EXAM 2

Question 1

What is the dose limiting factor for many chemotherapeutic drugs?

Answer 1

Myelosuppression

Question 2

What is the enzyme that regulates the overwinding or underwinding of DNA during replication and are the target for many chemotherapeutic drugs?

Answer 2

Topoisomerases

Question 3

When do most conventional chemotherapeutic drugs exert their antineoplastic effects on cells?

Answer 3

cells that are actively dividing (mitosis) or undergoing DNA synthesis

Question 4

What class of chemotherapeutic drugs are relatively non-phase specific (optimal to kill cancer cells during certain phases of the cell cycle)

Answer 4

alkylating agents

Question 5

Chemo drugs are most effective against what kind of cell proliferation?

Answer 5

rapidly dividing, thus any rapidly dividing cells cancerous or not will be more susceptible to the toxic effects of chemo.

Thus slow growing malignancies or cells are unresponsive or at best partially responsive to conventional chemotherapy

Question 6

hypoxia of some tumor’s causes resistance to both radiation and most chemo drugs with the exception of?

Answer 6

malignancies susceptible to treatment with the mitomycins

Question 7

Therapeutic index of chemo agents?

Answer 7

less than 1

Question 8

N/V with chemo agents is due to what two things?

Answer 8

GI effects

activation of the CTZ in the CNS

Question 9

The development of what drugs have facilitated the tolerance of emetogenic chemo agents?

Answer 9

serotonin antagonists (ZOFRAN) in additon to combination antiemetics regimens

Question 10

What two chemo drug classes are mentioned in the book that damage DNA are associated with secondary malignancies.

Answer 10

alkylating

topoisomerases

Question 11

MOA of alkylating agents?

Answer 11

Impair cell function by forming covalent alkyl bonds with nucleic acid bases resulting in intrastrand or interstrand DNA cross-links which are toxic to cells undergoing division.

Question 12

most important dose-limiting factor in the clinical use of alkylating drugs especially busulfan?

Answer 12

Bone marrow suppression

Question 13

Does Bleomycin cause myelosuppression?

Answer 13

mild

Question 14

Alkylating drugs include what sub classes of chemo agents?

Answer 14

nitrogen mustards
alkyl sulfonates
nitrosoureas
triazenes

Question 15

Why are alkylating agents more likely to kill malignant cells than nonmalignant cells?

Answer 15

malignant cells have higher a rate of proliferation, thus the alkylating agent targets the cells in the phase that is dividing more.

Question 16

Side effects with alkylating agents?

Answer 16

GI: mitotic arrest, cellular hypertrophy and desquamation of the epithelium.

Increased skin pigmentation is frequent

Powerful CNS stimulants manifesting as N/V.

Skeletal muscle weakness and seizures.

Pneumonitis and Pulmonary fibrosis.

Inhibition of plasma cholinesterase activity may be present up to 2-3 weeks after administration of chemo regimens.

Question 17

Rapid drug induced destruction of malignant cells can produce increased purine and pyrimidine breakdown leading to uric acid-induced nephropathy. To minimize the likelihood of this complication you can do what three things?

Answer 17

adequate fluid intake

alkalization of the urine

administration of allopurinol (be established before drug treatment)

Question 18

What chemo agent allows latent viral infections to unmask?

Answer 18

Nitrogen mustards specifically mechlorethamine

Question 19

One of the most frequently used chemo drugs that is great for oral use?

Answer 19

Cyclophosphamide which is a nitrogen mustard

Question 20

Your patient finished their chemo medication 2 weeks ago but can not remember the name of it, she has hemorrhagic myocarditis with symptoms of CHF, what drug did she likely just finish?

Answer 20

cyclophosphamide

Question 21

cyclophosphamide has less sig. degrees of WHAT and more WHAT?

Answer 21

Less thrombocytopenia and more alopecia

Question 22

development of fibrosing pneumonitis months to years after initiation of the chemo agent?

Answer 22

Cyclophosphamide (less than 1%)

Question 23

indications to discontinue cyclophosphamide?

Answer 23

dysuria and hematuria

Question 24

Inappropriate secretion of arginine vasopressin hormone seen in patient with doses given of greater than what with cyclophosphamide?

Answer 24

greater than 50mg/kg

Question 25

you have a patient taking cyclophosphamide and in an attempt to make hemorrhagic cystitis less likely they are being hydrated well. Why is this sometimes a problem?

Answer 25

adequate fluid intake coupled with the inappropriate secretion of arginine vasopressin (typically doses greater than 50mg/kg of cycloph.) makes for water intoxication.

Question 26

Nitrogen mustard that is powerful vesicant?

Answer 26

Mechlorethamine

Question 27

name a nitrogen mustard that does not produce alopecia, N/V is NOT likely, not a vesicant, and significant bone marrow depression is needed to achieve optimal therapeutic effects?

Answer 27

Melphalan

Question 28

Slowest acting nitrogen mustard in use, also used for the treatment of polycythemia vera?

Answer 28

Chlorambucil

Question 29

What class of alkylating agents does Busulfan belong to?

Answer 29

alkyl sulfonates

Question 30

Mephalan does not commonly cause what common side effect?

Answer 30

N/V

Question 31

This drug produces remission in up to 90% of patients with Chronic myelogenous leukemia but does not treat acute leukemia?

Answer 31

Busulfan

Question 32

Produces progressive pulmonary fibrosis in up to 4% of patients. Prognosis after appearance of clinical symptoms is poor with a median survival rate of 5 months, what drug am I?

Answer 32

Busulfan

Question 33

Why would you take allopurinol with Busulfan?

Answer 33

to minimize renal complications

Question 34

Nitrosoureas that does NOT produce myelosuppression (to a limiting factor at least)

Answer 34

STREPTOZOCIN

Question 35

If you were just started on a tricyclic then exaggerated pressor responses should be anticipated with direct or indirect sympathomimetics?

Answer 35

both

Question 36

if you were just started on a tricyclic pressor responses may be more pronounced with what type of hypotension medication?

Answer 36

indirect acting such a ephedrine.

Question 37

What is the recommended way to dose direct acting sympathomimetics if someone was just started on a tricyclic?

Answer 37

to titrate to the desired hemodynamic goal since they have more of an exaggerated response to sympathomimetics.

Question 38

If someone has been on tricyclics chronically what time period is that?

Answer 38

greater than 6 weeks

Question 39

How should you administer an initial dose of sympathomimetics to someone who has been on tricyclics chronically?

Answer 39

it would be prudent to cut the initial dose by 1/3

Question 40

Why might conventional sympathomimetics not be effective in treating hypotension in a patient chronically treated with tricyclic medications? (2 possibilities)

Answer 40

adrenergic receptors are either desensitized or catecholamine stores are depleted.

Question 41

If a patient is not responding to conventional sympathomimetics who is chronically treated with tricyclics (neo or ephedrine) then what would you give them that would most likely be effective?

Answer 41

norepinephrine may be the only effective management for hypotension.

Question 42

Treating someone with anticholinergics who also takes tricyclics can cause postoperative delirium and confusion, what medication would you give them that theoretically would be LESS likely to evoke that type of response?

Answer 42

glycopyrrolate would be less likely to evoke said response.

I assume this is in comparison to using scopolamine since it crosses the BBB

Question 43

If chronically on tricyclic meds, you will typically have a tolerance to WHAT and not a tolerance to WHAT?

Answer 43

Tolerance to the anticholinergic effects and orthostatic hypotension typically develops.
Tolerance to desirable effects often fails to develop.

(that sounds good, but it does not come in handy when you abruptly d/c the medication for whatever reason, should titrate if you can)

Question 44

How long does the comatose phase of tricyclic overdose last? How long after that phase is their a risk for life threatening cardiac dysrhythmias?

Answer 44

24-72 hours

10 days for dysrhythmias thus ECG monitoring is needed for this time.

Question 45

If a patient overdosed on tricyclics and has a seizure what should you treat it with and why?

Answer 45

benzodiazepine (diazepam) right away because it may precede cardiac arrest.

After initial seizure is under control you may need to use a longer acting anti seizure medication like phenytoin.

Question 46

If a patient who overdosed on Tricyclics had a seizure why would you then give them bicarb and/or hyperventilate them?

Answer 46

acidosis is associated with seizures, and acidosis my abruptly increase the unbound fraction of tricyclic meds in circulation and predispose to cardiac dysrhythmias. Thus alkalization of the plasma can temporarily reverse drug induced cardiotoxicity.