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Pediatric Pharmacology Exam 2 > Oncology (Chemo Agents) > Flashcards

Oncology (Chemo Agents) Flashcards

1
Q

Pediatric Treatment Principles (3)

A
  • Curative if at all possible
  • Get more Chemo than adults
  • Prevent long term complications
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2
Q

Dosing for anti-neoplastic agents

A

BSA is the standard for individualized based dosing

Mosteller Equation*****

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3
Q

Mosteller Equation

A

BSA = (ht*wt)/3600
ALL UNDER Sq root

ht = cm
wt = kg
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4
Q

Other options for dose adjustments (4)

A 
mg/m2
Units/m2
g/m2
Weight (kg) is sometimes used
o	Often used in children < 1 year of age
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5
Q

Corticosteroids (3)

A

Prednisone
Dexamethasone
Methylprednisone

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6
Q

Corticosteroids MOA

A

promotes decrease in lymphocytic cell lines

One of the mainstays, especially in Leukemia

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7
Q

Corticosteroids Side Effects (6)

Symptoms resolve by…

A
  • Hyperglycemia: May even require insulin while they are on the steroids
  • Fluid retention, facial swelling
  • Increased appetite (helps with nausea during induction)
  • Hypertension – Watch BP
  • Mood changes: Especially in children; children can get very cranky on steroids
  • Risk of GI ulcers

Symptoms typically resolve once treatment stops (typical duration of therapy is about 50 days)

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8
Q

Corticosteroids Special Considerations

A

Patients should be on acid suppression with a proton pump inhibitor or H2 receptor antagonist to protect against ulcers

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9
Q

Corticosteroids - tx of side effects (2)

A

Monitor blood pressure

Monitor blood sugar

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10
Q

Corticosteroids

What steroid is better at penetrating the spinal fluid?

A

Dexamethasone penetrates spinal fluid tissue better than prednisone

Choice of steroid however depends on the protocol

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11
Q 
Alkylating Agents (4)
MOA

Cell cycle

A

Highly reactive compounds

MOA - forms covalent (tight) bonds within DNA which leads to interference in cell replication

Cell cycle non-specific: Good thing

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12
Q

Common alkylating agents used in Pediatrics (3)

A

Cyclophosfamide
Ifosfamide
Busulfan

Used in pediatrics but more for bone marrow transplant conditioning

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13
Q

Less Commonly Used Alkylating agents in pediatrics (2)

A

o Decarbizine

o Temozolamide

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14
Q

Cyclophosfamide (Alkylating Agent)

Activated where?

A

Prodrug, must be activated in the liver to the active compound (CYP2B6 to 4-HC)

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15
Q 
Cyclophosfamide (Alkylating Agent)
Dosage forms (2)
A

IV doses used for cancers

PO used for other indications (FDA improved for minimal change disease in children)

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16
Q 
Cyclophosfamide (Alkylating Agent)
Side Effects (7)
A
  • Hemorrhagic cystitis (high doses require treatment with mesna): Leads to severe bleeding
  • Myelosupression: Since these agents cause bone marrow suppression, other non-cancer rapidly diving cells (ex: bone marrow, epithelial cells) will be affected
  • N/V (acute and delayed)
  • SIADH (Syndrome of Inappropriate Anti Diuretic Hormones)
  • Nasal stuffiness (decreases with infusing at least over 1 hr)
  • Pulmonary and cardiotoxicity
  • Alopecia
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17
Q 
Cyclophosfamide (Alkylating Agent)
Special Considerations(3)
A

Doses > 1800 mg/m2 should be infused over 1 – 6 hrs

Typical hydration with higher doses is 125 ml/m2/hr (D5 1/2NS)

Monitor UOP
Urine specific gravity (SG) must be < 1.01 prior to initiating the infusion and maintain urine SG < 1.01 (test urine with each void)
o Should be in IVF during infusion

18
Q

Ifosamide

Metabolized by?

A

Prodrug, must be metabolized to the active form (by CYP 3A4)

19
Q

Ifosamide

Dosage form

A

IV

20
Q 
Ifosamide
Side effects (7)
A

Neurotoxicty - requires neuro checks with infusions: See enceophalopathy, hallucinations, coma

Hemorrhagic cystitis - urine checks while on therapy is important

Nephrotoxicity: Fanconi syndrome due to renal tubular damage

Peripheral neuropathy

Cardiotoxicity – dose dependent

Interstitial pneumonitis, pulmonary fibrosis

Marrow supression, alopecia

21
Q 
Ifosamide
Drug Interactions (4)
A

Metabolized to the active form by CYP3A4

Inhibitors = less effective, inducers = > risk of toxicity

Anything that inhibits CYP3A4 will inactive this drug

If you give something that upregulates CYP3A4 you will see increased effects of this drug

22
Q

Hemorrhagic cystitis

What is it

A

Inflammation and damage to bladder epithelium leading to hematuria. Also can cause pain and irritation as well as long-term damage
o Caused by the metabolite, acrolein

23
Q

Hemorrhagic cystitis

How can it be avoided?

A

At higher doses mesna can be given to bind to the metabolite and limit the exposure to the bladder

Maintain good hydration

24
Q

Hemorrhagic cystitis

Tx (3)

A

Increase mesna dosing to 100% ifosfamide dose

Maintain good hydration

Sometimes patients may require bladder irrigations to washout the chemical

25
Q

Mesna

MOA

A

Binds to the urotoxic metabolites (acrolein and 4-hydroxyifosfamide) of ifosfamide and cyclophosphamide (to a lesser extent)

26
Q

With ifosfamide doses _____ mesna should be administered

A

> 1.2 g/m2

  • 60 – 100% of ifosfamide dose
  • Up to 6% will still develop urotoxicity with mesna
27
Q

Why do we use mesna?

A

to prevent bladder toxicity from ifosfamide and cyclophosfamide

28
Q

Dacarbazine (DTIC)
Used for
Dosage form
Side effects(2)

A

Used for solid and heme malignancies

Dosage form: IV only

Similar side effects to other alkylating agents
o Myelosuppression
o N/V

29
Q

Temozolamide (Temodar®)

Benefit

A

Newer alkylating agent
Benefit = PO administration
o IV formulation is available but used less
o Metabolized the active decarbazine

30
Q

Temozolamide (Temodar®)

FDA approved for (2)

A

FDA approved for glioblastoma and refractory astrocytoma therapies.

31
Q

Temozolamide (Temodar®)

Studied in children with… (2)

A

Studied in children for meduloblastoma, PNS tumors

32
Q

Platinum Alkylating Agent
MOA (3)

Cell phase…
Contains…

A

o Mechanism
Forms a covalent (strong) bond with DNA, platinum compound bound to DNA leads to inability for the cell to repair the DNA and ultimately cell death

  • Contain heavy metal (platinum)
  • Cell phase non-specific
33
Q

Platinum Alkylating Agent

Toxicity

A

• Toxicity – lots! Remember there will be a lot of toxicity with these

34
Q

Platinum Alkylating Agent

• Commonly used agents in pediatrics

A

o Cisplatin

o Carboplatin

35
Q

Cisplatin (Platinum Alkylating Agent)
Dosage form
Side effects (6)

A

• Dosage form: IV

  • Nephrotoxicity – Renal tubular nephropathy - associated with cation wasting (watch Mg, Na, and K)Requires aggressive hydration & high urine output
  • Prolonged myleosupression, thrombocytopenia
  • Hepatotoxicity
  • Peripheral neuropathy: Give Gabapentin for this pain – In general Gabapentin is given for the pain associated with alkylating agent side effect pain
  • Nausea and vomiting – see delayed nausea
  • Ototoxicity
36
Q

Cisplatin (Platinum Alkylating Agent)

Administration

A

Should be given with aggressive hydration – fluids should contain K+ and Mg+

37
Q

Carboplatin
(Platinum Alkylating Agent)
Dosage form
Special Considerations (2)

A

Dosage Form: IV – Usually dosed based on BSA or AUC

Special Considerations

  • Cleared vis renal excretion, so good kidney function is essential with hydration
  • Delayed nausea so dexamethasone can be used with anti-emetic regimen (unless otherwise contraindicated)
38
Q

Carboplatin
(Platinum Alkylating Agent)
Side effects are similar to cisplatin (2)

A

Notable exceptions…

  • Less emetogenic, nephrotoxic, and neurotoxic
  • More myelosupressive
39
Q

S phase specific drugs (2)

A

cytosine arabinoside

hydroxyurea

40
Q

S Phase specific - self-limiting (2)

A

6-mercaptopurine

methotrexate

41
Q

M phase specific drugs (3)

A

vincristine
vinblastine
paclitaxel

42
Q

Cycle non-specific drug (6)

A 
alkaylating agents
nitrosources
antitumor antibiotics
procarbazine
cisplatin
dacarbazine

Pediatric Pharmacology Exam 2 (9 decks)

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