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IHOP > Alkylating Agents Pharmacology > Flashcards

Alkylating Agents Pharmacology Flashcards

1
Q

Which atom is common in Alkylating agents?

A

Chlorides

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2
Q

MOA of Alkylating agents

A

-Cl ion acts as the leaving group
-the drug is now positively charged (+)
-the drug (+) forms a covalent bond with the base of the DNA (permanent)
-second Cl ion leaves -> the drug forms another covalent bond on two different bases

-> Cross-Linking of DNA

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3
Q

What are the possible results of crosslinking DNA?

A

-base excision
-miscoding
-strand breakage
-DNA adducts

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4
Q

What is a dangerous side effect of alkylating agents?

A

Secondary malignancies, especially leukemia

bc the drug causes damage binds covalently to other healthy cells and causes mutations

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5
Q

What are the Hallmark toxicities of all cytotoxic agents?

A

-Myelosuppression
-Mucositis
-Nausea
-Alopecia

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6
Q

What are the unique toxicities of alkylating agents?

A

-secondary leukemia
-Gonadotoxicity (infertility) -> counsel the patient

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7
Q

When does myelosuppression occur, how long does it last?

A
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8
Q

When does mucositis occur, and how long does it last?

A
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9
Q

What is the unique toxicity of Cyclophosphamide?

A

Hemorrhagic cystitis

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10
Q

Which toxic metabolite causes hemorrhagic cystitis?

A

Acrolein (metabolite of Cyclophosphamide)

Acrolein is excreted in the urine -> causes bleeding in the bladder

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11
Q

Which Chemoprotectant prevents hemorrhagic cystitis?

A

Mesna, it deactivates Acrolein (given at high dose of Cyclophosphamide, before chemotherapy)

usually, hydration is enough to flush out Acrolein

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12
Q

What is the brand name of Cyclophosphamide?
!!!

A

Cytoxan

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13
Q

Cyclophosphamide is myelosuppressive and ______

A

immunosuppressive

impairs the function of mature T-cells

(myelosuppressive = killing precursor blood cells, not mature blood cells)

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14
Q

Unique toxicity of Ifosfamide

A

-Hemorrhagic Cystitis (Acrolein)
-Neurotoxicity (Chloro-acetate aldehyde)

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15
Q

When should Mesna be used?

A

!!! ALLWAYS with Ifosfamide: + IV hydration
The dose of Ifosfamide is much higher than with Cyclophosphamide -> so it will definitely cause hemorrhagic cystitis if not given with Mesna

-high dose Cyclophosphamide + oral hydration (2-3L)

-impaired renal function and Cyclophosphamide

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16
Q

Which labs should be monitored when Ifosfamide is used?

A

-check for signs of neurotoxicity !!!

-Renal function
-Albumin (higher free fraction in Hypoalbuminemia)

17
Q

What is the brand name of Ifosfamide?
!!!

A

Ifex

18
Q

How does Cisplatin work?

A

Cl- leaves the drug -> ACTIVATION
the drug is positively charged and binds a covalent bond to DNA
-> causes Cross-linking

19
Q

Cisplatin binds to which specific part of the DNA?

A

N7 (nitrogen 7) of purine bases (often guanine)

20
Q

What are the toxicities of Cisplatin?

A

-N/V !!! (causes the most N/V of cancer drugs)
-Neuropathy (chronic)
-Nephrotoxicity (acute and chronic)
-Ototoxicity
-Gonadal toxicity (risk of infertility,)

21
Q

The highly reactive intermediate of Cisplatin leads to side effects by binding to which type of cells?

A

Kidney cells -> Nephrotoxicity

concentration-dependent

22
Q

What are chronic and acute signs of Nephrotoxicity?

A

Hypokalemia
Hypomagnesemia

have to give potassium and magnesium

23
Q

What should be given with Cisplatin to prevent Nephrotoxicity?

A

IV normal saline (1L) before and after treatment

NaCl is preferred over dextrose bc the reactive positive charged drug binds to Cl(-) from NaCl

increasing the infusion interval can help since it is concentration-dependent

24
Q

What is the key toxicity in Carboplatin?

A

Bone marrow suppression -> thrombocytopenia

-has some N/V, mucositis

25
Q

How is the dose of Carboplatin determined?

A

Calvert equation

dose (mg) = AUC x (GFR (CrCl) + 25)

don’t use if CrCl above 125 (125 is max that should be used in calculations)

26
Q

What are the toxicities of Oxaliplatin?

A

Bone marrow suppression, some nausea

-Unique peripheral neuropathy for a few days (worse at cold temperatures, winter, and cold drinks) !!! Counsel the patient !!!

-chronic use can cause irreversible peripheral neuropathy

IHOP (5 decks)

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