994-1998 | year=2001 | month=Jun 4 | volume=174 | issue=11 | pages=565–8 | pmid=11453328}}</ref>
In the United States, the JNC7 (The Seventh Report of the Joint National Committee on Prevention of Detection, Evaluation and Treatment of High Blood Pressure) recommends starting with a [[thiazide]] diuretic if single therapy is being initiated and another medication is not indicated.<!--
--><ref name="jnc7">{{cite journal | url=http://jama.ama-assn.org/cgi/content/full/289.19.2560v1 | author=Chobanian AV et al |journal=[[Journal of the American Medical Association|JAMA]] | title=The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report | year=2003 | volume=289 | pages=2560–72 | pmid=12748199 | doi=10.1001/jama.289.19.2560}}</ref>
This is based on a slightly better outcome for [[chlortalidone]] in the ALLHAT study versus other anti-hypertensives and because thiazide diuretics are relatively cheap.<!--
--><ref name="allhat">{{cite journal | url=http://jama.ama-assn.org/cgi/content/full/288/23/2981 | author=ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group | journal=[[Journal of the American Medical Association|JAMA]] | title=Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) | year=2002 | month=Dec 18 | volume=288 | issue=23 | pages=2981–97 | pmid=12479763 | doi=10.1001/jama.288.23.2981}}</ref>
A subsequent smaller study (ANBP2) published after the JNC7 did not show this small difference in outcome and actually showed a slightly better outcome for ACE-inhibitors in older male patients.<!--
--><ref name="anbp2">{{cite journal | doi= 10.1056/NEJMoa021716 | author=Wing LM, Reid CM, Ryan P et al | journal=[[N Engl J Med|NEJM]] | title=A comparison of outcomes with angiotensin-converting--enzyme inhibitors and diuretics for hypertension in the elderly | year=2003 | month=Feb 13 | volume=348 | issue=7 | pages=583–92 | pmid=12584366}}</ref>
Despite thiazides being cheap, effective, and recommended as the best first-line drug for hypertension by many experts, they are not prescribed as often as some newer drugs. Arguably, this is because they are off-patent and thus rarely promoted by the drug industry.<!--
--><ref name="promotion">{{cite journal | url=http://circ.ahajournals.org/cgi/content/full/99/15/2055 | author=Wang TJ, Ausiello JC, Stafford RS | journal=Circulation | title=Trends in Antihypertensive Drug Advertising, 1985–1996 | year=1999 | volume=99 | pages=2055–2057 | pmid=10209012}}</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]] | accessdate=2006-09-30}}</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 | author= Sheetal Ladva | title=NICE and BHS launch updated hypertension guideline | url=http://www.nelm.nhs.uk/Record%20Viewing/viewRecord.aspx?id=567178 | date=2006-06-28 | publisher=[[National Institute for Health and Clinical Excellence]] | accessdate=2006-09-30}}</ref>
==Available drugs==
===Diuretics===
[[Image: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:
** [[chlortalidone]]
** [[epitizide]]
** [[hydrochlorothiazide]] and [[chlorothiazide]]
** [[bendroflumethiazide]]
* Thiazide-like diuretics:
** [[indapamide]]
** [[chlorthalidone]]
** [[metolazone]]
* [[Potassium-sparing diuretics]]:
** [[amiloride]]
** [[triamterene]]
** [[spironolactone]]
Only the [[thiazide]] and thiazide-like diuretics have good evidence of beneficial effects on important endpoints of [[hypertension]], and hence, should usually be the 1st choice when selecting a diuretic to treat hypertension. The reason why thiazides-type diuretics are better than the others is (at least in part) thought to be because of their vasodilating properties.{{Fact|date=August 2007}}
Although the diuretic effect of thiazides may be apparent shortly after administration, it takes longer (weeks of treatment) for the full anti-hypertensive effect to develop.
===[[Adrenergic receptor]] antagonists===
[[Image:Propranolol.png|thumb|[[Propranolol]], the first beta-blocker to be successfully developed|{{ifdc|1=Image:Propranolol.png|log=2007 October 22}}]]
* [[Beta blocker]]s (no longer 1st line therapy in many countries - see Lancet [[29 October]] [[2005]]):
** [[atenolol]]
** [[metoprolol]]
** [[nadolol]]
** [[oxprenolol]]
** [[pindolol]]
** [[propranolol]]
** [[timolol]]
* [[Alpha blocker]]s:
** [[doxazosin]]
** [[phentolamine]]
** [[indoramin]]
** [[phenoxybenzamine]]
** [[prazosin]]
** [[terazosin]]
** [[tolazoline]]
* Mixed Alpha + Beta blockers:
** [[bucindolol]]
** [[carvedilol]]
** [[labetalol]]
Although [[beta blocker]]s lower blood pressure, they do not have as positive a benefit on endpoints as some other antihypertensives.<!--
--><ref name="betablockers">{{cite journal | author=Lindholm LH, Carlberg B, Samuelsson O | journal=[[The Lancet|Lancet]] | title=Should beta blockers remain first choice in the treatment of primary hypertension? A meta-analysis | year=2005 | month=Oct 29-Nov 4 | volume=366 | issue=9496 | pages=1545–53 | pmid=16257341 | doi=10.1016/S0140-6736(05)67573-3}}</ref>
In particular, [[atenolol]] seems to be less useful in hypertension than several other agents.<!--
--><ref name="atenolol">{{cite journal | author=Carlberg B, Samuelsson O, Lindholm LH | journal=[[The Lancet|Lancet]] | title=Atenolol in hypertension: is it a wise choice? | year=2004 | month=Nov 6-12 | volume=364 | issue=9446 | pages=1684–9 | pmid=15530629 | doi=10.1016/S0140-6736(04)17355-8}}</ref>
However, [[beta blocker]]s have an important role in the prevention of heart attack in people who have already had a heart attack.<!--
--><ref name="bbmi">{{cite journal | url=http://bmj.bmjjournals.com/cgi/content/full/318/7200/1730 | author=Freemantle N, Cleland J, Young P et al | journal=[[BMJ]] | title=Beta Blockade after myocardial infarction: systematic review and meta regression analysis | year=1999 | month=Jun 26 | volume=318 | issue=7200 | pages=1730–7 | pmid = 10381708}}</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 | url=http://hyper.ahajournals.org/cgi/content/full/42/3/239 | author= ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group | journal=Hypertension | title=Diuretic Versus alpha-Blocker as First-Step Antihypertensive Therapy | year=2003 | month=Sep | volume=42 | issue=3 | pages=239–46 | pmid=12925554 | doi=10.1161/01.HYP.0000086521.95630.5A}}</ref>
However, they may be useful for some men with symptoms of [[benign prostatic hyperplasia|prostate disease]].
===[[Adrenergic receptor]] agonist===
* [[Alpha-2 agonist]]s:
** [[clonidine]]
** [[methyldopa]]
=== Calcium channel blockers===
[[Calcium channel blocker]]s block the entry of calcium into muscle cells in artery walls.
* [[dihydropyridine]]s:
** [[amlodipine]]
** [[felodipine]]
** [[isradipine]]
** [[lercanidipine]]
** [[nifedipine]](Adalat)
** [[nimodipine]]
** [[nitrendipine]]
* non-dihydropyridines:
** [[diltiazem]]
** [[verapamil]]
===ACE inhibitors===
[[Image:Captopril.png|thumb|[[Captopril]], the prototypical ACE inhibitor]]
[[ACE inhibitor]]s inhibit the activity of [[Angiotensin-converting enzyme]] (ACE), an enzyme responsible for the conversion of angiotensin I into [[angiotensin]] II, a potent [[vasoconstrictor]].
* [[captopril]]
* [[enalapril]]
* [[fosinopril]]
* [[lisinopril]]
* [[perindopril]]
* [[quinapril]]
* [[ramipril]]
* [[trandolapril]]
* [[benazepril]]
=== Angiotensin II receptor antagonists ===
[[Image:Valsartan.svg|thumb|[[Valsartan]], an angiotensin II receptor antagonist]]
[[Angiotensin II receptor antagonist]]s work by [[receptor antagonist|antagonizing]] the activation of [[angiotensin receptor]]s.
* [[candesartan]]
* [[eprosartan]]
* [[irbesartan]]
* [[losartan]]
* [[olmesartan]]
* [[telmisartan]]
* [[valsartan]]
=== Aldosterone antagonists===
[[Aldosterone]] receptor antagonists:
* [[eplerenone]]
* [[spironolactone]]
[[Aldosterone]] antagonists are not recommended as first-line agents for blood pressure,<ref name="jnc7" /> but [[spironolactone]] and [[eplerenone]] are both used in the treatment of [[heart failure]].
===Vasodilators===
[[Vasodilator]]s act directly on arteries to relax their walls so blood can move more easily through them; they are only used in [[medical emergency|medical emergencies]].
* [[sodium nitroprusside]]
===Centrally acting adrenergic drugs===
Central alpha agonists lower blood pressure by stimulating alpha-receptors in the brain which open peripheral arteries easing blood flow. 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]]
*[[Methyldopa]]
*[[Moxonidine]]
Adverse effects of this class of drugs include sedation, drying of the nasal mucosa and rebound hypertension.
Some adrenergic neuron blockers are used for the most resistant forms of hypertension:
*[[Guanethidine]]
*[[Reserpine]]
==Future treatment options==
===Blood pressure vaccine===
Blood pressure vaccinations are being trialed and may become a treatment option for high blood pressure in the future. Research published in [[The Lancet]] on the [[8 March]] [[2008]] titled, “Vaccination against high blood pressure: a new strategy” showed patients experienced a drop in systolic and diastolic blood pressure after taking the vaccine.
Effective blood pressure vaccines would assist those people who forget to take their medication. It would also help those who stop taking their medication due to side effects or falsely believing they don't need them anymore once their blood pressure is lowered.<ref>http://www.my-blood-pressure.com/vaccine-study.html
Blood pressure vaccine study promising<!-- Bot generated title --></ref>
== Choice ==
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. For example, [[asthma]]tics have been reported to have worsening symptoms when using [[beta blocker]]s. Most drugs have other uses; sometimes the presence of other symptoms can warrant the use of one particular antihypertensive (such as beta blockers in case of [[tremor]] and [[nervousness]], and [[alpha blocker]]s in case of [[benign prostatic hyperplasia]]). The JNC 7 report outlines compelling reasons to choose one drug over the others for certain individual patients.<ref name="jnc7" />
== See also ==
* [[Blood pressure]]
* [[Hypertension]]
* [[Prehypertension]]
* [[Pulse pressure]]
== References ==
{{reflist}}
{{Antihypertensives and diuretics}}
{{Major Drug Groups}}
==External links==
*[http://www.adalat.com Official Adalat (Nifedipine) site, Bayer]
[[Category:Antihypertensive agents| ]]
[[Category:Blood pressure]]
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