Drugs & Medication

Antihypertensives are a class of 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 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.^[1]

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.^[2] 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.^[3] 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.^[4]

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.^[5]

In the United Kingdom, the June 2006 "Hypertension: management of hypertension in adults in primary care"^[6] 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.^[7]

Contents 1 Available drugs 1.1 Diuretics 1.2 Antiadrenergics 1.3 Calcium channel blockers 1.4 ACE inhibitors 1.5 Angiotensin II receptor antagonists 1.6 Aldosterone antagonists 1.7 Vasodilators 1.8 Centrally acting adrenergic drugs 1.8.1 Adrenergic neuron blockers 1.9 Herbals provoking hypotension 2 Choice 3 References

Available drugs

Diuretics

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

• Loop diuretics:
  • bumetanide
    ethacrynic acid
    furosemide
    torsemide
• Thiazide diuretics:
  • chlortalidone
    epitizide
    hydrochlorothiazide and chlorothiazide
• Thiazide-like diuretics:
  • indapamide
    metolazone
• Potassium-sparing diuretics:
  • amiloride
    triamterene

Although the above is a thorough list of diuretic agents, only the thiazide and thiazide-like diuretics have good evidence of beneficial effects on important endpoints of hypertension.

Antiadrenergics

Adrenergic receptor antagonists:

• Beta blockers:
  • atenolol
    metoprolol
    nadolol
    oxprenolol
    pindolol
    propranolol
    timolol
• Alpha blockers:
  • doxazosin
    phentolamine
    indoramin
    phenoxybenzamine
    prazosin
    terazosin
    tolazoline
• Mixed Alpha + Beta blockers:
  • bucindolol
    carvedilol
    labetalol

Although beta blockers lower blood pressure, they do not have as positive a benefit on endpoints as some other antihypertensives.^[8] In particular, atenolol seems to be less useful in hypertension than several other agents.^[9] However, beta blockers have an important role in the prevention of heart attack in people who have already had a heart attack.^[10]

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.^[11] However, they may be useful for some men with symptoms of prostate disease.

Calcium channel blockers

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

• dihydropyridines:
  • amlodipine
    felodipine
    isradipine
    nifedipine
    nimodipine
    nitrendipine
• non-dihydropyridines:
  • diltiazem
    verapamil

ACE inhibitors

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.

• captopril
  enalapril
  fosinopril
  lisinopril
  perindopril
  quinapril
  ramipril
  trandopril
  benzapril

Angiotensin II receptor antagonists

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

• candesartan
  irbesartan
  losartan
  telmisartan
  valsartan

Aldosterone antagonists

Aldosterone antagonists:

• spironolactone

Aldosterone antagonists are not recommended as first-line agents for blood pressure,^[2] but spironolactone is useful in the treatment of heart failure.

Vasodilators

Vasodilators act directly on arteries to relax their walls so blood can move more easily through them; they are only used in 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, like Clonidine, are usually prescribed when all other anti-hypertensive medications have failed.

• Clonidine
  Guanabenz
  Methyldopa

Adrenergic neuron blockers

• Guanethidine
  Reserpine

Herbals provoking hypotension

• Agrimony
  Celery
  Cornsilk
  Garlic
  Ginger
  Ginseng
  Goldenseal
  Hawthorn
  Mistletoe
  Nettle
  Parsley
  Pokeroot
  Sage
  Squill
  Wild Carrot

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.^[2]

References

1. ^ 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.
2. ^ ^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: 2560-72. PMID 12748199.
3. ^ 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. PMID 12479763.
4. ^ 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. PMID 12584366.
5. ^ Wang TJ, Ausiello JC, Stafford RS (1999). "Trends in Antihypertensive Drug Advertising, 1985–1996". Circulation 99: 2055-2057. PMID 10209012.
6. ^ Hypertension: management of hypertension in adults in primary care (PDF). National Institute for Health and Clinical Excellence. Retrieved on 2006-09-30.
7. ^ Sheetal Ladva (28/06/2006). NICE and BHS launch updated hypertension guideline. National Institute for Health and Clinical Excellence. Retrieved on 2006-09-30.
8. ^ 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. PMID 16257341.
9. ^ Carlberg B, Samuelsson O, Lindholm LH (Nov 6-12 2004). "Atenolol in hypertension: is it a wise choice?". Lancet 364 (9446): 1684-9. PMID 15530629.
10. ^ Freemantle N, Cleland J, Young P et al (Jun 26 1999). "Beta Blockade after myocardial infarction: systematic review and meta regression analysis". BMJ 318 (7200): 1730-7. PMID 10381708.
11. ^ ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group (Sep 2003). "Diuretic Versus alpha-Blocker as First-Step Antihypertensive Therapy". Hypertension 42 (3): 239-46. PMID 12925554.

1. Herbals Affecting Blood Pressure [Herbal Provoking Hypotension; Clark (2003) AAFP Board Review, Seattle ]