EXAM 2 Flashcards
What is the dose limiting factor for many chemotherapeutic drugs?
Myelosuppression
What is the enzyme that regulates the overwinding or underwinding of DNA during replication and are the target for many chemotherapeutic drugs?
Topoisomerases
When do most conventional chemotherapeutic drugs exert their antineoplastic effects on cells?
cells that are actively dividing (mitosis) or undergoing DNA synthesis
What class of chemotherapeutic drugs are relatively non-phase specific (optimal to kill cancer cells during certain phases of the cell cycle)
alkylating agents
Chemo drugs are most effective against what kind of cell proliferation?
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
hypoxia of some tumor’s causes resistance to both radiation and most chemo drugs with the exception of?
malignancies susceptible to treatment with the mitomycins
Therapeutic index of chemo agents?
less than 1
N/V with chemo agents is due to what two things?
GI effects
activation of the CTZ in the CNS
The development of what drugs have facilitated the tolerance of emetogenic chemo agents?
serotonin antagonists (ZOFRAN) in additon to combination antiemetics regimens
What two chemo drug classes are mentioned in the book that damage DNA are associated with secondary malignancies.
alkylating
topoisomerases
MOA of alkylating agents?
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.
most important dose-limiting factor in the clinical use of alkylating drugs especially busulfan?
Bone marrow suppression
Does Bleomycin cause myelosuppression?
mild
Alkylating drugs include what sub classes of chemo agents?
nitrogen mustards
alkyl sulfonates
nitrosoureas
triazenes
Why are alkylating agents more likely to kill malignant cells than nonmalignant cells?
malignant cells have higher a rate of proliferation, thus the alkylating agent targets the cells in the phase that is dividing more.
Side effects with alkylating agents?
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.
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?
adequate fluid intake
alkalization of the urine
administration of allopurinol (be established before drug treatment)
What chemo agent allows latent viral infections to unmask?
Nitrogen mustards specifically mechlorethamine
One of the most frequently used chemo drugs that is great for oral use?
Cyclophosphamide which is a nitrogen mustard
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?
cyclophosphamide
cyclophosphamide has less sig. degrees of WHAT and more WHAT?
Less thrombocytopenia and more alopecia
development of fibrosing pneumonitis months to years after initiation of the chemo agent?
Cyclophosphamide (less than 1%)
indications to discontinue cyclophosphamide?
dysuria and hematuria
Inappropriate secretion of arginine vasopressin hormone seen in patient with doses given of greater than what with cyclophosphamide?
greater than 50mg/kg
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?
adequate fluid intake coupled with the inappropriate secretion of arginine vasopressin (typically doses greater than 50mg/kg of cycloph.) makes for water intoxication.
Nitrogen mustard that is powerful vesicant?
Mechlorethamine
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?
Melphalan
Slowest acting nitrogen mustard in use, also used for the treatment of polycythemia vera?
Chlorambucil
What class of alkylating agents does Busulfan belong to?
alkyl sulfonates
Mephalan does not commonly cause what common side effect?
N/V
This drug produces remission in up to 90% of patients with Chronic myelogenous leukemia but does not treat acute leukemia?
Busulfan
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?
Busulfan
Why would you take allopurinol with Busulfan?
to minimize renal complications
Nitrosoureas that does NOT produce myelosuppression (to a limiting factor at least)
STREPTOZOCIN
If you were just started on a tricyclic then exaggerated pressor responses should be anticipated with direct or indirect sympathomimetics?
both
if you were just started on a tricyclic pressor responses may be more pronounced with what type of hypotension medication?
indirect acting such a ephedrine.
What is the recommended way to dose direct acting sympathomimetics if someone was just started on a tricyclic?
to titrate to the desired hemodynamic goal since they have more of an exaggerated response to sympathomimetics.
If someone has been on tricyclics chronically what time period is that?
greater than 6 weeks
How should you administer an initial dose of sympathomimetics to someone who has been on tricyclics chronically?
it would be prudent to cut the initial dose by 1/3
Why might conventional sympathomimetics not be effective in treating hypotension in a patient chronically treated with tricyclic medications? (2 possibilities)
adrenergic receptors are either desensitized or catecholamine stores are depleted.
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?
norepinephrine may be the only effective management for hypotension.
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?
glycopyrrolate would be less likely to evoke said response.
I assume this is in comparison to using scopolamine since it crosses the BBB
If chronically on tricyclic meds, you will typically have a tolerance to WHAT and not a tolerance to WHAT?
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)
How long does the comatose phase of tricyclic overdose last? How long after that phase is their a risk for life threatening cardiac dysrhythmias?
24-72 hours
10 days for dysrhythmias thus ECG monitoring is needed for this time.
If a patient overdosed on tricyclics and has a seizure what should you treat it with and why?
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.
If a patient who overdosed on Tricyclics had a seizure why would you then give them bicarb and/or hyperventilate them?
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.
