Exam 3: Lecture 1,2,3 Pharmacology of Cancer Drugs Flashcards
What is cancer?
Disease characterized by uncontrolled proliferation of abnormal cells.
Growth Characteristics of the malignant cell?
Genetic change
Uncontrolled proliferation
Invasiveness
Metastasis
G0 phase….
cell does not actively divide, doing whatever it does
How will cell go from G0 to G1?
gets signal
S phase…
Synthesis
G2 phase….
prepare for mitosis
M phase….
Mitosis occurs
1 cell differentiates to perform predetermined function
1 cell is able to divide if it gets stimulus
What makes cancer cells different?
2 new cells will retain ability to divide and they will proliferate without stimulus…leading to increase in cell mass
Classes of antineoplastic
Chemotherapy
Hormones
Targeted therapy
Classes of chemotherapy
Alkylating agents antibiotics Antimetabolites Natural products Miscellaneous agents
Classes of Targeted therapy?
Monoclonal antibodies
Tyrosine Kinase inhibitors
Many others
MOA Alkylators
positively charged ethylene ammonium ion binds to electron-rich nucleophilic sites on DNA
Causes:
intra/inter strand cross linking
DNA breaks
DNA mis-reading
Cell cycle non-specific, any phase
Cyclophosphamide (Cytoxan)
Absorption – 75% bioavailable PO
Distribution: crosses placenta, appears in milk. So no preg or nursing women.
Metabolism/elimination:
Hepatic activation to active and toxic metabolites
Renal elimination – T ½ 4 – 6 hours
Universal side effects fo chemo agents?
Myelosupppression
nausea and vomiting
alopecia
Cyclophosphamide (Cytoxan) adverse effects
Gonadal suppression
Hemorrhagic Cystitis ~15% pt
Cardiotoxicity
+ universal side effects
Myelosuppression
WBC will drop, hit nadir and then recover
recover occurs around 3rd week, which is why regimens are given every 3 weeks
Nadir is…
time of maximal bone marrow suppression
usually around day 8-10
cells affected by Myelosuppression…
WBC (Granulocyte disappear fastest, due to shortest life span) Platelet Erythrocyte (don't see much drop due to long life span)
make sure to draw someones blood before giving drug
Ifosfamide
sister drug for Cyclophosphamide
Ifosfamide Pharmacokinetics
Only given IV
Crosses placenta/milk
Hepatic activation to active and toxic metabolites
half life = 6 hrs
much slower activation than cyclophosphamide, dose higher
Ifosfamide Adverse effects
CNS toxicity, crosses BBB
Hemorragic cystitis much more common ~50%+
Hemorrhagic cystitis
Due to acrolein, which is toxic to bladder causing inflammation of bladder
Signs/Symptoms: Blood in urine pain when peeing urinary frequency Lower Abdominal Pain
Hemorrhagic cystitis prevention
lots of hydration, drink a lot of water
MESNA
MESNA
dimerized in urine, binds to acrolein and inactivates it so it cant effect bladder wall and prevent development of Hemorrhagic Cystitis