Alkylating Agents

Question 1

the 4 most commonly used Nitrogen mustards are

Answer 1

mechlorethamine
cyclophosphamide
melphalan
chlorambucil

Question 2

This drug is a rapidly acting nitrogen mustard administered IV to minimize local tissue irritation- must be prepared fresh

Answer 2

mechlorethamine

Question 3

what is the IV dose of mechlorethamine

Answer 3

0.4mg/kg

Question 4

once mechlorethamine is administered what happens to the drug

Answer 4

it undergoes rapid chemical transformation - it is only active for a few minutes

Question 5

what method can be used for mechlorethamine administration to prevent tissue toxicity

Answer 5

isolating blood supply to that tissue- to prevent tissue toxicity

Question 6

how is the action of mechlorethamine localized to a specific tissue

Answer 6

it is injected into the arterial blood supply to the desired tissue

Question 7

what is the clinical uses of mechlorethamine

Answer 7

hodgkin disease and less predictably in other lymphomas

Question 8

mechlorethamine is used in combination with what other three drugs called the MOPP regimen for the treatment of hodkins disease

Answer 8

vincristine
procarbazine
prednisone

Question 9

what are the major side effects of mechlorethamine

Answer 9

nausea
vomiting
myelosuppression

Question 10

what are the principle limitations on the amount of mechlorethamine given

Answer 10

leukopenia

thrombocytopenia

Question 11

what skin lesion is frequently associated with nitrogen mustard therapy

Answer 11

herpes zoster

Question 12

what conditions can mechlorethamine unmask?

Answer 12

latent viral infections

Question 13

what skin associations can occur with extraversion of mechlorethamine

Answer 13

several local tissue reactions such as brawny and tender indurations that may persist for prolonged periods of time

Question 14

explain the chain of events that cyclophosamide goes through after oral administration

Answer 14

cyclophosphamide is activated by the liver to -aldophosphamide- for transport to target tissues- aldophosphamide is converted to highly cytotoxic metabolites - phosphoramide and acrolein- then alkylate DNA

Question 15

what are the 4 clinical uses of cyclophosphamide

Answer 15

hodgkin disease
lymphosarcoma
burrito lymphoma
acute lymphoblastic leukemia of childhood

Question 16

cyclophosphamide is used in combination with what two other drugs after surgery for breast cancer

Answer 16

methotrexate

fluorouracil

Question 17

the potent immunosuppressive properties of cyclophosphamide make it useful for what two conditions

Answer 17

wegener granulomatosis

rheumatoid arthritis

Question 18

less than 1% of patients treated with cyclophosphamide have what 2 conditions

Answer 18

hypersensitivity reactions
and
fibrosing pneumonitis

Question 19

what 2 conditions are large doses of cyclophosphamide associated with

Answer 19

pericarditis
and
pericardial effusions (can progress to cardiac tamponade)

Question 20

what condition may not occur for as long as 2 weeks after the last dose of cyclophosphamide

Answer 20

hemorrhagic myocarditis with symptoms of CHF

Question 21

what are the indications to discontinue cyclophosphamide

Answer 21

dysuria and hematuria

Question 22

doses greater than 50mg/kg of cyclophosphamide is associated with what occurance

Answer 22

inappropriate secretion of arginine vasopressin hormones

Question 23

water intoxication with cyclophosphamide is compounded by what two situations

Answer 23

avoidance of hematuria-hydration

and inappropriate secretion of vasopressin hormones

Question 24

if cyclophosphamide is extravated what will occur

Answer 24

nothing- no thrombophlebitis

Question 25

melphalan is what type of derivative of nitrogen mustard

Answer 25

phenylalanine derivative of nitrogen mustard

Question 26

what are NOT common side effects of melphalan

Answer 26

nausea vomiting alopecia no changes of renal or hepatic

Question 27

what side effect of melphalan is possible

Answer 27

bone marrow suppression | pulmonary fibrosis

Question 28

what is the slowest acting nitrogen mustard in clinical use

Answer 28

chlorambucil

Question 29

chlorambucil is what type of derivative of mechlorethamine

Answer 29

aromatic!

Question 30

what is chlorambucil used in the treatment of

Answer 30

chronic lymphocytic leukemia and in primary waldenstrom macroglobulinemia

Question 31

when chlorambucil is used for polycythemia what is seen

Answer 31

increased incidence of leukemia and other tumors

Question 32

chlorambucil has CNS stimulation with large doses T/F

Answer 32

True

Question 33

side effects of chlorambucil

Answer 33

``` myelosuppression -reversible nausea vomiting pulmonary fibrosis hepatotoxicity-rarly ```

Question 34

busulfan produces remission in up to 90% of patients with "This"

Answer 34

chronic myelogenous leukemia

Question 35

this drug is a cell cycle nonspecific alkylating antienoplastic agent

Answer 35

busulfan

Question 36

busulfan has no value in the treatment of

Answer 36

acute leukemia

Question 37

4% of these patients experience -_____with busulfan

Answer 37

progressive pulmonary fibrosis

Question 38

what enhances the toxicity of busulfan

Answer 38

enhanced toxicity with administration of oxygen

Question 39

what are the two important side effects of busulfan

Answer 39

myelosuppression and thrombocytopenia

Question 40

why do we give allopurinol to busulfan

Answer 40

hyperuricemia

Question 41

explain the mechanism why nitrosoureas are good for the treatment of meningeal leukemias and brain tumors

Answer 41

their high lipid solubility results in passage across the blood brain barrier.

Question 42

what the exception of streptozocin what limits the clinical use of nitrosoureas

Answer 42

limited by profound drug induced myelosuppression

Question 43

what nitrosurea has the widest clinical use

Answer 43

carmustine

Question 44

what does carmustine inhibit the synthesis of

Answer 44

both RNA and DNA

Question 45

side effects of carmustine

Answer 45

interstitial pneumonitis and fibrosis (much like bleomycin)

Question 46

what is the delayed (6 weeks) side effect of carmustine

Answer 46

leukopenia and thrombocytopenia

Question 47

what nitrosurea is more effective than carmustine in the treatment of hodgkins disease

Answer 47

lomustine

Question 48

what is lomustine methylated analogue

Answer 48

semustine

Question 49

streptozocin has a unique affinity for ...

Answer 49

beta cells of the islets of langerhans

Question 50

since streptozocin has unique affinity for B cells of the islets of langerhans it has proven useful in the treatment of

Answer 50

human pancreatic islet cell carcinoma and malignant carcinoid

Question 51

what is the prototypical alkylating agents

Answer 51

mitomycin

Question 52

what is a side effect of streptozocin

Answer 52

hyperglycemia | mylesuppression - not occcur

Question 53

what is the prominent side effect of mitomyocin

Answer 53

myelosuppression characterized by severe leukopenia and thrombocytopenia

Question 54

what else can mitomyocin side effect in 3-12% of patients

Answer 54

pulmonary fibrosis- limit exposure to hyperoxia.

Question 55

what is a rare, but well recognized side effect of mitomycin

Answer 55

glomerular damage resulting in renal failure

Question 56

mitomycin is used for the palliative treatment of gastric adenocarcinoma with what two other medications

Answer 56

fluorouracil and doxorubicin