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Pharmaceutical Therapies For Hypertension

Conventional management of hypertension begins with lifestyle modification, followed by the possible addition of one or more antihypertensive drug therapies to achieve a target blood pressure goal of less than 140/90 mm Hg (< 130/80 mm Hg for persons with diabetes or renal disease). As described earlier, studies show that blood pressure over 115/75 mmHg can increase risk of vascular disease. However, it is also important to consider that overly aggressive blood pressure lowering in aging individuals with pre-existing, long-standing hypertension or other cardiovascular disease may be dangerous.

Thus, a blood pressure reduction regimen must be accompanied by close supervision and careful monitoring of blood pressure throughout the day. A diligent plan encompassing regular at-home blood pressure monitoring and regular healthcare practitioner-patient interaction will ensure optimal risk reduction and patient safety.

Antihypertensive drugs lower blood pressure by attenuating one or more of the blood pressure regulating mechanisms. Major “classes” of antihypertensive drugs are variably defined, but the most widely prescribed can be grouped into 3 categories based on their activities.


Reduction of blood volume is the first target of conventional antihypertensive therapies. Diuretics (thiazide diuretics, loop diuretics, potassium-sparing diuretics) are the most commonly prescribed drugs in this category. Diuretics exert effects upon the kidneys to increase the excretion of water. This drop in blood volume results in a drop in pressure.

Adverse effects of thiazide diuretics include sexual dysfunction, glucose intolerance, gout, low potassium level (hypokalemia), and low sodium level (hyponatremia). Conventional doctors often overlook the depletion of vital magnesium that can be caused by diuretics. Many patients do better by starting with the angiotensin II receptor blockers described later in this chapter. Those who require diuretic drugs should supplement with plenty of magnesium and potassium if dietary intake is low (dietary intake of magnesium is usually too low even for those who do not take diuretic drugs).

Cardioinhibitory drugs

Cardioinhibitory drugs decrease the rate and force with which the heart pumps, reducing cardiac output and lowering blood pressure.

Beta blockers lower heart rate and blood pressure by blocking the beta adrenoceptors. Normally, these adrenoceptors sense the hormones epinephrine (adrenaline) and norepinephrine in the blood, then respond by increasing heart rate and constricting blood vessels outside the heart. Beta blockers disrupt this interaction.

Beta blockers are contraindicated in individuals with COPD (chronic obstructive pulmonary disease) and asthma. Side effects include a worsening of blood glucose control (in diabetics), elevated triglycerides, and lower high-density lipoprotein (HDL—sometimes called the “good” cholesterol) levels. These drugs may exacerbate depressive symptoms, cause erectile dysfunction, and are associated with sleep disturbances, fatigue and lethargy.

A second group of drugs, calcium channel blockers, specifically bind to and block the channels (cellular pores) that allow calcium to flow into cardiac muscle cells. Since muscle fibers require calcium for contraction, reducing the availability of calcium in cardiac muscle lowers the force at which the heart contracts, lowering blood pressure. Additionally, certain calcium channel blockers, which are less specific toward calcium channels in the heart, also have vasodilating properties.

Side effects commonly associated with calcium channel blockers include flushing of the face and neck, headache, edema (swelling) usually in the ankles and feet, dizziness, fatigue, and skin rash.


Vasodilators increase the diameter of vessels, lowering their resistance and the pressure required to move blood through them. There are several types with differing mechanisms. Angiotensin-converting enzyme (ACE) inhibitors stop the activity of ACE, the enzyme which catalyzes the final step in the synthesis of the hypertensive hormone angiotensin II. By lowering levels of angiotensin II, ACE inhibitors promote the dilation of blood vessels, increasing the excretion of water and sodium from the kidneys, thereby lowering blood volume. Frequent side effects of ACE inhibitor use include dizziness, fatigue, weakness, headache and persistent dry cough.
Renin inhibitors, another group of vasodilators, also reduce angiotensin II levels at the first step of its synthesis. This class of drugs is associated with several side effects, which include diarrhea, dizziness, flu-like symptoms, fatigue, and cough.

The effects of angiotensin receptor blockers (ARB) are similar to ACE inhibitors. Instead of reducing the levels of angiotensin II, however, they reduce its bioactivity, preventing it from interacting with receptors on the surface of cells and signaling hypertensive effects.

In addition to efficiently lowering blood pressure (Heran 2008), a comprehensive review of published studies, which examined data for nearly 150,000 subjects, revealed that use of an angiotensin receptor blocker was associated with a 10% reduction in the likelihood of suffering a stroke, heart failure, or developing diabetes (Bangalore 2011).

Angiotensin receptor blockers also convey some surprising additional benefits. Studies show that suppressing the signaling of angiotensin receptors may blunt oxidative stress and encourage the activation of genes associated with enhanced longevity. Amazingly, animals genetically engineered not to express the primary angiotensin receptor were shown to live 28% longer than normal animals (Benigni 2009). Moreover, these animals have a greater number of mitochondria, the cellular components that provide the energy needed to function with youthful vigor (Cassis 2010). Other data indicate that angiotensin receptor blockers may help modulate the immune system in ways that discourage autoimmunity, suppress inflammation, and slow the progression of cardiovascular disease independent of their effects on blood pressure (Stegbauer 2011).

Angiotensin receptor blockers may cause dizziness, headache, or elevated blood levels of potassium (hyperkalemia); emerging evidence also suggests that some drugs in this class may cause severe gastrointestinal problems resembling celiac disease (Rubio-Tapia 2012). However, most individuals do not experience these effects.

For many of those with hypertension, taking an individualized daily dose of an angiotensin receptor blocker can keep blood pressure readings in optimal ranges over a 24 hour period.

Alpha blockers prevent the binding of norepinephrine to alpha adrenoceptors, which are located on vascular smooth muscle cells within blood vessel walls. They function much like beta blockers do in the heart, preventing the contraction of blood vessels in response to stress hormones. This class of medication can sometimes cause dizziness, lightheadedness, or fainting upon arising from a sitting or lying position.

Lethal Misconception About Anti-Hypertensive Drugs

A properly functioning heart is of little consequence without the means to maintain a predictable pressure throughout the circulatory system. A dangerous assumption made by doctors is that once a day dosing with an anti-hypertensive drug will keep a patient’s blood pressure under control over an entire 24-hour period. The reality is that these drugs will wear off in many patients within 12 to 18 hours, leaving the body vulnerable to dangerous daily blood pressure spikes. Few physicians understand that it is during periods of the day when blood pressure spikes above 115/75 that damage is inflicted. Therefore, keeping blood pressure suppressed for even 18 hours leaves patients exposed to the damaging effects of hypertension for 6 hours every day.

The best way to effectively monitor blood pressure is with an at-home blood pressure monitor. If one takes a 50 mg dose of losartan in the morning, and their blood pressure exceeds 115/75 at any time of the day thereafter, they should consult their physician about taking a second dose of losartan in the evening to ensure all-day blood pressure control.

It does not matter what drug or natural therapy one employs to lower their blood pressure. The objective is to use at-home blood pressure devices to achieve blood pressure readings no higher than 115/75 throughout a 24 hour period.

Blood Pressure Medications may confer Greater Protection if Taken at Bedtime in Some Populations

A 2011 study revealed that dosing schedules for antihypertensive medications may influence their efficacy (Hermida 2011).

In 661 patients with chronic kidney disease, ambulatory blood pressure was measured at baseline then tracked for over 5 years after adjusting medication scheduling according to one of two regimens. In the first group, all antihypertensive drugs were taken upon awakening, while a second group took at least one medication at bedtime. Not only did the second group have lower blood pressure during sleep, but a significantly greater percentage of them gained control over their daytime blood pressure compared to the morning dosing group.

After analyzing the study data, researchers uncovered a dramatic reduction in the risk of cardiovascular events and associated mortality – those taking blood pressure meds at bedtime had only about one-third the risk versus those taking all their blood pressure meds in the morning. Moreover, each 5 mmHg reduction in blood pressure during sleep was tied to a 14% reduction in cardiovascular events during the follow-up period.

While this study clearly shows that those with chronic kidney disease and hypertension benefited from a bedtime dosing regimen, it does not necessarily mean that a similar effect will be observed in other populations. However, Life Extension suggests that everyone taking a blood pressure lowering drug consult with their health care provider as to whether adjusting their dosing regimen to include at least one of their meds at bedtime may be wise.