BY AMBER SMITH
Some of the newer cardiac drugs were chemically designed in laboratories before going through years of expensive clinical trials and eventually gaining approval from the Food and Drug Administration.
Some of the older drugs, which are still in use today, were discovered by accident — and spent years becoming accepted, purified and widely used.
Harold Smulyan, MD, a professor emeritus at Upstate who specializes in cardiology and enjoys history, researched aspirin, atropine, digitalis, nitroglycerin and quinidine. He published “The Beat Goes On: The Story of Five Ageless Cardiac Drugs” in the American Journal of the Medical Sciences in 2018. This information is pulled from his work.
Discovered: 4,000 years ago
Came from: bark and leaves of the willow tree, whose sap contains salicin, which the body metabolizes into salicylic acid
First used: to treat pain, fever and inflammation
Documented in: clay tablets left by the Assyrians and Babylonians; also recorded use among Egyptian, Chinese and Greek civilizations in 1300 BC; by Greek physician Hippocrates (460-370 BC) and Roman anatomist Galen (200-216 AD); and by an English reverend in 1763 who wrote about the relief of fever in 50 patients, many of whom probably had malaria
Synthesized: around 1860; because salicylic acid was a gastric irritant that could cause bleeding in large doses, the Bayer company sought chemical analogues that would be better tolerated and eventually made aspirin available in tablet form in 1900
Used today to: relieve pain, reduce fever, prevent vascular heart disease
Side note: A pharmacist at Bayer who worked on an aspirin analogue was preoccupied at the time with the sales potential of a new Bayer cough remedy synthesized in 1897 called heroin.
Discovered: by ancient Greeks
Came from: glossy-coated black berries of the deadly nightshade plant
First used: as a cosmetic for women (Cleopatra used atropine to dilate her pupils in the last century BC), and a poison for assassins (the military made a deadly paste from atropine for the tips of their arrows during the Roman Empire and the Middle Ages)
Documented in: Greek mythology, with the plant being named Atropos, after one of the three goddesses of fate and destiny
Synthesized: by a German chemist in the 1830s
Used today to: increase slow heart rates or improve conduction in some types of irregular heart rhythms; and as an antidote to accidental organophosphate poisoning and to nerve gases used in warfare
Side note: Attracted to the sweetness of the berries, people have been poisoned accidentally
Discovered: as one of more than 20 herbs brewed in home remedies for perhaps hundreds of years before the 1700s
Came from: leaves of the foxglove, a tall wildflower with purple, bell-shaped blossoms
First used: as a treatment for “dropsy,” or edema caused by a buildup of bodily fluids, as described in 1775 by English physician and botanist William Withering, who is credited with identifying the therapeutic properties of digitalis after persuading an old woman to share the ingredients of a tea she made
Documented in: a 207-page book of Withering’s records and personal observations on the use of digitalis in 158 patients
Synthesized: commercially in the 1900s
Used today to: treat heart failure and atrial fibrillation
Side note: Withering belonged to a group of intellectuals who gathered monthly and included Erasmus Darwin (grandfather of Charles Darwin, pioneer of the theory of evolution), James Watt (inventor of the steam engine), Joseph Priestley (isolator of oxygen) and Founding Father Benjamin Franklin
Discovered: in the 1840s
Came from: the nitration of glycerin
First used: as an explosive, around the same time physicians were documenting how the chemical liquid relieved intense chest pains in their patients
Documented in: British medical presentations (amyl nitrite) and papers (nitroglycerine) as early as the 1860s; by the end of the 19th century, nitroglycerin was the established form of therapy for the relief of chest pain from coronary heart disease, or angina pectoris
Synthesized: in 1882 by Parke Davis & Co., which produced a pill in five different strengths, after initial use as a liquid medication
Used today to: relieve angina pain and treat heart failure by dilating peripheral veins; also remains the active ingredient in dynamite
Side note: While studying chemistry and engineering, the Swedish scientist Alfred Nobel spent a year in Paris, where he met the Italian chemist who nitrated glycerin but believed it was too dangerous to have practical use. Nobel saw its potential and took it back with him to Stockholm, where he and his father eventually succeeded in creating dynamite. But their research led to several serious explosions, one of which took the life of Nobel’s younger brother, Emil. Later in life, Nobel developed angina pectoris. His physicians advised him to take nitroglycerin, but he declined. He died in 1896 at age 63, leaving the majority of his wealth to establish five Nobel Prizes
Discovered: around the 1630s
Came from: powdered bark of the cinchona tree; the name given to the therapeutic substance was quinquina
First used: to relieve the fever of malaria
Documented in: accounts of Jesuit missionaries in South America using the powdered bark to treat fever, although legend suggests the native population was already using it for that purpose; two volumes published in 1749 are the first to reference the use of cinchona alkaloid in the treatment “rebellious palpitation,” likely the cardiac arrhythmia known today as atrial fibrillation
Synthesized: by American scientists in 1944, quinine was too late to save thousands of World War II troops who died of malaria in Africa and the South Pacific
Used today to: treat atrial and ventricular arrhythmias in selected patients, but quinidine is no longer recommended by the American Heart Association for treatment of atrial fibrillation; medications other than quinine are now used to treat malaria
Side note: A Portuguese doctor isolated the first alkaloid of quinquina, calling it cinchonine, but the more effective second alkaloid was isolated by two French pharmacists, who called it quinine. In the 1850s, an impurity of quinine was isolated and called quinidine
This article appears in the winter 2019 issue of Upstate Health magazine.