PISCS and the Meaning of Having a Pharmacist—A Story About a Philosophy I Have Always Cherished

There is a philosophy that I have always cherished.

It is a philosophy that quietly brings warmth to my daily prescription audits as a pharmacist.

It all started with a casual remark from someone I met at a conference.
At the time, I didn't really understand what those words meant, so I just brushed them off with a 'Hmm.'
—But that one remark would slowly change my life as a pharmacist.

—But that one remark would slowly change my life as a pharmacist.

The day I brushed it off with a 'Hmm'

It was a little while after I had started studying nephrology in earnest.

I met a pharmacist at a social gathering during a conference.

That person was passionate.
They spoke directly about their professional philosophy over drinks.
—I feel bad thinking about it now, but at the time, I looked at them with a bit of detachment, thinking, 'Wow, they're intense.'

In the flow of conversation, they said this quietly:

“The interactions listed in the package insert are definitely not enough, are they?”

—Huh?

For me at the time, the package insert was absolute.
I somehow assumed that what was written there was correct, and what wasn't written meant there were 'no particular issues.'

That’s why I didn't really understand the meaning of those words.
Since I was drunk and my thinking couldn't keep up, I just smiled vaguely and brushed it off with a 'Hmm.'

Looking back at myself then, I think I was immature.
—No, perhaps what was immature wasn't that I brushed it off, but that I didn't think about what it meant.

Even so, that remark remained strangely stuck in my head.

Looking into it out of curiosity

I had taken notes on that night's conversation.
Even though I had looked at them with detachment, thinking, 'Wow, they're intense,' I was somehow curious.
And those notes remained in the corner of my desk for a long time.

—The catalyst was a question from the ward.

One day, a nurse consulted me, saying,
“The patient is over-sedated...”

I checked the prescription.
The patient had been taking antidepressants for a while, and a cough suppressant had been added for cold symptoms.
The dosages for both were quite standard.
Their kidney function was also fine.
“Why?” I tilted my head in confusion.

At that moment, I suddenly remembered that note in the corner of my desk.

——"The interactions listed in the package insert are definitely not enough, are they?"

I pulled out that note.
The book titles, references, and unfamiliar terms written there.
I looked them up one by one.

And then, I encountered the concept of "PISCS."

To be honest, at the time, I hadn't paid much attention to metabolic pathways other than CYP3A4.
So, the moment I stepped into the world of PISCS, I realized just how narrow the map I had been looking at really was.

This was a concept proposed by Dr. Yoshiyuki Ohno and his colleagues.

The Shock of 'Caution for Concomitant Use' Being at a 'Contraindication Level'

I tried applying the combination from that case to the PISCS calculation formula.

First, I checked the package insert.
The package insert for the cough suppressant stated "Caution for concomitant use" regarding its use with that antidepressant.

——"Caution for concomitant use."
I had always thought it meant
that you just needed to be careful.

However, when I calculated it using PISCS,
it became clear that
the blood concentration could potentially rise several times over.

I got goosebumps.

I hurriedly went back and checked the prescription history of the patients I was in charge of.
Was there anyone taking the same combination?
Were there any cases I had overlooked
with similar combinations?

The result was that there were no issues.

——I felt relieved.
At the same time, I felt a chill.

The fact that there were "no issues" might have just been a coincidence.
There might have actually been more patients who had become over-sedated, and I just hadn't been able to see it.

I already knew now.

Once I knew, I had to think about it.

Encountering the Question

From then on,
in order to fully grasp the PISCS concept,
I started reading books and attending study sessions.

As I continued to learn,
I would encounter a certain question time and time again.

Within the pages of a book.
In the audio of a study session.
In casual conversations I had with someone.
Or as a voice that would suddenly arise within myself.

——“If you only act based on what is written in the package insert, you don't need to be a pharmacist. What is the point of having a pharmacist?”

I no longer know if it was something someone else said,
or if it was a thought of my own.
But at some point, that question
had taken up residence within me.

At first, I couldn't accept it right away.
The question was too heavy.

However, the more I learned about PISCS, and the more I continued my daily prescription audits, the more that question gradually seeped into me.

And before I knew it, that question
——had come to support my stance as a pharmacist
at a deep level.

It became a question that supports my foundation.

Now, that question is always at my back.

——Actually, I am the type who tends to drift toward the easy path if I'm not careful.
So, having such a heavy question at my back
keeps me grounded.

When considering the contribution rate.
When looking at combinations of prescriptions.
There was a day when I thought incredibly hard while facing a single prescription for a patient—that, too, was because this question was at my back.

I continue to answer that question every single day.

Deep Dive: The Core of the PISCS Perspective

I would like to show you
the perspective I encountered.

It will be a little technical,
so if it is difficult, I would be happy if you could just skim through it.

Roughly speaking, PISCS is this kind of perspective.

“To what extent the substrate drug depends on which metabolic pathway(contribution rate)” × “To what extent the inhibitor stops that pathway(inhibition rate)”

With this multiplication, we predict how much the blood concentration will rise.

Regarding the formulas and many more practical examples,
Inotaro-san explains them carefully on note.
I received permission from Inotaro-san himself, so please let me introduce them here.

In this article of mine,
I only want to convey the 'feel' of this way of thinking.

For example, the case I wrote about earlier where a cough suppressant was added to a patient taking antidepressants, leading to over-sedation.

When you look at this combination through the lens of PISCS, this is what you see.

• That antidepressant strongly inhibits the CYP molecular species that metabolizes the cough suppressant. The inhibition rate is close to 0.8–1, a level of almost complete inhibition

• In reports of co-administration with other drugs that have a similar inhibition strength, there is data showing that the blood concentration of the cough suppressant increased by about 11 times.

• Therefore, an increase of about 5 to 10 times could easily occur with this combination as well

And this also connects to the story I wrote before about colchicine and verapamil.

Colchicine also has about 20% renal excretion contribution and about 80% hepatic metabolism/biliary excretion.
So, even if the renal function numbers look normal, if the hepatic route is blocked, the blood concentration will rise.

——“Increases that aren't visible in the numbers” can be seen through the eyes of PISCS.

However,
I want to write this down because it is important.

The numbers that come out of PISCS are not absolute values.
They are, at most, a practical estimate that “this kind of thing could happen”.

I believe it is not a tool for pinpointing exactly “how many times it will increase,” but rather a tool for triggering an internal alert that says, “this might require caution.”

And whether or not you can trigger that alert definitely changes the quality of your work as a pharmacist.

Finally

For me, PISCS is a technique, and even more than that, it is a question.

“If I only act based on what is written in the package insert, I don't need to be a pharmacist. What is the meaning of having a pharmacist?”

I still carry that question on my back today.
The weight of that question keeps me standing when I am prone to drifting toward the easy path.

And it is precisely the weight of that question that
gives warmth to my daily prescription audits.

——If I may wish.

I hope that even one more pharmacist will want to read beyond the package insert.
And I hope that even one more person will want to become a little more familiar with their own medication.

Today, too, I will continue to answer that question.

▶Related Articles

This is an article that delves into actual clinical cases using the PISCS concept. By reading this after reading the current article, you should be able to see how the question, "What is the meaning of having a pharmacist?" plays out in real-life cases.

This is a list of 14 high-risk drugs based on the PISCS concept. For those who want to check alerts for "increases that are not visible in the numbers" using specific drug names.

This is a note article that carefully explains the formulas and practical examples. I recommend this for those who want to try calculating PISCS themselves.
(I have received permission from Inotaro-san himself to introduce this.)