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The Edward D. Freis Papers

Glossary

[Edward Freis speaking at his retirement party]. [11 January 1987].

Alpha blocker/antagonist (Adrenergic alpha-Antagonist) -- A drug that helps relax certain muscles and allows small blood vessels to remain open by blocking the effects of norepinephrine (adrenaline). Norepinephrine stimulates the muscles in the walls of smaller arteries and veins, causing them to constrict. By blocking the action of norepinephrine, alpha blockers allow the vessels to remain open and relaxed, improving blood flow and lowering blood pressure. However, they are not the first choice of medications to treat high blood pressure because they increase the risk of heart failure with long-term use.

Angiotensin blocker/antagonist (Angiotensin II receptor antagonist) -- A drug used to treat hypertension by blocking the body's AT1 receptors, which among other things causes the blood vessels to dilate. Additionally, these drugs reduce the body's ability to retain sodium and serve as diuretics. The combination of these three actions in turn lowers a patient's blood pressure.

Antihypertensive agents -- Drugs used in the treatment of acute or chronic vascular hypertension (high blood pressure).

Atherosclerosis -- A disease of the arterial blood vessels caused by the build up of plaques (hardened cholesterol, among other things) within the arteries. This so-called hardening of the arteries can either partially collapse the blood vessel (stenosis), reducing blood flow to affected organs, or it can excessively enlarge the arteries and cause an aneurysm. This in turn can cause high blood pressure, poor circulation, heart attacks or strokes in a patient.

Beta blocker/antagonist (Adrenergic beta-Antagonist) -- A drug that blocks the action of epinephrine (adrenaline) in the body. Norepinephrine stimulates the muscles in the walls of smaller arteries and veins, causing them to constrict. By blocking the action of norepinephrine, alpha blockers allow the vessels to remain open and relaxed, improving blood flow and lowering blood pressure.

Calcium channel blockers/antagonists -- Drugs that work by preventing the movement of calcium in the cells of the heart and blood vessels, thereby relaxing blood vessels and increasing the supply of blood and oxygen to the heart, while reducing its workload.

Chlorothiazide -- A diuretic drug similar to hydrochlorothiazide that inhibits the kidney's ability to retain water, resulting in an increased excretion of water and electrolytes (including sodium, potassium, chloride, and magnesium). This reduces the volume of the blood, which in turn reduces the amount of pressure needed to move it through a patient's circulatory system.

Cholesterol -- A sterol (a combination of steroid and alcohol) and a lipid found in the cell membranes of all body tissues, and transported in the blood plasma of all animals. Cholesterol plays a central role in many biochemical processes, but is best known for its association with cardiovascular disease. High levels of certain types of cholesterol can cause atherosclerosis (plaque build up in the arteries), which can lead to coronary heart disease and other cardiovascular conditions.

Clonidine -- A drug that lowers heart rate and blood pressure by tricking the brain into thinking it there is much more catecholamine (adrenaline) in the body than there is. In turn, the brain decreases production of catecholamine, which causes blood vessels to relax and remain open.

Diuretics -- Mercury based compounds that were used as hypotensive (blood pressure lowering) diuretics before the discovery of thiazide-based compounds. Mercurial diuretics are extremely toxic and have severe laxative side effects.

Diuretics -- These drugs effectively reduce blood pressure in hypertensive patients and produce the same blood volume changes as a low-salt diet. These diuretics also enhance the effects of other hypertension drugs, meaning that a patient's blood pressure can be controlled with smaller doses of the drugs, and thus with fewer side effects. As such, these medications were considered a major breakthrough in the treatment of hypertension, as patients were now more likely to comply with long-term treatment on the basis of convenience than they were on a diet-based treatment plan.

Ganglion blocking agents -- A group of anti-hypertensive drugs developed in the late 1940s, these agents work by interfering with nerve impulses from the brain that constrict blood vessels, thus achieving the same effect as surgical sympathectomy. As these drugs effect the body broadly, including blocking of sympathetic and parasympathetic systems, their therapeutic use has been largely supplanted by more specific drugs.

Guanethidine -- A ganglion blocking agent used to treat hypertension. One of the drugs Freis tested in the 1950s and found to be effective for treating congestive heart failure.

Hemodynamics -- The branch of physiology that studies the circulation of the blood and the forces involved.

Hexamethonium -- A ganglion blocking agent used to treat hypertension. One of the drugs Freis tested in the 1950s and found to be effective for treating congestive heart failure.

Hydralazine -- A medication used to treat high blood pressure. A vasodilator, hydralazine works by relaxing blood vessels and increasing the supply of blood and oxygen to the heart while reducing its workload. It is commonly used in the condition of pregnancy called preeclampsia.

Hydrochlorothiazide -- A diuretic drug that acts by inhibiting the kidney's ability to retain water, resulting in an increased excretion of water and electrolytes (including sodium, potassium, chloride, and magnesium). This reduces the volume of the blood, which in turn reduces the amount of pressure needed to move it through a patient's circulatory system.

Hypertension, essential -- Persistent and pathological high blood pressure for which no specific cause can be found, thought it is thought that it is a result of a complex interaction between many physical, physiological, and environmental factors. Over 95% of all cases of hypertension fall into this category.

Hypertension, malignant -- A severe and most lethal form of hypertension that runs a rapid course and damages the inner linings of the blood vessels, heart, spleen, kidneys and brain. Systolic and diastolic blood pressures are usually greater than 240 and 120, respectively.

Hypokalemia -- A potentially fatal condition in which the body fails to retain sufficient potassium to maintain health. This can be a serious side effect of taking diuretics such as hydrochlorothiazide.

Methyldopa -- A drug that works directly on the brainstem, methyldopa inhibits the brains' ability to send vasoconstriction messages to blood vessels via the peripheral sympathetic nervous system. Unable to receive the chemical signal to constrict, the blood vessels remain open and the patient's blood pressure decreases.

Pentaquine -- An anti-malarial agent that also had the side effect of lowering blood pressure. Its toxic side effects precluded it from being used as a routine treatment for hypertension.

Pentolinium -- One of the early ganglion blocking agents (drugs that interfere with vessel-constricting nerve impulses from the brain) used as an anti-hypertensive throughout the 1950s.

Propranolol -- A beta-adrenergic antagonist (beta-blocker) developed in the 1960s that effectively lowers blood pressure and can be used to control hypertension. Found to be just as effective as hydrochlorothiazide in clinical trials (and preferential for African-American patients), its use was often hindered by its price tag, which was twenty times higher than the same dose of hydrochlorothiazide.

Rauwolfia, or Rauwolfia serpentine -- A plant found on the Indian subcontinent, and long used by physicians there to treat the mentally disturbed. After being used for the same purpose in the United States, it was discovered that reserpine, an active alkaloid in the plant, is also useful as an antihypertensive agent.

Reserpine -- An antihypertensive alkaloid extracted from the Indian plant Rauwolfia serpentina. Originally used for psychiatric purposes, it soon became apparent that it also lowered patients' blood pressure. Freis and his colleagues soon found that drugs like reserpine were also plausible treatment for congestive heart failure.

Sympathectomy -- A surgical procedure that severs sympathetic nerves in the lumbar and thoracic region, used in the 1940s to treat severe hypertension.

Veratrum viride (veratrum alkaloids) -- An alkaloid compound derived from the herb Hellebore that, in sufficiently small doses, can significantly lower blood pressure and improve heart function. However, severe side effects including nausea and vomiting precluded widespread use of the compound as a therapeutic agent.