Overview
Antihypertensives aim to reduce
cardiac output and/or total peripheral resistance.
– For a review of how cardiac output and total peripheral resistance, please see our tutorial on
hypertension pathophysiology.
Lowering blood pressure in hypertensive patients reduces their risk of cardiovascular disease and cerebrovascular events.
– Recent guidelines recommend a target blood pressure of
less than 130/80 mmHg.
The following lifestyle modifications are typically suggested:
– Changes in diet, increased physical activity, stress reduction, smoking and alcohol cessation or reduction, and weight loss.
DASH:
Dietary changes to reduce hypertension are encapsulated by the Dietary Approaches to Stop Hypertension (DASH) plan, which recommends reductions in sodium and emphasizes whole grains, fruits, vegetables, low-fat dairy, fish, poultry, and legumes, nuts, and seeds.
In many individuals, however, lifestyle modifications are inadequate or even inappropriate for reducing blood pressure; these patients will need antihypertensive medications.
Initial treatment may rely on a single medication, depending on the stage of hypertension.
However, many patients ultimately require two or more drugs with complementary actions to reach their target blood pressure.
Individuals vary in their responses to antihypertensive medications, and that specific recommendations are made for some populations.
– For example, African Americans, the elderly, and patients with certain medical conditions may respond differently to an antihypertensive drug than other populations.
- *Resistant hypertension is when an individual's blood pressure remains elevated above the target goal, despite concurrently using three or more antihypertensive medications, including a diuretic.
Thiazide and thiazide-like diuretics
These drugs act on the distal convoluted tubule of the nephron to prohibit
sodium and water reabsorption; sodium and water are excreted in the urine, so blood volume and blood pressure are reduced.
Often a first line choice, particularly in
salt-sensitive individuals
They are associated with hypokalemia.
Chronic use causes vasodilation, which also contributes to reduction in blood pressure; the exact mechanism by which these diuretics cause vasodilation is uncertain.
Renin-Angiotensin System Inhibitors
Two drugs block the actions of angiotensin II, which is a powerful vasoconstrictor that also triggers the release of other blood pressure mediators, including aldosterone.
We show the
renin-angiotensin system:
– The liver releases angiotensinogen.
– The kidneys release renin, which transforms angiotensinogen to angiotensin I.
– Then, as angiotensin I circulates in the blood, especially in the pulmonary blood, it encounters angiotensin-converting enzyme (ACE), which is released from vascular endothelial cells.
– Angiotensin converting enzyme, as its name suggests, converts angiotensin I to angiotensin II.
– Angiotensin II binds with arterial receptors and induces vasoconstriction.
Angiotensin-converting enzyme inhibitors
ACE inhibitors prohibit the formation of angiotensin II by blocking the actions of angiotensin-converting enzyme.
Can cause hyperkalemia.
Angiotensin II also breaks down
bradykinin, which is an important vasodilator; thus, angiotensin-converting enzyme inhibitors effectively increase bradykinin levels, which ultimately enhances vasodilation.
– We show that increased bradykinin is associated with cough and angioedema.
Angiotensin-receptor blockers
Block the arterial receptors for angiotensin II.
Like ACE inhibitors, they prevent angiotensin II from increasing blood pressure.
Also like ACE inhibitors, they are associated with hyperkalemia.
However, since they don't prohibit the formation of angiotensin II, they don't effect bradykinin, so patients don't experience cough and angioedema.
"Blockers" that act directly on heart/vasculuature
Calcium channel blockers prevent calcium binding:
In the heart, receptors are located at the sinoatrial and atrioventricular nodes, as well as in the cardiac tissue; thus, calcium channel blockers reduce conduction velocity, contractility, and heart rate.
In the vasculature, prevention of calcium blocking reduces vasoconstriction.
Calcium channels are considered a first line treatment, particularly for African Americans, in whom other antihypertensive drugs are often less effective.
Calcium channel blockers are associated with swelling in the lower extremities, rash, flushing, and dizziness.
Beta blockers prevent norepinephrine and epinephrine binding
In the heart, block receptors (similar to calcium channel blockers)
Third generation beta blockers also produce vasodilation.
Beta blockers also block renin secretion from the kidney, which blocks the formation of angiotensin II and elevates bradykinin levels.
Commonly reported side effects include fatigue, cold hands/feet, depression, sleep disturbances, and erectile dysfunction.
Furthermore, some beta blockers can trigger bronchospasm in patients with asthma and chronic obstructive pulmonary disease.
Alpha blockers prevent norepinephrine from binding
In the vasculature, this reduces vasoconstriction.
Orthostatic hypotension is common, particularly in the elderly.
