Shadowing-Übung: Antimycobacterials | Anti-TB Drugs - Englisch Sprechen Lernen mit Video

What's up Ninja Nerds?

In this video today we're going to be talking about anti -mycobacterial drugs.

Very cool one.

Very short one.

Nice, right?

Finally we're going to have a short video.

But when we talk about these particular drugs, it's really important again to follow along with me.

Grab the key, grab the actual illustrations, all the notes that we have at our website.

We have a link down in the description box below.

Go check that out

so you guys can follow along with me i really think it'll aid in the learning process

but when we talk about anti -microbacterial drugs there's a lot of different ones

that we're going to talk about here

but we should focus on how do they work what's their mechanism of action

because if you're tested on that you should know what particular site

and what kind of like function they interact or inhibit with

and then after that we'll talk about what are they used for

so we'll talk about obviously tb mac infections the super rare leprosy

but if you get a question on the exam you'll know it

and then we'll talk about the adverse effects

that you got to watch out for all right so first thing

when we talk about this actual mycobacterium you know in order

for the actual mycobacterium to function it obviously needs to be able to replicate its dna

and actually also transcribe its dna make particular proteins

that allows for it to be able to control its structural

and functional proteins we need that to occur well we have particular drugs

that can inhibit this cute little pink enzyme you know what

this cute little pink enzyme is called this enzyme here is called RNA polymerase.

And what RNA polymerase does is, is it takes DNA, reads it, and from reading it, it makes a molecule called RNA.

Particularly, this would be mRNA.

Now, because it stimulates this particular step, mRNA then does what?

It actually interacts with ribosomes.

And those ribosomes will then synthesize particular types of proteins.

And These proteins can obviously be structural proteins.

They can be functional proteins, but either way, these bad boys are proteins and they're essential to the actual bacterial's function.

Well, if I give this particular drug called rifamycins, you know, there's actually two particular ones that I want you to remember that treat mycobacterial infections.

One is called rifampin.

This is going to be the very commonly utilized one.

And the other one is called rifabutin.

And rifabutin is actually an interesting one we utilize a little bit more commonly in MAC infections, particularly if someone has HIV positive.

Rifampin causes a lot of interactions with the CYP450 system, so rifabutin is a little bit more preferred.

But either way, these drugs are going to inhibit the RNA polymerase.

If you inhibit the RNA polymerase, can they take DNA and convert it into mRNA?

No. So this type of reaction here will occur.

There's less mRNA that's being formed.

That means that less proteins will be formed.

Proteins are integral to the actual structure and function of mycobacterium.

You lose that, you lose their ability to be able to survive.

They will then die.

So that's a really cool function of this particular drug.

Now, in the same way, focusing at the nucleic acid level, you know, nucleic acids are made up of nucleotides.

And from nucleotides, we use very specific molecules that we can add into them, that we can use to make nucleotides to incorporate into the DNA or incorporate into RNA.

There's this molecule here called para -aminobenzoic acid.

And And para -aminobenzoic acid is actually converted into something called dihydrofolate and then tetrahydrofolate.

And that's usually incorporated into particular types of like thiamine nucleotides.

So it's important to incorporate into DNA and into RNA particularly is a nucleotide like thiamine.

Now, if I give a particular drug,

right, dapsone, what dapsone will do is dapsone will actually inhibit the particular enzymes involved in converting para -aminobenzoic acid into dihydrofolate.

So it's involved in the metabolic pathway here.

So it'll inhibit this particular step.

When it inhibits the conversion of parametobenzoic acid into dihydrofolate, that means you get less of this, less of this, and less incorporation into DNA and RNA,

less of the actual nucleotides to make DNA, to make RNA.

And that is important because if we don't have that, we can't actually have the nucleic acids that we need to code for replication and transcription processes.

Pretty straightforward.

All right, so we got rifamycins, which is inhibiting the RNA polymerases, dapsone, which is inhibiting the metabolic pathway that makes nucleotides via the parametobenzoic acid pathway.

The next one that I want you guys to remember is streptomycin.

Now streptomycin is actually pretty cool.

Streptomycin is a kind of a second line agent that we can use in like TB infections.

But what streptomycin will do is it inhibits a very specific component here.

So you know how we need mRNA to interact with the ribosome.

Specifically, there's the two components, the 30S and the 50S ribosomal subunit.

Streptomycin will bind to the 30S ribosomal subunit and inhibit it from being able to interact with the RNA and make proteins.

So if you inhibit the 30S ribosomal subunit, what do you do to the actual protein synthesis?

You decrease protein synthesis.

So again, I want you to remember streptomycin inhibits the 30S ribosomal subunit, riflamycin inhibits the RNA polymerase enzyme, and dapsone inhibits the peraminobenzoic acid pathway,

leading to less tetrahydrofolate, less nucleotides that are needed in DNA and RNA.

All right.

The next thing here is isoniazid.

Now this one is a little bit kind of a complicated pathway.

I'm going to try to dumb it down a little bit, but what happens is isoniazid gets taken up into this actual mycobacterial cell.

When it gets taken up into the mycobacterial cell, it's converted into like a metabolite, kind of an active metabolite.

We're just going to kind of draw like little asterisks on this because now it's activated.

In order for it to be activated, there's a very specific enzyme that performs

that function to activate it once it's brought into the mycobacterium

and this is called catalase peroxidase also known as cat g enzyme

and what this does is it activates the isoniazid into this

active metabolite all right once it's in this active metabolite form

it then binds with another molecule that's present inside of the actual mycobacterium

and this molecule is called nad so it'll bind with nad

So then we get kind of this active metabolite of isoniazid plus we have bound to it the NAD molecule.

Once you have this, this molecule is very interesting because of what it can do is it finds a little enzyme here.

You see this enzyme right here?

This enzyme is called enoyl reductase.

And what enol reductase does is it helps to be able to stimulate the production of particular molecules

that are integral into the cell wall.

And obviously the cell wall is important for resisting osmotic forces.

If you don't have the integral component of it, you aren't able to resist osmotic forces and the actual bacterial cell will die.

What is that particular component that it makes?

Well, let's actually say that we take a slice of the cell wall out and zoom in on it.

100

There's different types of molecules that are integral to the actual cell wall.

101

And this would be from the outer portion all the way to the inner portion.

102

So outer to inner.

103

That inner layer here is going to be the inner cell membrane.

104

So this would be your cell membrane as the innermost layer.

105

So your phospholipid bilayer.

106

Then after that, in this pink layer, this is your peptidoglycan layer.

107

So this is your peptidoglycan layer.

108

Then after that, in this maroon color here, we have something called arabinogalactin.

109

Arabinogalactin.

110

So kind of like a sugar molecule, kind of like a polysaccharide molecule.

111

Then you have this fatty acid layer called mycolic acid.

112

So mycolic acid, very important component.

113

And on the outermost layer here in red, you have your glycolipid layer.

114

Now, what's really, really important is enol reductase helps to be able to synthesize the mycolic acid molecules, which are integral to the cell wall.

115

Whenever you give them isoniazid, it gets converted into this metabolite, binds with NAD, and now when it binds with NAD and it's in the activated form,

116

it can then inhibit the enol reductase.

117

If we inhibit the enol reductase, we then reduce the synthesis of mycolic acid.

118

If we reduce the synthesis of mycolic acid, we lose an integral component of the cell wall in the bacteria and then subsequently die.

119

So that's isoniazid.

120

I know it's a little bit complicated, but I hope that pathway makes it a little bit more simplified.

121

All right, to go along with mycolic acid, there's another particular drug.

122

We didn't completely know how this enzyme, this drug actually worked.

123

It's still questionable, but what we know is that this drug here called pyrazinamide works to inhibit mycolic acid formation.

124

And so there was questions of how exactly it does it.

125

Some of the most recent literature says that it inhibits a very specific enzyme.

126

And this enzyme is called fatty acid synthase.

127

And mycolic acid is kind of like a fatty acid.

128

So if you don't have this enzyme, guess what this enzyme actually does?

129

It helps to be able to synthesize the very important molecule that we incorporate into the cell wall.

130

What do you think it is?

131

Mycolic acid.

132

So if we inhibit this enzyme, we use pyrazinamide, we inhibit the actual fatty acid synthase.

133

Can we make the mycolic acid molecules that are integral to the actual cell wall?

134

No. So we'll decrease the actual synthesis of mycolic acid molecules.

135

So two drugs will inhibit mycolic acid.

136

One is isoniazid through this kind of complex pathway.

137

And the other one is pyrazinamide, which inhibits the fatty acid synthase.

138

So fatty acid synthase, pyrazinamide, enoreductase inhibition, isoniazid.

139

Okay, we're almost done.

140

Last one here.

141

Ethambutol is another interesting one.

142

So remember I told you that there was two important components here to the actual cell wall.

143

Mycolic acid is a big one that I want you to remember.

144

And then this maroon color one here is the arabinoglactin.

145

This is another important layer that I want you to remember.

146

This enzyme here is called arabinosoil transferase.

147

So you're like, what the heck?

148

This enzyme here is called arabinosoil transferase.

149

And what this enzyme does is, is it takes particularly like sugar molecules that are present inside of the bacteria.

150

The two sugar molecules that you actually would need to remember, one is called arabinose and the other one is called galactose.

151

What it'll do is it'll take a combination of these molecules, utilize them, and then convert them into arabinogalactin, okay?

152

Which is integral into making this particular molecule here that's incorporated into the cell wall.

153

So it'll use these molecules and make this thing called arabinogalactin.

154

That's what the job of this enzyme is.

155

If I give this drug called ethambutol, ethambutol will inhibit the arabinosyltransferase.

156

If I inhibit arabinosyltransferase, I can't take arabinose and galactose and make arabinogalactin.

157

If I can't make arabinogalactin, do I have the integrity of the actual cell wall?

158

No, I lose my integrity.

159

Therefore, the actual bacteria cell is susceptible to death.

160

So to quickly recap these, rifamycin inhibits RNA polymerases.

161

Shreptomycin inhibits the 30S ribosomal subunit.

162

Dapsone inhibits the pava pathway, which inhibits nucleotide formation.

163

Isoniazid inhibits fatty acid synthesis, particularly of mycolic acid by inhibiting enoyl reductase.

164

Pyrazinamide inhibits mycolic acid formation by inhibiting fatty acid synthase.

165

And ethambutol inhibits arabinoglactin formation by inhibiting arabinocyl transferase.

166

I know it was a lot, slightly complicated.

167

I apologize, but I hope this makes sense.

168

Now let's move on to the actual indications of these drugs.

169

We're going to talk about what are the actual clinical usages.

170

It's actually straightforward.

171

So mycobacterium tuberculosis.

172

We're not going to go through the entire pathophys and all the the clinical features of TB, we'll talk about that when we dedicate an actual lecture to tuberculosis and all these other ones.

173

But when we talk about tuberculosis, obviously we know it's due to the bacterium, mycobacterium tuberculosis.

174

Now, obviously that area, that bacterium loves the lungs.

175

So it loves to kind of stay, interact with macrophages and cause these types of nasty lesions that you can see within the lungs.

176

And then the problem is once it actually causes these lesions typically within the upper lobes of the lungs, what happens is it has the ability of, so actually if someone's severely immunosuppressed for some reason,

177

it can disseminate and spread to other organs of the body, where it can spread to the actual brain, causing like meningitis or encephalitis, spread to the actual bones, where it can cause osteomyelitis,

178

spread to the adrenals, where it can cause adrenal failure, spread to the liver, cause liver failure, spread to the actual lymph nodes, causing like lymphadenopathy or scrofula.

179

So a lot of things that can happen when you have this infection.

180

But the question is, sometimes people can be infected with TB, never know it, not have any idea, but when we do like the tubercular skin test,

181

the PPD test, and we see that the bump is maybe a particular size, but they don't have any active infection going on, but they have maybe the latent infection of TB, we can treat them for that.

182

Now, if they have the full -blown active infection where it's involving their lungs or it's disseminating, then we have an active TB treatment.

183

We should know what are the agents that we utilize in the latent

184

and what are the ones that we utilize in the active infection.

185

So in the latent TB, where they're not actually having active pneumonia infection.

186

They're not disseminating into the actual systemic vasculature and other parts of the body.

187

We utilize two particular drugs that we can use here, one or the other.

188

So one is you can use isoniazid, commonly abbreviated INH.

189

Just get used to that one.

190

I might use that sometimes.

191

So INH, we can do this for about six to nine months.

192

Some literature will say six months, some will say nine months.

193

It depends upon how frequently you take it.

194

The other one we can utilize is rifampin.

195

So rifampin would be the other option we could utilize here and we could use that one for four months.

196

So if a patient has latent TB, they test positive or they have a particular size of the tuberculin skin test, we can put them on one of these two drugs for that time duration.

197

Now, if they have active TB, they actually have active like caseating granulomas with inside of the lungs, or they have gone complexes, or they have ranky complexes, or they have dissemination to other areas of the body,

198

they have active TB, we treat them a little bit differently.

199

We utilize what's called a ripe regimen.

200

That sounds crazy, But you start off first with what's called the RIPE regimen.

201

So this is rifampin, isoniazid, pyrocinamide, and ethambutol.

202

So you utilize these four drugs first for at least two months.

203

Okay?

204

After the two months are up, you then move into the second part of the regimen, which you utilize rifampin and isoniazid for four months.

205

so it always works in this particular fashion for the first two months you use the ripe drugs

206

rifampin isoniazid pyrazinamide

207

and ethambutol for the second part of the regimen for the next four months you use rifampin

208

and isoniazid when you have a patient on isoniazid one of the common adverse effects is b6 deficiency

209

which can cause neuropathy it can cause anemia it can even increase the risk of seizures

210

so because of that we want to be able to give the patient b6

211

so we give them B6 supplements to be able to augment that and prevent them from developing B6 deficiency because of isoniazid.

212

Now, if a patient has active tuberculosis and it's actually seeding, it's spreading, so they have like miliary tibia, they have TB meningitis.

213

oftentimes we may add on streptomycin as a second line agent

214

but generally when you're at this point you're going to seek the id consult

215

because they're going to be way too sick for you to

216

be able to have to figure this out you'll see got an actual infectious disease specialist

217

and they'll be able to kind of figure out what is best in this situation

218

so what i think is the most important remember is what are the two drugs

219

that we can utilize in latent tb what are the length of the duration.

220

Then active TB, what are the actual regimen, RIPE and then rifampin and INH, two months for the RIPE, four months for the rifampin and INH, add B6.

221

It's very important.

222

Sometimes you can add streptomycin or other particular drugs into this regimen if they have more systemic or refractory TB.

223

All right, so the next one here is Mycobacterium leprase, so leprosy.

224

So in this one, I can't say that you'll often see this very often, but it's a Mycobacterium, so we should know the particular agents

225

that we utilize for this in the same way

226

that we know tuberculosis so typically it loves to involve the skin

227

so it likes to cause like these hypopigmented skin lesions that's one particular thing

228

so you may see particular skin lesions

229

and then the other thing is you actually may see nerve palsies

230

so it typically likes to cause like thickening of the nerves and

231

when it thickens up the nerves it actually may get compression

232

in particular areas one of the common areas is like the ulnar nerve

233

so you may see like an ulnar nerve palsy that might be one and then the other one is the peroneal nerve.

234

So you actually may see a peroneal nerve palsy in these situations as well.

235

So that would be the particular thing to think about.

236

Now, if somebody does have leprosy, what are the particular agents that we utilize in this?

237

It's often two particular drugs, dapsone and rifampin.

238

So I want you guys to remember dapsone and rifampin.

239

Sometimes we may add another drug in called clofazamine, but generally that's if they have like what's called the tuberculoid form of leprosy

240

so i don't want to go too far down

241

that road remember dapsone rifampin for leprae remember these isonized for

242

69 months for latent tb rifampin for four months for latent

243

tb active is ripe for two months rifampin high in age for four months

244

and then add on your b6 the last mycobacterium infection

245

that i want to talk about it's called a mac

246

so it's called mycobacterium avium intracellular complex infections let's talk about

247

that so with mycobacterium avium intracellular complex infections generally these love to cause like these like fibrocavitary like pneumonia

248

so we're obviously going to see like some type of pneumonia

249

like generally some type of like nodular fibrocavitary lesion what can

250

happen is in certain situations this can actually disseminate especially in

251

immunosuppressed individuals spread to the liver spread to the actual bone marrow

252

and even spread to the spleen in situations where a patient

253

tests positive for mycobacterium avium intracellular complex what do you treat

254

them with it's usually particularly like a three -part combination

255

so we you're going to utilize one drug is called fmbutol you guys remember

256

that one and then we'll add on another drug to that

257

and we usually utilize what's called rifampin so we'll add rifampin as another one

258

that we can utilize

259

and then the last one here is we add something called

260

a macrolide we talked about this in the antibiotic section

261

but this would be particularly like your clarithromycin your azithromycin the next thing to potentially consider is the plus

262

or minuses when will we add other particular agents on.

263

So these are the primary agents that we're going to utilize in the MAC infection.

264

But we may add on things like aminoglycosides.

265

You may add on things like fluoroquinolones, particularly in those severe or refractory cases.

266

Severe slash refractory cases.

267

But that would be the particular thing

268

that I want to want you guys to remember for the mycobacterium avium intracellular complex infections.

269

You always start with ethambutol, rifampin and a macrolide plus or minus an aminoglycoside or fluoroquinolone in the severe refractory cases.

270

One thing to add to these actual things here is that anytime you're actually giving somebody rifampin, so I would add this as an extra little side note in case they ask you this on the exam.

271

If a patient is HIV positive and they are going to be on rifampin, if you put them on rifampin, whether that be for mycobacterium leprae,

272

whether that be for tuberculosis or whether that be for mycobacterium avium intracellular complex

273

because rifampin can interact with the cyp 450 system you might want to switch to rifabutin

274

so this may be a question that they ask on the exam

275

because there is less interaction with the nrti's and

276

that is extremely important because remember when we treat hiv we use nrti's

277

or nrti's or protease inhibitors all those different drugs Well, if you give someone rifampin, rifampin may actually decrease the concentration of these NRTIs, but if you give them rifabutin,

278

there is no actual cytochrome P450 inhibition with this one.

279

So less effect on the NRTIs, NNRTIs, protease inhibitors, all those things.

280

So that's really, really important to remember.

281

So HIV positive patient that you're putting on rifampin, switch them to rifabutin because there's less kind of like drug interactions there.

282

All right, now that we've talked about that, let's hit the adverse reactions.

283

All right, so let's talk about the adverse effects of these antimicrobacterial drugs.

284

So first thing, rifampin.

285

What do we need to know about this one?

286

First thing is that they will ask you this on the exam.

287

Patient comes in, they're freaking out because they have red -orange urine.

288

That's a completely normal, harmless adverse effect of rifampin, but just be aware it is an adverse effect.

289

And I would probably let the patient know that before they go home.

290

Okay.

291

So watch out for any kind of like red, orange urine.

292

It's completely harmless, but just let them know that so they don't have like a heart attack.

293

Okay.

294

Then the other thing here is that it can actually cause false positive urine opiate tests.

295

I just thought that was an interesting thing to potentially no. So false positive urine opiates.

296

But I think the other big thing to remember here is the effect on the CYP450 system.

297

Remember I told you it acts as an inducer.

298

So because of that, if you give this, it's going to decrease the concentration of a particular drug that you're taking it with.

299

That's why if a patient is HIV positive and they're taking NRTIs or NNRTIs or produce inhibitors, if you give that with rifampin,

300

it can actually decrease the concentration of that drug because it is a CYP450 inducer.

301

So it's important to be able to remember that when you put them on rifampin.

302

Watch out for any other drugs that they're taking it with.

303

All right, pyraxenamide.

304

What's the important thing to remember for this one?

305

Monitor those LFTs.

306

Some people will say rifampin is hepatotoxic.

307

It is a very minor, minor, minor hepatotoxicity.

308

It's important to train the LFTs, but it's significantly less hepatotoxic in comparison to all these other ones.

309

So pyraxenamide is the big one that I would remember is hepatotoxic.

310

This one is an isoniazid.

311

So hepatotoxicity, watch for the bump in the LFTs.

312

So watch for any kinds of hepatotoxicity.

313

Next thing here, with pyraxenamide, it plays a particular role within the uric acid.

314

So it may actually reduce the uric acid in the actual urine and increase the uric acid inside of the blood.

315

And so this is called hyperuricemia.

316

So it may increase the uric acid in the blood, causing hyperuricemia.

317

So if the patient is actually in the vignette and they say, okay, putting them on pyrazinamide, but they have a history of gout, what should you potentially watch out for?

318

Worse exacerbations of their gout because you're gonna increase their uric acid levels, increase your uric acid crystal formation, and they can deposit into that big toe and then they come in, my toe's all jacked up.

319

So important to remember that with the pyrazinamide.

320

Ethambutyl, what is the important thing to remember for this one? affects the eye particularly the optic nerve

321

so this can actually cause optic neuritis important to remember

322

that they may have visual disturbances and decreased visual acuity

323

so optic neuritis whenever you put this medication on somebody watch

324

out for any types of visual dysfunction maybe follow up with the optometrist

325

or ophthalmologist all right so rifampin red orange urine false positive urine screens this is the big one cyp450 inducer perazinamide apatotoxic, hyperuricemia, watch out in gout.

326

Ethambutol, optic neuritis, consider doing like follow -up with the actual ophthalmologist or particularly optometry.

327

Dapsone, if you put somebody on dapsone, what should you potentially watch out for?

328

One of the big things is it can actually oxidize the hemoglobin and convert it into the ferric form.

329

Whenever that does that, you can't bind oxygen.

330

So oxygen won't be able to bind with this ferric form, this oxidized form.

331

And because of that, they can cause hypoxia, more of like a cytotoxic or histotoxic hypoxia

332

and this is actually called methemoglobinemia

333

so watch out for this one the other thing is

334

if a patient has a g6 pdh deficiency

335

and you give them dapsone it can increase their hemolytic events

336

and so it may cause an acute hemolysis event

337

and that's an important thing to remember along with like nitrofrantoin

338

and forloquinolones and and bactrim and things like

339

that the other thing is it can actually suppress the production of particular white blood cells such as neutrophil

340

so it may actually cause a neutropenia all right

341

so big thing to watch out for again methemoglobinemia g6 pdh deficiency

342

if they have that and you give them this drug it can cause an acute hemolytic crisis

343

and neutropenia ethambutol optic neuritis parazinamide hyperircemia hepatotoxicity rifampin watch out

344

for the cyp450 induction all right let's come down isoniazid and streptomycin all right isoniazid.

345

What do we got to remember about this bad boy?

346

This one actually will cause some injury to the liver.

347

So watch out for the bump in the LFTs.

348

You should monitor that when you have the patient on isoniazid or what else?

349

Pyrazenomide.

350

Not so much with the rifampin though.

351

Remember that.

352

The other thing, here's what's really interesting.

353

It can actually cause an anion gap metabolic acidosis through two ways.

354

So it can cause an anion gap metabolic acidosis by bumping your beta -hydroxybutyrate.

355

Do you remember what that is?

356

That's a ketone body.

357

So it may cause a keto acidosis

358

because of it causing an increased acetyl -CoA metabolism or increase through the acetyl -CoA pathway.

359

And it also can increase your lactate.

360

So it may cause a lactic acidosis and a ketoacidosis as a particular cause of their anion gap metabolic acidosis.

361

The other thing is it can cause a drug -induced lupus.

362

You're like, what the heck?

363

It's important to actually remember this because especially in your exams, especially in the step one,

364

they may ask you what are the particular drugs to remember that can cause drug -induced lupus.

365

And this is one of them, but you can remember this by the ship mnemonic.

366

sulfa drugs, hydralazine, isoniazid, procainamide, and phenytoin, just remember these because they can come up on your exam.

367

The next thing is it can cause a B6 deficiency.

368

Now, B6 deficiency can do two things.

369

One of the things with the B6 deficiency is it may alter the myelination of particular neurons and lead to neuropathy.

370

So watch out for any types of peripheral neuropathy.

371

The other thing is it can also alter the activity of particular enzymes inside of the actual red blood cell

372

or alter the ability to make red blood cells.

373

And this can lead to anemia, whether this is like a aplastic anemia or a sideroblastic anemia, it can drop your red blood cells.

374

The other thing is it can actually cause seizures.

375

So it may actually reduce your seizure threshold and these can actually be refractory.

376

So you can actually give a patient like multiple benzos if they're in status epilepticus and it'll not work.

377

So watch out for any refractory to benzos in patients who have a B6 deficiency.

378

You give them some B6, they actually might start responding to some of the benzos okay

379

so isoniazid watch for hepatotoxicity watch the anion gap for any

380

metabolic acidosis watch for drug -induced lupus remember the mnemonic

381

and then seizures refractory to benzos and then with b6 deficiency you can particularly see anemia and neuropathy

382

last one here is your streptomycin remember that's

383

that second line in your mycobacterium tuberculosis we don't it's not

384

a part of the ripe regimen it's not a part of the second part for the four months afterwards.

385

It's more of the add -on for like miliary TB or more of your TB meningitis.

386

And these ones, it's important to remember it's an aminoglycoside.

387

Aminoglycosides are nephrotoxic.

388

They will jack those kidneys up.

389

So watch for any signs of nephrotoxicity.

390

So monitor their creatinine, monitor their BUN, their urine output.

391

The other thing is it can actually really hurt their inner ear, causing ototoxicity.

392

Particularly, it can actually hit the eighth cranial nerve right

393

so particularly watch out for the vestibular cochlear nerves watch out for any ototoxicity

394

and it also can affect the growth of the baby

395

so it's important to remember that is teratogenic teratogenic is a big one here

396

so avoid this in patients who are pregnant

397

and then the last thing is you want to be careful

398

if you give this to a patient who has a history

399

of myasthenia gravis it should be contraindicated in what's called myasthenia

400

gravis i'm gonna put mg the reason why is it alters with the actual uh response of the antibodies

401

that actually bind at the particularly at the nicotinic receptor on the muscle cells

402

and so this may alter that in a particular way

403

so it's important to remember do not give this in patients

404

who have myasthenia gravis do not give this in patients who are pregnant

405

and watch the actual renal function

406

and again watch for any kind of changes in their hearing

407

when you put a patient on streptomycin all right my friends you think we're done

408

but we got to review this we got to we got to anchor this stuff into our cerebral cortex.

409

So let's do some cases and see if we can actually anchor this stuff into our cerebral.

410

All right, Nationals, let's do some practice problems or kind of like really understand what we talked about here on the whiteboard.

411

So you're performing rounds, you're with your infectious disease and they say, okay, I'm going to ask you some questions about their mechanism of action.

412

Let's see if you guys can pick out which drug it is based upon what I'm kind of prefacing you with.

413

So first one is which drug inhibits the RNA polymerase?

414

So this cute little enzyme here that takes DNA, makes RNA

415

and helps to be able to synthesize particular types of bacterial proteins this would be your rifamycins right

416

so your rifampin rifabutin things of that nature next one is

417

which one of the drugs actually inhibits the 30s ribosomal subunit inhibiting protein synthesis

418

that are needed in the bacteria this would be streptomycin great

419

which one of these drugs actually works to inhibit the arabinosyl transferase

420

which takes arabinose and galactose and makes arabinol arabinoglactin which is an important component of the actual cell wall.

421

You guys know this would be which particular structures?

422

Come on, let's see if you guys remember this one.

423

Come on.

424

This is the ethambutol. So ethambutol.

425

Which drugs actually inhibit the fatty acid synthase that takes particular fatty acids

426

and helps to be able to make what's called mycolic acid, which is an important component of the actual cell wall?

427

This would be pyrazenamide.

428

Which of the particular drugs helps to be able to inhibit the enzyme

429

that actually helps to convert what's called the paramina benzoic acid into dihydrofolate and then subsequently tetrahydrofolate,

430

which is needed to be able to make nucleotides to incorporate into the DNA.

431

This would be, which particular drug do you guys remember?

432

Dapsone.

433

Right, okay, good.

434

Next one is which one of the drugs is actually going to be taken into the fungal cell, acted on by the catalase peroxidase, and whenever that happens, it turns it into an inactive,

435

I mean, it turns from an inactive into a very active type of molecule.

436

There, it binds with NAD.

437

And when it binds with NAD, this molecule here actually can inhibit enol reductase.

438

And what that does is it decreases the synthesis of mycolic acid in the cell wall.

439

This is going to be isoniazid.

440

All right, great.

441

So we covered all of these particular drugs, okay?

442

Next question is, this patient has latent tuberculosis.

443

What are the particular treatment options for those with latent TB.

444

You guys remember that we always can consider two options.

445

One is we can do isoniazid for about six to nine months, right? or rifampin for about four months.

446

The next question is you have a patient with active tuberculosis.

447

If they have active tuberculosis, you always do the ripe regimen.

448

So rifampin, isoniazid, parazenamide, and fambutal for two months.

449

Then you subsequently follow after that with rifampin and isoniazid for four months

450

and add on B6 because B6 is important because if you're taking isoniazid, that can actually cause a B6 deficiency and lead to neuropathy and seizures, et cetera.

451

So it's important to remember that.

452

The other thing is if a patient is HIV positive and also has an active TB or a latent TB, you should consider switching rifampin to rifabutin.

453

And the reason why is rifampin can actually act at that cytochrome P450 system.

454

And when you give rifabutin, it doesn't actually have to have as much interaction with the CYP450 system because what can happen is rifampin is a CYP450,

455

what's called inducer.

456

And because it's actually acting as an inducer, it decreases the concentration of the particular the drug that's being metabolized by the CYP450 system.

457

And patients who are taking HIV medications like NRTIs, it would decrease the efficacy of those drugs or the concentration of those drugs.

458

So that's why you switch to rifabutin because it's not an inducer.

459

And if they have TB meningitis or miliary meningitis, you should really seek infectious disease expertise, but you can consider adding on streptomycin.

460

All right, another patient has what's called the MAC infection, so mycobacterium avium intracellular infection.

461

What are the particular treatment options?

462

Because this is another type of mycobacteria.

463

So we can actually consider treating these patients with what?

464

We can do rifampin or also known as rifabutin if they have HIV.

465

We can also consider ethambutol.

466

And then lastly, we can add on a macrolide like azithromycin.

467

Okay.

468

Now, if they have severe refractory cases, you can add on something like a fluoroquinolone or an amino glycoside.

469

So again, ethambutol, rifampin, and a macrolide for a MAC infection.

470

And the big ones to remember here is

471

that fmbutol is a part of that triad

472

and rifampin is a part of that

473

so again for latent tb isoniazid 69 months or rifampin for four months

474

if it's active it's going to be the ripe for two months

475

and then after rifampin isoniazid for four months add b6 could switch to rifabutin

476

if they have hiv okay add streptomycin refractory or miliary types of tb or what's called tuberculosis meningitis.

477

If it's a MAC, ethambutol, rifampin, and macrolide, add -on, aminoglycosides, and fluoroquinolones in refractory cases.

478

All right, you have another person who has another mycobacterial infection called mycobacterium leprae, which is leprosy.

479

If they have leprosy, this obviously causes these hypopigmented and nasty skin lesions, and this can also lead to nerve palsies.

480

It thickens the nerve, which can actually cause compression of the ulnar nerve, the peroneal nerve, and this can cause a lot of problems there as well.

481

So we treat these patients with dapsone and rifampin.

482

Dapsone and rifampin, you can add on clofazamine and tuberculoid leprosy.

483

So rifampin, dapsone, mycobacterium leprae, ethambutol, rifampin, macrolide, and mycobacterium avium intracellular.

484

Rifampin for four months, isoniazid for six to nine months, and latent.

485

Ripe for two, rifampin, isoniazid for four if it's active TB.

486

Switch rifampin to rifabutin if any patient has HIV, because it can reduce the efficacy of the NRTIs.

487

All right, boom.

488

Now, the next thing that we have to think about is what are the adverse drug reactions?

489

So a big thing to think about here is we talked about all of these already and what they're treating.

490

But let's start off with the rifamycins first.

491

What I want you guys to remember, especially with rifamibin, cause red -orange urine.

492

And this is actually completely harmless.

493

This is something to think about if a patient starts getting really scared.

494

The other thing is it can actually cause a false positive urine opiate.

495

So if someone's actually getting drug screened, remember it can potentially cause a false positive.

496

The other thing, it's what's called rifampin.

497

It's a CYP450 inducer, meaning that it can actually work to actually increase the activity of the cytochrome P450 metabolism,

498

which will decrease the concentration of the drug.

499

All right, so those are big things to remember.

500

The next one that we should talk about here is going to be isoniazid.

501

This is the big one.

502

It's really, it actually hepatotoxic.

503

You should be monitoring patients' LFTs, and it can also produce what's called a metabolic acidosis.

504

It can actually increase the production of ketone bodies and it can actually increase the production of lactate.

505

So watch out for any metabolic acidosis that have an anion gap that's elevated.

506

The other thing is it can actually suppress the bone marrow and potentially lead to anemia.

507

One of the ways that we think this is actually maybe sideroblastic anemia due to the B6 deficiency.

508

And then the other thing is it can actually cause drug -induced lupus.

509

Remember the mnemonic SHIP, right?

510

So we said sulfa drugs, hydralazine, isoniazid, and then we also have phenytoin and procainamide.

511

And then remember it can also cause seizures.

512

It can lower the seizure threshold whenever patients have B6 deficiency, having them become refractory to benzodiazepines, and it can also cause neuropathy.

513

All right.

514

Pyrazenamide, we said that this is also hepatotoxic.

515

So watch those LFTs and it can also increase the uric acid.

516

So watch out for this in patients who have gout.

517

And then butol can cause optic neuritis, so it can cause changes in their vision, so make sure that they're getting annual eye exams if they're on this drug.

518

And then we have a patient who's on dapsone for, again, what was that for?

519

Leprosy.

520

We can actually watch out for any methemoglobinemia, G6PDH deficiency that can actually, if they take this and they have that underlying disease, it can actually cause an acute hemolytic crisis,

521

what it causes severe anemia.

522

And then watch out for neutropenia, okay?

523

Okay.

524

And then we also have streptomycin, which any aminoglycoside within this category is nephrotoxic, ototoxic, teratogenic as well.

525

And then again, can be contraindicated to myasthenia gravis because it can worsen the myasthenia gravis.

526

All right, engineers, that covers the antimicrobacterials.

527

I hope it made sense.

528

I hope that you guys enjoyed it.

529

As always, until next time.

530

Thank you.

📺 Gleicher Kanal

✨ Empfohlenes Video

116 Sätze

TB - mycobacterium tuberculosis شرح عربي

IELTS PrepTOEFL PrepUniversity Students

84 Sätze

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

IELTS PrepTOEFL PrepCambridge Exam Prep

28 Sätze

Explanation of Vaccine Adjuvants

IELTS PrepTOEFL PrepUniversity Students

23 Sätze

Your Brain on Drugs: Marijuana

IELTS PrepTOEFL PrepUniversity Students

28 Sätze

What is Nuclear Medicine | Dr. Paulien Moyaert

IELTS PrepTOEFL PrepUniversity Students

34 Sätze

Genetic Engineering and Diseases – Gene Drive & Malaria

IELTS PrepTOEFL PrepUniversity Students

192 Sätze

Other Corneal Disorders - CRASH! Medical Review Series

IELTS PrepTOEFL PrepUniversity Students

219 Sätze

Review of Musculoskeletal System (Bones & Muscles) - Biology Lectures Series

IELTS PrepTOEFL PrepUniversity Students

20 Sätze

Science in 1 minute: how does ibuprofen work?

IELTS PrepTOEFL PrepUniversity Students

50 Sätze

Nanotechnology and Its Applications

IELTS PrepTOEFL PrepUniversity Students

41 Sätze

The different types of mutations | Biomolecules | MCAT | Khan Academy

IELTS PrepTOEFL PrepUniversity Students

131 Sätze

The medicine myth | Denis Noble, Nessa Carey, Guy Brown

IELTS PrepTOEFL PrepUniversity Students

Wortschatz und Sprechhinweise zu dieser Lektion

Dieses Video enthält 530 Sätze und 6759 Wörter zum Nachsprechen. Der gesprochene Teil dauert 35:55. Der Sprecher spricht schnell, etwa 188 Wörter pro Minute – rechne mit verbundenen und verkürzten Lauten. Nur 77 % der Wörter gehören zu den 3.000 häufigsten im Englischen, der Wortschatz ist also anspruchsvoll.

Wichtiger Wortschatz in diesem Video

15 lernenswerte Wörter aus dem Video, mit Aussprache und Bedeutung:

Wort	Aussprache	Bedeutung
acid Substantiv	/ˈæsɪd/	Säure
enzyme Substantiv	/ˈɛn.zaɪm/	Enzym
molecule Substantiv	/ˈmɑ.lɪ.kjul/	Molekül
infection Substantiv	/ɪnˈfɛkʃən/	Ansteckung, Infektion
nerve Substantiv	/nɝv/	Nerv
deficiency Substantiv	/dɪˈfɪʃənsi/	Mangel
tuberculosis Substantiv	/tʃuːˌbɜː(ɹ)kjʊˈləʊsɪs/	Tuberkulose
decrease Verb	/dɪˈkɹiːs/	abnehmen
urine Substantiv	/ˈjʊɹɪn/	Urin, Harn
ripe Adjektiv	/ɹaɪp/	reif
layer Substantiv	/ˈleɪ̯ɚ/	Lage, Schicht
component Substantiv	/kəmˈpoʊ.nənt/	Komponente
pathway Substantiv	/ˈpæθˌweɪ/	Bahn, Pfad
convert Verb	/kənˈvɝt/	konvertieren, umwandeln
integral Adjektiv	/ˈɪntəɡɹəl/	integral, ein Ganzes ausmachend

Phrasal Verbs, die du hören wirst

Wort	Bedeutung
come down Verb	herunterkommen
figure out Verb	herausfinden
pick out Verb	auswählen, heraussuchen
watch out	Achtung, Vorsicht

Aussprache, auf die du achten solltest

Der Sprecher verwendet 75 Kurzformen und abgeschwächte Formen, zum Beispiel you're, they're, we're. Sprich sie in der kurzen Form, so wie du sie hörst.

Die „th“-Laute: pathway /ˈpæθˌweɪ/, synthesis /ˈsɪnθəsɪs/, threshold /ˈθɹɛʃ(h)oʊld/, eighth /eɪtθ/, ethambutol /ɛˈθæm.bjəˌtɔl/
Die Laute „sh“ und „zh“: infection /ɪnˈfɛkʃən/, deficiency /dɪˈfɪʃənsi/, seizure /ˈsi.ʒɚ/, potentially /pəˈtɛnʃ(ə)li/, concentration /ˌkɑn.sənˈtɹeɪ.ʃən/
Lange Wörter – auf die Betonung achten: deficiency /dɪˈfɪʃənsi/, tuberculosis /tʃuːˌbɜː(ɹ)kjʊˈləʊsɪs/, metabolic /mɛtəˈbɒlɪk/, incorporate /ɪŋˈkɔɹ.pɚ.eɪt/, potentially /pəˈtɛnʃ(ə)li/

So übst du mit diesem Video

Höre dir das ganze Video einmal an, ohne zu sprechen, und notiere die Wörter, die du nicht kennst.
Beginne mit 0,75-facher Geschwindigkeit, sprich Satz für Satz nach und wechsle zur normalen Geschwindigkeit, sobald es leichtfällt.
Nimm dich auf und vergleiche mit dem Original; achte dabei auf Wörter wie acid, enzyme, molecule.

Grammatik in diesem Video

Die Strukturen, die der Sprecher am häufigsten verwendet, mit den genauen Worten aus dem Video:

Struktur	Im Video
Bedingungssätze if + Satz, will/would + Verb – eine Bedingung und ihre Folge	if they're in status epilepticus and it'll not
Passiv be + Partizip Perfekt – wichtig ist, was geschieht, nicht wer es tut	is called · being formed · will be formed
Relativsätze who / which + Satz – eine Zusatzinformation über eine Person oder Sache	rifamycins, which is · molecules, which are · arabinoglactin which is
Present Perfect have/has + Partizip Perfekt – eine vergangene Handlung, die jetzt noch wichtig ist	have bound · have gone · we've talked

Was ist die Shadowing-Technik?

Shadowing ist eine wissenschaftlich fundierte Sprachlerntechnik, die ursprünglich für die professionelle Dolmetscherausbildung entwickelt und durch den Polyglotten Dr. Alexander Arguelles populär gemacht wurde. Die Methode ist einfach aber wirkungsvoll: Du hörst englisches Audio von Muttersprachlern und wiederholst es sofort laut — wie ein Schatten, der dem Sprecher mit nur 1–2 Sekunden Verzögerung folgt. Anders als passives Hören oder Grammatikübungen zwingt Shadowing dein Gehirn und deine Mundmuskulatur, gleichzeitig echte Sprachmuster zu verarbeiten und zu reproduzieren. Studien zeigen, dass es Aussprachegenauigkeit, Intonation, Rhythmus, verbundene Sprache, Hörverständnis und Sprechflüssigkeit signifikant verbessert — was es zu einer der effektivsten Methoden für die IELTS Speaking-Vorbereitung und reale englische Kommunikation macht.

Shadowing-Technik: die vollständige Schritt-für-Schritt-Anleitung lesen →

Shadowing-Übung: Antimycobacterials | Anti-TB Drugs - Englisch Sprechen Lernen mit Video

Homeostasis

Anatomy of the Heart and Coronary Circulation

Pharmacokinetics | Drug Absorption

TB - mycobacterium tuberculosis شرح عربي

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

Explanation of Vaccine Adjuvants

Your Brain on Drugs: Marijuana

What is Nuclear Medicine | Dr. Paulien Moyaert

Genetic Engineering and Diseases – Gene Drive & Malaria

Other Corneal Disorders - CRASH! Medical Review Series

Review of Musculoskeletal System (Bones & Muscles) - Biology Lectures Series

Science in 1 minute: how does ibuprofen work?

Nanotechnology and Its Applications

The different types of mutations | Biomolecules | MCAT | Khan Academy

The medicine myth | Denis Noble, Nessa Carey, Guy Brown

Wortschatz und Sprechhinweise zu dieser Lektion

Wichtiger Wortschatz in diesem Video

Phrasal Verbs, die du hören wirst

Aussprache, auf die du achten solltest

So übst du mit diesem Video

Grammatik in diesem Video

Was ist die Shadowing-Technik?