Chapter 2: Pharmacologic Principles

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Welcome to the deep dive.

If you work in healthcare,

or maybe you've just wondered, you know, what actually happens when you take a medication?

Well, this deep dive is definitely

we're really digging into the foundations today with pharmacologic principles.

It's all about how drugs move through and affect the body.

Yeah, absolutely.

This is core knowledge for safe practice.

So pharmacology, what are we talking about?

Big picture.

Right.

So pharmacology,

basically, it's the science of drugs.

And a drug is just any chemical that affects, well, how the body works, it's physiologic processes.

And there are sub areas too, like pharmacognosy, which looks at natural sources, think plants and minerals,

and toxicology.

That's the study of adverse effects, the bad stuff.

Got it.

So our goal today is kind of follow that drugs journey right from those two effects.

Exactly.

We need to connect the dose given to the actual patient outcome.

And we do that by looking at three main phases.

Three phases.

Okay.

What are they?

Pharmaceutics, pharmacokinetics, and pharmacodynamics.

Think of it as the drugs life cycle.

All right, phase one, pharmaceutics.

Before we even get to the body, let's talk names.

Drugs have like three different names.

They do.

There's the chemical name, super complex, describes the structure, not one you'll use often clinically.

Right.

Then the generic name, that's the non -proprietary one, shorter, the one healthcare pros mostly use, think ibuprofen.

Okay, ibuprofen.

Got it.

And finally, the trade name or brand name.

That's the manufacturer's registered trademark, like Advil or Motrin for ibuprofen.

Easier to remember maybe, but you got to be careful not to mix up brands.

Good point.

Okay, so pharmaceutics is about how the form of the drug matters, like tablet versus liquid.

Precisely.

Pharmaceutics studies how that dosage form impacts the drug's effect.

If you take a solid drug, like a tablet, it first has to dissolve in the GI tract.

That's dissolution.

It needs to break down to get absorbed.

Exactly.

It has to disintegrate and become absorbable.

And does the form change how fast that happens?

Oh, absolutely.

Think about it.

Liquids, elixirs, syrups, they're already dissolved, so they get absorbed fastest.

Makes sense.

Standard tablets and capsules are next, but then you have the really slow ones.

Like coated tablets.

Right.

Especially in taric -coated tablets.

That coating is designed specifically not to break down in the stomach's acid.

Ah, so it waits until it gets further down.

Yep.

It waits for the more alkaline environment of the intestines.

This either protects the drug itself from the acid, or really importantly, it protects the stomach lining from an irritating drug.

Okay, that leads perfectly into a huge safety point, doesn't it, about crushing pills?

Crucial point.

You see those letters on drug packaging?

SRSA, CR, XL, XT, sustained release, extended release, controlled release, all mean the same thing.

Do not CR -oo -ish.

Why not?

What happens?

If you crush these, you destroy that slow release mechanism.

You're basically dumping the entire intended dose, maybe 12 or 24 hours worth, into the patient's system all at once.

Wow.

That sounds like instant overdose potential.

It is.

High risk of toxicity.

And same goes for those in taric -coated tablets.

Crush them and you lose the protection.

You might irritate the stomach badly, or the stomach acid could just destroy the drug before it even has a chance to work.

So bottom line, check if a tablet can be crushed before you even think about doing it.

Always.

Check the drug guide.

Check with pharmacy.

Never assume.

Okay.

All right, so the drug is dissolved.

Now we move into pharmacokinetics.

This is all about what the body does to the drug.

And there's an acronym for this, right?

ADME.

That's the one.

Absorption, distribution, metabolism, and excretion.

ADME.

Hashtag tag tag A.

Absorption and roots of administration.

Let's start with A.

Absorption, getting the drug into the bloodstream.

You mentioned bioavailability.

Yes, bioavailability.

It's the measure, usually a percentage, of how much of the administered drug actually reaches the systemic circulation unchanged.

And it's not always 100 % for pills, is it, because of the first pass effect?

Exactly right.

The first pass effect is a big factor for oral drugs.

When a drug is absorbed from the GI tract, it first travels through the portal vein directly to the liver.

The liver gets first crack at it.

It does.

And the liver starts metabolizing, breaking it down before it even gets to the That's why oral bioavailability is often less than 100%.

So if you need 100 % bioavailability,

you avoid the GI tract.

Precisely.

Intravenous, or A, administration bypasses the liver completely.

It goes straight into the bloodstream.

So IV drugs are considered 100 % bioavailable.

And that explains why roots matter so much,

like under the tongue, sublingual.

Sublingual or buccal, which is in the cheek pouch, these routes absorb the drug directly through the mucous membranes in the mouth.

Straight into the bloodstream.

Straight into the capillaries there, which drain into the systemic circulation, bypassing the liver's first pass effect.

That's why something like sublingual nitroglycerin works so fast for angina.

Okay, this difference between IV and oral is massive then.

You gave the example of Lasix.

Yes, Lasix, a diuretic.

Give it IV, and you see effects like increased urination within minutes.

Give the same drug orally.

You wait longer.

You wait 30 to 60 minutes for it to even start working,

and less of the drug might actually be effective because of that first pass metabolism.

So the absolute rule is you cannot just switch routes without an order.

5e dose is not the same as a PO dose.

Never.

It requires a specific order from the prescriber because the dosing and effect can be drastically different.

Safety first, hashtag, hashtag, B, distribution.

Okay, ADME.

D is for distribution.

The drugs in the blood, where does it go?

Distribution is about how the drug gets transported by the bloodstream to its site of action.

It travels fastest to organs with the best blood supply, heart, liver, kidneys, brain.

And slower to places like muscle or fat.

Slower to muscle, fat, and skin, yeah.

But a key concept here is protein binding.

Protein binding.

Sounds important.

It is.

Many drugs bind, at least partially, to proteins circulating in the blood.

Mainly albumin.

Think of albumin as a bus.

The drug hops on the bus.

Okay.

But here's the thing.

Only the drug that is not on the bus,

the unbound or free drug, can actually leave the bloodstream and get to the target tissues to do its job.

So the bound drug is inactive.

Temporarily, yes.

It's kind of like a reservoir.

Only the free drug exerts the pharmacological effect.

Ah, okay.

And this matters clinically because low protein levels.

Huge implications.

If a patient has low albumin dire,

maybe they're malnourished, have severe liver disease or extensive burns, there are fewer seats on the bus.

Meaning more free drug floating around.

Exactly.

More free active drug.

This can significantly increase the risk of drug toxicity, even if you're giving what seems like a normal dose.

Wow.

And what if two drugs both like to bind to protein?

Good question.

If you give two drugs that are both highly protein -bound, they compete for those limited binding sites on albumin.

One bumps the other off.

Essentially, yes.

They displace each other.

This leads to higher levels of free drug for both medications, which can be a really dangerous drug interaction.

Okay.

And distribution isn't always easy, right?

Like the blood -brain barrier.

Right.

Some areas have special barriers.

The blood -brain barrier is tightly regulated, making it tough for many drugs, like certain antibiotics, to get into the brain and spinal fluid.

Good for protection.

Tricky for treating CNS infections.

Hashtag, tag, tag, tag C, metabolism, biotransformation.

All right.

Next up in ADME is M -metabolism, also called biotransformation.

This is mainly the liver's job, right?

Changing the drug.

Primarily the liver, yes.

Metabolism is the process of biochemically altering the drug.

Usually the goal is to make it inactive and more water -soluble, so it's easier for the Not always.

Sometimes metabolism actually activates a drug.

A drug given in an inactive form is called a pro -drug and relies on metabolism to convert it into its active form.

Interesting.

And what enzyme system does most of this work?

You mentioned it briefly.

The cytochrome P450 system.

It's a large class of enzymes, mainly in the liver.

These guys are workhorses.

They metabolize the vast majority of medications, especially drugs that are lipid soluble or fat -loving.

P450.

And this system is where a lot of drug interactions happen.

Absolutely.

It's ground zero.

Some drugs act as enzyme inhibitors.

Inhibitors.

They slow things down.

They do.

They basically jam up the P450 enzymes, slowing down the metabolism of other drugs that use the same enzyme pathway.

So the other drug builds up.

Builds up, accumulates.

This can lead to increased drug effects, longer duration of action, and potentially toxicity.

You gave the war for an example earlier with fluconazole.

Perfect example.

Fluconazole inhibits the P450 enzyme that metabolizes warfarin.

So warfarin levels climb and the risk of serious bleeding goes way up.

Okay.

So inhibitors slow metabolism down.

What about inducers?

Enzyme inducers do the opposite.

They stimulate the P450 enzymes, making them work faster, revving up metabolism.

So the drug gets cleared out too quickly.

Right.

This leads to lower drug levels, shorter duration of action, and possibly loss of therapeutic effect.

The drug might not work as well or at all.

Things like genetics or liver disease can affect this too.

Definitely.

Liver disease like cirrhosis drastically reduces metabolic capacity,

and genetics play a huge role in how active someone's P450 enzymes are naturally.

Hashtag tag tag D, excretion and timing.

Which brings us to the final letter in ADME.

E for excretion.

Getting the drug and its metabolites out of the body.

Mostly the kidneys.

Primarily the kidneys, yes.

They filter the blood.

Remember how metabolism often makes drugs more water soluble?

Yeah, you said that helps elimination.

It does.

Water soluble compounds are easier for the kidneys to handle through processes like glomerular filtration and tubular secretion.

Some excretion also happens via the bile into the intestines and even lungs or sweat glands for some drugs.

Okay.

You mentioned something called enterohepatic recirculation.

Sounds complicated.

It's sort of like recycling.

Some drugs, after being metabolized by the liver and excreted into the bile, get released into the intestine.

Down there, enzymes can sometimes cleave off the water soluble part, making the drug lipid soluble again.

So it gets reabsorbed.

It can get reabsorbed back into the bloodstream, go back to the liver, get conjugated again, excreted in bile again.

This cycle can make drugs persist in the body much longer than you'd expect.

Wow.

Okay, so how do we measure how long a drug sticks around?

Half -life.

Exactly.

Half -life t is the time it takes for one -half, or 50%,

of the original amount of the drug in the body to be eliminated.

And why is knowing the half -life so important?

It helps determine dosing frequency and predict how long it takes to reach steady state.

Steady state.

That's the goal, right?

Where input equals output.

Right.

Steady state is when the amount of drug being absorbed is equal to the amount being eliminated over a dosing interval.

This results in consistent drug levels in the blood, which usually correlates with maximum therapeutic benefit.

And how many half -lives does that take?

Generally, it takes about four to five half -lives for a drug to reach steady state, or for most of a drug to be eliminated after stopping it.

Okay.

And to make sure we're in the right range, especially for tricky drugs, we measure levels.

Peak and trough.

Yes, particularly for drugs with a narrow therapeutic window.

The peak level is the highest concentration the drug reaches in the blood.

Too high suggests a risk of toxicity.

The trough.

The trough level is the lowest concentration, usually measured right before the next dose is due.

Too low suggests the drug might not be effective enough.

A subtherapeutic effect.

Aeropedic drug monitoring uses these levels to adjust doses safely.

All right.

We've covered ADME, what the body does to the drug.

Now we flip it.

Pharmacodynamics.

What the drug does to the bottle.

Exactly.

Pharmacodynamics looks at the drug's actions and effects at its site of activity.

How does it actually interact with cells to produce a response?

How do drugs work?

Is there one main way?

There are three main mechanisms.

The most common is through receptor interactions.

Receptors.

Like docking stations on cells.

Kind of, yeah.

Receptors are usually specific protein structures on or inside cells that a drug molecule can bind to.

Think of it like a lock and key.

Okay.

If a drug binds to the receptor and activates it, producing a response similar to what the body's own chemicals would do, it's called an agonist.

It mimics the natural response.

Correct.

But if a drug binds to the receptor and blocks it, preventing the body's natural chemicals or other drugs from binding and causing an effect, it's an antagonist.

So it inhibits or blocks the response?

Yeah.

Got it.

Agonist stimulates, antagonist blocks.

What's the second way?

The second way is through enzyme interactions.

Drugs can interact with enzyme systems in the body.

Most commonly, they inhibit the action of a specific enzyme.

Less commonly, they might enhance it.

So they interfere with a biochemical process by targeting the enzyme involved.

Precisely.

And the third mechanism is less specific.

It's called non -selective interactions.

Non -selective.

Meaning they don't target specific receptors or enzymes.

Right.

These drugs target cell membranes or various cellular processes more generally.

Think of some cancer drugs or antibiotics that physically disrupt cell structures or metabolic activities without binding to a single specific receptor site.

Hashtag tag IV.

Pharmacotherapeutics and patient safety.

Okay.

So we know how drugs move kinetics and how they work dynamics.

Now,

pharmacotherapeutics,

that's the clinical application, right?

Using drugs to treat patients.

Yes.

This is where we put it all together, the clinical use of drugs to prevent and treat diseases.

It's all about defining patient -specific goals, those measurable outcomes we want to achieve.

And there are different types of therapy, aren't there?

Yep.

Several categories.

There's acute therapy for critically ill patients, maybe using vasopressors in shock.

Maintenance therapy aims to prevent progression of a chronic condition, like blood pressure meds.

Supplemental or replacement therapy provides something the body is missing, like insulin for diabetes or thyroid hormone.

Palliative therapy focuses purely on comfort and symptom relief when cure isn't possible.

Makes sense.

Then, supportive therapy helps maintain body functions during recovery from illness, like giving fluids and electrolytes.

Prophylactic therapy aims to prevent illness, like antibiotics before surgery.

And empirical therapy is when we treat based on high suspicion before definitive diagnostic results are back, like giving a broad spectrum antibiotic for a suspected infection.

Lots of different goals.

And a key safety concept here is the therapeutic index.

Hugely important.

The therapeutic index is basically a ratio that compares the drug level that causes toxic effects to the level that causes therapeutic effects.

So, a measure of the drug safety margin.

Exactly.

A drug with a low therapeutic index, or narrow therapeutic index, means there's only a small difference between an effective dose and a toxic dose.

Those are the risky ones.

They require much more careful monitoring.

Think drugs like warfarin, digoxin, lithium.

Small changes in dose or patient condition can easily push them into the toxic range.

That's why we monitor those peak and trough levels we talked about.

Right.

Connects back.

Now, what about drug interactions?

Can they ever be good?

They can be intentional and beneficial.

Additive effects are when two drugs with similar actions are given together, and the result is just the sum of their individual effects.

One plus one equals two.

Okay.

But synergistic effects are when the combined effect is greater than the sum.

One plus one, two.

Like they boost each other.

Exactly.

You might combine two blood pressure meds that work differently, and together they lower BP much more effectively than either one alone.

It's a common strategy.

And the opposite.

Antagonistic effects.

The combination results in effects that are less than the sum, one plus one, two.

One drug might block or reduce the effect of the other.

And then there's just plain incompatibility,

like mixing IV meds.

Right.

Incompatibility is a physical or chemical issue, usually with parenteral drugs.

You mix two things in an IV line, and they form a precipitate, a cloudy solution, or change color.

That means chemical degradation, and you absolutely cannot administer that.

Good to know.

What about food?

Can that interact?

Definitely.

Food can significantly alter drug absorption or metabolism.

Classic example.

Leafy green vegetables are high in vitamin K.

Which counteracts warfarin.

Exactly.

It decreases warfarin's anticoagulant effect.

Another big one is grapefruit juice.

I heard about that one.

Yeah.

Grapefruit juice inhibits that cytochrome P450 system we discussed, specifically an enzyme called CYP3A4 in the gut wall.

So it decreases metabolism of certain drugs?

Yes.

Leading to higher drug levels and increased risk of toxicity for several common drugs,

like some statins for cholesterol and certain calcium channel blockers for blood pressure.

Always check for food interactions.

Okay.

Important point.

Now, adverse events versus adverse reactions.

What's the difference?

It's a key distinction.

An adverse drug event, ADE, is really broad.

It's any undesirable occurrence involving medication.

This includes medication errors, like giving the wrong dose, even if it doesn't cause harm.

So an error is an ADE.

What's an ADR?

An adverse drug reaction, ADR, is more specific.

It's an unexpected, unintended, undesirable, or excessive response to a medication given at therapeutic dosages.

It's not due to an error.

It's a reaction to the drug itself when used normally.

Okay.

ADE is broad, includes errors.

ADR is a reaction at normal doses.

And ADRs have categories.

They do.

A pharmacologic reaction is basically an extension of the drug's normal effect, just too much of it.

Your blood pressure med lowers BP too much, causing dizziness or fainting.

That's a pharmacologic ADR.

Predictable, almost.

In a way, yes.

Then there's an allergic reaction or hypersensitivity.

This involves the patient's immune system reacting to the drug.

It can range from a skin rash or to severe, life -threatening anaphylaxis.

Requires prior sensitization.

Usually, yes.

And the third main type is really interesting, the idiosyncratic reaction.

Idiosyncratic, meaning unexpected and weird.

Pretty much.

It's an abnormal, unexpected response that's peculiar to an individual patient, and it's often due to underlying genetic differences.

It's not an allergy, not a predictable pharmacologic effect.

Like the G6PD example you mentioned.

Exactly.

Glucose 6 -phosphate dehydrogenase deficiency is a classic example.

People with this genetic trait lack an important enzyme in their red blood cells.

If they're exposed to certain drugs that cause oxidative stress, common ones like aspirin,

certain antibiotics like sulfonamides, their red blood cells break down rapidly.

Causing hemolytic anemia.

Wow, just from a common drug because of their genes.

It highlights how individual genetics can drastically alter drug response.

We also need to think long -term toxic effects, right?

Like birth defects.

Yes.

Teratogenic effects refer to drugs that can cause structural defects in a fetus if taken during pregnancy.

Mutagenic effects are permanent changes to genetic material, DNA.

And carcinogenic effects are those that cause cancer.

Hashtag tech had V.

Sub -specialties and antidotes.

Just looping back quickly to those sub -specialties.

Pharmacognosy studying natural sources, it's still relevant.

Think about hormones like conjugated estrogens originally derived from pregnant mares or heparin anticoagulant coming from pig intestines or cow lungs.

Still using natural sources?

Yes.

And toxicology poisons.

What's the priority there?

If you encounter a poisoned patient, the absolute first priority is always the ABCs maintain airway, breathing, circulation.

Basic life support first.

Okay.

Then deal with the poison.

Then focus on preventing absorption of the poison if possible, like using activated charcoal, and speeding up its elimination from the body.

But knowing specific antidotes is critical too.

Antidotes.

Reversals.

Exactly.

For an acetaminophen Tylenol overdose, the specific antidote is acetylcysteine.

It helps prevent severe liver damage if given promptly.

Acetaminophen, acetylcysteine.

Got it.

What's another key one?

For opiate overdose, the caroene, morphine, oxycodone, the specific antagonist, the anticoat, is naloxone, brand name Narcan.

It rapidly reverses the respiratory depression caused by opioids.

Essential to know.

Hashtag tag outro.

Wow.

Okay.

That was quite the journey through the sources today.

We really traced that drug's path, didn't we?

From the dosage form itself, pharmaceutical.

Then through everything the body does to it.

Absorption, distribution, metabolism, excretion.

That's pharmacokinetics.

All the way to how the drug actually works at its target site.

Pharmacodynamics.

It really highlights how all these pieces fit together.

They absolutely do.

And applying this knowledge within the nursing process is how we ensure safe and effective medication use for our patients.

You know, thinking about that G6PD example and the variations in the P450 system,

it really drives home how different people can react to the same drug.

It really does.

And that leads to a fascinating question for you to think about as clinicians and students.

If we know genetic variations can so profoundly change how a patient responds, what does that mean for the future?

You mean beyond standard dosing?

Yeah.

How do we move towards more personalized medicine?

How do we prepare for a time when we might routinely tailor drug choices and doses based on an individual's unique genetic makeup, rather than just relying on population averages?

It's something we'll all need to grapple with.

That's a powerful thought tailoring therapy, right down to the DNA.

Definitely something to keep in mind as we practice.

Well, thank you for walking us through all that.

We appreciate you diving into the sources with us today.

My pleasure.

Until next time.