Anti-neoplastic drugs I Flashcards
1
Q
what are the general characteristics of all anti-cancer drugs?
A
- have low therapeutic index
- are highly toxic - block abnormal cell growth, causing destructive of: bone, skin GI tract, reproductive organs
- can be categorized based on
- cell cycle specificity: CCS vs CCNS
- drug designation: irritant vs vesicants
2
Q
cell cycle specific CCS vs CCNS anti-cancer drugs have what differing characteristics?
A
- CCS
- drugs target a specific phase of the cycle
- killing is TIME-DEPENDENT
- CCNS
- drugs target any stage of the cell cycle
- killng is DOSE DEPENDENT (these drugs bind DNA*)
3
Q
irritant vs vesicant anti-cancer drugs have what differing characteristics?
A
- irritants: cause damage inside the blood vessel
- vesicants: cause damage outside of the blood vessel → blister / necrosis
4
Q
anti-cancer antibiotics
- include what drug classes / drugs?
- all share what characteristics?
A
- includes
- anthracyclines: - rubicins: daunorubicin, doxorubicin, idarubicin, epirubicin
- non-anthracyclines: - mycins: bleomycin, mitomycin
- are all
- NCCS
- part of ABVD non-Hodgkin’s lymphoma regimen
5
Q
anthracyclines - MOA
A
= - rubicins
-
are antibiotic anti-cancer drugs:
- MOA: intercalate between DNA-bases & induces:
- double strand breaks (d/t Topo-2 inhibition)
- single strand breaks d/t superoxide ion release
- mitochondrial membrane damage
- are NSSC (bind DNA)
- are vesicants (cause extra-vascular damage)
- MOA: intercalate between DNA-bases & induces:
6
Q
anthracyclines - clinical uses
A
= - rubicins
- in general, used to tx solid tumors and hematological cancers. specifically:
- daunorubicin: leukemia - ALL & AML)
- doxorubicin: solid & nonsolid tumors - soft tissue sarcoma & bladder cancer
7
Q
anthracyclines -PK
A
- extensive hepatic metabolism -by CYP-2D6
- are p-glycoprotein substrates
8
Q
anthracyclines - AE
A
-rubins:
- irreversible cardiotoxicity - major
- extravasation - skin bruising / necrosis
- red colored urine & tears - harmless
9
Q
why do the anthracyclines cause cardiotoxicity?
A
-rubins:
- largely via Topo-2B inhibition, which causes double stranded DNA breaks in cardiac myocytes
- superoxide radicals & mitochondrial membrane damage also contribute to cardiotoxicity
10
Q
why do anthracyclines cause extravasation?
A
-rubins:
- because they are vesicants that cause extra-vascular damage that allows their escape to distant areas, causing bruising
11
Q
which of anthracyclines AE’s can be mitigated by “rescue” agent?
what is this agent?
how does it work?
A
-rubins
-
dexrazoxane - an iron chelating agent
- works by reducing super-oxide formation
- can be used as:
- an immediate antidote for extravasation
- preventative therapy for cardio-toxicity
12
Q
how do the anthracyclines differ in terms of AEs?
A
-rubicns:
can all cause: cardiotoxicity, extravasation, red tears and urine
- daunorubicin - highest cardiotoxicity risk
- can also cause bone marrow suppression*
- idarubicin / epirubicin - reduced cardiotoxicity risk relative to daunorubicin
- doxorubicin - ?
13
Q
anthracyclines - C/I
A
- severe myocardial insufficiency
- hepatic impairment
- drug induced myelosuppression
14
Q
daunorubicin
- what kind of drug?
- MOA?
- clinical indications?
- AE/CI?
A
-
is an anthracycline (an antibiotic anticancer drug, thus NCCS)
- MOA: intercalates with DNA
- indications: exclusively leukemia (ALL & AML)
- AEs: cardiotoxicity, extravasation, red urine & blood
- cardiotoxicity - severe
- also can cause myelosuppression
15
Q
doxorubicin
- what kind of drug?
- MOA?
- clinical indications?
- AE/CI?
A
-
is an anthracycline (an antibiotic anticancer drug, thus NCCS)
- MOA: intercalates with DNA
- indications: solid & non solid tumors:
- soft tissue sarcoma
- bladder cancer
- AEs: cardiotoxicity, extravasation, red urine & blood
