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© Phoebe Bell

Medical menagerie: a gallery of venomous creatures

An extra from How a bee sting saved my life: poison as medicine

A guide to venom-based drugs and the creatures we got them from.

Captopril

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Trade name: Capoten
Source: Brazilian pit viper, Bothrops jararaca
Used to treat: hypertension
FDA approval: 1981

Captopril was the first venom-derived drug to obtain approval from the US Food and Drug Administration (FDA). It’s mostly used to treat high blood pressure (hypertension), though it is also prescribed for some types of congestive heart failure. The drug acts as an angiotensin-converting enzyme (ACE) inhibitor, effectively turning off one of the body’s main pathways for vein constriction that increases blood pressure.

It’s also cited as a classic example of biopiracy: in the 1970s, Brazil and other countries had no laws to protect their biological resources. The Brazilian viper was well known to Brazilians, as it and its relatives in the genus Bothrops are responsible for more deaths in South America than any other snakes and 90 per cent of bites. Local tribes are said to have used its venom on their arrow tips to induce blood loss and shock, hence perhaps its nickname as the arrowhead viper. Based on local knowledge, scientists from the UK and US began looking at the venom, and discovered a compound of interest. It wasn’t long before the company now known as Bristol-Myers Squibb patented the drug as their own. The indigenous Brazilian tribes didn’t receive a penny of the billions captopril brought in. This economic snub has led Brazil and countries around the world to enact laws that ensure if the next big thing is found even tangentially using any of their country’s natural resources, they get a share in the profits. 

Eptifibatide

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Trade name: Integrilin
Source: dusky pygmy rattlesnake, Sistrurus miliarius barbouri
Used to treat: acute coronary syndromes
FDA approval: 1998

Eptifibatide is a peptide designed to mimic a small portion of a protein that was discovered in the venom of the dusky pygmy rattlesnake. It and another drug, tirofiban, were both vying for approval around the same time, and both have similar actions. They are used as anti-clotting agents to prevent cardiovascular problems like heart attack or angina by stopping platelets from aggregating.

The small snake that eptifibatide comes from is abundant in its native range, which extends through several southern states in the US from Louisiana to Florida. According to the University of Florida it has not killed a single person with its venomous bite. That’s not really surprising considering the dusky pygmy rattlesnake grows to a maximum of about two feet long, much smaller than its more dangerous cousins. But while it may not kill, the venom of this little rattler is known to be excruciatingly painful. 

Tirofiban

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Trade name: Aggrastat
Source: saw-scaled viper, Echis carinatus
Used to treat: acute coronary syndromes
FDA approval: 1999

Tirofiban, like eptifibatide, is derived from an anti-clotting protein found in snake venom. They both block the same receptor, thus they both work to prevent blood clots. But a study in 2010 suggested tirofiban is cheaper to use, a fact that has stirred up controversy and discussion among pharmacists and doctors as to whether the two are really interchangeable.

One thing is certain: the snake tirofiban is derived from is far more dangerous than that of eptifibatide. While the dusky pygmy rattlesnake doesn’t appear to have killed anyone (as far as documented cases go), the saw-scaled viper is one of India’s ‘Big Four’: the four species of snake that cause the most deaths annually. Less than 10 per cent of people who are bitten will die from the viper’s potent venom. It has been such a medical problem that doctors have produced nine different antivenoms that target it. Perhaps not surprisingly, given the actions of tirofiban, the most dangerous symptoms of envenomation are blood-clotting trouble and internal bleeding, which can lead to acute kidney failure. 

Bivalirudin

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Trade names: Angiomax and Angiox
Source: medicinal leech, Hirudo medicinalis
Used to treat: coagulation during surgery
FDA approval: 2000

Bivalirudin is a peptide derived from leeches that is used to prevent blood clots during angioplasty, a procedure that uses a tiny balloon to widen clogged blood vessels. It works by acting as a direct thrombin inhibitor, shutting down the blood’s coagulation pathway by blocking it at one of its key steps.

The peptide it is based on, hirudin, is found in the saliva of Hirudo medicinalis, a kind of leech that has been involved in medical practice for centuries. Long before we understood the causes of many diseases, people believed that excess blood or ‘bad blood’ were to blame for just about everything. Thus, some societies would perform bloodletting with the aid of leeches to treat a wide variety of illnesses. But before you laugh at such outdated notions, you should know that leech therapy isn’t just a thing of the past – medicinal leeches are still sometimes used to enhance circulation in skin grafts or reattachment surgeries, and there are doctors who will use leeches to treat muscle cramps and varicose veins. Now, though, we know that the leeches’ therapeutic effects have nothing to do with the blood they remove, but rather the more than 60 compounds in their venom that have anaesthetic, anti-coagulant, vasodilatory and anti-inflammatory properties. 

Ziconotide

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Trade name: Prialt
Source: cone snail, Conus magus
Used to treat: chronic pain
FDA approval: 2004

Ziconotide is a synthetic peptide based on a conotoxin from the ‘magician’s cone’ snail (Conus magus). For some people with unrelenting chronic pain, it really does seem like magic; the peptide selectively blocks certain types of calcium channels that neurons rely on when sending pain signals to the brain. The downside is that scientists were not able to find a way to safely and effectively administer it intravenously or orally, so it has to be directly injected into the spinal fluid to work and thus has a narrow safety range.

The magician’s cone snail uses its version of ziconotide not to relieve pain but to paralyse prey. The snail lives natively in the Indian and Pacific Oceans, where it feeds on small fishes. Because its prey are so much faster than it is, the snail needs potent neurotoxins in its venom to capture its meals. And boy, does it have them. These little snails produce hundreds of different conotoxins, each with its own specific molecular targets, making them one of the most exciting sources of potential new drugs. While ziconotide is the first, there are already a few other cone snail toxins that have been transformed into potential pharmaceuticals, awaiting the results of clinical trials.

Exenatide

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Trade name: Byetta
Source: Gila monster, Heloderma suspectum
Used to treat: type 2 diabetes
FDA approval: 2005

Exenatide is a synthetic version of a hormone found in the saliva of the Gila monster, a large, venomous lizard. In humans, exenatide mimics our bodies’ natural hormones that stimulate insulin release when blood sugar rises. Thus it’s used to treat type 2 diabetes. It’s also being investigated for the treatment of obesity, even in children, because in addition to causing insulin release, it helps suppress appetite and increase feelings of fullness. The original venom component, exendin-4, is one of more than a dozen toxic peptides that have been isolated from Gila monster venom.

The lizards are found throughout the southwestern US and into Mexico, and have a fierce reputation. According to Native American legend, Gila monsters can spit venom and kill a man with just their breath. They can’t really spit venom. But while they’re not the most cuddly lizards around, their breath does smell terrible and they can envenomate with their bites. They are known for biting and holding on like their lives depend upon it. Though their venom isn’t fatal, it certainly isn’t comfortable, and perhaps their tenacity is partially to blame for their bad rep.

Batroxobin

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Trade names: Baquting and Reptilase
Source: lancehead snake, Bothrops atrox 
Used to treat: thrombic disorders
FDA approval: not approved

Batroxobin isn’t approved clinically in the US, but it is commonly used in laboratories to measure fibrinogen levels and blood coagulation capability. Batroxobin acts directly upon fibrinogen, a component of our body’s coagulation cascade, to induce clotting. Because of this unique feature, doctors and scientists can use it to gain better insights into the blood of a patient, particularly if there’s something going wrong with how it clots. Outside of the US (largely in China), batroxobin is used to treat a range of disorders, including stroke, pulmonary embolism, deep vein thrombosis, myocardial infarction and perioperative bleeding.

The snake that the compound comes from is an infamous danger in the tropical areas of Central and South America that it calls home. It is sometimes called by the name ‘fer-de-lance’, which actually covers several closely related Bothrops species, many of which are very deadly. Bothrops species are indicated in 90 per cent of all snake bites from South America, and are responsible for more deaths than any other group.