Extreme Pharmacology: How Crank Out-Sciences Batman Begins
Let’s take this information and apply it poor Chev Chelios. His symptoms match spot-on with a reduction in the excitatory drive to his heart. This is definitely a dangerous situation to be in, although there’s some argument over time-course and severity, a side discussion that shows that there’s disagreement even among the experts. Mark Neveldine and Brian Taylor told me they spoke to several doctors, including Mark’s brother and a longtime friend of Brian’s. As Brian said, they reverse engineered the end-point (of Chelios’ bad heart condition) and figured out what would get them there. In preparing this article, I spoke to a number of medical professionals who gave me opinions that ranged from it could kill him instantly to that he could survive indefinitely. An anesthesiologist pointed out that rats that have been sympathecotimized (i.e. sympathetic nerves cut) still survive, and a neurobiologist pointed me to Addison’s disease, an autoimmune disease of the adrenal gland which people can survive for some time. A related condition called Addisonian crisis, can be fatal, but seems to have a significant part of its effect on dropping cortisol levels, though decreased epinephrine would contribute. In agreement with Neveldine and Taylor’s sources, the Critical Care nurse I interviewed said the time-course of an hour seemed within reason. Despite this overall disagreement, all agreed that the situation would be dangerous and saluted the filmmakers’ cleverness.
In a second phone call from Doc, he explains further about adrenaline’s role in the body:
Doc: Excitement, fear, danger. It causes your body to manufacture a chemical called ephedrine. Now what these guys have done is introduce an inhibitor to your system.
Chelios: Huh?
Doc: Dude, your only chance is to massively increase the level of ephedrine in your body to force out the inhibitors. Get to the emergency room. Get yourself some epinephrine. The shit’s potent, so don’t overdo it. Probably a fifth of injection will do.
It may not seem obvious, but that dialogue dropped the jaw of every pharmacologist. The basic principle of pharmacology is that drugs that have an effect on the body must interact with the body in some way. In the case of epinephrine, which is a chemical your body makes, it binds to its receptor which then has effects (like increasing heart rate). Drugs that affect the same receptor generally have one of two effects:
- The drug can be an agonist, meaning that it mimics the effect of the natural chemical.
- The drug can be an antagonist, meaning that it binds to the receptor, but blocks function.
In our case, ephedrine, the artificial epinephrine, binds to the same receptor and causes the same effects as the real thing (an agonist). On the other hand this Beijing Cocktail seems to contain drugs that are antagonists to the adrenergic receptor, and that’s why Chelios is experiencing his sluggish problems. It’s also worth noting that Doc Miles does screw this up in the movie: he calls ephedrine the natural adrenaline and epinephrine the artificial one (it’s the other way around). A minor error, but one that Doc Miles shouldn’t have made.
What’s particularly cool about the Doc’s ramble is that he’s dead-on about forcing out inhibitors. How? Well, when a scientist has a new drug that they think is an antagonist, they do what’s called a competition experiment. If the antagonist binds to the receptor, then increasing the concentration of an agonist to a high enough level should displace or kick out the antagonist. Which if you hadn’t noticed, is exactly what Doc Miles recommended Chelios do to try and offset the effects of the Beijing Cocktail. Nice work, Doc.
So, Chelios follows his doctor’s orders (always a good idea) and heads for a hospital. After being denied epinephrine in the pharmacy (it is a controlled substance), a young punk tells him:
Nasal spray. It’s got epinephrine in it, it’ll get you tweaked.
Which is, as noted above, absolutely true. When Chelios does, in a hilarious scene, finally score a syringe of epinephrine, he ends up injecting the whole thing. This causes him to go into a frenzy and leads to the next great exchange between Doc and Chelios:
Doc: You took the whole thing didn’t you? I told you to take a fifth of a syringe. Your chest on fire?
Chelios: Check.
Doc: But you’re cold.
Chelios: Check.
Doc: And you’ve got a steel hard-on, don’t you.
Chelios: Let me check. (Looks down) Check.
Doc: That’s the stimulation of your blood vessels. Your urinary sphincter is tight as a knot right now. You couldn’t piss right now to save your life.
Chelios: Urinary sphincter, check.
Doc: That shit [the epinephrine] will be out of your system in 30 minutes if it doesn’t kill you first.
As silly as the dialogue may seem, this is all pretty much exactly how it would work in real life. Writer/director Mark Neveldine told me, “Sometimes you want to find the serious places in the fact, and then find the comedy within those facts. Like the steel hard-on, that shit’s funny…and just talking about medical facts in such a ridiculous scenario is what makes the movie.”
As the movie draws near its insane ending, Chelios finally gets to Doc, who hooks him up to a saline drip with epinephrine and methamphetamine. This gives us our last piece of scientific dialogue:
The solution I’m giving you is acting as a competing inhibitor meaning that it’s pushing the poison right out of your receptors. Now that’s just a temporary fix.
The question that Chelios doesn’t ask, but you should, is: If you’ve got Chelios on a solution that is (on the short-term) competing off the antagonist why won’t that work as a cure? Good question. The answer is that because we don’t know what the Beijing Cocktail actually consists of, we don’t know its off-rate (the length of time it binds to the receptor) or metabolic breakdown rate (the speed at which the body breaks down the drug). But, in case you think that the directors are finally twisting the facts to fit their plot, you should know that a number of drugs (lethal ones at that) have nearly permanent binding to their targets. Even if you can dislodge the drug from the receptor temporarily, if you can’t metabolize and excrete it, it will re-bind to its target.
Chelios ultimately decides he wants one hour to confront Verona, and Doc ingeniously alters an insulin pump so that it delivers epinephrine. Once found, Verona tells him there’s an antidote, and the climactic scene sets up our hero trying to save his skin or take down everyone else with him. Want to know how it ends? Go rent the movie and see for yourself…and improbably, learn a little bit about pharmacology from Dwight Yoakam along the ride.