Antihypertensive is a class of drugs used to treat hypertension (high blood pressure). Antihypertensive therapy seeks to prevent complications of high blood pressure, such as stroke and myocardial infarction. Evidence suggests that a reduction in blood pressure of 5 mmHg may reduce the risk of stroke by 34%, ischemic heart disease by 21%, and reduce the likelihood of dementia, heart failure, and death from cardiovascular disease. There are many classes of antihypertensives, which lower blood pressure in different ways. Among the most important and most widely used drugs are thiazide diuretics, calcium channel blockers, ACE inhibitors, angiotensin II receptor antagonists (ARBs), and beta blockers.
The type of drug used for hypertension has been the subject of several major studies and produced national guidelines. The fundamental goal of treatment should be the prevention of an important hypertensive endpoint, such as heart attack, stroke, and heart failure. Patient age, associated clinical conditions and end-organ damage also play a role in determining the dose and type of drug given. Some classes of antihypertensives differ in side effects profiles, ability to prevent endpoints, and costs. The selection of more expensive, cheaper agents will be equally effective, possibly negatively impacting the national health care budget. In 2009, the best available evidence supports thiazide diuretics as a first-line treatment option for high blood pressure when the drug is needed. Although clinical evidence suggests calcium channel blockers and thiazide-type diuretics are the preferred first-line treatment for most people (both from the efficacy and cost point of view), ACE inhibitors are recommended by NICE in the UK for those younger than 55 years of age.
Video Antihypertensive drug
Diuretics
Diuretik membantu ginjal menghilangkan kelebihan garam dan air dari jaringan dan darah tubuh.
- Diuretik loop:
- bumetanide
- asam ethacrynic
- furosemide
- torsemide
- Diuretik tiazid:
- epitizide
- hydrochlorothiazide dan chlorothiazide
- bendroflumethiazide
- methyclothiazide
- polythiazide
- Diuretik seperti thiazide:
- indapamide
- chlorthalidone
- metolazone
- Diuretik hemat kalium:
- amiloride
- triamterene
- spironolactone
- eplerenone
In the United States, JNC8 (the Eight National Joint Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) recommends thiazide-type diuretics to be one of the first-line drugs for hypertension, either as monotherapy or in combination with calcium channel blockers, ACE inhibitors, or angiotensin II receptor antagonist. There is a fixed-dose combination drug, such as an ACE inhibitor and a thiazid combination. Although thiazides are cheap and effective, they are not prescribed as often as new drugs. This is because they have been associated with an increased risk of new-onset diabetes and are therefore recommended for use in patients over 65 where the risk of new-onset diabetes is proportional to the benefits of controlling systolic blood pressure. Another theory is that they are not patents and thus rarely promoted by the drug industry.
Maps Antihypertensive drug
Calcium channel blocker
The calcium channel blockers use the same membrane as well as the ducting of the oscillator.
- Dihydropiridin:
- amlodipine
- cilnidipine
- Clevidipine
- Felodipine
- isradipine
- lercanidipine
- levamlodipine
- nicardipine
- Nifedipin
- nimodipine
- nisoldipine
- nitrendipine
- non-dihidropiridin:
- diltiazem
- verapamil
JNC8 recommends calcium channel blockers to be either first-line treatment either as monotherapy or in combination with thiazide-type diuretics, ACE inhibitors, or angiotensin II receptor antagonists for all patients regardless of age or race.
ACE inhibitors
ACE inhibitors inhibit angiotensin-converting enzyme (ACE) activity, the enzyme responsible for angiotensin I conversion to angiotensin II, strong vasoconstrictors.
- captopril
- enalapril
- fosinopril
- lisinopril
- moexipril
- perindopril
- quinapril
- ramipril
- trandolapril
- benazepril
A systematic review of 63 trials with more than 35,000 participants showed ACE inhibitors significantly doubled serum creatinine levels compared with other drugs (ARB, blockers, blockers, etc.), and the authors suggest this as the first line of defense. AASK trials show that ACE inhibitors are more effective in slowing decline in kidney function compared to calcium channel blockers and beta blockers. Thus, ACE inhibitors should be a drug-therapy option for patients with chronic kidney disease regardless of race or diabetic status.
However, ACE inhibitors (and angiotensin II receptor antagonists) should not be the first-line treatment for black hypertension without chronic kidney disease. Results from the ALLHAT trial showed that thiazide-type diuretics and calcium channel blockers were more effective as monotherapy in improving cardiovascular outcomes compared to ACE inhibitors for this subgroup. In addition, ACE inhibitors are less effective in lowering blood pressure and have a 51% higher risk of stroke in black hypertension when used as initial therapy compared with calcium channel blockers. There is a fixed-dose combination drug, such as an ACE inhibitor and a thiazid combination.
Side effects of ACE inhibitors include dry cough, hyperkalemia, fatigue, dizziness, headache, loss of taste and risk for angioedema.
The angiotensin II receptor antagonist
Antagonis reseptor Angiotensin II bekerja dengan antagonisasi aktivasi reseptor angiotensin.
- azilsartan
- candesartan
- eprosartan
- irbesartan
- losartan
- olmesartan
- telmisartan
- valsartan
- Fimasartan
In 2004, an article in BMJ examined evidence for and against the suggestion that angiotensin receptor blockers may increase the risk of myocardial infarction (heart attack). This issue was debated in 2006 in the medical journal of the American Heart Association. To date, there is no consensus as to whether ARB has a tendency to increase MI, but there is also no substantive evidence indicating that ARBs are capable of reducing MI.
In the VALUE trial, the vallartan angiotensin II receptor inhibitor resulted in a statistically significant increase of 19% (p = 0.02) of relative increase in secondary endpoints of defined (fatal and non-fatal) myocardial infarction compared with amlodipine.
CHARM's alternative experiment showed a significant increase in myocardial infarction 52% (p = 0.025) with candesartan (compared with placebo) despite a decrease in blood pressure.
Indeed, as a consequence of the AT1 blockade, ARBs raise the level of Angiotensin II several times over the base by releasing a negative feedback loop. Increased levels of circulating Angiotensin II result in uninterrupted stimulation of AT2 receptors, which are also regulated. Unfortunately, recent data suggest that stimulation of AT2 receptors may be less useful than previously proposed and may even be dangerous under certain circumstances through mediation of the promotion of growth, fibrosis, and hypertrophy, as well as proatherogenic and proinflammatory effects.
Adrenergic receptor antagonist
- Beta blocker
- atenolol
- bisoprolol
- betaxolol
- carteolol
- carvedilol
- labetalol
- metoprolol
- nadolol
- nebivolol
- oxprenolol
- penbutolol
- pindolol
- propranolol
- timolol
- Alpha blockers:
- doxazosin
- phentolamine
- indoramin
- phenoxybenzamine
- prazosin
- terazosin
- tolazoline
- Alpha Beta blocker mix:
- bucindolol
- carvedilol
- labetalol
Although beta blockers lower blood pressure, they have no positive benefits at the endpoint because of some other antihypertensives. In particular, beta-blockers are no longer recommended as first-line treatment because of the relatively adverse risk of stroke and new onset of type 2 diabetes when compared with other drugs, whereas certain specific beta-blockers such as atenolol appear to be less useful. in the treatment of hypertension as a whole rather than some other agents. A systematic review of 63 trials with over 35,000 participants indicated? -blockers increase the risk of death, compared with other antihypertensive therapies. They, however, have an important role in the prevention of heart attacks in people who have already had a heart attack. In the United Kingdom, the guideline "Hypertension: Hypertension Management in Adults in Primary Care" in June 2006 from the National Institute for Health and Clinical Excellence, reduced the role of beta-blockers because of their risk of provoking type 2 diabetes.
Despite lowering blood pressure, alpha blockers have significantly worse outcomes than other antihypertensives, and are no longer recommended as first-line options in the treatment of hypertension. However, they may be useful for some men with symptoms of prostate disease.
Vasodilator
Vasodilators act directly on the smooth muscle of the arteries to loosen their walls so that blood can move more easily through them; they are only used in emergency hypertension or when other drugs fail, and are rarely self-administered.
Sodium nitroprusside, a very potent short-acting vasodilator, is most commonly used to reduce rapid and temporary blood pressure in emergencies (such as malignant hypertension or aortic dissection). Hydralazine and its derivatives are also used in the treatment of severe hypertension, although it should be avoided in emergencies. They are no longer indicated as first-line therapy for high blood pressure due to side effects and safety issues, but hydralazine remains the drug of choice in gestational hypertension.
Renin Inhibitor
Renin comes one step higher than the angiotensin converting enzyme (ACE) in the renin-angiotensin system. The renin inhibitor can effectively reduce hyptertension. Aliskiren (developed by Novartis) is a renin inhibitor that has been approved by the US FDA for the treatment of hypertension.
Aldosterone receptor antagonist
Antagonis receptor aldosterone:
- eplerenone
- spironolactone
Aldosterone receptor antagonists are not recommended as first-line agents for blood pressure, but spironolactone and eplerenone are both used in the treatment of heart failure and resistant hypertension.
Alpha-2 adrenergic receptor agonist
Alpha agonists are lowering blood pressure by stimulating alpha receptors in the brain that open peripheral arteries that facilitate blood flow. These 2 alpha receptors are known as autoreceptors which provide negative feedback in neurotransmission (in this case, the adrenaline vasoconstriction effect). Central alpha agonists, such as clonidine, are usually prescribed when all other anti-hypertensive drugs have failed. To treat hypertension, this drug is usually given in combination with a diuretic.
- clonidine
- guanabenz
- guanfacine
- methyldopa
- moxonidine
Adverse effects of this class of drugs include sedation, nasal mucosal drying and rebound hypertension.
Some indirect anti-adrenergics are rarely used in treatment-resistant hypertension:
- guanethidine - replaces norepinephrine in the vesicles, decreases its tonic release
- mecamylamine - antinicotinic and ganglion blockers
- reserpine - indirectly through irreversible VMAT inhibition
For the most resistant and severe disease, oral minoxidil (Loniten) in combination with diuretics and? -blocker or other sympathetic nervous system suppressors may be used.
Endothelin receptor blocker
Bosentan is a new class of drugs and works by blocking endothelin hormone receptors. Particularly indicated only for the treatment of pulmonary arterial hypertension in patients with moderate to severe heart failure.
Initial drug choice
For mild elevated blood pressure, 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 before the elevated blood pressure is observed. Therefore, the use of hypertensive drugs can be initiated in individuals with clear normal blood pressure but who exhibit evidence of nephropathy related to hypertension, proteinuria, atherosclerotic vascular disease, as well as other evidence of organ damage associated with hypertension.
If lifestyle changes are not effective, then drug therapy begins, often requiring more than one agent to lower hypertension effectively. What type of drug should be used initially for hypertension has been the subject of several major studies and national guidelines. Considerations include factors such as age, race, and other medical conditions. In the United States, JNC8 (2014) recommends any medication from any of the following four classes to be a good choice for initial therapy or as an adjunct treatment: thiazide-type diuretics, calcium channel blockers, ACE inhibitors, or angiotensin receptor antagonists II.
The first major study to demonstrate the mortality benefit of antihypertensive treatment was the VA-NHLBI study, which found that chlorthalidone was effective. The largest study, Antihypertensive and Lipid-Lowering Treatment to Prevent Trial Heart Attack (ALLHAT) in 2002, concluded that chlorthalidone, (thiazid diuretics as effective as lisinopril (inhibitors of angiotensin-converting enzymes) or amlodipine (ALLHAT) doxazosin, an alpha-adrenergic receptor blocker, has a higher incidence of heart failure, and the doxazosin arm of the study is discontinued.)
The smaller subsequent study (ANBP2) showed little benefit in the results of thiazide diuretics observed in the ALLHAT study, and actually showed slightly better results for ACE-inhibitors in older white male patients.
Effective thiazide diuretics, recommended as the best first-line treatment for hypertension by many experts, and much more affordable than other therapies, but they are not prescribed as frequently as newer drugs. Chlorthalidone is the most powerful thiazide drug supported by evidence as providing death benefit, although it should be noted that in the ALLHAT study, a dose of chlorthalidone was only 10 mg/day used; doctors in the US usually prescribe chlorthalidone at a dose of 12.5 mg (half of 25 mg tablets), because no 10 mg chlorthalidone formulation is currently available in the US. Chlorthalidone has been repeatedly 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 on the usual doses prescribed in routine clinical practice. Patients with exaggerated hypokalemic responses to low doses of thiazid diuretics should be suspected of having Hyperaldosteronism, a common cause of secondary hypertension.
Other drugs have a role in treating hypertension. Side effects of thiazide diuretics include hypercholesterolemia, and impaired glucose tolerance with an increased risk of developing type 2 diabetes mellitus. Thiazide diuretics also drain potassium circulating unless combined with potassium potassium or potassium supplements. Some authors challenge thiazides as first-line treatment. However, as Merck's Manual on Geriatrics states, "thiazide-type diuretics are very safe and effective in the elderly."
The current UK guidelines recommend starting patients over the age of 55 years and all those from the first African/Afrocaribbean ethnic on calcium channel blockers or thiazide diuretics, while younger patients from other ethnic groups should be initiated in ACE-inhibitors. Furthermore, if multiple therapies are required to use ACE-inhibitors in combination with calcium channel inhibitors or (thiazides) diuretics. Third treatment then of the three groups and if necessary arise later to add a fourth agent, to consider either a further diuretic (eg spironolactone or furosemide), alpha-blocker or beta-blocker. Prior to the decline in beta-blockers as first-line agents, a range of British combination therapy used the first letter of the drug class and was known as the "ABCD rule".
Patient factors
The choice between drugs is to a large degree determined by the characteristics of patients prescribed for, drug side-effects, and costs. Most drugs have other uses; sometimes other symptoms may warrant the use of a specific antihypertensive. Examples include:
- Age can affect drug choices. Current UK guidelines recommend starting patients over the first 55 years of age on calcium channel blockers or thiazide diuretics.
- Anxiety can be increased with the use of beta blockers.
- Asmatics have been reported to have worsening symptoms when using beta blockers. Benign prostatic hyperplasia can be enhanced by the use of alpha blockers.
- Chronic kidney disease. ACE inhibitors or ARBs should be included in the treatment plan to improve kidney outcomes irrespective of race or diabetic status.
- Diabetes mellitus. ACE inhibitors and angiotensin receptor blockers have been shown to prevent kidney and retinal complications of diabetes mellitus.
- Gout may be exacerbated by thiazide diuretics, while losartan reduces urate serum.
- Kidney stones can be repaired with the use of thiazid type diuretics
- Heart block. ? -blockers and nondihydropyridine calcium channel blockers should not be used in patients with larger heart block from first stage. JNC8 does not recommend? -blockers as initial therapy for hypertension
- Heart failure can be aggravated by nondihydropyridine calcium channel blockers, alpha blocker doxazosin, and alpha-2 mononidine and clonidine agonists. On the other hand,? -blockers, diuretics, ACE inhibitors, angiotensin receptor blockers, and aldosterone receptor antagonists have been shown to improve yield.
- Pregnancy. Although? -methyldopa is generally regarded as a first-line agent, labetalol and metoprolol also acceptable. Atenolol has been associated with intrauterine growth retardation, as well as decreased growth and weight of the placenta when prescribed during pregnancy. ACE inhibitors and angiotensin II receptor blockers (ARBs) are contraindicated in women who are or who intend to become pregnant.
- Racing. The JNC8 guidelines specifically show that when used as monotherapy, thiazide diuretics, and calcium channel blockers have been found to be more effective at reducing blood pressure in black hypertension than? -blockers, ACE inhibitors, or ARBs.
- Tremors may warrant the use of beta blockers.
The JNC8 guidelines show the reasons for choosing one drug over another for certain individual patients.
History
The first known example of effective antihypertensive treatment was in 1947 using pentaquine, an antimalarial.
Chlorothiazide was discovered in 1957.
Research
Blood pressure vaccine
Vaccinations are being tested and may be a treatment option for high blood pressure in the future. CYT006-AngQb was only moderately successful in the study, but a similar vaccine was under investigation.
References
Source of the article : Wikipedia
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