تدريب Shadowing: Pharmacokinetics | Drug Absorption - تعلم التحدث بالإنجليزية عبر الفيديو

what's up ninja nerds in this video today we're gonna be

talking about pharmacokinetics also to really enhance your learning experience I

promise you go through it with me in this particular way you're going to understand it you're going to remember

and you're gonna do well in those exams go down the

description box below we have a link to our website on our website we have all the diagrams

that we're gonna talk about where it's empty you guys can

follow along with me filling in the blanks okay please do

that also if you want to you have a completely filled off illustration

and also some really comprehensive notes to follow along with me

so let's get started talking about pharmacokinetics all right we talk about pharmacokinetics first thing is absorption

when we talk about absorption we really need to understand how drugs are administered okay

because that obviously plays a role in absorption

because absorption is basically the drug being administered

and getting into the circulation that's all it is so it's basically a drug that we give to a a patient, once we give it via a specific route of administration,

the process by which it actually reaches the bloodstream is absorption.

Pretty straightforward.

Now, what are the different routes?

We're not going to go crazy here, but obviously the most common one that you guys should remember is enteral, right?

So PO, you take the medication orally.

So that'd be one.

The other one that can go via the GI route is the other end, right up the stink hole.

That would be the rectal administration.

So some type of suppository.

The other thing that you want to remember is we can do this via injections.

So parenteral, we can actually do injections so we can inject it into the dermis.

You see how there's different layers.

So here's the epidermis here.

And then right underneath it is in this kind of like maroon color here is the dermis.

So we can do intradermal injections.

We can inject it into the subcutaneous tissue, sub-Q injections.

We can inject it into the muscle, intramuscular injections.

You know, not only that, but we can also take and squeeze some type of ointment or topical agent onto the skin of the epidermis, so it works there locally.

That would be a topical agent.

Not too hard to figure out, right?

The other thing is we can inject this medication directly into a vein.

What is that called?

Intravenous administration.

We can also give these medications by having the patient inhale it getting into their lungs.

This would be inhaled administration.

And then the last two that I want you guys to remember is, sometimes you can take a medication and put it between the actual lip, all right, and the teeth.

So this is the buccal administration.

So buccal, some people say buckle, I don't really care, whichever one you like.

And then the last one to remember is underneath the tongue, so sublingual, so sublingual.

So these are the different routes of administration, how we can actually give a drug to a patient.

The most common ones that I think you guys should definitely remember is going to be PO, because this is mainly the one that most people do outpatient, intravenous via in the hospital,

And then some of these injections, particularly like subcutaneous or intramuscular injections, but I'd say the IV and PO would be the big ones that I want you guys to remember.

Now, when a drug is actually taken, most commonly PO, in order for that drug to be able to pass through the gastrointestinal tract and get into the bloodstream,

it has to be absorbed.

And so the mechanisms by which a drug is absorbed is very, very important.

So what are those mechanisms by which a drug can get absorbed?

So for example, you take a particular medication, runs down the gullet, into the stomach, gets broken down by particular types of gastric acid,

and maybe even there are certain types of molecules down here that even break it down a little bit more.

But what happens is the drug has to be able to pass across the gastrointestinal lining.

That means it has to pass through particular types of cell membranes.

So there has to be a very specific transport mechanisms

that allow for the drug to be shuttled from the lumen of the gastrointestinal tract into the lumen of the vasculature.

What are those mechanisms?

Well, the mechanisms depend upon the actual drug characteristics.

What am I talking about?

Alright, so the first one that I want you guys to know is what's called just your simple or passive diffusion process.

So passive diffusion is when you take a particular drug like this

and it passes through the actual cell membrane of the gastrointestinal tract

and through the cell membrane on the basolateral membrane right into the blood.

So when it does this, the mechanism by which it does this is via moving from areas of high concentration to areas of low concentration.

That's the concept of simple diffusion.

Now in order for this drug to be able to pass across this lipid bilayer on this apical surface

and on the basolateral surface, it has to have a couple particular characteristics.

One is this drug would have to be very small or it would have to be hydro phobic.

These are extremely important.

If a drug is small

and it's hydrophobic it would be able to fit easily between the actual cell membrane

or passively and diffuse across the cell membrane.

So when something is lipid like or it's non polar like it's easily able to pass across the lipid bilayer.

So small hydrophobic molecules will easily diffuse via passive diffusion.

Now let's say that you have another molecule here, another drug that you're trying to absorb and move it across here.

But this drug is a a little bit bigger.

So it's a little bit larger, or maybe not just necessarily large, but maybe it's hydrophilic.

So hydrophilic agents will not be able to easily move across the cell membrane.

Because of that, they will require specific types of transporters, special types of proteins that will facilitate their entry into the cell.

And these proteins that allow for this drug to be carried

that are going to facilitate this entry allows for this to be able to again move

from areas of high concentration to areas of low concentration, but it just can't do it by passing simply through the cell membrane.

It needs a particular protein.

This is called facilitated diffusion.

So this is called facilitated diffusion.

So some drugs will do this.

And again, it just depends upon the characteristic of the drug.

Obviously, the difference between these two is size and solubility.

One is hydrophobic, one is hydrophilic.

The other thing that you would need to remember is that sometimes same thing, maybe you have a drug that's larger, maybe it's charged, maybe it's hydrophilic,

just like we talked about with the facilitated diffusion.

But the difference here is you're not pumping this drug from areas of high concentration to low concentration.

You're pumping this drug from areas of low concentration to areas of high concentration.

This is not a passive process, this is an active process.

And whenever you need to pump something against its concentration gradient, this requires energy, ATP.

And so this would be an active transport process

that would move this large hydrophilic drug from areas of low concentration to areas of high concentration.

So this would be active transport.

So this is another way that we can transport drugs across particular membranes.

100

Now what I want you to remember is we're talking about this with respect to the gastrointestinal tract and oral route.

101

But remember, if you take something rectally, it has to move across the GI tract there.

102

If you take something intradermally, it has to pass through different parts of cell layers or tissues before it can actually get into the nearby capillaries.

103

Same thing with subcutaneous.

104

It needs to pass through other layers to get to the actual vasculature, intramuscular.

105

So remember, the only one that will actually move directly into the bloodstream without having to pass through a membrane is intravenous.

106

So remember that.

107

All right, so we have active transport, which will pump the drug from low to high large hydrophilic.

108

The last one is when you have a gargantuous molecule and I'm talking just a really large molecule.

109

So for example, you know, there's a drug we can give orally B12.

110

It's just too big.

111

There's no dang transporter that's going to be big enough to transport this drug across the actual cell membrane.

112

So because of that, if I have a large drug that there's just no transporter that's big enough, that's going to be able to get this thing across.

113

What I might need to do is do something called bulk transport.

114

And bulk transport is a process where the drug may bind onto little receptors that are present on the actual cell membrane.

115

And when it binds onto these receptors, let's draw little pink receptors here,

116

it'll bind to it and then trigger this invagination of the drug via a process called endocytosis.

117

And then once it's endocytosed, it's taken into the actual cell and then it'll be exocytosed out into the actual vasculature.

118

What is this process by where I take this cell, take this large drug into the actual cell via an invagination process?

119

It's called endocytosis.

120

So the mechanisms by which we transport drugs across cell membranes, specifically via a PO route as the best example,

121

can move across the cell membrane to get into the bloodstream based upon four mechanisms.

122

One, passive diffusion from high to low, hydrophobic small.

123

Facilitated hydrophilic large needs a protein carrier to move it from high to low.

124

Active transport low to high hydrophilic large molecule but it needs to be pumped via ATP driven process.

125

Endocytosis too big to be able to be transported needs a receptor mediated endocytosis to be taken in

126

and then exocytosed into the bloodstream.

127

An example of this would be B12.

128

But these are the mechanisms by which we absorb particular drugs across the GI tract

129

or across any other thing that has to move across a membrane.

130

The only one that doesn't move across a membrane is intravenous.

131

Most of these other ones have to cross a membrane.

132

Whenever you cross a membrane to get from wherever it was externally into the bloodstream, you have to pass a membrane.

133

When you pass a and you do it by one of these four mechanisms.

134

The best example of this is just PO, okay?

135

Now, let's talk about things that can actually affect this absorption process, because not everything is beautiful and perfect as we made it here.

136

Sometimes there's certain types of pH changes, blood flow, changes in surface area, the speed at which things move through the GI tract,

137

and even little things called P-glycoproteins, which can alter and change the absorption of capabilities.

138

Let's talk about that now.

139

All right, so we know the absorption mechanisms.

140

Now, what we need to talk about is what are the ways

141

that we can actually kind of maybe decrease absorption, increase absorption?

142

Is there particular things?

143

Because when we take a medication, we want, for the most part, most of that medication to get into the bloodstream.

144

So when we give the medication, whatever route we give it, we do want that to have the maximum efficacy, which I want most of the medication to reach the bloodstream.

145

So is there particular things that I need to take into consideration as a clinician

146

when I prescribe a medication that could affect the absorption of that drug?

147

Yes.

148

The first one is pH.

149

Now drugs usually exist in two forms.

150

Okay.

151

A weak acid.

152

So you guys remember a little bit of chemistry.

153

I thought this was never coming back, but remember Remember when we have like an acid, we can use the abbreviation HA, so that's the weak acid.

154

And then what will happen is that weak acid can disassociate to something called a proton and then the conjugate base.

155

So these are the two molecules that I have here.

156

Now if I have this weak acid, which one of these would be easily absorbed across this actual cell membrane?

157

you think about it, this would probably be a little bit more difficult to absorb.

158

Why?

159

Because this right here, this bad boy is charged.

160

And charged molecules are more difficult to be able to absorb.

161

Okay?

162

To cross a cell membrane, if something's extremely charged, it's going to be moving against something that's, again, you have those phospholipids structures.

163

So on the end, the phosphate groups are a little bit more negatively charged.

164

It's going to repel this molecule here.

165

So in order for me to be able to make sure that this weak acid, this drug gets absorbed, I want it to exist in this type of environment,

166

the HA, because this one is not charged.

167

So we call this one non-polar, if you will, right?

168

Just how we would call this one charged, we would call it polar.

169

So this one easily absorbed, this one not as easily absorbed.

170

So if I want most of my drug to be absorbed in this form, I need it to be most of the reaction to go in this direction.

171

So in order for me to push the reaction in this direction, I need more protons to be inside of the actual environment where I put this drug.

172

So for example, let's say for whatever reason I put this drug in an acidic environment.

173

So I put this drug in an acidic environment.

174

If I put this drug in an acidic environment, what am I going to do to the number of protons?

175

I'm going to increase the number of protons in the environment.

176

If I increase the number of protons, what does the Chapley's Principle say?

177

That whenever you have lots of molecules on this side, you need to shift this reaction in this direction so

178

that you can have it shift to the other one that there's less of.

179

And so in this case, this side of the reaction becomes very high, I need to shift it to the other side to even it out.

180

So I make more of this weak acid that is in the non-polar, non-charged, easily absorbable form.

181

So in an acidic environment, a weak acid will form this type of component.

182

And HA is much more easily absorbed across the actual phospholipid bilayer and into the bloodstream.

183

So why is this important?

184

Whenever I give a drug and that drug exists in a weak acid form, weak acid, in order for me to enhance the absorption of that drug,

185

I need to put that weak acid in an acidic environment for it to be easily absorbed.

186

So in acidic environments, what would be an acidic environment within the GIT?

187

Well, obviously the stomach, but not much absorption occurs in the stomach.

188

If you think about it, the stomach does empty some acidic substances right into the proximal duodenum.

189

So probably the most acidic part of where a drug is absorbed, which is the duodenum, would be the proximal part of the duodenum.

190

This would be an acidic environment where most weak acids are absorbed.

191

So what I want you guys to remember is, if we think about this, here's my purple marker, this is going to increase the protons,

192

the area where there would be best absorption would be in the proximal duodenum.

193

Because a drug can exist as a weak acid in two forms,

194

the nonpolar form, or the non-charge form or the polar charge form.

195

The one that's more easily absorbed is the non-polar non-charge form.

196

The only way for me to convert it from the polar

197

charge form to the non-polar is to shift this reaction to the left.

198

The only way I can shift it to the left is if I increase the number of my protons, which means I need to make the environment that it's in very acidic.

199

That's why the proximal duodenum is best for absorbing weak acids.

200

All right, good.

201

Let's move on to the next thing.

202

So if we have weak acids, we probably are going to have to have some weak bases that other drugs can exist in.

203

Because again, they can exist in a weak acid or they can exist in a weak base form.

204

For example, aspirin, that would be a weak acid.

205

So aspirin would be best absorbed in like potentially the stomach, but more the proximal duodenum.

206

Okay.

207

If you think about another drug like amphetamines though, amphetamines are a little bit more of a basic drug.

208

So they would be more absorbed where?

209

And like the distal part of the small intestine, like the ileum.

210

But let me explain what happens with these.

211

So now we're going to take, for example, a weak base.

212

Weak bases are usually going to look something like this when we use them in that kind of generic form.

213

A BH positive and this disassociates into a B and H+.

214

Okay, again when you think about this, this guy right here is which one?

215

This is the part of the weak base that is going to be polar, not easily absorbed.

216

This is the one that's going to be non-polar, easily absorbed.

217

So if that's the case, if I want this to go in this direction, I want it to go to this direction so that this molecule, this weak base will be in this form

218

because it's easily going to pass across the cell membrane and get into the blood.

219

So what do I need to do to the environment?

220

Well, I need to shift this reaction this way

221

or the other way I can think about this is decrease

222

the concentration of one of these things in the actual environment here, so maybe lowering the amount of protons, that will decrease this side so then I have to shift the reaction this way.

223

But the whole goal here is what do I want to do?

224

I want to shift the reaction in this direction.

225

So if I want to shift the reaction in this direction, guess what I'm going to do?

226

I'm going to make the environment more alkaline.

227

If I make the environment more alkaline, I'm going to decrease the number of protons that are in the environment that this drug is in.

228

If I decrease the number of protons, that decreases the concentration of the actual molecules on this side of the reaction.

229

So we want it to be even.

230

If it's down like this, we need to shift it to the other side to increase the concentration to bring it to equal, according to Le Chatelier's principle.

231

So I'm going to shift the reaction this way.

232

That means I'm going to make more of this actual weak base in the non-polar or non-charge form,

233

which is the one that's easily absorbed.

234

So we say

235

that this would be weak basis would be best absorbed in the parts of the GI tract where it's very alkaline.

236

Definitely not near the stomach, definitely not the proximal duodenum, definitely be more distal small intestine like the distal ileum.

237

So it's important to remember that that's where the drugs will actually be best absorbed.

238

Okay, we understand how these can affect the absorption of drugs based upon what? pH.

239

So weak Weak bases are absorbed best in the proximal, I'm sorry, the distal ileum.

240

Weak acids are best absorbed in the proximal duodenum, so remember that.

241

Alright, the next thing that affects absorption of particular drugs is blood flow.

242

It's very straightforward.

243

We need good blood flow to supply particular organs in order for, again, if you need, think about absorption, it's the movement of the drug into the bloodstream.

244

It's the drug getting into the bloodstream.

245

If there's less blood flow to a particular organ where the drug is supposed to be absorbed, you're gonna get decreased absorption.

246

So, in situations where there is a marked reduction in blood flow, what would be a disease by which there is a reduction in blood flow?

247

Any kind of shock state, right?

248

So if a patient has any kind of circulatory shock, septic shock, cardiogenic shock, hypovolemic shock, in these shock states, there's decreased blood flow to these organs.

249

If there's decreased blood flow to these organs, there's going to be decreased absorption to the GI tract.

250

That means less of the drug is going to get absorbed into the bloodstream.

251

If there's less blood flow to the skin, That means less of the actual drug is going to be absorbed into the bloodstream.

252

So just remember that with decreasing blood flow in situations like shock states,

253

this will reduce the blood flow to these particular organs such as reduced GIT perfusion, reduced skin perfusion.

254

That means that any drug that you're taking orally or any drug

255

that you're taking rectally is going to have less absorption into the bloodstream.

256

Any drug that you're taking via the skin, intramuscular, intradermal, subcutaneous, These are all going to be diminished.

257

The only way that you can ensure that you get blood, the drug into the bloodstream would be intravenous.

258

So that's why in generally in situations when a patient is in shock,

259

we don't give medications generally via orally or via some type of injection like the intradermal, intramuscular, subcutaneous.

260

It's usually gonna be intravenous because we'll guarantee that 100% of the drug is getting into the bloodstream.

261

All right, so we know how pH affects absorption, we know how blood flow affects absorption.

262

The next thing is total surface area and contact time.

263

It's pretty straightforward.

264

If I have a drug that I'm taking orally, and I have, let's say for example, diarrhea, right?

265

You're peeing out the poop hole.

266

If that happens, the motility or the movement of the drug is moving through the GI tract so dang fast,

267

there isn't even a timeframe that's appropriate for you to move

268

this drug across the actual lumen of the GIT across the cells and into the blood be a passive transport, facilitated diffusion, active transport, endocytosis,

269

all of this is going to be inhibited.

270

So in diarrhea, what happens to the absorption of the drug?

271

You're going to decrease the absorption of the drug

272

because you're decreasing the amount of contact that the drug will have with the actual, the cells of the GIT.

273

Whereas in the opposite situation, if a patient is constipated, they're having slow transit time.

274

means that this drug has so much dang time it can file its taxes

275

and what happens is it's going to have

276

so much time to be able to move across this actual cell

277

because it's going to have tons of contact time lots of

278

opportunities to passive transport active transport some type of endocytosis process

279

and reach into the bloodstream so in situations like constipation there'll be more contact time

280

and you can increase the absorption of that drug pretty straightforward right so So decreased blood flow, shock states, you're gonna have less absorption of the drug.

281

Weak acids best absorbed in an acidic environment like the proximal duodenum.

282

And then again, weak bases best absorbed in the alkaline environment like the distal ileum.

283

The next thing is with this total surface area

284

so I want you to think about the the surface area of the intestine it's like you know

285

when if you remember back from anatomy it's like the surface area like a tennis court

286

if you stretched it out that's how much surface area could cover it's massive.

287

Think about diseases

288

that decrease the surface area by either destroying the micro villi

289

destroying the villi these things are naturally supposed to increase the surface area of the intestines.

290

In situations, for example, inflammatory bowel disease, celiacs, some type of gastroenteritis,

291

what happens to the microvilli, the villi, and therefore the total surface area?

292

It decreases.

293

We know the relationship.

294

Total surface area, as it increases, absorption increases.

295

These will do what to your total surface area?

296

They're going to decrease your total surface area.

297

So what's it going to do to the absorption of the drug?

298

It's going to decrease the absorption of the drug, my friend.

299

So in situations when a patient has some type of diarrhea, will decrease the absorption of the drug.

300

If they have constipation, they'll increase the absorption of the drug based upon contact time.

301

If you have diseases that destroy the microvilli, the brush borders, the villi in general, such as an IBD, celiacs,

302

gastroenteritis, you're going to decrease their surface area and decrease the absorption of the drug.

303

The last thing that I want to talk about, because this is actually an interesting process here, is that some situations, people can develop multi-drug resistance because you know the GI tract?

304

Sometimes if you take a particular drug, what happens is there's special transporters.

305

So let's say that we take a drug orally.

306

We take the drug, gets into the GI tract, moves across the cell membrane, which most of the mechanisms,

307

passive diffusion, active, facilitated diffusion, or endocytosis.

308

Once it does, it can potentially move into the bloodstream.

309

But there's some situations where they have this thing called a P-glycoprotein on their basal, I'm sorry, on their apical surface.

310

And what happens is instead of the drug going to be pushed into the bloodstream and then effectively being absorbed, what happens?

311

This process becomes inhibited because this P-glycoprotein will spit the drug right back out into the GIT.

312

And then you will poop the drug out or you won't be able to absorb the drug.

313

So in P-glycoprotein, what this does is this can decrease the absorption of the drug.

314

And this is actually seen in a lot of multi-drug resistant situations.

315

So remember that.

316

Sometimes patients can actually exhibit these P-glycoproteins, which will excrete the drug rather than it being absorbed.

317

All right, so for absorption, we've talked about the mechanisms.

318

We talked about the factors that affect it via pH, blood flow, total surface area, contact time, and P-glycoproteins.

319

Now what I need to do, which is actually probably the most important thing for absorption, is talking about something called bioavailability.

320

All right, so when we talk about this next really important component here, bioavailability.

321

So you can remember this by the, well, I kind of already gave you the answer, but F.

322

So it's the fraction of drug that actually does enter into the systemic circulation.

323

And here's what I want you to understand about this.

324

When you give a drug via the different routes that we talked about, what are the two most important ones that most patients will receive at some point in time in their life?

325

If they're in the hospital, IV.

326

And when you give a drug IV, does it has to pass through any type of membrane?

327

No, it's the only one that does not have to pass through any type of membrane.

328

So it goes directly into the blood.

329

So when you give a hundred milligrams of a particular drug IV, a hundred milligrams will get into the actual bloodstream.

330

So because of that, the amount of drug that is administered that gets into the bloodstream and absorbed is 100%.

331

So the bioavailability, the amount of drug that's there

332

and available for use and to exert its different types of effects is 100%.

333

However, if you give a drug orally or some other particular route that has to pass through membranes is affected by pH,

334

is affected by specific blood flow patterns, is affected by total surface area,

335

contact time, P glycoproteins, the actual different solubility of the drug if it's lipophilic, if it's hydrophilic, etc. The size,

336

all of those things come into play.

337

And maybe, likely, not all of that drug that you take orally is going to make it into the bloodstream.

338

So the bioavailability of that drug is not going to be 100%.

339

So when we can talk about bioavailability, we're really comparing IV to the other route, which most commonly is PO.

340

When you give a drug, the concentration of that drug when you give it IV, what you'll see is, let's say here is at 100%,

341

100% of the drug, you'll see that this drug will reach 100% when you give this drug,

342

and over time, it'll decrease in its concentration until it's eventually completely eliminated, because it'll become metabolized and excreted.

343

So this would be the actual concentration of the drug when it's given IV.

344

Okay, and there's a particular area under the curve that will determine that.

345

Now, the other thing here is if I give a drug orally, it needs to be given orally.

346

And what will happen is when I give it orally, you'll see the concentration will rise, but it won't make it likely to 100%.

347

It may get close 50, 60, 80, depending upon the drug and a lot of other characteristics.

348

But eventually what you'll see is that this drug concentration will fall as it starts to become metabolized and excreted.

349

So this would be the oral route, the PO route.

350

What I want to consider is the area under the curve of these things.

351

And what I can do is, I can come up with a particular formula for a drug that is actually given PO or not IV,

352

and determine the bioavailability of the drug.

353

Remember, IV, it's always 100%.

354

So if I give, like I said, 100 milligrams of a drug IV, 100 milligrams of that drug will get into the actual bloodstream.

355

So its bioavailability or this fraction is going to be one or 100%.

356

But if I give a drug orally, what has to happen is it has to be absorbed.

357

Maybe not all the drug gets absorbed because of various different reasons pH, blood flow, the size of the drug, the solubility of the drug, the total surface area, the contact time,

358

the expression of P glycoproteins, all of that stuff.

359

And then other things that we didn't talk about, like instability that it might be exposed to, first pass metabolism of the liver that we didn't get into yet.

360

That will actually play a huge role before the actual drug makes it into the systemic circulation.

361

So maybe you give 100 milligrams of this actual drug orally, and you know what?

362

50 milligrams of that drug gets absorbed into the systemic circulation.

363

So when you do this, you have to take into consideration what would it be if I were to actually compare this.

364

So now, the bioavailability of the drug would be, okay, if I were to give this IV, the bioavailability of this drug would be 100 milligrams, right?

365

So what I do is I consider, so I use a formula.

366

So the formula that we're actually going to talk about here is bioavailability is equal to the AUC, the area under the curve,

367

oral administration over the area under the curve IV administration.

368

What we're going to do is just going to say how much of

369

that drug was given IV and then how much of

370

that drug was given orally

371

and what I can actually take into consideration is how much of that drug actually got into the bloodstream.

372

So generally what I say is, let's say if I were to give this drug IV, the amount of that drug that would get into the bloodstream is 100 milligrams correct

373

because i know

374

if i give a drug iv whatever drug i give the

375

dosage wise all of that's going to get into the bloodstream

376

doesn't have to pass through any cell membranes there's no first pass effect there's no effect on instability solubility all that stuff

377

but if i give a drug orally it does have factors

378

that are going to influence that

379

and it might not all be absorbed into the actual bloodstream let's say

380

that i gave a drug 100 milligrams only 50 milligrams of it got absorbed

381

so that's the the milligram dosage that's the auc the area under into the curve orally.

382

So what I'm gonna do is I'm gonna say 50 milligrams of that drug got absorbed.

383

And if it was IV, 100 milligrams of it would actually reach the circulation.

384

So the bioavailability is what?

385

It's 50%.

386

So only 50% of the drug actually reached the systemic circulation.

387

That's the bioavailability.

388

So again, it's important to be able to remember this concept because when we give a particular drug, if we want 100% of the drug to be able to get into the systemic circulation, I give it IV.

389

If I want to give it and maybe not have all of it reach the systemic circulation, you can give it orally.

390

But again, it depends upon the drug, depends upon a lot of factors here.

391

So what are some things that do affect the bioavailability of a drug?

392

The first thing is solubility.

393

So if I think about this very simply, if I have a drug that is extremely hydrophobic or lipophilic, whichever one.

394

It's the same kind of concept.

395

hydrophobic.

396

It's also maybe a small, it's not very highly charged.

397

So it's a non-polar molecule.

398

These drugs are going to easily pass across the cell membranes, across the GI tract, whatever membrane that it has to move across and get into the bloodstream.

399

So there'll be much, much more absorption of the drug and much more bioavailability, meaning the amount of drug that gets into the bloodstream is going to be more.

400

So I would expect that what would happen to my bioavailability here, it would increase.

401

Now, if I take the opposite situation where I have a drug that's extremely hydrophilic, okay, loves water, it's also a large drug,

402

what's going to happen to the absorption of this drug?

403

It's going to decrease.

404

And so the amount of drug that I actually administer

405

and then the amount of drug that actually gets into the actual bloodstream will be very small.

406

So my bioavailability will decrease.

407

So obviously that's one particular factor that affects how much of that drug reaches the systemic circulation, which is solubility.

408

The more lipid soluble it is, the smaller the molecule is, the easier it is for it to pass across membranes and get into the blood.

409

The more hydrophilic, larger it is, the more difficult it is for it to move across the cell membrane and then again get into the blood.

410

The next thing is instability according to the area that it actually gets administered.

411

So for example, if I have most commonly oral administration, I give a particular drug like penicillin G.

412

Penicillin G is not good orally.

413

You wanna know why?

414

Because if I give this drug orally, guess what ends up happening to this dang thing?

415

You have all of these protons that are being excreted by those parietal cells.

416

This will destroy the penicillin G and literally almost none of

417

that drug will actually exist by the time it has to be able to get absorbed and moved into the bloodstream.

418

So because of that, this actual hydrochloric acid, as there's increased hydrochloric acid,

419

it'll break down the amount of penicillin G and if there's less penicillin G that gets into the bloodstream, what happens to the bioavailability of the drug?

420

It decreases.

421

Thus why penicillin G is given IM or IV.

422

The other concept here is that sometimes drugs can actually be affected by enzymes that are excreted into the GIT.

423

You know our pancreas makes special types of proteases.

424

And there's a particular drug called insulin.

425

You ever seen insulin given orally?

426

No, there's a reason why.

427

Because guess what proteases do?

428

Proteases will break down the insulin.

429

If you break down the insulin, you render this actual insulin molecule ineffective now.

430

And also the amount of drug that's supposed to cross the

431

GI tract get into the actual circulatory system is going to decrease

432

so what happens to the bioavailability of this drug it decreases

433

thus why insulin is given what you can give it iv

434

or you can give us by some type of other injection right

435

but that's the whole component here

436

that you have to be able to remember all right the next thing

437

that we also talk about factors

438

that affect bioavailability besides the solubility besides the actual instability of the environment

439

that that it gets absorbed across is also the first pass effect.

440

And I think that this is probably one of the most important concepts when it comes to bioavailability.

441

When you take a drug orally, right, we know that it's going to be exposed to a lot of different things that we've already talked about.

442

But once it actually moves across the actual GIT and into the bloodstream, when it moves into the bloodstream that's actually going to be going particularly to the liver,

443

what is this circulation?

444

This is not the systemic circulation.

445

You see this baby blue here?

446

This right here is called the portal system.

447

It's called the hepatic portal system.

448

Now, the portal system will actually be the movement of the drug from the actual GIT

449

into the actual blood that will then move to the liver.

450

From the liver, right?

451

So now, taking into consideration, you gave 100 milligrams of this drug, maybe at this point in time, based upon solubility of the drug, based upon instability of the drug,

452

based upon the size of the drug, based upon the blood flow, based upon the pH, based upon the total surface area, the contact time, the P glycoproteins,

453

maybe if you give 100 milligrams of this drug, maybe only like, I don't know, 90 milligrams made it into the actual portal system.

454

Let's just say.

455

Then, let's just say that 100 milligrams, you give 100 milligrams, only 90 milligrams got into the portal system.

456

10 milligrams got lost somewhere in that process.

457

Then what happens, it has to go to the liver.

458

Whenever blood flow from the portal system goes to the liver, the liver will always take a portion of the drug and say, hey, you know, no free lunch here, buddy.

459

I always get a little bit of this drug.

460

So only a certain amount of this drug is actually going to be remaining

461

and going into the systemic circulation after I'm done.

462

I have to, I own a little bit of this drug.

463

So it's going to take some of that drug, 90 milligrams of that drug, and some of it, it will actually metabolize.

464

What I mean by that is that in most cases, it'll render this drug inactive.

465

So maybe the amount that you inactivate, let's say for some reason, it's 60 milligrams that you inactivate.

466

I will only be able to push into the bloodstream.

467

Now in my systemic circulation, I have 30 milligrams left that will then pass to the tissues and be distributed to the tissues.

468

So because of that, that is a massive drop in the actual concentration of the drug.

469

So if you think about that, 30 milligrams is what I actually got into the bloodstream.

470

And if I were to give 100 milligrams of this drug IV, 100 milligrams would get in there.

471

So it would be 30 divided by 100, and that would give me the bioavailability of this drug.

472

That's why it's extremely important to understand bioavailability.

473

Now, why I want you to understand this is, I want you to give you guys an example of something like this, that actually does happen like this.

474

You know there's a drug called nitroglycerin.

475

Nitroglycerin we give to patients who have maybe some type of anginal chest pain.

476

Normally we give this sublingual because it doesn't have to go through the first pass.

477

So you know what things do not go through first pass?

478

Something that doesn't get administered orally generally.

479

Okay, so if something's given orally, it's going to have to be absorbed across the GI tract into the portal system.

480

If you give something rectally, very small portions of it may also get into the portal system.

481

but otherwise IV, topical, intramuscular, intradermal, subcutaneous, all of those other routes,

482

they will not have to go again through the portal system

483

and they won't be having this first pass effect by the liver.

484

So because of that, I would want to change the actual delivery of my drug

485

if it's getting chewed up by the liver.

486

So nitroglycerin, if you give it PO, just as an example, you give it PO, let's say that you gave 100 milligrams of that drug PO.

487

When you actually to get it to the systemic circulation to be delivered to the tissue, the heart, guess how much is actually remaining?

488

10 milligrams.

489

That means that 90 milligrams of drug was chewed up during the process of moving across the GIT,

490

first pass effect, and then getting into the bloodstream.

491

So guess what?

492

Because of it, the first pass effect, it chews up so much of the nitroglycerin.

493

So guess what we'd wanna do?

494

Maybe not give nitroglycerin orally, have it bypass the first pass effect give it sublingually, give it IV, give it IM,

495

all of those will forgo the actual first pass metabolism.

496

That's why it's super important to understand this.

497

All right, so when we talk about bioavailability, again, it's basically the concept, if you were to give a drug IV, 100% of that drug will get into the bloodstream.

498

If you give it orally, it has a lot of factors that can affect its absorption process.

499

So if you take the amount of drug that actually gets into the bloodstream when you gave it orally, and divide it by the amount that would get into it, If you give an IV,

500

that will give you the percentage or bioavailability of that drug.

501

The factors that can affect it is solubility.

502

You want the actual bioavailability to go up?

503

Give small hydrophobic or lipophilic drugs.

504

You want it to go down?

505

Give large hydrophilic drugs.

506

You want the bioavailability of the drug to go down?

507

Give a drug that gets completely demolished by the actual gastric pH.

508

Or gets broken down by proteases.

509

The bioavailability of that drug will decrease significantly.

510

And then if a drug gets chewed up by the liver via first pass metabolism, guess what?

511

You're gonna have very little of that drug in the actual bloodstream, the systemic circulation.

512

So if a lot, and I mean a lot of the drug gets chewed up by first pass, consider giving another route that will bypass the first pass,

513

such as IV, IM, sub-Q, sublingual.

514

And use this as an example of nitroglycerin.

515

You give the sublingual, you get a good chunk of it that gets into the bloodstream

516

because it doesn't get chewed up by the liver.

517

If you give it via orally, it gets chewed up by the liver so much

518

that very little of it actually gets into the bloodstream to exert its effects.

519

And that's why certain drugs are given via certain routes.

520

All right, guys, so we're going to work on some questions here to really test your knowledge of absorption.

521

So first thing, we have an 18-year-old female brought to the emergency department for a drug overdose.

522

Which route out of all of these would be the best, the most desirable for administering the antidote?

523

realizing that when we give a drug any particular way we have to think about the amount of drug

524

that actually reached the systemic circulation so the bioavailability of that antidote

525

which one of these has 100 bioavailability it would not be oral it wouldn't be subcutaneous wouldn't be i am

526

iv is the only one that you have 100 bioavailability

527

and i would want

528

that in a drug overdose i wouldn't want only a small percentage of it

529

or not the whole amount of the drug to get in there so

530

So IV is definitely going to be the best bet for these because you're going to get 100% bioavailability.

531

All right, second question to really test your knowledge.

532

So we have drug A.

533

It's a weekly basic drug with a PKA of 7.8.

534

Now, again, when we think about these, ideally we want the PKA to get close to the pH or at least equal the pH

535

because then we have somewhat of a kind of equal amount of the charged base and the non-charged base in this situation.

536

So if we give this weak basic drug in an oral situation, which one of the following sites will absorption occur best?

537

That's all that we're kind of looking at.

538

So in other words, I want

539

that weak base for its pKa of this actual weak base to be very close to the actual pH of the solution.

540

So which one of these would it actually absorb best?

541

Now thinking back to this, whenever we have a base, go back to our diagram here.

542

So this is going to be in the bottom part.

543

Here's our weak base, it's in this BH positive form.

544

It can disassociate into B and H+.

545

In this non-polar form, this is the form that will actually easily be absorbed across the actual membrane.

546

So if we think about that, we know that the distal ileum is going to be the best situation.

547

So we know in an alkaline environment, this weak base will be better absorbed.

548

And compared to an acidic environment, it will not.

549

And the reason why is you have to think about this equation in what's called the Chatelais principle, right?

550

So if we have a situation here where we have lots of protons in this actual equation here, Le Chatelier will say that this side of the reaction is way too high and it will shift to the left.

551

And then we won't get good absorption.

552

But if we decrease the concentration of the protons, meaning that we have an alkaline environment, it will shift the reaction to the right.

553

We have more of this nonpolar molecule, which easily absorbs.

554

So which one out of all of these do we see

555

that it's actually going to be more basic and it's closest to the pKa of this weak base, we would say definitely right here, the jejunum.

556

It's definitely going to be the most basic solution would be best for the weak base.

557

And it's about only 0.2 away from this actual pKa.

558

So we want the pH to be very close

559

or almost equal to the pKa to allow for the best absorption of that drug.

560

All right, guys, so that will cover all that we needed to talk about for the pharmacokinetics component here for absorption.

561

I hope this made sense.

562

I hope that you guys did enjoy

563

and learned a lot stick around We're gonna move into the next part now of our pharmacokinetic series

564

And that's gonna be talking a little bit more about what the distribution of a drug, so I'll see you guys there

📺 نفس القناة

Antimycobacterials | Anti-TB Drugs

IELTS PrepTOEFL PrepUniversity Students

Anatomy of the Heart and Coronary Circulation

University StudentsWorking Adults

✨ فيديو موصى به

872 جمل

Advance English Learning | The Mechanics of Fast Speech: Assimilation, Elision, and Intrusion

IELTS PrepTOEFL PrepUniversity Students

84 جمل

المفردات وملاحظات التحدث لهذا الدرس

هذا الدرس في المحادثة بمستوى C1 مبني على الفيديو “Pharmacokinetics”. أكثر الكلمات تكرارًا في الفيديو: drug, actual, absorption, bloodstream, absorbed. يحتوي هذا الفيديو على 564 جملة و7926 كلمة للتدرب على الترديد. مدة الكلام 42:31. يتكلم المتحدث بسرعة، نحو 186 كلمة في الدقيقة، لذا ستسمع كثيرًا من وصل الكلمات واختزال الأصوات. 82% من الكلمات ضمن أكثر 3,000 كلمة شيوعًا في الإنجليزية، ويُستحسن مراجعة الباقي قبل البدء.

أهم المفردات في هذا الفيديو

أصعب 15 كلمة في الفيديو، مع النطق والمعنى:

الكلمة	النطق	المعنى
absorb فعل	/æbˈsɔɹb/	اِتَّسَعَ, اِحْتَوَى
absorption اسم	/æbˈsɔɹp.ʃn̩/	اِسْتِيعَاب
bloodstream اسم	/ˈblʌd.stɹɪim/	مجرى الدم
milligram اسم	/ˈmɪlɪɡɹæm/	مِلِّيغْرَام
orally ظرف	/ˈɔːɹəli/	فَمَوِيًّا
membrane اسم	/ˈmɛm.bɹeɪn/	غِشَاء
molecule اسم	/ˈmɑ.lɪ.kjul/	جُزَيْء
tract اسم	/tɹækt/	جِهَاز
systemic صفة	/sɪˈstɛm.ɪk/	نِظَامِيّ
polar صفة	/ˈpoʊlɚ/	قُطْبِيّ
proton اسم	/ˈpɹoʊ.tɑn/	بْرُوتُون
diffusion اسم	/dɪˈfju.ʒən/	اِنْتِشَار
duodenum اسم	/ˌduəˈdinəm/	اِثْنَا عَشَرِيّ, عَفْج
injection اسم	/ɪnˈd͡ʒɛk.ʃən/	حُقْنَة, حَقْن
facilitate فعل	/fəˈsɪlɪteɪt/	سَهَّلَ

الأفعال المركبة التي ستسمعها

الكلمة	المعنى
pass through فعل	اِخْتَرَقَ, نَفَذَ
go down فعل	نَزَلَ
come back فعل	عَادَ, رَجَعَ
come up with فعل	جَاءَ بِـ, أَتَى بِـ
go up فعل	صَعِدَ, يَصْعَدُ

جمل تستحق التكرار

جمل قصيرة وكاملة من الفيديو يمكنك استخدامها في الحديث اليومي:

What am I talking about?
These will do what to your total surface area?
You ever seen insulin given orally?
You see this baby blue here?
You want the actual bioavailability to go up?

القواعد في هذا الفيديو

أكثر التراكيب التي يستخدمها المتحدث، مع العبارات نفسها من الفيديو:

التركيب	في الفيديو
الجمل الشرطية if + جملة، will/would + فعل — شرط ونتيجته	If they have constipation, they'll increase
المبني للمجهول be + اسم المفعول — التركيز على ما يحدث لا على من يفعله	are administered · being administered · would be inhaled
جمل الوصل who / which + جملة — معلومة إضافية عن شخص أو شيء	transport, which will · glycoproteins, which can · absorbed, which is
المضارع التام have/has + اسم المفعول — حدث ماضٍ ما زال له أثر الآن	we've talked · we've already talked

نطق يحتاج إلى انتباه

يستخدم المتحدث 96 من الصيغ المختصرة، مثل you're, I'm, gonna. انطقها بصيغتها القصيرة كما تسمعها.

أصوات “sh” و“zh”: absorption /æbˈsɔɹp.ʃn̩/, circulation /ˌsɝkjʊˈleɪʃən/, diffusion /dɪˈfju.ʒən/, injection /ɪnˈd͡ʒɛk.ʃən/, constipation /ˌkɒnstɪˈpeɪʃən/
الكلمات الطويلة — انتبه لموضع النبر: circulation /ˌsɝkjʊˈleɪʃən/, solubility /ˌsɔljuˈbɪlɪti/, facilitate /fəˈsɪlɪteɪt/, endocytosis /ˌɛndəʊsaɪˈtəʊsɪs/, hydrophobic /haɪdɹəˈfoʊbɪk/

أصوات يجدها متحدثو العربية صعبة:

/p/ — ليس /b/: انطقه مع نفخة هواء: absorption /æbˈsɔɹp.ʃn̩/, polar /ˈpoʊlɚ/, proton /ˈpɹoʊ.tɑn/, proximal /ˈpɹɒksɪməl/, portal /ˈpɔːɹtl̩/
/v/ — ليس /f/: مع اهتزاز الأوتار الصوتية: passive /ˈpæs.ɪv/, intravenous /ɪntɹəˈviːnəs/, villus /ˈvɪləs/, vasculature /ˈvæskjʊlət͡ʃə(ɹ)/, inactivate /ɪˈnæktɪveɪt/
تتابع الصوامت — لا تضف حركة بينها: absorb /æbˈsɔɹb/, absorption /æbˈsɔɹp.ʃn̩/, bloodstream /ˈblʌd.stɹɪim/, membrane /ˈmɛm.bɹeɪn/, tract /tɹækt/

كيف تتدرب بهذا الفيديو

استمع إلى الفيديو كاملًا مرة واحدة دون أن تتكلم، ودوّن الكلمات التي لا تعرفها.
ابدأ بسرعة 0.75×، وردّد جملة جملة، ثم عُد إلى السرعة العادية عندما يصبح الأمر سهلًا.
سجّل صوتك وقارنه بالأصل، مع الانتباه إلى كلمات مثل absorb, absorption, bloodstream.

ما هي تقنية التظليل الصوتي؟

التظليل الصوتي (Shadowing) تقنية تعلم لغة مدعومة علمياً، طُورت أصلاً لتدريب المترجمين الفوريين المحترفين. الطريقة بسيطة لكنها قوية: تستمع لصوت إنجليزي أصلي وتكرره فوراً بصوت عالٍ — كظل يتبع المتحدث بتأخير 1-2 ثانية. تُظهر الأبحاث تحسناً كبيراً في دقة النطق والتنغيم والإيقاع وربط الأصوات والاستماع والطلاقة.

تقنية الشادوينغ: اقرأ الدليل الكامل خطوة بخطوة →

تدريب Shadowing: Pharmacokinetics | Drug Absorption - تعلم التحدث بالإنجليزية عبر الفيديو

Antimycobacterials | Anti-TB Drugs

Homeostasis

Anatomy of the Heart and Coronary Circulation

Advance English Learning | The Mechanics of Fast Speech: Assimilation, Elision, and Intrusion

Heart Failure Medications: What to Monitor Before You Give Them (Video 4 of 5)

🏥 Locating Organs with Surface Landmarks: Do You Know Where Key Organs Are?

Explanation of Vaccine Adjuvants

Pediatric Diarrhea – Pediatrics | Lecturio

SVINutes: Collateral Circulation

Physiology Chapter 1 | Introduction to Physiology & Homeostasis Explained

Nanotechnology and Its Applications

RCoA Primary Examination: SOE Physics Question Example

WHAT DO PEPTIDES ACTUALLY DO?

Your Brain on Drugs: Marijuana