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Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke and myocardial infarction.

The antihypertensives are a class of drugs that are used to treat hypertension (high blood pressure).[1] Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34%, of ischaemic heart disease by 21%, and reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease.[2] There are many classes of antihypertensives, which lower blood pressure by different means; among the most important and most widely used are the thiazide diuretics, the ACE inhibitors, the calcium channel blockers, the beta blockers, and the angiotensin II receptor antagonists or ARBs.

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. 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.[3] As of 2009, the best available evidence favors the thiazide diuretics as the first-line treatment of choice for high blood pressure when drugs are necessary.[4]

Contents

Available agents

Diuretics

Hydrochlorothiazide, a popular thiazide diuretic

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

Only the thiazide and thiazide-like diuretics have good evidence of beneficial effects on important endpoints of hypertension, and hence, should usually be the first 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.[citation needed] 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. 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.[5] 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.[6] 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.[7]

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. 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 where the risk of new-onset diabetes is outweighed by the benefits of controlling systolic blood pressure [8]

Another theory is that they are off-patent and thus rarely promoted by the drug industry.[9]

Adrenergic receptor antagonists

Propranolol, the first beta-blocker to be successfully developed

Although beta blockers lower blood pressure, they do not have a positive benefit on endpoints as some other antihypertensives.[10] In particular, atenolol seems to be less useful in hypertension than several other agents.[11] They do, however, have an important role in the prevention of heart attacks in people who have already had a heart attack.[12] In the United Kingdom, the June 2006 "Hypertension: Management of Hypertension in Adults in Primary Care"[13] 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.[14]

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

Adrenergic receptor agonists

Calcium channel blockers

Calcium channel blockers block the entry of calcium into muscle cells in artery walls.

ACE inhibitors

Captopril, the prototypical ACE inhibitor

ACE inhibitors inhibit the activity of Angiotensin-converting enzyme (ACE), an enzyme responsible for the conversion of angiotensin I into angiotensin II, a potent vasoconstrictor.

Angiotensin II receptor antagonists

Valsartan, an angiotensin II receptor antagonist

Angiotensin II receptor antagonists work by antagonizing the activation of angiotensin receptors.

Aldosterone antagonists

Aldosterone receptor antagonists:

Aldosterone antagonists are not recommended as first-line agents for blood pressure,[5] but spironolactone and eplerenone are both used in the treatment of heart failure.

Vasodilators

Vasodilators act directly on the smooth muscle of arteries to relax their walls so blood can move more easily through them; they are only used in hypertensive emergencies or when other drugs have failed, and even so are rarely given alone.

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).[16][17] Hydralazine and its derivatives are also used in the treatment of severe hypertension, although they should be avoided in emergencies.[17] 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.[16]

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.

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:

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 on the vaccine CYT006-AngQb 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.[18]

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, asthmatics have been reported to have worsening symptoms when using beta blockers. 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 blockers in case of benign prostatic hyperplasia). The JNC 7 report outlines compelling reasons to choose one drug over the others for certain individual patients.[5]

Non-drug treatment options

Several studies have found that hibiscus tea has a substantial antihypertensive effect attributable to the flower's ACE-inhibiting anthocyanin content, and possibly to a diuretic effect. One study found that hibiscus conferred an antihypertensive effect comparable to 50 mg./day of the drug captopril.[19][20][21][22][23]

Another potential treatment is Coenzyme Q10[24], which a meta analysis of 12 studies found reductions in systolic pressure of 10-17 points and a reduction in diastolic pressure of 8-10 points[25] with doses of roughly 200mg/day.

See also

References

  1. ^ MeSH Antihypertensive+Agents
  2. ^ Law M, Wald N, Morris J (2003). "Lowering blood pressure to prevent myocardial infarction and stroke: a new preventive strategy". Health Technol Assess 7 (31): 1–94. PMID 14604498. http://www.hta.ac.uk/fullmono/mon731.pdf. 
  3. ^ Nelson MR, McNeil JJ, Peeters A et al. (Jun 4 2001). "PBS/RPBS cost implications of trends and guideline recommendations in the pharmacological management of hypertension in Australia, 1994-1998". Med J Aust 174 (11): 565–8. PMID 11453328. 
  4. ^ Wright JM, Musini VM (July 2009). "First-line drugs for hypertension". Cochrane Database Syst Rev 8 (3): CD001841. doi:10.1002/14651858.CD001841.pub2. PMID 19588327. 
  5. ^ a b c Chobanian AV et al. (2003). "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report". JAMA 289 (19): 2560–72. doi:10.1001/jama.289.19.2560. PMID 12748199. http://jama.ama-assn.org/cgi/content/full/289.19.2560v1. 
  6. ^ ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group (Dec 18 2002). "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)". JAMA 288 (23): 2981–97. doi:10.1001/jama.288.23.2981. PMID 12479763. http://jama.ama-assn.org/cgi/content/full/288/23/2981. 
  7. ^ Wing LM, Reid CM, Ryan P et al. (Feb 13 2003). "A comparison of outcomes with angiotensin-converting--enzyme inhibitors and diuretics for hypertension in the elderly". NEJM 348 (7): 583–92. doi:10.1056/NEJMoa021716. PMID 12584366. 
  8. ^ Zillich AJ, Garg J, Basu S, et al. (August 2006). "Thiazide diretics, potassium and the development of diabetes: a quantative review". Hypertension 48 (2): 219–224. doi:10.1161/01.HYP.0000231552.10054.aa. PMID 16801488. http://ovidsp.tx.ovid.com/sp-2.3/ovidweb.cgi?&S=MNMGFPBEGMDDFMPFNCELJBGJPEOAAA00&Link+Set=S.sh.2.14.15.17.22.46. 
  9. ^ Wang TJ, Ausiello JC, Stafford RS (20 April 1999). "Trends in Antihypertensive Drug Advertising, 1985–1996". Circulation 99 (15): 2055–2057. PMID 10209012. http://circ.ahajournals.org/cgi/content/full/99/15/2055. 
  10. ^ Lindholm LH, Carlberg B, Samuelsson O (Oct 29-Nov 4 2005). "Should beta blockers remain first choice in the treatment of primary hypertension? A meta-analysis". Lancet 366 (9496): 1545–53. doi:10.1016/S0140-6736(05)67573-3. PMID 16257341. 
  11. ^ Carlberg B, Samuelsson O, Lindholm LH (Nov 6-12 2004). "Atenolol in hypertension: is it a wise choice?". Lancet 364 (9446): 1684–9. doi:10.1016/S0140-6736(04)17355-8. PMID 15530629. 
  12. ^ Freemantle N, Cleland J, Young P, et al. (June 26 1999). "Beta Blockade after myocardial infarction: systematic review and meta regression analysis". BMJ 318 (7200): 1730–7. PMID 10381708.& PMC 31101. http://bmj.bmjjournals.com/cgi/content/full/318/7200/1730. 
  13. ^ "Hypertension: management of hypertension in adults in primary care" (PDF). National Institute for Health and Clinical Excellence. http://www.nice.org.uk/download.aspx?o=CG034quickrefguide. Retrieved 2006-09-30. 
  14. ^ Sheetal Ladva (2006-06-28). "NICE and BHS launch updated hypertension guideline". National Institute for Health and Clinical Excellence. http://www.nelm.nhs.uk/Record%20Viewing/viewRecord.aspx?id=567178. Retrieved 2006-09-30. 
  15. ^ ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group (September 2003). "Diuretic Versus alpha-Blocker as First-Step Antihypertensive Therapy". Hypertension 42 (3): 239–46. doi:10.1161/01.HYP.0000086521.95630.5A. PMID 12925554. http://hyper.ahajournals.org/cgi/content/full/42/3/239. 
  16. ^ a b Brunton L, Parker K, Blumenthal D, Buxton I (2007). "Therapy of hypertension". Goodman & Gilman's Manual of Pharmacology and Therapeutics. New York: McGraw-Hill. pp. 544–60. ISBN 978-0071443432. 
  17. ^ a b Varon, J; Marik, Pe (Jul 2000). "The diagnosis and management of hypertensive crises" (Free full text). Chest 118 (1): 214–27. doi:10.1378/chest.118.1.214. ISSN 0012-3692. PMID 10893382. http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=10893382.  edit
  18. ^ Chu, Jennifer (12 March 2008). "Taking a Shot at Hypertension". Technology Review. http://www.technologyreview.com/Biotech/20401/. 
  19. ^ Mozaffari-Khosravi H, Jalali-Khanabadi BA, Afkhami-Ardekani M, Fatehi F, Noori-Shadkam M (January 2009). "The effects of sour tea (Hibiscus sabdariffa) on hypertension in patients with type II diabetes". J Hum Hypertens 23 (1): 48–54. doi:10.1038/jhh.2008.100. PMID 18685605. http://www.nature.com/jhh/journal/v23/n1/full/jhh2008100a.html. 
  20. ^ McKay DL, Chen CY, Saltzman E, Blumberg JB (February 2010). "Hibiscus sabdariffa L. tea (tisane) lowers blood pressure in prehypertensive and mildly hypertensive adults". J. Nutr. 140 (2): 298–303. doi:10.3945/jn.109.115097. PMID 20018807. http://jn.nutrition.org/cgi/pmidlookup?view=long&pmid=20018807. 
  21. ^ "AHA 2008: Hibiscus Tea Reduces Blood Pressure". 11 November 2008. http://www.medscape.com/viewarticle/583351. 
  22. ^ Herrera-Arellano A, Miranda-Sánchez J, Avila-Castro P, et al. (January 2007). "Clinical effects produced by a standardized herbal medicinal product of Hibiscus sabdariffa on patients with hypertension. A randomized, double-blind, lisinopril-controlled clinical trial". Planta Med. 73 (1): 6–12. PMID 17315307. 
  23. ^ Herrera-Arellano A, Flores-Romero S, Chávez-Soto MA, Tortoriello J (July 2004). "Effectiveness and tolerability of a standardized extract from Hibiscus sabdariffa in patients with mild to moderate hypertension: a controlled and randomized clinical trial". Phytomedicine 11 (5): 375–82. PMID 15330492. 
  24. ^ http://www.ncbi.nlm.nih.gov/pubmed/7752851
  25. ^ http://www.ncbi.nlm.nih.gov/pubmed/17287847







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