MUST READ........Drugs Commonly Used to Treat High Blood Pressure AND DOSES

The list of drugs and drug combinations most commonly used to treat hypertension (high blood pressure) is remarkably long.

The fact that there are so many drugs to choose from means at least two things. First, it means there is no “best” drug for hypertension, that is, there is no drug that works well for almost everyone without causing unacceptable adverse effects. If there were, drug companies would have stopped their efforts to develop new antihypertensive drugs long ago—and the list of approved drugs would be much shorter.

Second, with so many drugs to choose from, as long as you and your doctor are patient and persistent, it is extremely likely that an effective and well-tolerated treatment regimen will be found for your hypertension. In other words, while there is no universal “best” treatment for hypertension, there is likely to be a “best” treatment for you.

In this article, we will describe the kinds of drugs that are used for hypertension, and what steps your doctor should take in choosing (from the incredible array of options) your optimal treatment. Finally, we will provide a reasonably complete list of all the drugs currently used in the U.S. (and in most developed countries) for the treatment of hypertension.

Choosing the Right Treatment

Doctors generally use a systematic approach to selecting the optimal therapy for hypertension.

Step 1: For people who have been diagnosed with mild or moderate hypertension, it is important to begin by recommending lifestyle changes that have been shown to help reduce blood pressure. These include dietary changes, salt restriction, regular exercise, and smoking cessation.

Step 2: If these lifestyle measures do not result in sufficient blood pressure control after several weeks, it is usually time to add drug therapy.

Drug Therapy Approaches

There are five major categories of drugs that have been proven effective in treating hypertension. These are:

• Thiazide diuretics
• Angiotensin-converting enzyme (ACE) inhibitors
• Calcium blockers
• Beta-blockers
• Angiotensin receptor blockers (ARBs)

Single Drug Therapy: If you have stage 1 hypertension (where your systolic pressure is less than 160 mm Hg, and your diastolic pressure is less than 100 mm Hg), the general recommendation is to begin with a single drug from one of these five categories.

In general, drugs from each of these classes (with the exception of the beta-blockers, which are generally less effective as single drugs) tend to work equally well in controlling hypertension. Specifically, there is roughly a 50-50 chance that any particular drug will work adequately in any given person with stage 1 hypertension.

However, individuals will respond quite differently to these medications. Jim might respond quite nicely to a thiazide, but fail with a calcium blocker, and the case with Jane might be the exact reverse. There is generally no way ahead of time to predict which person will do well with which kind of medication. So, what doctors and patients are left with is an educated trial-and-error approach.

In “guessing” on the best initial single drug to try, most experts now recommend beginning either with either a thiazide diuretic (usually chlorthalidone or hydrochlorothiazide), a long-acting calcium blocker, or an ACE inhibitor. ARBs are generally thought of as substitutes for ACE inhibitors, and generally, are used only when ACE inhibitors are poorly tolerated.

There are no hard and fast rules about which drugs to use in which people, but there are certain tendencies that are useful in selecting single-drug therapy:

• Younger patients more often respond well to ACE inhibitors.
• Black patients and elderly patients tend to do better with thiazide diuretics or calcium channel blockers.
• Black patients tend to do poorly with ACE inhibitors.
• Beta blockers are usually a relatively poor choice for single-drug therapy and are generally used only if there is another medical reason to use beta-blockers (such as the need to treat angina or heart failure, or to control the heart rate in a person with atrial fibrillation).

In general, lower doses of blood pressure medicine are as effective as higher doses and cause fewer side effects. So, when trying to find effective single-drug therapy, doctors usually begin with a low dose. They may decide to increase the dose a bit if the initial dose is ineffective—but it is rarely useful to “push” the dose of a single-drug therapy into the higher dosage ranges. Instead, if a drug fails to work at a relatively low dose, it is time to switch to a low dose of a different drug.

Using this type of trial-and-error approach, about 80% of people with stage 1 hypertension eventually can be treated adequately with a single hypertensive drug.

Combination Drug Therapy: Using more than one medication to treat hypertension is necessary under two conditions. First, combination therapy is used in people who have stage 1 hypertension and at least two or three unsuccessful attempts have been made to treat their blood pressure with single-drug therapy.

Second, combination drug therapy is used in people who have stage 2 hypertension (that is, their systolic pressure is 160 mm Hg or higher, or their diastolic pressure 100 mm Hg or higher.) Single-drug therapy is extremely unlikely to work in these people, so combination therapy is usually selected from the outset.

With so many drugs to choose from, how can doctors ever decide which drugs to combine? Thankfully, several clinical trials have been conducted that offer substantial guidance in choosing appropriate combination therapy for hypertension.

The best evidence (from the ACCOMPLISH trial) suggests that clinical outcomes (including the risk of stroke, heart attack, and cardiovascular death) are most improved with combination therapy when a long-acting calcium blocker is used together with an ACE inhibitor or an ARB. So, today most doctors will try this combination first.

If the blood pressure remains elevated with combination therapy using a calcium blocker plus an ACE or ARB drug, a thiazide drug will usually be added as a third drug. And if this combination still fails to control the blood pressure, a fourth drug (usually spironolactone, a non-thiazide diuretic) may be added.

The vast majority of patients with hypertension will achieve successful therapy long before a third or fourth drug needs to be considered. The rare individual who fails to respond adequately to this kind of combination therapy should be referred to a hypertension specialist.

Avoiding Adverse Effects

Any of the drugs used to treat hypertension has the potential of causing problems. And when choosing the “best” drug regimen for treating a person with hypertension, it is critical to find a drug (or drugs) that not only effectively reduce the blood pressure, but that also is well tolerated.

It has been very helpful that using low doses of hypertension drugs is as effective as using higher doses. The ability to get by with low doses greatly reduces the risk of adverse effects.

Still, these drugs can cause problems, and it is important for you to be aware of the potential adverse effects. While each of the myriads of hypertension drugs has its own individual “side effect profile,” for the most part the potential adverse effects of these drugs are related to their category. The major category-related adverse effects are:

• Thiazide diuretics: hypokalemia (low potassium levels), frequent urination, worsening of gout
• ACE inhibitors: a cough, loss of sense of taste, hyperkalemia (elevated potassium levels)
• Calcium blockers: constipation, swelling of the legs, headache
• Beta blockers: worsening of dyspnea in people with chronic obstructive pulmonary disease or asthma, sexual dysfunction, fatigue, depression, worsening of symptoms in people with peripheral artery disease
• ARBs: allergic reactions, dizziness, hyperkalemia

With so many drugs to choose from, it is rare that a doctor will ask a person with hypertension to tolerate significant adverse effects. if you are being treated for hypertension and you are experiencing any troublesome side effects, you should certainly talk to your doctor about finding a treatment regimen that you can tolerate better.

Most Common Hypertension Drugs

As noted at the beginning of this article, the list of drugs that have been approved for the treatment of hypertension is quite long. Here is a reasonably complete listing of these drugs. The generic name of each drug is listed first, followed by the trade names.

Diuretics: Diuretics ("water pills") increase the amount of sodium and water excreted into the urine by the kidneys. It is thought that they lower blood pressure mainly by reducing the volume of fluid in the blood vessels.

Diuretics commonly used for hypertension:

• Acetazolamide - Diamox
• Chlorthalidone - Thalidone, also sold as Tenoretic and Clorpres
• Hydrochlorothiazide - HydroDiuril, also sold as Microzide and Esidrix
• Indapamide - Lozol
• Metolazone - Zaroxolyn, also sold as Mykrox

Diuretics less commonly used for hypertension:

• Amiloride hydrochloride - Midamor
• Bumetanide - Bumex
• Ethacrynic acid - Edecrin
• Furosemide - Lasix
• Spironolactone - Aldactone
• Torsemide - Demadex
• Triamterene - Dyrenium

Beta-blockers: Beta-blockers block the effect of adrenaline on the cardiovascular system, slow the heart rate, and reduce stress on the heart and the arteries.

• Acebutolol - Sectral
• Atenolol - Tenormin
• Betaxolol - Kerlone
• Bisoprolol - Zebeta, also sold as Ziac
• Carteolol - Cartrol
• Carvedilol - Coreg
• Labetalol - Normodyne, also sold as Trandate
• Metoprolol - Lopressor, also sold as Toprol
• Nadolol - Corgard
• Penbutolol - Levatol
• Propranolol - Inderal, Inderal LA
• Timolol - Blocadren

Calcium Channel Blockers: Calcium channel blockers can reduce blood pressure by dilating the arteries and, in some cases, reducing the force of the heart's contractions.

• Amlodipine - Norvasc, also sold as Caduet and Lotrel
• Diltiazem - Cardizem, also sold as Dilacor and Tiazac
• Felodipine - Plendil
• Isradipine - DynaCirc
• Nicardipine - Cardene
• Nifedipine - Procardia XL, also sold as Adalat
• Nisoldipine - Sular
• Verapamil hydrochloride - Isoptin, also sold as Calan, Verelan, and Covera

Angiotensin Converting Enzyme Inhibitors: The angiotensin-converting enzyme inhibitors (the "ACE inhibitors") can lower blood pressure by dilating the arteries.

• Benazepril - Lotensin
• Captopril - Capoten
• Enalapril - Vasotec, also sold as Vaseretic
• Fosinopril - Monopril
• Lisinopril - Prinivil, also sold as Zestril
• Moexipril - Univasc
• Quinapril - Accupril
• Ramipril - Altace
• Trandolapril - Mavik

Angiotensin II Receptor Blockers: The angiotensin II receptor blockers (the "ARBs") also reduce blood pressure by dilating the arteries.

• Candesartan - Atacand
• Irbesartan - Avapro
• Losartan - Cozaar
• Telmisartan - Micardis
• Valsartan - Diovan

Other, Less Commonly Used Hypertension Drugs

• Clonidine - Catapres
• Doxazosin - Cardura
• Guanabenz - Wytensin
• Guanfacine - Tenex
• Hydralazine hydrochloride - Apresoline
• Methyldopa - Aldomet
• Prazosin - Minipress
• Reserpine - Serpasil
• Terazosin - Hytrin

Combination Drugs for Hypertension: Numerous combination drugs have been marketed for hypertension, and it is almost impossible to keep track of new ones that come along, or old ones that fade away. The following is a reasonably complete list of the most commonly prescribed combination drugs used for hypertension.

• Amiloride and hydrochlorothiazide - Moduretic
• Amlodipine and benazepril - Lotrel
• Atenolol and chlorthalidone - Tenoretic
• Benazepril and hydrochlorothiazide - Lotensin HCT
• Bisoprolol and hydrochlorothiazide - Ziac
• Captopril and hydrochlorothiazide - Capozide
• Enalapril and hydrochlorothiazide - Vaseretic
• Felodipine and enalapril - Lexxel
• Hydralazine and hydrochlorothiazide - Apresazide
• Lisinopril and hydrochlorothiazide - Prinzide, also sold as Zestoretic
• Losartan and hydrochlorothiazide - Hyzaar
• Methyldopa and hydrochlorothiazide - Aldoril
• Metoprolol and hydrochlorothiazide - Lopressor HCT
• Nadolol and bendroflumethiazide - Corzide
• Propranolol and hydrochlorothiazide - Inderide
• Spironolactone and hydrochlorothiazide - Aldactazide
• Triamterene and hydrochlorothiazide - Dyazide, also sold as Maxide
• Verapamil extended release) and trandolapril - Tarka

A Word From Verywell

Hypertension is an extremely common medical problem that can have severe consequences if it is not treated adequately. However, with so many treatment options, you should expect your doctor to find a therapeutic regimen that will greatly decrease your risk of a bad outcome from hypertension, without disrupting your everyday life.

Table 2. Antihypertensives: Drug Dosing and Interactions with ARVs

Back to Hypertension Chapter

Generic Drug Name	Usual Starting Dosage/Dosage Titration	Comments/Drug Interactions
Thiazide Diuretics
Pros: Cardioprotective in ALLHAT study; first-line therapy in JNC 7, VA/DoD guidelines. Thiazide diuretics and CCBs may be more effective than other antihypertensives for African American patients. Cons: Risk of hypokalemia. Monitor electrolytes periodically. Other potential adverse effects include rash, hyperglycemia, sexual dysfunction, and frequent urination. Should not be given to patients with a history of gout, as they may trigger attacks.
Chlorthalidone	Start at 12.5-25 mg QD; may increase up to 50 mg QD; dosages >50 mg carry risk of hypokalemia without added benefit
Hydrochlorothiazide (HCTZ)	Start at 12.5-25 mg QD; may increase up to 50 mg QD (dosages >25 mg carry risk of hypokalemia with limited added benefit)
Beta-Blockers (BBs)
Pros: Useful for patients with concomitant CAD, CHF, previous MI, or those in need of rate control owing to atrial fibrillation or flutter. Cons: May be associated with increased risk of stroke (particularly in smokers) and insulin resistance. When discontinuing, taper over course of 14 days to avoid rebound hypertension, angina, MI, or arrhythmia. May be less effective for patients without CAD, especially elderly patients. Use with caution in patients with reactive airway disease. Potential adverse effects include bradycardia, hypotension, fatigue, and sexual dysfunction.
Atenolol	Start at 25-50 mg QD or divided BID; maximum 100 mg per day	ATV may ↑ atenolol concentrations; no dosage adjustment appears to be necessary.
Metoprolol	Start at 50 mg BID; maximum 225 mg BID	CYP 2D6 substrate; PIs may ↑ metoprolol levels.
Metoprolol Extended Release	Start at 50-100 mg QD; maximum 400 mg QD	CYP 2D6 substrate; PIs may ↑ metoprolol levels.
Propranolol	Start at 20 mg BID; maximum 640 mg per day in divided doses
Propranolol Extended Release	Start at 60 mg QD; maximum 640 mg QD	Extended-release formulation cannot be substituted for immediate-release form on a mg per mg basis; may require dosage change.
Mixed Alpha-/Beta-Blockers
Pros: Useful for patients with known CAD or CHF. Cons: Same as for BBs. Avoid in patients with decompensated heart failure who are dependent on sympathetic stimulation.
Carvedilol	Start at 6.25 mg BID; titrate slowly; usual dosage: 12.5-50 mg/day, divided BID	CYP 2D6 substrate; PIs may ↑ carvedilol levels.
Labetalol	Usual dosage: 200-800 mg/day, divided BID	IV form useful in hypertensive emergencies.
ACE Inhibitors
Pros: Cardioprotective, renal protective. Cons:Avoid during pregnancy; use with caution in patients who are elderly, are fluid depleted, or have renal insufficiency. Risk of hyperkalemia. Check electrolytes 1 week after starting ACEI. Other potential adverse effects include angioedema, cough, renal insufficiency, and sexual dysfunction.
Benazepril	Start at 10 mg QD; maximum 80 mg per day; usual dosage: 20-40 mg QD or divided BID; may need BID dosing for continuous BP control	Start at 5 mg QD if patient is elderly, has renal insufficiency, or is taking a diuretic.
Fosinopril	Start at 10 mg QD; maximum 80 mg per day, but no additional effect over 40 mg per day; usual dosage: 10-40 mg QD or divided BID; BID dosing may be needed for continuous BP control	Start at 5 mg QD if patient is elderly, has renal insufficiency, or is taking a diuretic.
Lisinopril	Start at 10 mg QD; maximum 80 mg QD but no additional effect over 40 mg per day; usual dosage: 20-40 mg QD	Start at 2.5-5 mg QD if patient is elderly, has renal insufficiency, or is taking a diuretic.
Ramipril	Start at 2.5 mg QD; maximum 20 mg QD; usual dosage: 2.5-20 mg QD or divided BID; may need BID dosing for continuous BP control	Start at 1.25 mg QD if patient is elderly, has renal insufficiency, or is taking a diuretic.
Angiotensin Receptor Blockers (ARBs)
Pros: Cardioprotective, renal protective. Cons:Avoid during pregnancy; use with caution in patients who are elderly, are fluid depleted, or have renal insufficiency. Risk of hyperkalemia. Other potential adverse effects include angioedema and renal dysfunction.
Candesartan	Usual starting dosage: 16 mg QD, may be divided BID; maximum 32 mg per day	Start at lower dosage in patients with moderate or worse hepatic impairment, volume depletion.
Irbesartan	Start at 150 mg QD; maximum 300 mg QD	Start at 75 mg QD for patients with volume depletion.
Losartan	Start at 50 mg QD; maximum 100 mg QD or divided BID	Start at 25 mg QD for patients with volume depletion or hepatic insufficiency.
Telmisartan	Usual starting dosage: 40 mg QD; maximum 80 mg QD	Start at 20 mg QD in elderly, patients with hepatic impairment or volume depletion; monitor closely.
Valsartan	Start at 80 mg QD; maximum 320 mg QD
Calcium Channel Blockers (CCBs)
Pros: CCBs and thiazide diuretics may be more effective than other antihypertensives for African American patients. Cons: Metabolism of CCBs is inhibited by PIs; if CCBs must be used with PIs, reduce initial dosage and titrate up while monitoring for side effects (eg, hypotension, conduction block, bradycardia, and peripheral edema). Metabolism of CCBs may be induced by the NNRTIs EFV and NVP, leading to blunted antihypertensive effect. Avoid immediate-release forms. Avoid in patients with CHF.
Amlodipine	Start at 2.5 mg QD; maximum 10 mg daily	See Cons above.
Diltiazem Sustained Release	Start at 60 mg BID; maximum 360 mg per day in divided doses
Diltiazem Extended Release	Start at 120 mg QD; maximum 540 mg QD
Nifedipine Extended Release	Start at 30 mg QD; maximum 120 mg QD
Verapamil Sustained Release	Start at 120 mg QD; maximum 480 mg per day, but divide BID if using >240 mg per day	Immediate-release formulation is not recommended for treatment of hypertension.
Verapamil Extended Release	Covera HS: Start at 180 mg QHS; maximum 480 mg QHS Verelan PM: start at 100 mg QHS; maximum 400 mg QHS	Immediate-release formulation is not recommended for treatment of hypertension.
Potassium-Sparing Diuretics and Aldosterone Antagonists
Pros: Indicated in CAD, and CHF with EF <40%, class IV heart failure. May be useful in patients with hypokalemia; often combined with a thiazide diuretic. Cons: May cause hyperkalemia: monitor K+
Spironolactone	Usual dosage is 50 mg to 100 mg QD or divided BID	Monitor for hyperkalemia; check K+ 1 week after starting spironolactone. Potential adverse effects include liver toxicity, gynecomastia, and sexual dysfunction.
Triamterene	Start at 100 mg BID; maximum daily dosage is 300 mg	Monitor for hyperkalemia; check K+ 1 week after starting triamterene.
Direct Vasodilators and Anti-Adrenergic Agents
(Note: Alpha-blockers used for treatment of benign prostatic hypertrophy are not recommended as monotherapy for hypertension; however, these may cause hypotension especially in patients who are taking other antihypertensive medications.)
Clonidine	PO: Start at 0.1 mg BID; increase to usual maintenance dosage of 0.2-1.2 mg divided BID to TID; maximum 2.4 mg in divided doses Patch: Start at 0.1 mg/24-hour patch, increasing to desired effect; maximum dosage is 0.6 mg/24-hour patch	Possible adverse effects include bradycardia, sedation. Risk of rebound hypertension upon discontinuation: taper over course of 7 days.
Hydralazine	Start at 25 mg BID; increase by 10-25 mg/dose to effective dosage; may divide effective daily dosage BID; maximum 200 mg per day in divided doses	Possible adverse effects include lupus-like syndrome, requiring discontinuation (increased risk at higher dosages). May cause reflex tachycardia; use with caution in patients with CAD.
Doxazosin	Start at 1 mg QHS; maximum 16 mg per day	Not a first-line agent. Possible adverse effects include risk of CHF, dizziness, postural hypotension, drowsiness, and syncope; all more likely if doxazosin is given with other vasodilators, including PDE-5 inhibitors. Risk of syncope with initial dosages; start at lowest dose QHS. If drug is interrupted, restart at 1 mg QHS dosing.
Prazosin	Start at 1 mg BID or TID; usual maintenance dosage 20 mg/day divided BID or TID; maximum 40 mg divided BID or TID	Not a first-line agent. Possible adverse effects include risk of CHF, dizziness, postural hypotension, drowsiness, and syncope; all more likely if prazosin is given with other vasodilators, including PDE-5 inhibitors. Risk of syncope with initial dosages; start at lowest dose QHS. If drug is interrupted, restart at 1 mg QHS.
Terazosin	Start at 1 mg QHS; usual daily dosage 1-5 mg QD or divided BID; maximum 20 mg per day	Not a first-line agent. Possible adverse effects include risk of CHF, dizziness, postural hypotension, drowsiness, and syncope; all more likely if terazosin is given with other vasodilators, including PDE-5 inhibitors. Risk of syncope with initial dosages; start at lowest dosage QHS. If drug is interrupted, restart at 1 mg QHS dosing.

From Hypertension
Primary Care of Veterans with HIV
Office of Clinical Public Health Programs
Veterans Health Administration, 2009

Diuretics

There are three classes of diuretic drugs that are used to treat hypertension. Most commonly used are thiazide diuretics such as hydrochlorothiazide or chlorthalidone. There is not usually an increased urine flow after the first one or two days of taking these medications. Nevertheless, it is best to take them in the morning to prevent annoying urine production overnight. They are effective in lowering blood pressure in the great majority of patients, especially those over 60, African Americans, and those with diabetes. Diuretics increase the effectiveness of all other categories of antihypertensives. That is why they are an essential part of almost any multidrug regimen for hypertension.
Special Points: Diuretics are the original antihypertensives. Therefore, their efficacy and adverse effects are very well understood. No drug is more effective overall in reducing blood pressure than a diuretic when given with dietary salt restrictions. Adverse effects are usually slight, and can often be anticipated and prevented (see below). The recent large scale clinical trial, ALLHAT, compared outcomes amongst hypertensive subjects with cardiovascular risk factors who were randomized to receive either a diuretic (chlorthalidone), an angiotensin converting enzyme inhibitor (ACEI; ramipril) or an calcium channel blocker (CCB; amlodipine) reported that the more modern drugs were no more effective overall in preventing cardiovascular disease than the diuretic and no more effective in lowering blood pressure. For this reason, the Joint National Commission on Hypertension Detection Evaluation and Treatment (JNCVII) recommended thiazide diuretics as first line therapy for patients with hypertension, unless there were special reasons to select another type of drug.
Thiazide diuretics reduce calcium excretion and have beneficial effects in preventing bone loss and fractures, especially in elderly subjects.
Diuretics increase the effectiveness or all other classes of antihypertensive agents. Therefore, almost any subject, except those with a contraindication, should receive a diuretic if their blood pressure requires more than one drug for its management.
Adverse Effects: Diuretics increase the excretion of potassium and can lead to hypokalemia (low blood potassium concentration) which predisposes to irregular heart beats, and muscular weakness. However, a combination of a thiazide or loop diuretic with a distal, potassium sparing agent (such as in the combined medications, Maxzide or Moduretic), prevents potassium loss and obviates this problem. Diuretics lead to some increase in uric acid and should not normally to be used in patients with gout. They cause a small increase in blood glucose, but it is unclear whether this predisposes to diabetes in the long term. Over treatment with diuretics can lead to low blood pressure, orthostatic hypotension (weakness, dizziness and possibly fainting on standing) and a feeling of tiredness and lethargy, all of which can be prevented or reversed by holding the diuretic for a day or two and resuming, if necessary, at a lower dosage.
Different Drugs: Thiazide diuretics include: hydrochlorothiazide (usual starting dose 12.5 to 25 mg daily) or chlorthalidone (similar dose range). Loop diuretics include: furosemide (Lasix), bumetanide (Bumex), and torsemide (Demadex), torsemide has a rather longer duration and is preferred in patients with heart failure. Ethacrinic acid (Edecrin) is used in the rare patients who are allergic to diuretics. Loop diuretics are not as effective as thiazides in lowering blood pressure in patients with hypertension. They are used especially to treat edema (swelling of the ankles) or heart failure. However, unlike thiazides, they effective in patients with poor kidney function in lowering blood pressure or treating edema.
Distal, potassium retaining diuretics include: amiloride (Midamor) and Triamterene (Dyrenium), together with spironolactone (Aldactone) and eplerenone (Inspra). All these agents can raise serum potassium. This is usually beneficial in patients receiving thiazide or loop diuretics who have increased loss of potassium in the urine. Thus these drugs are often prescribed together. However an increase in serum potassium predisposes to cardiac arrhythmias and can be especially dangerous in patients with a thickened heart (left ventricular hypertrophy) or coronary artery disease. Spironolactone causes problems with sexual performance and sometimes breast swelling in males, but is free of these kinds of effects in females. Eplerenone does not have these adverse effects, but is more expensive.

ANGIOTENSIN CONVERTING ENZYME INHIBITORS (ACEIs)

ACEIs are widely used to treat hypertension because they are effective, have relatively few side effects and in reduce the complications of hypertension such as heart attacks and strokes. They have a special use in patients with diabetes mellitus who have protein the urine ("diabetic nephropathy") and in patients with chronic kidney disease (CKD) in whom they appeared to have beneficial actions in slowing the loss of kidney function above that achieved by other agents.
ACEIs block the action of the renin angiotensin system (RAS). Renin is released from the kidney during low blood pressure, low salt intake or diuretic usage and generates angiotensin II, which constricts blood vessels, retains salt and water by the kidneys and raises blood pressure. Therefore, these drugs target important hypertensive mechanisms. Younger and white subjects are particularly likely to have an activated RAS whereas elderly and African American subjects are less likely. Therefore, ACEIs are especially effective in the former. They interact very well with diuretics. Diuretics enhance the action of ACEIs, whereas ACEIs themselves act on the kidney to retain some potassium, thereby reducing the adverse affect of low blood potassium that can occur during diuretic therapy. Indeed, there are a number of combination drugs in which an ACEI and a diuretic are included in the same medication.
Individual Drugs: The following are examples of ACEIs in clinical practice: benazepril (Mylan), captopril (Capoten), enalapril (Vasotec), fosinopril (Monopril), Lisinopril (Prinivil), moexipril (Univasc), quinapril (Accupril), ramipril (Altace) and trandolapril (Mavik). There are some small differences in how long these drugs act in the circulation, they are relatively small and, with the exception of the very short acting captopril, any of these agents are usually affective when given once or sometimes twice daily as antihypertensive agents.
Adverse Effects: The quality of life of patients receiving ACE inhibitors is not impaired. They do not affect concentration, sleep, exercise abilities, sexual performance or wellbeing. However, 10 to 20 percent of subjects develop an irritant cough. If this occurs, the drug should be withdrawn and the patient advised that they should not have long term therapy with an ACEI since this is an effect common to all drugs of this class. Very rarely, they can cause a dangerous swelling of the tongue, lips and throat, which, in extreme circumstances, can seriously interfere with breathing and requires emergent treatment. Patients with chronic kidney disease often have a temporary worsening of kidney function as shown by a rise in blood urea nitrogen (BUN) or creatinine concentration, but this is temporary and modest, and is not necessarily a contraindication to prolonged therapy. Indeed, ACEI treatment has been shown in some, but not all studies do delay the onset of end stage renal disease (ESRD). ESRD is the requirements for dialysis or renal transplant in patients with progressive kidney disease.
Biochemical changes with ACEIs are usually insignificant in patients with normal kidney function. However, in those with impaired kidneys, they can raise the serum potassium concentration to levels that are dangerous and require either a change in therapy, or increasing thiazide or loop diuretic dosage to promote potassium loss. Such patients should discuss with their physician or a nutritionist how to restrict of dietary potassium intake. Generally, ACEIs improve blood glucose and maybe beneficial in patients at risk for developing diabetes mellitus. These drugs can reduce the thickness of the heart (left ventricular hypertrophy), which occur after prolonged hypertension and predisposes to congestive heart failure (CHF). ACEIs are strongly indicated in patients who have congestive heart failure since numerous studies have shown that cardiac performance and life expectancy is improved in patients who receive these drugs even if they are not hypertensive.
Special Indications: As these include patients with chronic kidney disease (but see the adverse effects above), early diabetes mellitus, congestive heart failure, or left ventricular hypertrophy.

ANGIOTENSIN RECEPTOR BLOCKERS (ARBs):

ARBs also block the renin angiotensin system (RAS), similar to ACEIs, but have a different mechanism of action by blocking the actions of angiotensin II in the tissues rather than the generation of angiotensin II, which is the action of ACEIs. These drugs also have an excellent acceptability and preservation of quality of life. Moreover, they do not cause an irritant cough or the rare danger of swelling of the lips, tongue and throat, that can occur with ACEIs. In general, the indications for their use, their effectiveness and beneficial interactions with thiazides and loop diuretics are similar to ACEIs. Some studies have suggested they are particularly effective in preventing stroke and that they may have an additional action to diminish the progression of Alzheimer’s disease in those with early dementia, but this requires conformation.
Individual Drugs ARBs include: candesartan (Atacand), eprosartan (Teveten), irbesartan (Avapro), losartan (Cozaar), olmesartan (Benicar), telmisartan (Micardis) and valsartan (Diovan). As with ACEIs, there are only minor differences between agents in this class of drugs. All are effective in lowering blood pressure when given once, or perhaps twice daily.
Adverse Effects: As discussed, these drugs do not cause irritant cough, but otherwise have a similar spectrum of adverse actions to ACEIs.
Special Indications: These are similar to ACEIs except that they have not been shown to be beneficial in patients with congestive heart failure and maybe particularly helpful in preventing stroke and progression of Alzheimer’s disease.

BETA BLOCKERS, ALPHA BLOCKERS AND SYMPATHOLYTIC DRUGS

This group of drugs was introduced next after diuretics, to be used for hypertension. They act on a part of the nervous system that controls blood pressure, known as the sympathetic nervous system. Blockade of the sympathetic nervous system reduces blood pressure by relaxing blood vessels, and decreasing the rate and force of contraction of the heart. Therefore, beta blockers and sympatholytics typically slow the heart rate which can occasionally cause problems in subjects with a slow heart rate.
The actions of these agents are enhanced in patients taking diuretic drugs and therefore are a good second or third line selection in those patients who are not controlled with a diuretic and an ACEI or ARB. Unfortunately, alpha blockers have been shown to be less affective than other groups of blood pressure lowering agents in preventing the complications of heart failure and heart attacks in hypertensive subjects. Therefore, they are not routinely used and so will not be discussed further.
Beta blockers are affective in lower blood pressure and reducing its complications. However, their popularity has diminished because of a large range of annoying adverse effects. Although these are rarely serious, they do adversely impact the quality of life of some patients, and this limits their popularity. Nevertheless, beta blockers have been shown in many trials to prevent the probability of a recurrence in patients who have had a heart attack. Therefore, they are strongly indicated in these patients even if they cause some side effects or the patient does not have high blood pressure.
Sympatholytic agents act in the brain to decrease the drive to the sympathetic nerves. In this sense, the effects are somewhat similar to beta blockers, but because of their action in the brain, they have a different, and often rather worse, spectrum of adverse effects.
Individual Agents: The following are some beta blockers that are in current use: nadolol (Corgard), propranolol (Inderal), atenolol (Tenormin), metoprolol (Toprol), carvedilol (Coreg) and labetalol.
There are significant differences between many of the drugs in this class. Some such as atenolol abd metoprolol work on a selective part of the sympathetic nervous system and do not have so many adverse effects regarding precipitating asthma. Others such as carvedilol and labetalol act on additional parts of the sympathetic nervous system and are therefore more potent. The physician may change therapy from one to another beta blocker if it is insufficient or producing adverse effects.
Adverse Effects: The most frequent adverse effects of beta blockers are: slow heart rate, depression and irritability, impaired sleep, decreased exercise capacity, wheezing and precipitation of asthma, sexual dysfunction, and an increase in serum potassium (hyperkalemia). These effects are mostly dose dependent and, if encountered, may be amendable to reduction in dosage.
Special Indications: Beta blockers have some additional effects that make them attractive therapy for certain of patients. Thus, they are effective in reducing the frequency of migraine attacks, their slowing of the heart can be beneficial in people who have fast and irregular heart rates or atrial fibrillation, they reduce the symptoms and bad outcome in patients who have angina (chest pain on exertion due to narrowed coronary arteries), they reduce tremor of the hands in patients with essential tremor and they are protective in patients who have had a prior heart attack. They are used increasingly in patients with congestive heart failure.
Central Sympatholytic Agent: These agents include the following: clonidine (Catapres), and alpha methyldopa (Aldomet). Catapres is available as a patch similar to a band-aid which provides slow release of the drug over the course of a week. This is especially beneficial in patients who have difficulty in remembering to take the medication, but often leads to allergic skin troubles after some months.
Adverse Effects of Central Sympatholytic Agent: These include many of the problems encountered with beta blockers. In addition, these agents can cause a dry mouth, difficulty in focusing the eyes, constipation, and sleepiness during the daytime.

CALCIUM CHANNEL BLOCKERS (CCBs)

These are very effective in lowering blood pressure. They act directly on the blood vessels to cause relaxation. They are used sometimes as first line therapy but more often with diuretics or ACEIs or ARBs as second or third line therapy. They are especially effective in lowering blood pressure in elderly, black, obese, and diabetic patients. They are excellent in preventing stroke but rather less effective than diuretics, ACEIs, and ARBs in preventing heart failure.
Individual drugs: They fall into two categories. The first are called dihydropyridine CCBs and include amlodipine (Norvasc), felodipine (Plendil), nifedipine (Procardia), and nicardipine (Cardene). The second, termed nondihydropyridine CCBs include two drugs, diltiazem (Dilacor, Cardizem, Cartia, and Tiazac), and verapamil (Calan, Covera, Isoptin, Verelan). Both groups are effective in lowering the blood pressure but have different effects on the heart and rather different adverse effects. Dihydropyridine drugs generally do not impair the function of the heart and do not cause much cardiac slowing but can cause swelling of the ankles. Nondihydropyridine drugs, especially verapamil, slow the heart, similar to beta blockers and cause constipation, especially in elderly subjects.
Adverse Effects: They are usually well tolerated, and most patients have few side effects. However, dihydropyridine CCBs do cause swelling of the ankles (edema), which is worse in hot weather and at higher dosage. This usually does not indicate a major problem such as heart failure but an increased passage of fluid from the plasma into the tissues of the skin. The only way to manage edema of this type is to reduce the dose or change to another agent, although occasionally, ACEI will be beneficial.
Non-dihydropyridine CCBs cause cardiac slowing. This typically reduces the heart rate by about 10%. It can be beneficial in some patients with a fast heart rate or who have irregular heartbeat (atrial fibrillation), but in those with a slow initial heart rate, it can cause symptoms of decreased cardiac output (tiredness, lethargy, and dizziness on exertion). This group of drugs also can cause constipation, especially in the elderly but rarely cause edema.

OTHER DRUGS

There are a number of other drugs available to treat hypertension, but they are either rather new and expensive or suffer from some particular adverse effects and therefore are usually reserved only for exceptional circumstance, for example, when patients remain hypertensive despite receiving 3 or 4 other drugs from established categories described above.
These drugs will not be discussed in detail since they are used infrequently.