USMLE® Step 1 style questions USMLE
USMLE® Step 2 style questions USMLE
A 25-year-old woman comes to the emergency department because of intense abdominal pain. She describes it as a sharp pain and rates it as a 10 on a 10-point scale. She says it started last night and cannot identify any triggers. She denies nausea, vomiting, diarrhea, or menstrual abnormalities. She reports having had previous episodes that have been relieved with oxycodone and requests this for the pain.
Worldwide, opioids are the most common cause of drug related deaths.
Because of their potential for addiction and overdose, opioids are regulated substances in many countries.
But others are exogenous, meaning that they come from the environment, like heroin and morphine, which come from the opium poppy—a flowering plant that oozes a milky white liquid—while others like fentanyl are synthesized in the laboratory.
To understand how opioids work, let’s zoom into a region of the brain tissue that has opioid receptors.
Normally, in the absence of endorphins, inhibitory neurons secrete a neurotransmitter that prevents nearby neurons from releasing the neurotransmitter dopamine.
Now, let’s say someone goes to play a rigorous game of badminton.
Exercise releases endorphins which activate the three major opioid receptors located on the inhibitory neurons, called the mu, kappa, and delta receptors.
As endorphins bind to these receptors, they block the inhibitory neuron from releasing neurotransmitters, allowing the dopamine secreting neurons to freely unload dopamine.
The dopamine then gets picked up by a third neuron in the same area.
So that’s how it works normally.
But when a powerful exogenous opioid binds to the opioid receptors, the result is a massive flood of dopamine.
This helps with pain control, but it can also cause an incredible state of euphoria within the regions of the brain involved in the reward pathway, which is an emotional “high”.
Now remember, the purpose of the reward pathway is to train the brain to repeat activities that cause dopamine-mediated pleasure, so when opioids stimulate this reward pathway, the brain learns to do that behavior again and again.
With exogenous opioids there are multiple routes to get the drug to the brain.
One way is by ingesting it; that route is the slowest.
A faster route would be inhalation because the drug is rapidly absorbed through the lungs.
The fastest route, though, is direct injection of the substance into the blood.
Typically, the faster the exogenous opioid reaches the brain the stronger the relationship between the behavior and the reward.
Over time, people that are consistently using a drug—even when taking them exactly as prescribed—can develop tolerance, which means that with repeated use they have a reduced response, and therefore an increased dose is needed to achieve the original response.
At a cellular level, there are two theories that explain why this might happen.
One theory is that opioid receptors might become less sensitive to a drug, and the other theory is that the neurons may remove opioid receptors from the cell wall in a process called down-regulation, leaving less receptors available for binding.
In either scenario, tolerance leads to the need for higher and higher doses of a drug, and often that tolerance remains for a long time even after tapering off the drug.
Alright, so now let’s say that you’re at rest, there aren’t any drugs or anything stimulating your reward pathway.
Now, let’s say you finally get a text with exam results that you’ve been waiting weeks for.
All of a sudden you may feel sweaty and flushed, your heart rate may jump a bit.
You’re now above your normal level of homeostasis, because something has changed, right?
But it doesn’t stay that way for long, and after the text message, your brain brings things back down to this baseline.
With repeated drug use, a few things start to happen.
Let’s say you take the drug at a specific time and setting, like 3:00 P.M. in the bedroom.
Being a depressant, it makes everything go lower: heart rate, blood pressure, and wakefulness.
Your brain, being the smart brain that it is, will pick up on the pattern.
Now, next time at 3:00 P.M. in the bedroom the brain preemptively increases heart rate, blood pressure and wakefulness, since it knows that when you take the drug, everything’s going to decrease again.
Now, let’s say 3:00 P.M. in the bedroom rolls around, but there’s no drug…
In that situation, the brain still increases everything but the changes aren’t countered with the effects of the drug, and so the person can feel awful; these are called withdrawal symptoms.
These symptoms can persist to the point where a person may need drugs just to feel normal, and if that’s the case, they are considered to be dependent on that drug.
Now, on the flipside, let’s say that you use the drug in an unfamiliar setting, like at 11:00 P.M. at a party.
Well in that situation, your body’s not ready for the drug and there’s no physiologic “counterbalance” to help offset the effect of the drug.