Cancer Drugs & Chemotherapeutic Agents: Dactinomycin, Doxorubicin, Bleomycin etc. – White Blood Cell Pathology

00:02 We have a drug here called dactinomycin.

00:04 You’d find that children might be acting out, so you’re looking at childhood cancers.

00:08 It intercalates the DNA, making it difficult for the DNA to properly carry its action.

00:14 So once you know it’s childhood cancers that you’re affecting, then you start thinking about the childhood cancers, Wilms tumor, the renal cell cancer in your child, Ewing’s sarcoma.

00:25 This is your translocation that you know about called 11;22, and you have involvement at the diaphysis of the bone in Ewing’s sarcoma.

00:34 Rhabdomyosarcoma, especially the young type, and you’re referring to embryonal rhabdomyosarcoma, a.k.a. sarcoma botryoides, usually used for childhood tumors.

00:47 Myelosuppressions, what are you looking for? Doxorubicin, Adriamycin.

00:51 Here, it generates free radicals, noncovalently intercalated DNA, breaks into DNA, and also inhibits replication.

01:01 So there are many points of your proper DNA mechanism or replication that completely slows it down.

01:07 The clinical uses: part of what’s known as ABVD, and this is your Adriamycin, which is part of regimen that you probably need to know for Hodgkin.

01:16 Also, used for myelomas, solid tumors, a lot of places.

01:21 In the process though, what you’re worried about definitely is cardiotoxicity, dilated cardiomyopathy, marked alopecia, and toxic tissue because of extravasation.

01:33 It actually comes out, cause damage to the tissue.

01:36 Doxorubicin, Adriamycin, ABVD, Hodgkin.

01:41 Bleomycin, a G2 phase inhibitor, specifically, includes a formation of free radicals.

01:48 Again, just like we saw with your doxy, and it breaks your DNA strand.

01:53 Can use this in testicular cancer.

01:55 It’s also part of your ABVD.

01:57 The B in ABVD is your bleomycin.

02:01 The A was Adriamycin, which is part of that doxorubicin.

02:04 Well, bleomycin, it may then cause pulmonary fibrosis, B and B, if that helps you.

02:10 Also, myelosuppression.

02:12 There, etoposide, or toposide, in general; teniposide and etoposide.

02:16 teniposide and etoposide.

02:18 Well, these are the drugs that then inhibit topoisomerase 2.

02:21 Therefore, it increases DNA degradation.

02:24 It’s used between S and G2.

02:27 It can be used for small cell lung cancer, which is also called oat cell.

02:31 If you want, take a look at the ETO in etoposide.

02:34 How would you pronounce OTE? Oh, ote, if that helps you.

02:39 So etoposide, oat cell cancer.

02:42 What’s another name for small cell? Oh, yes, oat cell cancer of the lung.

02:47 Also, testicular and prostate, and you’re worried about alopecia and myelosuppression, etoposide, topoisomerase 2, oat cell cancer of the lung, and testicular.

02:57 Cyclophosphamide, ifosfamide, covalently X-linked.

03:04 You need to memorize guanine N-7.

03:07 Bioactivation by the liver.

03:10 Non-Hodgkin’s lymphoma, hemorrhagic cystitis, look for blood in the urine, and maybe treated by giving mesna.

03:21 Know your couple of rescues, please.

03:23 Mesna, leucovorin.

03:26 Nitrosourea: You have carmustine, lomustine, semustine, lustines, requires bioactivation.

03:37 This, you need to make sure C –, carmustine, C – crosses the blood-brain barrier into the CNS.

03:45 Therefore, brain tumors, including GBM, glioblastoma multiforme.

03:52 Is it always effective? Unfortunately, it’s not.

03:55 May then, unfortunately, because of its crossing, cause CNS toxicity.

04:02 Busulfan: alkylates the DNA.

04:06 CML, also used for ablating bone marrow in hematopoeietic stem cell transplantation.

04:13 Don’t forget about that.

04:13 That’s big.

04:15 And here, once again, another B, busulfan, pulmonary fibrosis.

04:20 What was the other one that start with the B resulting in pulmonary fibrosis? Very good.

04:25 We had our bleomycin.

04:31 Here, we have our vinca alkaloids.

04:34 So, we’re in the M phase.

04:35 Vincristine and vinblastine.

04:38 Use the -cristine and the -blastine to advantage.

04:41 You’ll see why.

04:43 Mechanism, what does it do? Well, in the M-phase, it literally inhibits the polymerization of your microtubule.

04:50 And therefore, the microtubules will not properly pull your chromosomes apart.

04:56 That’s your vinca alkaloid.

04:58 It’s part of your MOPP regimen for Hodgkin, and this would then be oncovin, which is your vincristine.

05:06 Also, it could be used for choriocarcinoma, vincristine.

05:11 Toxicity.

05:12 Okay, the C in vincristine will be for CNS toxicity.

05:18 Also, oncovin, also choriocarcinoma, CCC.

05:24 If you’re dealing with vinblastine, it’s going to affect the bone marrow.

05:29 B – blastine, B – bone marrow suppression.

05:34 Vinca alkaloids.

05:37 Taxol, another method in which you can affect the M phase.

05:42 Here, literally, the spindle is not going to break down.

05:45 You’re going to inhibit taxing.

05:48 You can use this for, perhaps, ovarian and breast cancers in a female, obviously.

05:52 And hypersensitivity is what you’re looking for.

05:55 The paclitaxel and vinca alkaloids will be affecting your M phase.

06:00 Don’t forget though, the vinca alkaloids will behave by inhibiting the polymerization.

06:04 And then here, it will hyperstabilize the taxols, will hyperstabilize the polymerized microtubule.

06:11 In other words, it will freeze the “tubules” so that it doesn’t break down, therefore, cannot replicate.

06:20 Make sure that you know the actual medical pharmacologic language when dealing with vinca alkaloids, and also, taxols.

06:28 Hyperstabilization, inhibition of polymerization.

06:33 Cisplatin, carboplatin, plat-, your platinum drugs.

06:38 Cross-link DNA.

06:40 Testicular cancer, ovarian cancer.

06:44 Acoustic, acoustic nerve damage, eighth cranial nerve, platin.

06:51 Hydroxyurea: Last time you saw hydroxyurea was to then inhibit what’s known as -- or to help a patient increase your hemoglobin F.

07:02 It inhibits ribonucleotide reductase.

07:05 Memorize ribonucleotide reductase, hydroxyurea.

07:09 Next, it is used and could be used for melanoma, CML.

07:14 And the reason we have sickle disease, even though it’s not a cancer is the fact that it increases hemoglobin F.

07:21 In sickle cell disease, remember your completely deficient hemoglobin A, you’re then going to increase quite a bit of hemoglobin S when you have polymerization.

07:31 This is not good.

07:32 You are then going to or wish to increase hemoglobin F, which will then cause a left shift.

07:38 This is then going to also cause bone marrow suppression and GI upset.

07:44 Here, we have prednisone.

07:45 What is a steroid doing here? Well, it may trigger apoptosis, as we know.

07:50 Remember, the lymphopenia stuff that we talked about earlier.

07:54 It may even work on non-dividing cells.

07:56 Most common glucocorticoid in cancer therapy used in CLL, chronic lymphocytic leukemia.

08:02 May be part of that MOPP regimen, your last P.

08:06 We have also immunosuppressed.

08:08 Meaning to say that it may be used in autoimmune diseases, which then require immunosuppression.

08:13 Obviously, when utilizing prednisone, you’re worried about Cushing-like symptom, cataract, osteoporosis, everything that you would expect with prednisone or cortisol type of side effect, including your peptic ulcer disease in the stomach.

08:28 Here, we have our tamoxifen and raloxifene.

08:32 First and foremost, these are going to be your estrogen receptor modulators.

08:37 These are then going to behave as antagonist in the breast and agonist in the bone.

08:41 So therefore, these are partial agonists.

08:44 It will block the binding of estrogen to the estrogen receptor-positive cells.

08:49 You’re looking at your ER positive breast cancers.

08:53 Also, osteoporosis because it is going to be an agonist towards your bone.

08:58 We’re going to divide our tamoxifen, raloxifene as such.

09:01 Tamoxifen may increase the risk of endometrial cancer due to the partial agonist type of effective estrogen.

09:08 Whereas, raloxifene does not increase the risk of endometrial cancer because it is an endometrial antagonist.

09:16 Raloxifene seems to be a little bit better in terms of not having as much of a risk as tamoxifen.

09:23 Here, we have Herceptin or trastuzumab.

09:26 Your patient is HER-2/neu positive, which is Erb-B2.

09:29 HER-2 stands for human epidermal receptor growth factor.

09:34 This is a metastatic breast cancer or really, really Erb-B2 positive, extremely, extremely dangerous breast cancer, extremely cardiotoxic.

09:44 Imatinib would be used for 9 and 22.

09:48 We talked about tyrosine kinase.

09:50 It could also be used forth on a c-kit positive, or CD117.

09:55 And by c-kit, we mean that also, you’ve heard of gastrointestinal stromal tumor, and you could have tyrosine kinase there as well.

10:02 And so therefore, imatinib would be a drug to utilize in such issues.

10:06 CML and GIST, gastrointestinal stromal tumor, which is a smooth muscle benign tumor found in the stomach.

10:16 Rare, but of all the benign tumors in the stomach, GIST is the most common.

10:21 Fluid retention toxicity.