When I first studied pharmacology, I thought of medication in fairly simple terms.
You take a drug; it is absorbed; the plasma concentration rises; it acts on receptors; and with time it is metabolized and leaves the body. For exams, it was enough to memorize terms like bioavailability, peak plasma concentration, and half-life.
Becoming a doctor did not change this much. When prescribing, I thought about how many times a day to take it, before or after meals, and whether it interacted with other drugs. Pharmacology mattered, but it stayed inside the books.
Then Parkinson’s disease turned pharmacology into an entirely different subject.
You take one pill and wait. Twenty minutes pass — nothing. Around forty minutes, the body seems to loosen a little. After an hour, walking becomes easier.
“The medication is coming up.”
But some days, the same pill brings no change even after an hour. Some days the body suddenly frees up only after nearly two hours. Other days, just as things improve, dyskinesia appears. And a few hours later, the body grows heavy again.
Pharmacology no longer means only a plasma concentration graph to me.
It is the study of observing, over time, how the body changes after taking a drug.
Chapter 1. From swallowing the pill to feeling its effect
We casually say “I took my medication.” Pharmacologically, though, swallowing the pill is only the beginning of the process.
For an oral drug to actually work, it must pass through many steps.
Ingestion → disintegration → dissolution → gastric emptying → intestinal absorption → bloodstream → tissue distribution → target organ → drug effect
For levodopa in Parkinson’s disease, one more chain matters.
Intestinal absorption → rising plasma levodopa → crossing the blood–brain barrier → conversion to dopamine in the brain → change in the motor circuits → change in how the body moves
So the time you swallow the pill and the time the medication starts working cannot be the same.
Taking the morning dose does not mean the body improves right away. Even after the dose, the body may stay in the OFF state for a while. Then, at some point, a small change appears.
The hand feels a little easier. Standing up from a chair becomes possible. The foot lifts off the floor. Walking begins to feel natural.
I think of this change as the first sign of response.
Between the time of the dose and the time of that first sign, there is an interval. During that interval, the drug is traveling through the body.
The stomach is not just a passageway
Levodopa is not well absorbed in the stomach. It must move past the stomach into the small intestine before real absorption can begin. If it lingers in the stomach, the onset of effect can be delayed.
Parkinson’s disease can affect not only movement but also the autonomic nervous system and gastrointestinal motility. So even if you take the same drug at the same time, the time it takes to pass from stomach to small intestine is not always the same.
Today it came up in forty minutes; tomorrow it might take eighty.
The patient says:
“The medication is slow today.”
And here an important question arises.
“Is the dose insufficient, or has it simply not come up yet?”
The two can feel similar in the body, but pharmacologically they are different problems.
If you assume the effect is lacking and take an extra dose, and then the earlier dose begins to absorb late, the two doses can overlap. The body may jump abruptly from OFF to ON, or overshoot the therapeutic window into dyskinesia.
That is why recording when the first change began matters as much as recording how much was taken.
Chapter 2. Plasma concentration and drug effect are not the same thing
One of the most familiar figures in any pharmacology book is the plasma concentration curve.
After a dose, the concentration rises, reaches a peak, and falls again.
Several terms attach to this picture.
Tmax is the time to peak plasma concentration; Cmax is that peak concentration; the half-life is the time it takes the plasma level to fall by half.
It is a tidy picture.
But the real body is not tidy.
At first, I assumed my body would follow the plasma curve — improving as the level rose, worsening as it fell.
In broad strokes, yes. But once you actually keep records, the two are not the same curve.
A small rise in plasma levodopa does not immediately produce ON. Only when enough effect has built up does a meaningful change appear in the body.
I began to understand this through the concept of a threshold.
Suppose we describe the body’s state as an output from 0 to 100.
Morning output is 20. You take the dose. The effect increases little by little, but the output does not leap straight to 80. It climbs from 20 to 30, 40, 50 — and then, at some point, walking and moving become clearly easier.
That point is what I feel as ON.
The same holds when the effect declines. Even as the plasma level slowly falls, the body may keep moving well for a while. Then, past some line, the output can seem to drop suddenly.
So I came to keep two curves apart in my mind.
The plasma concentration is the drug’s curve; the output is the body’s curve.
What I want to record in a medication diary is the second one.
Chapter 3. Feeling the medication response curve in the body
Living with Parkinson’s disease for years, each day began to feel like a single curve.
You wake up. The body is heavy. You take the dose. You wait. The first sign appears. The body improves bit by bit. At some point, walking is easy. That is ON.
Climb a little higher, and the body may begin to move too much — dyskinesia.
Things settle with time. Then the body slowly grows heavy again. The decline begins, and eventually OFF returns.
Written in the simplest terms, a day looks like this:
OFF → rising phase → ON → peak → declining phase → OFF
At first I thought only about ON and OFF. But the longer I kept records, the more I realized the important parts lie in between.
The rising phase
You have taken the dose, but you are not fully ON yet. Small changes appear in the body. Recording this point lets you compare whether today’s dose is coming up faster or slower than usual.
ON
The stretch where the body moves relatively naturally. But ON is not one single thing. There is an ON where you can barely get around, and an ON where movement is genuinely comfortable.
That is why recording the degree of output, not just ON/OFF, can help.
The peak
The highest part of the drug’s effect. It can be a good ON — but if it climbs too high, dyskinesia may appear.
A higher peak is not automatically a better one.
The declining phase
I watch this stretch closely.
It is not yet full OFF, but the body has started to change. Strength fades, steps shorten, movements slow, or the feet begin to stick to the floor.
If the next dose’s effect starts rising at this point, the curve may not fall very deep. If the next dose starts late, a deep trough can open up between the two doses.
So when looking at a day’s medication response, do not only ask how high the peak went. Also ask:
How much of the current effect is still left when the next dose comes up?
Between pharmacokinetics and pharmacodynamics stands the patient
Pharmacology distinguishes two things.
Pharmacokinetics (PK) is what the body does to the drug — absorption, distribution, metabolism, excretion.
Pharmacodynamics (PD) is what the drug does to the body — acting on receptors, changing neural circuits, and ultimately changing symptoms.
What a person with Parkinson’s disease actually experiences is the combined result of both.
If a dose works late, pharmacokinetic factors like absorption and gastric emptying may be involved. If the drug has come up but the change in the body is not enough, the day’s disease state, the brain’s responsiveness, and daily conditions all deserve thought.
And at the end of all of it, one result remains:
How much can my body move right now?
I began calling that the “output.”
Closing Part 1
Studying pharmacology again, the first thing that changed was how I look at medication.
I used to look at the dose.
Now I look at the curve.
Not only how much was taken, but:
- when it was taken
- when the first sign came
- how fast it rose
- how high it reached
- how long it lasted
- when it began to fall
And one thing more:
How much of the current effect remains when the next dose comes up.
A day’s medication response is not a set of separate single-pill effects. The next dose’s curve overlaps the one before it, and meals, sleep, activity, and the state of the gut all shake that curve.
The result is the day the patient actually lives.
So this is how I now define pharmacology for myself:
Pharmacology is the study of drugs — and the study of the changes that drugs and the body create together, in time.
And living with Parkinson’s disease, I learn those changes with my own body, every day.
This article is for education, to help understand how medication response changes in Parkinson’s disease. Any change to an individual’s medication type, dose, or timing should be discussed with the treating clinician.