Chapter 1: Issues for Practitioners in Drug Therapy

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Welcome to the Deep Dive.

You know, when you look around modern life, it really runs on prescriptions.

It's kind of staggering, actually.

It really is.

I mean, the sheer volume.

Right, between 2013 and 2016, almost half of Americans took at least one prescription drug in, what, a month.

And even more for certain groups,

like men aged 45, 64.

I think the figure was like 64 % using three or more.

It's significant.

It really is.

And for you listening, especially if you're heading into advanced practice,

the weight of that prescribing responsibility, it's just massive, whether it's a pad or the ERX screen.

Absolutely.

So this Deep Dive is really aimed at you, the advanced practice student.

We're digging in to chapter one of pharmacotherapeutics for advanced practice.

It's all about that foundational framework.

Right.

It's not just about knowing the drugs themselves, but mastering the whole system around them, the legal stuff, the ethics, the safety.

Exactly.

So our mission today, it's got three main parts.

First, we want to walk through that intense process a drug goes through for FDA approval.

That gauntlet, yeah.

Then second, really analyze your role as the prescriber, you know, your responsibilities, how you pick the right drug.

And third, we need to nail down the actual mechanics writing prescriptions correctly, electronically too, and thinking about patient adherence.

Okay, so let's kick things off with the FDA, the Food and Drug Administration.

Their big job is making sure drugs are pure and safe.

Right.

That's the core mission.

And they oversee this incredibly long process, clinical trials, could take what, up to nine years sometimes?

Nine years.

Wow.

So it really is a journey from the lab to the actual patient.

It is.

And it starts before humans are even involved with preclinical trials.

That's testing in animals.

Okay.

You're looking for initial effectiveness,

toxicity signs, any really bad reactions.

If that looks okay, the company files what's called an investigational use application with the FDA.

And then you move to human testing.

And you move to humans, yeah.

And that's broken down into four phases.

Figure 1 .1 in the text lays this out nicely.

So walk us through those phases.

Why not just jump to testing on sick people if the animal studies look good?

Well, safety first, always.

Phase I involves maybe 20 to 100 healthy volunteers.

It's purely about safety and kinetics.

Kinetics.

You mean how the body handles the drug.

Exactly.

We focus hard on

absorption, distribution, metabolism, or biotransformation, and elimination.

How does the body take it in, move it around, break it down, get rid of it?

Gotcha.

And what are the safe ways to give it?

What dosage ranges seem okay?

You need all that baseline info.

Okay, so once you establish that baseline safety in healthy people, then phase two brings in patients with the actual condition.

Precisely.

Phase E now would involve up to several hundred patients who have the disease the drug is supposed to treat.

Now you're looking at effectiveness and continuing to watch safety very closely in this specific group.

Right.

Then comes phase three.

This is the big one.

Large -scale trials, often thousands of patients.

You're confirming effectiveness, really solidifying the safety profile.

And this is probably where you start seeing less common side effects.

Often, yes.

Those things that didn't show up in smaller groups might become apparent now.

It's only after successful phase three trials that the company can submit their application to the FDA for review to actually sell the drug.

But it doesn't stop even when it's approved on the market, does it?

There's phase four.

Correct.

Phase four is post -marketing surveillance.

This is crucial.

Once millions of people are potentially using the drug, you're monitoring its real -world performance.

What kind of things are you looking for then?

Long -term effectiveness, how it compares to other treatments already out there, quality of life impacts, cost effectiveness,

and importantly, rare or long -term adverse events.

So a drug could still be pulled off the market even after approval.

Absolutely.

Based on phase four findings, drugs can have their use restricted, get new warnings added, or even be withdrawn completely.

Now, you mentioned the long timeline, up to nine years.

But there are ways to speed things up for critical needs, aren't there?

Yes, definitely.

For serious diseases where there aren't good treatments available, the FDA has several pathways to accelerate the process.

Like the fast -track system.

Exactly.

Fast -track breakthrough therapy,

accelerated approval, priority review.

These are mechanisms.

Priority review, for instance, cuts the FDA's review time down from the standard 10 months to just six.

That's a big difference.

It is.

And we saw another mechanism used a lot recently, the emergency use authorization, or EUA.

Right, for COVID -19.

Yeah, for treatments like remdesivir and the vaccines.

An EUA allows use during a public health emergency when the evidence is still developing.

But the potential benefit outweighs the potential risk, and there are adequate alternatives.

Okay, so the FDA focuses on safety and efficacy.

But once a drug is approved, another big concern is the potential for abuse or misuse.

That brings in the DEA, right?

That's right.

The Drug Enforcement Administration.

The Controlled Substances Act of 1970 is the key legislation here.

It established the drug scheduling system.

Which categorizes drugs based on abuse potential.

Purely based on their potential for abuse or

and whether they have accepted medical use.

And if you, as a practitioner, plan to prescribe any controlled substance, you absolutely must register with the DEA first.

You get a unique DEA number.

Let's quickly run through those schedules.

Box 1 .1 in the chapter lists them.

What's the key takeaway for prescribers, especially regarding how they're handled?

I think the biggest practical difference day to day is about refills.

Schedules 1 and 2 are the highest risk.

Schedule 1, that's heroin, LSD, stuff with no medical use.

Exactly.

High abuse potential, no accepted medical use in the US.

You won't be prescribing those routinely.

Schedule 2 drugs also have high abuse potential, but they do have legitimate medical uses.

Like strong pain medications or some ADHD meds.

Correct.

Certain amphetamines, potent opioids.

The absolute crucial rule for Schedule 2, no refills allowed, period.

Wow.

So a new prescription every single time.

Every single time.

In a true emergency, you can phone in a prescription, but you must follow up with a written or electronic prescription to the pharmacy within typically 72 hours.

Okay.

What about the lower schedules?

3, 4, and 5.

As you go down, the abuse potential decreases.

Schedule 3 drugs have less potential than S2.

Think certain narcotics mixed with non -narcotics, like some codeine combination products.

These can be refilled.

How many times?

Up to five times within a six month period from the date the prescription was written.

Okay.

And Schedule 4.

Lower abuse potential than S3,

often associated more with psychological dependence than physical.

Think drugs like lorazepam valium.

Anti -anxiety meds often fall here.

Same refill rules generally apply up to five times in six months.

And Schedule 5 is the lowest risk.

Lowest potential for abuse.

These are often preparations with very small amounts in narcotics, mainly used as cough suppressants or antidiarrheals.

Refill rules might be less strict, sometimes governed more by state law.

Now, to help track these controlled substances and prevent misuse, we have PDMPs.

Yes.

Prescription drug monitoring programs.

Almost every state had one by 2014.

It's essentially a state -level database.

What does it track?

It tracks controlled substance prescriptions dispensed within that state.

So as a prescriber, you can log in and see if your patient has recently received controlled substances from other prescribers.

Ah, so it helps identify potential prescriber shopping.

Exactly.

Patients trying to obtain the same or similar drugs from multiple doctors simultaneously.

Now, there's some controversy around privacy and scope, but fundamentally, it's a tool.

It gives you information to start a conversation if you see a pattern that concerns you.

Perhaps about addiction or diversion.

Okay.

And one more identifier we need to touch on the NPI.

Right.

The National Provider Identifier.

This is different from the DEA number.

The NPI was mandated by IPI.

I pay it.

It's a unique 10 -digit number assigned to all healthcare providers.

Think of it as your universal ID for healthcare transactions.

Transactions like?

Billing, insurance claims, referrals, and yes, increasingly for prescriptions, especially electronic ones.

It's all about standardizing identification to improve efficiency and accuracy across the healthcare system.

You'll need one regardless of whether you prescribe controlled substances.

All right.

This is where things get really practical for the advanced practitioner on front lines.

Selecting the right drug for the right patient.

It sounds simple, but it's not.

Not at all.

It always, always starts with a thorough history and a good physical exam.

That's non -negotiable.

And then comes the core decision -making process.

The risk -benefit analysis.

Absolutely.

That is your fundamental ethical and clinical duty.

You have to weigh the potential good the drug can do against all the potential harms or risks.

What kind of questions should be going through your head?

Box 1 .2 has a good list.

You need to ask,

is this truly the best option for this specific patient and their diagnosis?

Are there any contraindications, reasons they absolutely should not take this drug?

Is the dose right?

Is the frequency right?

And you mentioned lifestyle earlier.

Hugely important.

Does the regimen fit the patient's life?

Yeah.

Asking someone to take a pill four times a day when they work a busy job or are in school.

That might be setting them up for failure for non -adherence.

Maybe a once -daily option, even a slightly different, would be better overall.

That leads into another challenge, the pressure to prescribe.

Patients sometimes come in expecting a prescription, even if it's not clinically needed.

Oh, definitely.

The classic example is antibiotics for a viral cold.

The patient feels awful.

They want a fix.

They think antibiotics are the fix.

But they don't work for viruses.

Exactly.

So your ethical responsibility there is to not prescribe the unnecessary antibiotic and, crucially, to explain why.

It's about patient education and antimicrobial stewardship, protecting antibiotic effectiveness for when they're truly needed.

Resisting that pressure is key.

And speaking of education, that's vital once you do decide to prescribe something.

Absolutely critical.

It's a huge part of patient safety.

You have to explain what the drug is supposed to do, the intended therapeutic effect.

But also the potential downsides.

Yes.

You must discuss potential side effects.

And you have to highlight any black box warnings.

Those are the really serious ones.

Yes.

Black box warnings signify the potential for serious, permanent, or even fatal side effects.

Patients need to be aware of those specific risks.

Does warning people about side effects make them more likely to happen, like a nocebo effect?

Well, the placebo effect is real.

And its opposite, the nocebo effect can be too.

But studies actually show that anticipating potential side effects, knowing what might happen, often improves adherence.

Oh, so?

Because if they start feeling a mild side effect you warned them about, like nausea, they're less likely to panic and stop the medication immediately.

They think, ah, my provider mentioned this might happen.

It's probably okay.

It manages expectations.

That makes sense.

Any other practical tips for safety here?

One big one.

Encourage your patients to use just one pharmacy whenever possible.

Why is that?

Because the pharmacist then has a complete picture of all their medications, prescription, and sometimes even OTCs.

They act as a vital second check for potential drug interactions that maybe you missed, or that arise from prescriptions written by different specialists.

It's an invaluable safety net.

Okay, let's talk cost.

It's a huge factor in health care, and it often leads to using generic drugs.

Generic substitution is pretty common, sometimes even required by insurance or state law, right?

Very common, and for good reason, cost savings.

The text notes generic prices drop significantly, like over 9 % from 2016 to 2017, way more than inflation.

That makes a real difference for patients and the system.

But patients sometimes worry, is the generic really the same as the brand name?

What does the FDA require?

The FDA requires rigorous proof of therapeutic equivalence.

This is a key concept.

What does therapeutic equivalence actually mean in scientific terms?

It means the generic drug has to perform essentially the same way in the body as the brand name drug.

Specifically, they look at pharmacokinetic measures.

Like that ADME stuff we talked about.

Exactly.

They measure the peak concentration of the drug in the blood serum and the total exposure over time, which is called the area under the plasma concentration curve, or AUC.

For a generic to be approved, its peak concentration and its AUC must generally fall within a range of 80 % to 125 % of the brand name drug's values.

That range, 80 % to 125%, sounds kind of wide.

It sounds wider than it usually is in practice.

Most of GOOV generics are actually much closer.

Typically, within just a few percent, the text mentions an average of about 3 % difference in mean AUC from the brand name.

The range allows for normal biological variability.

So the FDA has a system for rating this.

How do we know if a generic is considered equivalent?

Table 1 .1 touches on this.

Yes.

The FDA publishes ratings in what's often called the orange book.

You're looking for the A codes.

A codes like AA, AN, AO, AP, AT, or AB generally mean the products are considered therapeutically equivalent.

So A means OK to substitute?

Generally, yes.

AB rated drugs, for example, meet the necessary bioequivalence requirements.

B codes, on the other hand.

B means stop.

B means not therapeutically equivalent.

These are drugs that might have documented bioequivalence problems.

Or there isn't enough data to prove equivalence.

You shouldn't substitute a B rated drug without consulting the prescriber.

OK, that's helpful.

Now, shifting gears slightly,

what about things that aren't FDA approved drugs, like complementary and alternative medicine SAM?

Right.

This is a really important area to ask patients about because use is high.

The text mentions about 33 % of adults use some form of CAM back in 2012.

Things like fish oil, glucosamine, and melatonin are very popular.

But they aren't regulated like drugs.

That's the crucial point.

Herbal preparations, vitamin supplements.

They are generally sold as foods or dietary supplements, not as drugs.

Meaning they don't go through those rigorous FDA says as we discussed.

Correct.

There aren't the same legislative standards for proving safety, efficacy, purity, or even the quantity of the active ingredients stated on the label.

So what's the risk for patients and prescribers?

Significant risks.

Just because something is natural doesn't mean it's safe.

These products can have potent pharmacological effects.

They can cause side effects just like synthetic drugs.

And critically, they could have serious interactions with prescription medications.

So you absolutely have to ask patients if they're taking any supplements or herbals?

Every single time.

It has to be part of your standard medication history.

OK, let's get down to the brass tacks writing the actual prescription.

Whether it's on paper or electronic, it's a legal document, isn't it?

Figure 1 .3 shows an example.

Absolutely.

It's a communication tool between you, the patient, and the pharmacist.

Clarity and accuracy are paramount to prevent errors.

What are the essential components?

Patient's name and address.

Full legal name, current address,

your information to name, address, phone number, the date it was written.

And the drug itself.

Drug name, generic name is usually preferred.

You can add the brand name and parentheses if needed.

The strength or concentration.

And the dose.

Any specific rules for writing the dose to avoid mistakes?

Yes, very important ones.

Always use a leading zero for doses less than one.

Write 0 .75 milligrams, not 0 .75 milligrams, but never use a trailing zero after a whole number.

Write 10 milligrams, not 10 .0 grams, because that could easily be misread as 100 milligrams.

Little details that make a big difference.

Huge difference.

Also, be super clear with units.

Use MGG, ML.

Spell out things that can be ambiguous like microgram or unit.

Don't use potentially confusing abbreviations.

Like OD for once daily.

Right.

Write daily or once daily.

OD can be mistaken for OD, right eye, or QOD every other day.

Clarity trumps brevity here.

Okay.

What else?

Quantity refills.

Specify the quantity to dispense and the number of refills allowed.

Remember, schedule two drugs, zero refills.

And if you don't want the pharmacist to substitute a generic.

You usually have to indicate that explicitly, either by signing on a specific line like

or sometimes by actually writing brand medically necessary on the prescription, depending on state law.

It seems like handwritten prescriptions have a lot of potential pitfalls.

Electronic prescribing, ERX, must help with this.

Tremendously.

CMS actually mandated e -prescribing for Medicare Part D controlled substances starting back in January 2021, pushing wider adoption.

What are the main benefits of ERX?

Several big ones.

First, legibility, no more deciphering handwriting.

That alone reduces errors.

Studies show ERX can decrease adverse drug events by somewhere between 12 percent and 20 percent.

Plus, ERX systems often have built in clinical decision support.

They can automatically check for drug interactions, drug allergy interactions, duplicate therapies, even incorrect dosing based on the patient's age, weight, or kidney function labs, if integrated.

So it adds another layer of safety checks.

A very significant layer.

It doesn't eliminate all errors, but it catches a lot.

What are some common prescribing errors that still happen, even with technology?

Failing to get a complete and accurate allergy history is still a big one.

And really drilling down, is it a true allergy like hives or anaphylaxis, or is it a sensitivity or intolerance like nausea?

That distinction matters.

Also, forgetting to ask about those OTCs and herbals we just discussed.

And a surprisingly common one.

Failing to explicitly stop a previously prescribed medication when starting a new one for the same condition.

The patient might end up taking both.

Yikes.

Okay, and finally,

if a serious adverse drug event does occur despite all precautions, what's the prescriber's responsibility?

You have a professional and sometimes ethical responsibility to report it.

Serious adverse reactions to drugs are typically reported to the FDA's MedWatch program.

And for vaccines?

For vaccine adverse events, there's a separate system called VAERS, the Vaccine Adverse Event Reporting System.

This reporting is vital for that ongoing phase four post -marketing surveillance we talked about.

We've touched on adherence a few times, but let's really focus on it.

It's a massive problem, isn't it?

Patients not taking their medication as prescribed.

It's a huge challenge, and it directly leads to poor health outcomes, hospitalizations, increased costs,

everything we want to avoid.

The text cites a sobering statistic.

The one about chronic medications.

Yeah, that study by Carter from 2009 found that among patients newly prescribed medication for a chronic condition, only about 20 % were actually adherent a year later.

20%.

That's incredibly low.

What drives non -adherence?

Cost is a big one, right?

High out -of -pocket cost is definitely a major barrier.

But it's more complex than just cost.

Box 1 .4 in the chapter lists several factors.

Like the patient's perception?

Yes, the patient's whole perception of the encounter matters.

Do they feel you listened?

Do they trust you?

How approachable were you?

Also the regimen itself?

Simplicity is key.

The fewer times a day they have to take it, the easier it is.

The fewer pills, the better.

And critically, does the patient actually believe the medication will help them?

Do they believe the benefits outweigh the risks or side effects?

So if you suspect non -adherence, what should you do?

First, document your suspicion and the evidence for it.

Then you need to explore why.

Gently ask the patient, is it cost?

Is it side effects?

Did they forget?

Do they have trouble swallowing pills?

Maybe they don't think they need it anymore.

And then try to address the specific barrier.

Exactly.

Problem solved with the patient.

Can you switch to a cheaper generic?

A different dosage form?

A simpler schedule?

Can you provide reminder tools?

Just ignoring non -adherence isn't an option.

We also need to think about specific patient groups, right?

Dosing isn't always standard.

Definitely not.

Pediatric dosing, for example, is usually based on weight or sometimes body surface area.

This requires careful calculations and errors can happen.

Plus, many drugs haven't been extensively studied in children, limiting data.

And older adults, geriatric patients.

With geriatric patients, a major concern is often declining kidney function, even if their basic labs look okay.

Reduced renal clearance increases the risk of drug accumulation and toxicity.

You often need to start low and go slow with dosing.

This leads us towards more individualized approaches, like pharmacogenomics.

Yes, this is a rapidly growing and incredibly important field.

Pharmacogenomics studies how a person's genes affect their response to drugs.

How big of a factor is genetics?

It can be huge.

The text states genetic factors can account for 20 % to even 95 % of the variability we see in how different patients react to the same drug at the same dose.

So testing can help predict who will respond well or who might have side effects.

Precisely.

It can help us understand why one patient gets great relief from a drug, while another gets nothing but side effects.

It allows for more personalized, targeted prescribing decisions, moving away from the trial and error approach for some medications.

It's becoming integral to truly personalized medicine.

Okay, let's try to bring all these principles together by looking at the case studies from the chapter.

Case study one is AJ, a 16 -year -old soccer player.

Right.

AJ comes in with shortness of breath, mainly when exercising.

She also has a history of eczema and allergies, and mentions using an OTC and a histamine sometimes.

So what prescribing principles jump out here?

First, the absolute need for that thorough history we keep mentioning.

You have to know about the eczema, the allergies, and especially that OTC and a histamine use.

Is she taking it regularly?

Could it be interacting or contributing?

You need the full picture.

And then thinking about treatment,

maybe an inhaler.

Likely an inhaled bronchodilator like albuterol for exercise -induced symptoms.

But the key clinical pearl here relates to adherence and education.

How so?

It's not enough to just prescribe the inhaler.

You need to instruct AJ exactly how and when to use it, say, 30 minutes before soccer practice or games.

And crucially, you need to explain the benefit in terms she cares about.

Using this correctly will help prevent the shortness of breath so she can play soccer successfully.

Ah, connecting the medication directly to her personal goal.

Exactly.

That link makes adherence much more likely than just saying use this before exercise.

Okay, good point.

Now, case study two involves Mrs.

S, who's 45.

She's dealing with quite a few issues already.

Yes.

Mrs.

S is a classic example of polypharmacy risk.

She has anxiety, type 2 diabetes, insomnia, fibromyalgia, and she's already taking four medications.

Dulaglutide, metformin, zolpidem, and fluoxetine.

And she comes in complaining of new anxiety and palpitations.

Right.

So the immediate prescribing principle here, before you even think about adding another drug,

is caution and assessment due to existing polypharmacy.

What's the first step?

You absolutely must use a drug interaction checker.

With four drugs already on board, the potential for interactions causing your new symptoms is significant.

Could the zolpidem or fluoxetine be contributing?

Is there an interaction between them?

So investigate the current regimen first.

Always.

The other huge principle here is avoiding the prescribing cascade.

What's that again?

That's when you prescribe a new drug to treat the side effect of an existing drug instead of addressing the original problem drug.

For Mrs.

S, are the palpitations a side effect of one of her current meds?

If so, adding another drug to treat the palpitations is the wrong move.

You might need to adjust or change one of the existing medications first.

Assess before you add.

Hashtag tag outro.

So if we were to boil down the key takeaways from this deep dive into chapter one, it's that responsible prescribing is, well, it's really complex, isn't it?

It definitely is.

It's multi -layered.

Yeah, you're constantly integrating things.

You've got the federal regulations from the FDA ensuring safety,

the DEA rules for controlled substances.

Then there's the core clinical judgment, that constant risk benefit analysis for each individual patient.

Right.

And layered on top of all that is the communication piece.

Educating the patient, ensuring they understand, working with them to overcome barriers like cost or side effects to actually achieve adherence.

It all has to work together.

That foundation is absolutely vital as you prepare for practice.

But here's something else to think about.

A final provocation based on the source material.

Okay.

The text mentions this issue of online pharmacies, tens of thousands of them out there.

And apparently something like 96 % operate outside of US laws.

And there's a wider global issue with counterfeit or substandard medications.

That's a scary thought.

It is.

So the question for you, the future advanced practitioner is, how do you navigate patient safety when your patients might be tempted purely because of cost to use these unregulated foreign or online sources for their medications?

That really ties accessibility and affordability directly to safety risks in a globalized world.

Exactly.

How do you ensure safe prescribing in that environment?

It's a complex challenge with no easy answers.

Definitely something important to keep in mind as you move forward in your practice.

Well, thanks for joining us for this deep dive into the foundations of prescribing.

Hope it was helpful.

We'll catch you next time on the deep dive.