Medication

Antihypertensives

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Antihypertensives
Last update: 27-11-2024

How else can it be called?

  • Blood pressure medication

  • Antihypertensive agents

  • Hypertension medication

  • Blood pressure-lowering drugs

What should we know?

Lifestyle changes, including dietary adjustments and regular exercise, are by far the most important factors in controlling blood pressure. However, a combination of therapies, including antihypertensives, is often needed.

Regardless of the cause of high blood pressure, there is a wide range of medications available to treat it. These are typically used in stages until a personalized treatment plan that works for each hypertensive patient is found.

What are the different types of antihypertensives?

The main types of medications used in the treatment of high blood pressure are:

  • Diuretics
  • Beta blockers
  • Calcium channel blockers
    • Dihydropyridines
    • Non-dihydropyridines
  • Renin-angiotensin system blocking drugs
    • Angiotensin-converting enzyme (ACE) inhibitors
    • Angiotensin II receptor blockers (ARBs)
    • Renin inhibitors
  • Centrally acting agents (including alpha-1 blockers and alpha-2 blockers)
  • Vasodilators
  • Neprilysin and angiotensin receptor inhibitors (ARNIs)

Diuretics

Diuretics are often the first choice for treating high blood pressure.

Diuretics increase the elimination of urine and salt from the body, which helps lower blood pressure both by reducing fluid volume and by decreasing resistance to blood flow in the blood vessels.

After taking diuretics, you may notice that you urinate more frequently and more quickly after consuming liquids.

The side effects of diuretics are typically minimal, but one notable concern is the loss of potassium (hypokalemia). This requires monitoring potassium levels in the blood through regular testing and, in some cases, taking potassium supplements. Dietary sources of potassium, such as oranges or bananas, are usually insufficient to correct deficiencies caused by diuretics. Additionally, reducing salt intake can enhance the effectiveness of diuretics and minimize potassium loss.

The main types of diuretics used to treat high blood pressure are:

  • Thiazides or thiazide diuretics: These are considered first-line medications for high blood pressure, usually in combination with other drugs, particularly those that block the renin-angiotensin system (e.g., ACE inhibitors or ARBs). Common thiazides include chlorothiazide, chlorthalidone, hydrochlorothiazide, indapamide, and metolazone.
  • Loop diuretics (high-ceiling diuretics): These are not typically used for high blood pressure, as they are no more effective than thiazides and may cause electrolyte imbalances. However, in cases of resistant high blood pressure associated with advanced chronic kidney disease, loop diuretics may be combined with thiazides, such as chlorthalidone.
  • Potassium-sparing diuretics: These are used in combination with other diuretics to manage high blood pressure, as they help prevent potassium depletion. Common potassium-sparing diuretics include spironolactone, amiloride, and triamterene.

Indications for diuretics in high blood pressure

  • High blood pressure caused by excess fluid volume.
  • High blood pressure in elderly patients.
  • Obesity-induced hypertension.
  • High blood pressure with heart failure.

Classification of diuretics, dosage and duration of action

GroupNameDose (mg/day)Duration of action (h)
ThiazidesChlorothiazide125-5006-12
 Hydrochlorothiazide12,5-5012-24
 Chlorthalidone12,5-5024-48
 Indapamide1,25-524
 Metolazone0,5-1024
 Bendroflumethiazide2,5-524
Loop diureticsFurosemide20-4808-12
 Ethacrynic acid25-10012
 Bumetanide0,5-58-12
 Piretanide3-66-8
Potassium-sparing diureticsSpironolactone25-1008-24
 Triamterene50-15012-24
 Amiloride5-1012-24

Beta blockers

Beta-blockers work by blocking many of the effects of adrenaline in the body, particularly its stimulating effects on the heart. This causes the heart to beat more slowly and with less force. Specifically, beta blockers act by inhibiting the effects of adrenaline on beta-adrenergic receptors in the body.

There are two types of beta receptors:

  • Beta-1 adrenergic receptors: Control heart rate and rhythm.
  • Beta-2 adrenergic receptors: Control smooth muscle function.

By taking beta blockers, the heart beats more slowly and exerts less force, helping to reduce blood pressure.

Beta blockers are primarily used for their antihypertensive effect (to treat high blood pressure). However, they are also used as:

Types of beta blockers:

  • Selective Beta Blockers (Cardioselective): These primarily block beta-1 receptors, which control the heart's frequency and rhythm. Common selective beta blockers for hypertension include acebutolol, atenolol, betaxolol, bisoprolol, celiprolol, esmolol, nebivolol and metoprolol.
  • Non-Selective Beta Blockers (Non-Cardioselective): These block both beta-1 and beta-2 receptors. Common non-selective beta blockers for hypertension include carteolol, nadolol, oxprenolol, labetalol, carvedilol, penbutolol, propranolol and sotalol. If a patient has conditions such as asthma, COPD, or hypoglycemia, a selective beta blocker is preferred to avoid potential complications from beta-2 receptor blockade.

Effects of beta blockers on high blood pressure:

  • Reduce cardiac output.
  • Reduce stroke volume.
  • Reduce heart rate.
  • Inhibit renin secretion.
  • Exert a central antisympathetic effect.
  • Stimulate the production of kinins.
  • Stimulate the release of atrial natriuretic peptide.
  • First-generation beta blockers (e.g., propranolol, metoprolol, atenolol) significantly reduce the risk of stroke, heart attack, and heart failure.

Common side effects of beta blockers include tiredness, dizziness, headache, cold hands and feet, bradycardia (low heart rate), etc.

Beta blockers are particularly indicated in cases of:

  • Hypertension and tachycardia.
  • Ischemic heart disease.
  • Hypertension associated with migraines or glaucoma.

Classification of beta blockers

NameDose (mg/day)Duration of action (h)
Atenolol25-10024
Bisoprolol5-2024
Metoprolol5-20012-24
Nadolol20-24024
Oxprenolol30-2408-12
Propranolol40-2408-12
Labetalol200-12008-12
Carvedilol50-5012-24

Calcium channel blockers

Calcium channel blockers, prevent calcium from entering cells. This reduces the tendency of small arteries to narrow, decreases myocardial contractility, and lowers peripheral vascular resistance.

There are two types of calcium channel blockers:

  • Dihydropyridines: Primarily act on the arteries. Amlodipine is one of the best-tolerated medications in this group.
  • Non-Dihydropyridines: Primarily affect the heart. Examples include verapamil and diltiazem.

As side effects, the following ones are described: oedema (ankle swelling), flushed skin and headache, orthostatic hypotension, constipation and bradycardia (very slow heart rate).

Calcium channel blockers are particularly indicated in cases of:

  • Hypertension and myocardial ischemia.
  • Hypertension and ventricular arrhythmias.
  • Hypertension and atrial fibrillation.
  • Hypertension and paroxysmal supraventricular tachycardias.

Classification of calcium channel blockers, dosage and duration of action

GroupSubgroupNameDose (mg/day)Duration of action (h)
DihydropyridinesFirst generationNifedipine30-1208
 Second generationAmlodipine2,5-1024
  Felodipine5-4024
  Nitrendipine10-4024
  Lacidipine424
  Nicardipine20-4012-16
  Isradipine2512-16
 Third generationManidipine10-2024
Benzothiazepines Diltiazem90-3608
Phenylalkylamines Verapamil80-4808

Renin-angiotensin system blocking drugs

1. Angiotensin-Converting Enzyme Inhibitors (ACEIs)

Similar to calcium channel blockers, ACE inhibitors reduce the tendency of small arteries to narrow, but they work through a different mechanism.

ACE inhibitors prevent the production of angiotensin II, a substance in the body that raises blood pressure and causes blood vessels to constrict. Without angiotensin II, renin levels are regulated, helping to lower blood pressure and reduce vascular resistance.

ACE inhibitors are commonly prescribed for:

  • Essential hypertension.
  • Hypertension and diabetes or hypercholesterolemia.
  • Hypertension and congestive heart failure or ventricular dysfunction.
  • Hypertension and kidney dysfunction.

The most frequently reported side effects include cough, hypotension (low blood pressure), headaches, angioedema, skin rashes and increased urea levels.

ACE inhibitors should not be used in pregnant women or women at risk of pregnancy and individuals with renal artery stenosis.

Classification with dose and duration of action of ACEIs

GroupNameDose (mg/day)Duration of action (h)
Sulfhydryl groupCaptopril12,5-1506-12
Carboxyl groupEnalapril5-4012-24
 Benazepril10-2010-20
 Cilazapril2,5-512-24
 Lisinopril5-4012-24
 Perindopril2-1612-24
 Quinapril5-8012-24
 Ramipril2,5-512-24
 Trandolapril2,5-512-24
Phosphoryl groupFosinopril5-4012-24

2. Angiotensin II receptor blockers (ARBs)

Angiotensin receptor blockers (ARBs) work in a manner similar to ACE inhibitors (ACEIs) but are associated with fewer side effects.

One significant advantage of ARBs is that they can typically be taken once daily, improving convenience and adherence to treatment.

The most commonly used ARBs are losartan and valsartan.

3. Renin inhibitors

The medication from this group, aliskiren, was withdrawn in Europe due to its adverse effects, including heart and kidney problems, hypotension, and increased potassium levels in the blood.

It is recommended not to combine these three types of medications because there is no additional benefit in the treatment of high blood pressure. Moreover, the risk of undesirable effects, such as kidney damage and elevated potassium levels, is increased.

Alpha blockers (centrally acting agents)

Alpha blockers, also called alpha adrenergic agonists, are used to treat hypertension as they promote the relaxation of small blood vessels, improve blood flow, and help reduce blood pressure.

There are two main types of alpha blockers:

  • Alpha-1 blockers: Prazosin, terazosin, doxazosin, indoramin.
  • Alpha-2 blockers: Clonidine, guanfacine, methyldopa (alphamethyldopa), reserpine, monoxidine, and rilmenidine.

Alpha blockers are typically considered second-line treatments for hypertension and are usually used in combination with diuretics.

In addition to lowering blood pressure, alpha blockers can help reduce "bad” or LDL cholesterol levels.

Alpha-1 blockers are also used to treat benign prostatic hyperplasia (BPH).

These medications act on the central nervous system and are now used less frequently.

Currently, alpha blockers are mainly recommended in specific combination therapies for treatment-resistant hypertension, where other medications have been ineffective.

The most common use of alphamethyldopa is during pregnancy.

Other antihypertensives

  1. Vasodilators

    Vasodilators include medications such as hydralazine, minoxidil, diazoxide, and sodium nitroprusside.

    These drugs work by directly relaxing the smooth muscles of the arterioles, causing them to dilate. This dilation can lead to reflex tachycardia (an increased heart rate) and salt retention. For this reason, they are typically used in combination with a diuretic and a beta blocker to counteract these side effects.

    Hydralazine is often used as a third-line drug for hypertension. Careful dosing is necessary, as doses greater than 200 mg may increase the risk of a syndrome similar to lupus erythematosus.

    Minoxidil can cause hypertrichosis (increased hair growth), but it is effective in cases of hypertension that are refractory to other treatments.

    Sodium nitroprusside and diazoxide are used exclusively in hypertensive crisis.

    Hydralazine and diazoxide have been used for severe arterial hypertension.

    Nitroprusside is typically used in hypertensive emergencies when extremely high blood pressure poses an immediate threat to life.

  2. Neprilysin and angiotensin receptor inhibitors (ARNIs)

    This combination therapy includes sacubitril (a neprilysin inhibitor) and valsartan (an angiotensin receptor blocker, ARA II). The combination promotes peripheral vasodilation of the arteries, helping to lower blood pressure.

Active ingredients and brand names of antihypertensives

  • Diuretics
    • Thiazides
      • Chlorthalidone
      • Hydrochlorothiazide
      • Indapamide
      • Xipamide
    • Loop diuretics (High-Ceiling Diuretics)
      • Bumetanide
      • Furosemide
      • Torsemide
    • Potassium-Sparing Diuretics
      • Amiloride
      • Spironolactone
      • Triamterene
    • Powerful diuretics with potassium-sparing diuretics
      • Amiloride / Hydrochlorothiazide
      • Spironolactone / altizide
      • Spironolactone / chlorthalidone
      • Triamterene / furosemide
  • Beta blockers
    • Cardioselective beta blockers alone
      • Acebutolol
      • Atenolol
      • Betaxolol
      • Bisoprolol
      • Celiprolol
      • Esmolol
      • Metoprolol
      • Nevivolol
    • Non-cardioselective beta blockers alone
      • Carteolol
      • Carvedilol
      • Labetalol
      • Nadolol
      • Oxprenolol
      • Penbutolol
      • Propranolol
      • Sotalol
      • Timolol
    • Associations of beta blockers with other antihypertensives
      • Atenolol / Chlorthalidone
      • Bisoprolol / Hydrochlorothiazide
      • Bisoprolol / Ramipril
  • Calcium channel blockers (Calcium antagonists)
    • Phenylpiperazine
      • Cinnarizine
      • Flunarizine
    • Dihydropyridines
      • First generation dihydropyridines
        • Nifedipine
      • Second generation dihydropyridines
        • Amlodipine
        • Felodipine
        • Isradipine
        • Lacidipine
        • Nicardipine
        • Nimodipine
        • Nisoldipine
        • Nitrendipine
      • Third generation dihydropyridines
        • Manidipine
    • Benzothiazepines
      • Diltiazem
    • Phenylalkylamine derivates
      • Verapamil (Iproveratril)
  • Angiotensin-converting enzyme (ACE) inhibitors
    • Sulfhydryl group
      • Captopril
    • Carboxyl group
      • Benazepril
      • Enalapril
      • Lisinopril
      • Quinapril
      • Ramipril
    • Phosphoryl group
      • Fosinopril
  • Angiotensin II receptor blockers (ARBs)
    • Candesartan
    • Irbesartan
    • Losartan
    • Olmesartan
    • Telmisartan
    • Valsartan
  • Alpha blockers
    • Alpha-1 blockers
      • Doxazosin
      • Indoramin
      • Prazosin
      • Terazosin
    • Alpha-2 blockers
      • Clonidine
      • Guanfacine
      • Methyldopa (Alphamethyldopa)
  • Vasodilators
    • Diazoxide
    • Hydralazine
    • Minoxidil
    • Sodium nitroprusside
  • Neprilysin and angiotensin receptor inhibitors (ARNIs)
    • Sacubitril/Valsartan
  • Antihypertensive associations
    • Candesartan + Hydrochlorothiazide
    • Captopril + Hydrochlorothiazide
    • Enalapril + Hydrochlorothiazide
    • Irbesartan + Hydrochlorothiazide
    • Lisinopril + Hydrochlorothiazide
    • Losartan + Hydrochlorothiazide
    • Olmesartan + Hydrochlorothiazide
    • Olmesartan + Hydrochlorothiazide + Amlodipine
    • Quinapril + Hydrochlorothiazide
    • Valsartan + Hydrochlorothiazide
Medically reviewed by Yolanda Patricia Gómez González Ph.D. on 27-11-2024

Bibliography

  • 2023 ESH Guidelines for the management of arterial hypertension. The Task Force for the management of arterial hypertension of the European Society of Hypertension. Available on: https://journals.lww.com
  • Vascular Diseases for the Non-Specialist: An Evidence-Based Guide, Tulio Pinho Navarro, Alan Dardik, Daniela Junqueira, Ligia Cisneros, ISBN: 978-3-319-46057-4 Pag. 241.
  • First Aid for the Basic Sciences: Organ Systems (3rd Ed) 2017, Tao Le, William L. Hwang, Vinayak Muralidhar, Jared A. White and M. Scott Moore, ISBN: 978-1-25-958704-7, Pag. 91.

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