Bendroflumethiazide

Definition

Antihypertensive drugs are medicines that help lower blood pressure.

Purpose

The overall class of antihypertensive agents lowers blood pressure, although the mechanisms of action vary greatly. Within this therapeutic class, there are several subgroups. There are a very large number of drugs used to control hypertension, and the drugs listed below are representatives, but not the only members of their classes.

The calcium channel blocking agents, also called slow channel blockers or calcium antagonists, inhibit the movement of ionic calcium across the cell membrane. This reduces the force of contraction of muscles of the heart and arteries. Although the calcium channel blockers are treated as a group, there are four different chemical classes, leading to significant variations in the activity of individual drugs. Nifedipine (Adalat, Procardia) has the greatest effect on the blood vessels, while verapamil (Calan, Isoptin) and diltiazem (Cardizem) have a greater effect on the heart muscle itself.

Peripheral vasodilators such as hydralazine (Apresoline), isoxuprine (Vasodilan), and minoxidil (Loniten) act by relaxing blood vessels.

There are several groups of drugs which act by reducing adrenergic nerve stimulation, the excitatory nerve stimulation that causes contraction of the muscles in the arteries, veins, and heart. These drugs include the beta-adrenergic blockers and alpha/beta adrenergic blockers. There are also non-specific adrenergic blocking agents.

Beta-adrenergic blocking agents include propranolol (Inderal), atenolol (Tenormin), and pindolol (Visken). Propranolol acts on the beta-adrenergic receptors anywhere in the body, and has been used as a treatment for emotional anxiety and rapid heart beat. Atenolol and acebutolol (Sectral) act specifically on the nerves of the heart and circulation.

There are two alpha/beta adrenergic blockers, labetolol (Normodyne, Trandate) and carvedilol (Coreg). These work similarly to the beta blockers.

Angiotensin-converting enzyme inhibitors (ACE inhibitors) act by inhibiting the production of angiotensin II, a substance that both induces constriction of blood vessels and retention of sodium, which leads to water retention and increased blood volume. There are 10 ACE inhibitors currently marketed in the United States, including captopril (Capoten), benazepril (Lotensin), enalapril (Vasotec), and quinapril (Acupril). The primary difference between these drugs is their onset and duration of action.

The ACE II inhibitors, losartan (Cozaar), candesartan (Atacand), irbesartan (Avapro), telmisartan (Micardis), valsartan (Diovan) and eprosartan (Teveten) directly inhibit the effects of ACE II rather than blocking its production. Their actions are similar to the ACE inhibitors, but they appear to have a more favorable side effect and safety profile.

In addition to these drugs, other classes of drugs have been used to lower blood pressure, most notably the thiazide diuretics. There are 12 thiazide diuretics marketed in the United States, including hydrochlorothiazide (Hydrodiuril, Esidrex), indapamide (Lozol), polythiazide (Renese), and hydroflumethiazide (Diucardin). The drugs in this class appear to lower blood pressure through several mechanisms. By promoting sodium loss they lower blood volume. At the same time, the pressure of the walls of blood vessels, the peripheral vascular resistance, is lowered. Thiazide diuretics are commonly used as the first choice for reduction of mild hypertension, and may be used in combination with other antihypertensive drugs.

Recommended dosage

Recommended dosage varies with patient, drug, severity of hypertension, and whether the drug is being used alone or in combination with other drugs. Consult specialized references for further information.

Precautions

Because of the large number of classes and individual drugs in this group, consult specialized references for complete information.

Peripheral vasodilators may cause dizziness and orthostatic hypotension-a rapid lowering of blood pressure when the patient stands up in the morning. Patients taking these drugs must be instructed to rise from bed slowly. Pregnancy risk factors for this group are generally category C. Hydralazine has been shown to cause cleft palate in animal studies, but there is no human data available. Breastfeeding is not recommended.

ACE inhibitors are generally well tolerated, but may rarely cause dangerous reactions including laryngospasm and angioedema. Persistent cough is a common side effect. ACE inhibitors should not be used in pregnancy. When used in pregnancy during the second and third trimesters, ACE inhibitors can cause injury to and even death in the developing fetus. When pregnancy is detected, discontinue the ACE inhibitor as soon as possible. Breastfeeding is not recommended.

ACE II inhibitors are generally well tolerated and do not cause cough. Pregnancy risk factor is category C during the first trimester and category D during the second and third trimesters. Drugs that act directly on the renin-angiotensin system can cause fetal and neonatal morbidity and death when administered to pregnant women. Several dozen cases have been reported in patients who were taking ACE inhibitors. When pregnancy is detected, discontinue ACE inhibitors as soon as possible. Breastfeeding is not recommended.

Thiazide diuretics commonly cause potassium depletion. Patients should have potassium supplementation either through diet, or potassium supplements. Pregnancy risk factor is category B (chlorothiazide, chlorthalidone, hydrochlorothiazide, indapamide, metolazone) or category C (bendroflumethiazide, benzthiazide, hydroflumethiazide, methyclothiazide, trichlormethiazide). Routine use during normal pregnancy is inappropriate. Thiazides are found in breast milk. Breastfeeding is not recommended.

Beta blockers may cause a large number of adverse reactions including dangerous heart rate abnormalities. Pregnancy risk factor is category B (acebutolol, pindolol, sotalol) or category C (atenolol, labetalol, esmolol, metoprolol, nadolol, timolol, propranolol, penbutolol, carteolol, bisoprolol). Breastfeeding is not recommended.

Interactions

Health care personnel should consult specific references for food and drug interactions.

Key Terms

Adrenergic

Activated by adrenalin (norepinephrine), loosely applied to the sympathetic nervous system responses.

Angioedema

An allergic skin disease characterized by patches of circumscribed swelling involving the skin and its subcutaneous layers, the mucous membranes, and sometimes the viscera-called also angioneurotic edema, giant urticaria, Quincke's disease, or Quincke's edema.

Arteries

Blood vessels that carry blood away from the heart to the cells, tissues, and organs of the body.

Laryngospasm

Spasmodic closure of the larynx.

Pregnancy category

A system of classifying drugs according to their established risks for use during pregnancy. Category A: Controlled human studies have demonstrated no fetal risk. Category B: Animal studies indicate no fetal risk, but no human studies; or adverse effects in animals, but not in well-controlled human studies. Category C: No adequate human or animal studies; or adverse fetal effects in animal studies, but no available human data. Category D: Evidence of fetal risk, but benefits outweigh risks. Category X: Evidence of fetal risk. Risks outweigh any benefits.

Sympathetic nervous system

The part of the autonomic nervous system that is concerned especially with preparing the body to react to situations of stress or emergency; it contains chiefly adrenergic fibers and tends to depress secretion, decrease the tone and contractility of smooth muscle, and increase heart rate.