10 heart drugs with weird origins

We take medicines every day – but do you think about where they come from? Most modern drugs are created in the lab – but some have unusual or downright bizarre origins, as Rick Karsan explains.

1. ACE Inhibitors

Brazilian viper Jararaca

Pedrinho / Via Wikimedia Commons

ACE inhibitors are a frequently used class of drugs in heart medicine, used to treat high blood pressure and heart failure, and often prescribed following a heart attack. One common example is ramipril.

But did you know that that the active ingredient in the first ACE inhibitor, captopril, was originally derived from snake venom? Launched in 1981, captopril was based on an ingredient of the venom of the poisonous Brazilian Viper (Bothrops Jararaca).

Nobel Prize winner John Vane initially tested peptides from the venom on dog lungs, finding that they were able to block the activity of angiotensin converting enzyme, from here Vane tentatively proposed an ACE inhibitor research programme to what is now Bristol Myers Squibb. Many revisions, tests and trials later, in 1975 captopril was born.

Captopril is rarely prescribed today but is still licenced for use in high blood pressure, heart failure and even kidney disease caused by diabetes. It was the first effective oral ACE inhibitor and its legacy of subsequent developments in this drug group has helped to manage the blood pressures of millions of people.

2. Aspirin

Willow tree

The origins of aspirin tablet can be traced for thousands of years, as far back as the ancient Egyptians. The active ingredient, acetyl salicylic acid, was developed from salicylin, a compound derived from the bark of willow trees between two and three years old.

We know that salicylin has been in medical use since before 1534 BC, thanks to two papyrus sheets from an Ancient Egyptian textbook which recommended its use in non-specific pain.

Willow bark was also tested as a potential anti-malarial in what is considered to be the world’s first documented clinical trial in 1758 by Reverend Edward Stone.

Aspirin’s development into the modern drug of today began in 1838 after the production of salicylic acid in 1899. After further tests and revision, aspirin was born and went into production in 1901.

Aspirin is regularly used today, for pain relief and in particular to reduce the risk of stroke or heart attack in people who have already had one, or whom are considered to be at risk.

3. Digoxin

Purple foxglove

Digoxin belongs to the class of drugs known as cardiac glycosides. It is primarily used to treat heart failure but may also be used in the management of certain abnormal heart rhythms, including atrial fibrillation and atrial flutter.

The active ingredient in digoxin originates from the purple foxglove (digitalis purpurea). Historically, the use of digitalis can be traced back to ancient Egypt. The English doctor William Withering is credited with the first published description of its use in 1785.

Used incorrectly, digitalis can be highly toxic, and in the case of overdose can cause nausea and vomiting, as well as abnormal heart rhythms.  

4. Warfarin

Warfarin: rat and mouse killer pellets

Warfarin, which belongs to the class of drugs called coumarins, is the most widely used anticoagulant in the world. Warfarin is used to prevent blood clots in conditions such as atrial fibrillation and rheumatic heart disease. It is also prescribed to prevent clots after the insertion of artificial heart valves.

You might already know that warfarin was developed for use as rat poison before it was used in human medicine. But did you know that it was discovered in the 1920s after previously healthy cattle in the Northern Plains of America and the prairies of Canada started dying of internal bleeding?

When no other cause was found, attention turned to the diet of the livestock. It was found that cattle were grazing on hay made from sweet clover (Melilotus alba and Melilotus officinalis).

The incidence of bleeding was found to be highest when the hay was damp and as a result became infected with the moulds Penicillium nigricans and Penicillium jensi. Normally damp hay would have been discarded but as this was during the period of the Great Depression, money was tight and frugality took precedence.

It was later found that the natural chemical coumarin, which is responsible for the smell of newly mown hay, turned into dicoumarol once it was infected with the mould. Warfarin is derived from dicoumarol.

5. Nitrates (GTN)

Box of explosives 

Glyceryl trinitrate (GTN) belongs in the class of medications known as nitrates. GTN is now used to manage angina.

In fact, it is the same thing as the explosive nitroglycerin – used to make dynamite and gunpowder. The name glyceryl trinitrate was chosen by the medical community to avoid alarming patients who were aware that nitroglycerin was an explosive.

The blood vessel dilating properties for which nitrates are largely used was observed in 1847 by Abscanio Sobrero, who noticed that exposure to nitroglycerin caused headaches. This was due to expansion of blood vessels with the unintentional high dose causing the pain.

It was William Murrell who engineered the use of nitrates for angina and to reduce blood pressure.

6. Statins

Oyster mushrooms  

a.bower / Via Flickr 

Statins are mainly used to lower cholesterol and to lower risk of a heart attack in people who are considered to be at risk. They are used in people who already have heart disease to stabilise fatty plaques, thereby reducing the risk of a heart attack.

The history of cholesterol-lowering medication statins can be traced back to Japan. In 1970, Japanese microbiologist Akira Endo isolated the first known compound to lower cholesterol called citirin from Penicillium citrinum.

The first compound derived from this was called mevastatin. Trials of mevastatin were found to be positive in animals at lowering cholesterol, but it was considered to be too toxic to give to humans.

In 1978 Alfred Alberts discovered lovastatin in oyster mushrooms. This formed the basis for the development of many of today’s statins. It is naturally found in oyster mushrooms (Aspergillus terreus and Pleurotus ostreatus), red yeast rice and pu-erh (a type of tea).

7. Quinidine

Cinchona tree 

EOL Learning and Education Group / Via Flickr 

Quinidine is an antiarrhythmic drug, used in the treatment of some heart rhythm problems, such as atrial fibrillation and paroxysmal supraventricular tachycardia (PSVT). It’s also used in the treatment of atrial fibrillation in horses.

Quinidine is a derivative of quinine, which originally came from the bark of the cinchona tree. Quinine is the flavouring found in bitter lemon and tonic water.

Historically, tonic water was drunk in British India due to its antimalarial properties. The bitter taste led colonials to mix it with gin, thus giving rise to the gin and tonic.

Quinine itself is still used for the treatment of malaria, as well as muscle cramps.

8. Alteplase

Hamster 

Torben Schink / Via Wikimedia Commons

Alteplase is a drug used in the emergency management of heart attacks where more invasive methods, such as angioplasty or heart bypass surgery, are not available.

The drug works by breaking down the blockage in the blood vessels supplying the heart.

Alteplase belongs to the class of medications known as tissue-type plasminogen activator (t-PA). t-PAs are found in most mammalian tissue, with the first purified form obtained from human uterine tissue.

As techniques developed, genetic expression and cloning techniques were used to produce large amounts, much like insulin. Alteplase itself is now largely developed from Chinese hamster ovary cells.

9. Aprotinin

 

Anders Gustavson / Via Flickr 

Aprotinin is a drug largely used in heart surgery to reduce bleeding in patients with the aim of reducing the need for blood transfusions.

Aprotinin is a trypsin inhibitor which prevents the breakdown of blood clots. It was independently discovered in the 1930s and initially isolated from cow parotid glands (a type of salivary glands), and later purified from cow lungs.

Initially it was used to treat pancreatitis but has been used to prevent blood loss during surgery since the 1960s.

10. Fibrates

Spraying insecticide in field 

IITA / Via Flickr 

Fibrates, like statins, are used to lower cholesterol. The first fibrate, clofibrate was developed in the 1950s. It was noticed that farm workers in France who had become ill after being exposed to insecticides sprayed on fields had particularly low cholesterol levels.

Clofibrate was developed using a different chemical compound with the same properties as the insecticide and trialled on humans. It is no longer used because by the late 1970s it had been found to have negative effects which outweighed the positive effects. Still, it was the very first cholesterol lowering drug in the 1960s and preceded the development of statins.

Clofibrate also aided the development of newer fibrate medication, which are still used either in combination with a statin for high-risk patients, or to reduce high levels of triglycerides (a type of cholesterol) to prevent inflammation of the pancreas.

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