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Poppers and Viagra®: The history and science of the dangerous cocktail

Poppers and Viagra®, though often used in BDSM and kink, are a potentially lethal combination due to the way they interact in the same signaling pathway. They should never be used together, not even during the same day. I wrote this science-heavy article in an attempt to explain why they can never be used safely together. Trigger Warning: post contains references to enzymes and proteins.

The power of boners: Viagra is born

To understand the surprising link between Viagra and poppers, we need to take a trip back in history to how Viagra came to be the wonderdrug it is.

In the early 1970s, a group of enzymes called phosphodiesterases (PDEs) had been discovered, and by the late 1980s, science was investigating a newly isolated member of this group, PDE5, which was found to relax blood vessels. As human blood pressure is a function of peripheral resistance, relaxing the vessels would be an efficient way to reduce the pressure. Pfizer had discovered a new drug, then called UK-92480, that showed promising results in early studies. However, its effect was short lived, requiring three doses a day.

In addition to the problem of taking three pills a day, the research team at Pfizer also tested the drug in combination with nitrates, commonly used for chest pain, and discovered alarming drops of blood pressure. This was the first hint that this newly discovered drug would not play well with other blood vessel dilators.

Peculiarly, volunteers also complained of two side effects: muscle aches, and increased erections.

For the reasons above, UK-92480 never turned out to be a good blood pressure medication. The power of boners was irresistible though, and in 1997, Pfizer applied for approval for the drug, named sildenafil, as a boner pill, and started marketing it as Viagra.

The science of boners: why cGMP can make you hard (and make you blind)

The human body is an incredibly complex machine. Its actions are regulated by complex cascades of chemicals. Many drugs disrupt this cascade for your benefit. For example, when you take a pill of ibuprofen after a night of drinking, it inhibits cyclooxygenase, which in turn inhibits prostaglandins, resulting in reduced inflammation and pain.

The target of Viagra is cyclic guanosine monophosphate (cGMP), a chemical that among other things, relaxes blood vessels. Relaxed vessels mean stronger erections. It does this indirectly. cGMP is broken down by the phosphodiesterases, and by focusing on the subtype 5 (PDE5), Viagra is able to focus its effects on the corpus cavernosum (the little blood tank in your penis responsible for erections).

Messing with the PDEs comes with a cost, though. While PDE5 is mostly concentrated in the penis and the lungs (Viagra is also useful for pulmonary hypertension), the other PDE members are all around the body. PDE6, a sister chemical, is responsible for making the eye adapt to light, and Viagra mildly fucks around with this as well, resulting in the common side effect of seeing everything blue. This effect is related to the sometimes permanent eye damage caused by poppers

Poppers take a shortcut

While Viagra is a carefully selective and engineered chemical, with an excellent safety record, poppers are equivalent to moonshine.

Poppers, chemically members of the alkyl nitrite family, don’t really care about the regulation PDEs provide. Instead, they convert into nitric oxide (NO), and directly (well, technically via guanylate cyclase) stimulate the production of cGMP, the same chemical Viagra tries to carefully control in your penis. This reaction is rapid and strong, taking effect in a matter of seconds.

This combination of rapid poppers rush of cGMP, and Viagra inhibiting the breakdown of it, has disastrous consequences. Neither drug alone is particularly dangerous, but together they have pharmacological synergy, which means that they do together more than the sum of their parts: a dangerous relaxation of blood vessels, and a drop in blood pressure.

 Ok, I feel dizzy, but so what?

Blood pressure equals life. Even short disruptions in sufficient pressure cause dizziness and fainting, sometimes resulting in traumatic or even lethal injury. Sustained loss of blood pressure due to relaxation of blood vessels results in shock, and eventually starves the body of oxygen and life.

While a 100mg dose of Viagra will by itself cause no more than drop of 8 millimeters mercury (mmHg) of blood pressure, when combined with nitric oxide donors such as poppers, the effect is much bigger. In a 1999 study, healthy volunteers were given both sildenafil and glyceryl trinitrate (a.k.a nitroglycerin, the boom-boom thing, but also a nitric oxide donor with the same mechanism of action as poppers), and the largest reported drop in blood pressure was 51 mmHg. This is a huge drop, enough to be potentially life threatening.

But wait, there’s more! Blue people.

To make things worse, poppers have another way of starving your body of oxygen.  They convert the oxygen-carrying protein hemoglobin into methemoglobin, a version that is unable to carry oxygen. This condition, methemoglobinemia, literally turns you blue. While this in sufficient amounts (such as in an extreme poppers overdose) is lethal by itself, it further makes it more difficult for tissues to get the oxygen they need.

(Methemoglobin also distorts pulse oximetry readings in a very peculiar way, so if you ever meet a bondage top who has a $20 pulse oximeter from China and wants to keep you safe with it while giving you poppers, run away quickly.)

So how long do I have to wait to use poppers after popping some Viagra?

So far we have only talked about sildenafil (Viagra), but unfortunately other erection aids make timing more complicated. While sildenafil has a half-life of about 4 hours, tadalafil (Cialis) has 17.5 hours. Due to this, it is not safe to use erection aids and poppers during the same day, and in the case of tadalafil, perhaps not even on the next day.

Further reading
  • The history of Viagra: https://cosmosmagazine.com/biology/how-i-discovered-viagra
  • How nitric oxide converts to cGMP: https://www.sciencedirect.com/science/article/pii/S0735109704004401
  • Drinking poppers will cause methemoglobinemia:
    •  https://pubmed.ncbi.nlm.nih.gov/12510403/
    • https://www.atsjournals.org/doi/full/10.1164/rccm.201806-1044IM
  • Cardiovascular risk profile of sildenafil: https://www.sciencedirect.com/science/article/abs/pii/S000291490000895X

 

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