Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Thera IX > 08a Major Organ Toxicities (Antimetabolites/Alkylators) Lee > Flashcards

08a Major Organ Toxicities (Antimetabolites/Alkylators) Lee Flashcards

1
Q

What are the common toxicities associated with Anti-Metabolites?

A

Myelosuppression, mucositis, alopecia, N/V, tumor lysis syndrome (TLS)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What needs to be added to MTX IV treatment when using Intermediate or High-dose?

A

Leucovorin rescue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are some major toxicities associated with MTX?

A

Stomatitis/Mucositis. Myelosuppression (dose limiting). Neurologic. Renal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the Purine Analogues used?

A

Mercaptopurine (6-MP, Purinethol). Thioguanine (6-TG, Tabloid)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the toxicities associated with Purine Analogues (Mercaptopurine, Thioguanine)?

A

Cholestatic Liver Dysfunction! Myelosuppression, Mild N/V/D, stomatitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the issue with What are the toxicities associated with Purine Analogues (Mercaptopurine, Thioguanine) and Allopurinol?

A

6-MP metabolized by Xanthine Oxidase, which is inhibited by Allopurinol. Azathioprine, an immunosuppressant, a prodrug to 6-MP. Thus, REDUCE dose of Azathioprine and 6-MP by 75%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the Pyrimidine Analogues used?

A

Fluorouracil (5-FU); Capecitabine (Xeloda; oral 5-FU); Cytarabine; Gemcitabine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the toxicities like for the Pyrimidine Analogues (Fluorouracil; Capecitabine)?

A

Depends on route, dose, and schedule. Bolus: Myelosuppression. Continuous infusion: Mucositis, diarrhea, hand/foot syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is Grade 1 Hand/Foot Syndrome?

A

Numbness, dysesthesia or paresthesia, tingling, painless swelling or erythema, and/or discomfort of hands or feet not disrupting normal activities

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is Grade 2 Hand/Foot Syndrome?

A

Painful erythema and swelling of hands or feet and/or discomfort affecting ADLs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is Grade 3 Hand/Foot Syndrome?

A

Moist desquamation, ulceration, blistering or severe pain of hands or fee, or severe discomfort preventing work or performance of ADLs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is Hand/Foot Syndrome also known as?

A

Palmar-Plantar Erythrodyesthesia (PPE)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the toxicities associated with Pyrimidine Analogue Cytarabine (Ara-C)?

A

Toxicities with high-dose: Conjuntivitis, Cerebellar dysfunction (coordination/balance)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the toxicities associated with Pyrimidine Analogue Gemcitabine (Gemzar)?

A

Myelosuppression. Mild N/V, stomatitis, increased LFTs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are some toxicities with Efudex, Carax 0.5% cream (topical 5-FU)?

A

Application-site reaction, erythema, dryness, burning, pain, ulceration, allergic contact dermatitis. Cases of miscarriage/birth defect when applied to mucous membranes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the common toxicities associated with Alkylators?

A

Sterility/infertility/teratogenicity. Second malignancies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Which Alkylators unique toxicity is Nephrotoxicity?

A

Cisplatin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the Platinum Alkylators used?

A

Cisplatin (Platinol); Carboplatin (Paraplatin); Oxaliplatin (Eloxatin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the toxicities associated with Platinum Alkylators?

A

Severe N/V (acute and delayed) w/ Cisplatin. Hypersensitivity with repeated use. Ototoxicity. Neurotoxicity (peripheral and loss of taste). Renal toxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is Renal Toxicity like with the Platinum Alkylators?

A

Cisplatin (Dose limiting toxicity (DLT)) > Carboplatin > Oxaliplatin. Dose-related toxicity of distal convoluted tubule and collecting duct

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the unique toxicities associated with Cyclophosphamide (Cytoxan, Neosar, oral and injectables)?

A

Highly emetogenic for doses > 1500 mg/m2. Hemorrhagic cystitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are the more common toxicities associated with Busulfan?

A

Severe Synusoidal Obstruction Syndrome (SOS) of liver. Seizures. Hyperpigmentation of the skin (Busulfan Tan). Endocardial fibrosis (Busulfan Lung) < 1%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is some patient education for Alkylator: Procarbazine (Matulane)?

A

Ethanol causes Disulfiram-Like reactions. Safe handling. Alert dietitian, provide list of foods to avoid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are the different complications of the GI Tract?

A

Xerostomia/Dry mouth (radiation). Stomatitis/Mucositis/Esophagitis (MTX, 5-FU, High-dose). N/V (Cisplatin and others). Diarrhea (5-FU, Irinotecan). Constipation (Vincristine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

How does Radiation (RT) to H/N cause Xerostomia?

A

Damage salivary glands. Loss of salivary buffering capacity, pH, IgA. Reversible w/in 6-12 months after end of treatment. Increase oral bacteria –> Infection

26
Q

What can be used to reduce Xerostomia?

A

Amifostine (Ethyol) 200mg/m2 or 500mg IV prior to RT. Pilocarpine (Salagen) 5-10mg PO TID, cholinergic

27
Q

What is Mucositis/Stomatitis?

A

Non-specific effect of chemotherapy and radiation on basal epithelium of mouth. Pain, may progress to ulceration; may extend esophagus, entire GI tract. Symptoms: Local pain, anorexia, N/D, thrush

28
Q

What are the main causes of Mucositis/Stomatitis?

A

Antimetabolites (MTX, FU, Cytarabine), Anthracyclines, High-dose Chemotherapy, Allogenic BMT

29
Q

How can Mucositis/Stomatitis be prevented?

A

Active rinses w/ mouthwashes. Sodium bicarbonate rinse, saline rinse, before eating and drinking. Cryotherapy (chew on ice before high dose melphalan - marginally effective). Paliformin

30
Q

What is the treatment for Mucositis/Stomatitis?

A

Palliative = symptom control. Topical anesthetics. Kaolin, Benadryl, Antacids. Mouthwashes

31
Q

What is the site of action of MTX?

A

Inhibits DHF Reductase

32
Q

What is the site of action of Leucovorin?

A

Increases the depleted N5, N10 Methylene THF

33
Q

What is the site of action of 5-FU?

A

Inhibits Thymidylate Synthetase, if given with Leucovorin it increases this inhibition

34
Q

What are the different Leucovorin options?

A

Leucovorin IV/PO. Levoleucovorin Injection (Fusilev) - dose 1/2 of LV

35
Q

What are the indications for Leucovorin?

A

Rescue after high-dose MTX. Reduces toxicity and counteracts effects of impaired elimination and inadvertent overdoses of MTX. In combo w/ 5-FU in palliative treatment of advanced metastatic colorectal cancer

36
Q

At what point is Leucovorin usually given with MTX?

A

When MTX > 500mg. Severe BM suppression and mucositis unless rescured by Leucovorin

37
Q

What is Calcium Leucovorin?

A

A reduced folate which can replenish the folate pool depleted by MTX. It allows DNA synthesis to begin again even in presence of MTX. Begin 24-36 hrs after initiation of MTX. Starting dose 10-15mg/m2 IV

38
Q

When can Calcium Leucovorin be stopped?

A

When MTX < 5x 10-8M (0.05 um) at 72 hrs

39
Q

When should precaution be used with Leucovorin?

A

If ascites or third space fluid collection –> Prolonged excretion and increased toxicity of MTX - may require Leucovorin dose increase as well as prolonged Leucovorin rescure

40
Q

When should MTX levels be obtained?

A

24, 48, 72 hrs after MTX started

41
Q

What should be done at 48 hrs if MTX level is less than 1x10^-6 M?

A

Continue Leucovorin 10-15mg/m2 Q6h x8 doses, IV

42
Q

What should be done at 48 hrs if MTX level is greater than 1x10^-6 M?

A

Increase Leucovorin to 50-100mg/m2 Q6h x8 doses IV until it falls below 1x10^-6, then follow other schedule

43
Q

How should MTX never be written?

A

QD!!! It is a weekly dose, not daily

44
Q

What is some patient education for MTX?

A

Inform MD if any signs of: Neutropenia (fever, chills, sore throat, cough). Bleeding, bruising. Mouth sores, SOB. Liver toxicity.

45
Q

How can nephrotoxicity from High-Dose MTX be prevented?

A

SCr < 1.5 or CrCl > 60. Intensive hydration. Alkalinization of urine to pH > 7 with Na Bicarbonate in IV fluids

46
Q

Which DDI with MTX causes a decreased elimination of MTX?

A

Probenecid and PPIs

47
Q

What is the MOA of Nephrotoxicity caused by Cisplatin?

A

Proximal tubular damage. Elevated BUN/SCr, chronic Mg wasting. SCr poorly coorelate w/ CrCl

48
Q

How can nephrotoxicity caused by Cisplatin be prevented?

A

Vigorous hydration with saline + Mg, K. Ensure diuresis w/ furosemide. Use analogue: Carboplatin. Uroprotectant: Amifostine

49
Q

What is Amifostine (Ethyol)?

A

Prodrug to free thiol that binds and detoxifies Cisplatin - “free radical scavenger”. Used to prevent cumulative renal toxicity associated w/ repeated administration of Cisplatin. Reduction of moderate to severe Xerostomia (dry mouth) in radiation treatment for head and neck cancer

50
Q

What are the side effects associated with Amifostine (Ethyol)?

A

Hypotension, N/V

51
Q

What drugs cause Hemorrhagic Cystitis (bladder toxicity)?

A

Cyclophosphamide, Ifosfamide. Caused be metabolite, ACROLEIN

52
Q

What is used for prevention of Hemorrhagic Cystitis caused by Cyclophosphamide, Ifosfamide?

A

Mesna (binds to acrolein preventing its contact w/ bladder wall and subsequent damage). Suprahydration, patient should drink ~3L fluid/d x sever days and frequent voiding

53
Q

What are the ADRs with Mesna?

A

N/V (sulfur smell)

54
Q

What can be used for treatment of Hemorrhagic Cystitis is severe bleeding?

A

Bladder irrigation w/ saline, cytoscopy w/ fulguration. Bladder instillation w/ aminocaproic acid, formalin, or hydrocortisone

55
Q

What is the dosing of Mesna like for IFX bolus?

A

IFX bolus: Mesna = 20% of Ifosfamide dose given at 0, 4, 8hr after IFX

56
Q

What is the dosing of Mesna like for IFX continuous infusion?

A

Mesna continuous infusion at 60-100% IFX dose, then extra 12-24 hrs after end of IFX (till acrolein level falls to non-toxic level in the bladder)

57
Q

What are the signs/symptoms of Ifosfamide-induced Encephalopathy?

A

Decrease in arousability and disorientation leading to somnolence, drowsiness, lethargy, hallucination, encephalopathy, stupor, personality changes, paranoia, mutism, muscle twitching, incontinence, seizures, coma

58
Q

What are the risk factors for Ifosfamide-Induced Encephalopathy?

A

High dose, bolus dose, low albumin. Avoid concurrent benzos (also cause CNS effects) - difficult to diagnos

59
Q

What is used in the treatment of Ifosfamide-induced Encephalopathy?

A

Methylene blue; 50mg IV TID

60
Q

What is a caution with Busulfan?

A

Seizures d/t its good CNS penetration

Thera IX (29 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions