by Toxic Panacea (B.Sci, M.Pharm, BAC>0.05)
Most people might sit back and relax as they sip this classic contemporary cocktail. However, one can’t help pondering on the pharmacological conundrum of a drink which contains both a stimulant AND a depressant. The question begs, will it wake you up or f@@k you up?
You will probably need a drink to get through this conundrum, so here’s what I suggest:
30mL espresso
30mL of Vodka
30mL of Kahlúa
—> into a cocktail shaker
+ ice and SHAKE
DISCLAIMER: TWO in ONE hour NOT advisable if you are martini-naive (friend of a friend’s advice).
We all (like to think we) know, one drink per hour, eat a cheeseburger and she’ll be right? But let’s review some FACTS about alcohol. Alcohol follows zero-order kinetics (I don’t recommend using this in your argument to the officer). Zero-order kinetics means you can keep drinking all you want (preferably not) and the elimination rate remains constant, regardless of the concentration in the blood. Alcohol dehydrogenase will NOT work any faster. The elimination rate doesn’t seem to be listed in MIMs so a reputable source cough-google-cough describes this is as 15mg/dL/hr (give or take gender and a billion other variables). Of interest (possibly only to me), at really low concentrations, alcohol follows FIRST order kinetics (with a half-life of 4 hours). However, in this scenario, I am picturing sipping cocktails at a pleasant pace discussing how many doctors and nurses (and other HCPs) we could buy compared to all the promised advantages of trickle-down economics, or possibly a conversation on what our first order of drinks will be. What is first order kinetics I hear you ask? Don’t worry, more on this later (cue to keep sipping your martini).
On this journey, I discovered that ONE standard drink contains 10 grams of alcohol. I actually feel like I’ve failed as both a pharmacist and a martini enthusiast for not knowing this already. The part of me that tells me to stop self-deprecating insists that this is not the point of cocktails. Or pharmacy (usually… though handy information for anti-freeze ODs).
Ok so now for a bit of maths:
No. of standard drinks = Volume of Container (L) x % of alcohol volume x by 0.789
shot of vodka (30mL) = 0.03x40x0.789 = 0.9468
shot of Kahlua (30mL) = 0.03x20x0.789 = 0.4734
Number of standard drinks in my Martini = 1.4202
Therefore, 14.202grams of alcohol in my espresso martini (I thought I would let you work this maths step solo, if you can’t, it’s probably time to quit now and go and make yourself that second drink).
So, divide this by 5L of blood volume to get a concentration of 0.28404 g/dL
Umm… what about the volume of distribution?
The volume of what?
You just incorrectly assumed that the whole 14.202g went straight into the 5L of plasma.
Yeah…
But it doesn’t. It goes into other stuff. Tissue and what not.
Ok… so what is the body’s volume of distribution?
It’s different for different drugs.
Huh??
Some drugs go into more tissue than others… so they go into a bigger volume of distribution.
Now you’re just making stuff up.
Well it IS a theoretical value…
So where does this leave us with alcohol?
Well the VD for alcohol is 37L in a 70kg person… so we just need to….
….Just tell me what the plasma concentration will be!
It’s 0.038g/dL!!
This reading would imply you possibly just injected your espresso martini (what doesn’t kill you makes you drunk?). Apparently, alcohol has an oral bioavailability of 80% (another reputable source), so let’s assume the concentration is 0.031g/dL. Please take my calculated concentration with a grain of salt (or coffee, in this scenario) but to help us define the therapeutic window:
– to drive legally in NSW, BAC must be <0.05g/dL (i.e. ONLY ONE espresso martini!)
– A concentration of 0.35g/dL could make you comatose or dead.
So, if your blood alcohol is 0.031g/dL, and humans eliminate alcohol at roughly 15mg/dL/hr, then it will take you 2hrs to completely eliminate the alcohol in my martini. Experience as a martini-drinker makes me confident with my calculations (very scientific, N definitely > 1). Note to P Platers: it’s pretty hard to achieve BAC=0.00 after one of my martinis!
FUN FACT: while food slows the absorption of alcohol, it doesn’t reduce it!
As a pharmacist, it occurs to me that the concentration in the blood does not always correlate to effect (e.g. aspirin knocks out the life of a platelet FOREVER [10 days], not just while aspirin [half-life 20mins] hangs around in the body. Apologies, that was more ominous than intended. FYI: always check with your doctor with regards to aspirin before any operation. To reconcile this dilemma, I went looking for some concentration/effect curves. According to the same reputable source, a BAC of < 0.06g/dL has a stimulant-like effect (euphoria, relaxed, chatty) and at a BAC > 0.08g/dL (e.g. 3 of my martinis) it is a central nervous system depressant (slowed cognition & impaired sensory/motor function). Based on this, I need not continue, as we can conclude that ONE martini will be entirely stimulatory. But I’ll continue anyway (as queen would say, don’t stop me now!).
It’s at this point we discuss caffeine, my CNS stimulant which gets me through my day. The 30mL espresso contains (a very unpredictable) 212mg of caffeine with a bioavailability of 99%, but I don’t need this information because the elimination of caffeine follows first-order kinetics! As a student, I found first order kinetics counterintuitive, which was unfortunate because pretty much ALL drugs follow first-order kinetics. (Let’s not talk about second order unless we’re talking a second order of martinis). For first-order, the rate that caffeine gets metabolised is dependent on the concentration of caffeine in the blood. So basically… the same PROPORTION (but not amount in mg) of caffeine gets removed at a constant rate i.e. HALF of the caffeine gets removed every 5 hours since caffeine has a half-life of 5 hours (prolonged in liver disease AND by alcohol). It takes roughly 4-5 half-lives to remove most of a drug. Theoretically this means that my morning cup of coffee should keep me going for 20-25hours. Caffeine concentration/effect curves sound like they would promise too much and were therefore not included.
If you have 3-4 martinis, it is likely that you will have enough alcohol in the blood to have a depressant effect (and it will take ~8 hours to metabolise the alcohol), though presumably you will hit the 0.1g/dL ‘depressant-to-stimulant’ threshold quite quickly. The caffeine will still take roughly 20 hours to metabolise the majority of the drug (cool huh?) Drink 10 Martinis and you will have more depressant than stimulant effect (and likely comatose if it’s your first time on the block).
Ok, but where does alcohol and caffeine work in the body? It’s all very well jabbering about pharmacokinetics, but how does it actually make you the life of the party (for better or worse?). Well hold on to your hats, you’re in for a ride. Alcohol increases extracellular adenosine (an inhibitory neurotransmitter in the brain, having somnogenic, anxiolytic, motor-depressant and impairing properties). Caffeine BLOCKS the adenosine receptor (increases motor activity, arousal and reinforcing effects). So because caffeine sits in the adenosine1 receptor, you are a little less sleepy and a little less ataxic (unco) than if you’d had alcohol alone. And because you have extracellular adenosine, you are a little less anxious than if you’d only had coffee. WHAT COULD POSSIBLY GO WRONG? Oh dear, contradictory pharmacology, it’s like giving dobutamine and bisoprolol together. Or enoxaparin and tranexamic acid. Or IV naloxone and morphine. But the caffeine-alcohol saga is a bit more complicated than that. When caffeine binds to adenosine2A receptors, it can actually potentiate the alcohol-induced dopamine release (= more reward and more reinforcement).
According to a review article I read, college students who drank caffeinated alcohol drinks were more likely to be legally intoxicated and have significantly higher prevalence of serious alcohol-related consequences (compared to alcohol alone). Then again, people who love those energy drinks can sometimes have a baseline level of crazy (no offence intended!) Funnily enough, there are some experiments out there where they’ve given subjects alcohol/caffeine vs alcohol/placebo vs placebo/caffeine combinations and tested simple reaction times, coordination (using the grooved peg-board test), tapping reflexes, physiological indicators, biochemical variables and not found much to note except that subjects were subjectively more drunk with the combo (sample sizes very small).
Based on my (mostly pulled out of my ass) pharmacology, you would theoretically need to drink 10 martinis in quick succession to have a similar elimination time for caffeine and alcohol (though this would likely kill you first). While interesting anecdotally, we are unable to draw meaningful conclusion from the data collected. There is far too much variability in both alcohol tolerance and caffeine sensitivity to predict anything sensical. Furthermore, assessing cognition and performance without being subjective is difficult in the social setting. A randomised controlled study with a larger number of subjects is required for any meaningful conclusion. Blinded is inevitable. Ethics of such, ambiguous. No conflicts of interest were ever promised.