Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

BCOP > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

Anthracyclines MOA -4

A

nonspecific: Inhibits topoisomerase II.

prevents the religation of DNA during DNA replication causing DNA strand breaks.

Intercalations between base pairs in the DNA -> more breaks.

Form oxygen free radicals->inc cytotoxicity. (except mitoxantrone, so less cardiomyopathy)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Anthracylines DLTs -2

A

myelosuppression (primarily leukopenia),

chronic cardiomyopathies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Anthracylines ADRs -4

A

Dose dependent nausea and vomiting,

alopecia,

radiation recall,

turns urine red (except mitoxantrone turns urine blue)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Anthracylines DAs -4

A

Hepatic.

50% dec if bili 1.2-3.0

75% dec if bili > 3.0

generally omitted if bilirubin > 5.0 mg/dL.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Anthracylines administration issues. How do you manage? -3

A

potent vesicants.

Apply cold ice pack and evaluate for antidote use

(99% DMSO 1-2 ml applied to site every 6 hours for 7-14 days) or Totect®.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Etoposide MOA -4

A

G2 specific:

Forms a complex with topoisomerase II

  • > inhibits enzyme
  • > single stranded DNA breaks
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Etoposide DLTs -1

A

myelosuppression- primarily leukopenia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Etoposide ADRs -2

A

nausea and vomiting (with oral dosing),

alopecia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Etoposide Administration Issues -3

A

IV infusion should be infused over 30-60 minutes to avoid hypotension.

Oral dose is 2x greater than the IV.

conc <0.4mg/ml (stability)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Camptothecins MOA -4

A

synthesis cycle specific:

Inhibit topo I

  • > “cleavable complexes” stabilized
  • > reversible single stranded DNA breaks
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Camptothecins DLTs -topo -2 irino -1

A

leukopenia and thrombocytopenia (topotecan);

diarrhea (irinotecan)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Camptothecins ADRs -4

A

neutropenia,

nausea, vomiting, diarrhea

alopecia,

increased liver enzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Irinotecan Diarrhea Concepts -4

A

SN-38 active metabolite broken down by UGT1a1.

Both early and late.

Treat early with anticholinergics (atropine) (cholinergic syndrome resulting from the inhibition of acetylcholinesterase activity by irinotecan).

Treat late with loperamide.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Vinca Alkaloids MOA -3

A

M phase specific:

Bind to Tubulin,

inhibits polymerization and thus Microtubule formation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Vinca Alkaloids DLTs -4

A

leukopenia and thrombocytopenia (vinblastine and vinorelbine),

neurologic toxicity,

constipation,

paralytic ileus (vincristine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Vinca Alkaloids ADRs

A

Neurologic toxicity,

constipation,

abdominal cramps (much less than vincristine)

vincristine ONLY -rare bone marrow suppression and SIADH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Vinca Alkaloids DAs -4

A

Hepatic.

50% dec if bili 1.5-3.0

75% dec if bili > 3.0

generally omitted if bilirubin > 5.0 mg/dL.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Vinca Alkaloids administration issues. How do you manage? -2

A

potent vesicants

#apply warm pack and administer
hyaluronidase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

M phase specific (3pts)

A

drugs that work in mitosis (vincas, taxanes, ixabepilone)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

S phase specific (2pts)

A

DNA synthesis (antimetabolites and tecan’s)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

G2 phase specific (2pts)

A

after mitosis, before synthesis (bleomycin, etoposide)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

G1 phase specific (2pts)

A

after synthesis, before mitosis (steroids, asparaginase)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

nonspecific cell cycle agents

A

cell kill proportional to dose (kill both nml and malignant cells to the same extent)

everything else (alkylating agents, anthracyclines, antitumor antibiotics, nitrosureas, misc)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

cell phase/cycle specific agents -2

A

preferentially kill proliferating cells

admin as “continuous infusion”

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

targeted therapy agents -3

A

effect on specific “tumor cells”

prevent from entering cell cycle

target signals that trigger cell growth, metastasis, and immortality

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

alkylating agent DLT -1

A

myelosuppression (usually neutropenia)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

mechlorethamine administration issues -2

A

potent vesicant.

extravasation= 4mL 10% sodium thiosulfate + 6mL sterile water for injection inject SQ around site

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

what is the cyclophos ADR that you always forget?

A

SIADH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

bendamustine renal dosing

A

DO NOT USE if CrCl <40

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

thiotepa and excretion in sweat -3

A

for high dose BMT doses:

bath 3-4 times daily

no tight clothes, to prevent skin breakdown

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

dacarbazine unique ADRs -3

A

inc LFTs

flu-like sx

injection site pain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

platinum MOA

A

form a reactive electrophile that covalently binds to DNA (alkylating-like)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

crcl calculation

A

((140-age) x wt in kg) / (SCr x 72) (x0.85 for females)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

cisplatin DLT -1

A

N/V (acute and delayed)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

carboplatin DLT -1

A

myelosuppression (thrombocytopenia)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

platinum ADR -6

A

nephrotox,

hypomag,

hypoK,

ototox,

peripheral neuropathies,

myelosuppression

carbo=less of all but myelos
oxal=minimal nephrot, otot

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

oxaliplatin and peripheral neuropathy -3

A

cummulative…“stop and go”

acute= 1st 2 days, resolves within 14d, primarily peripheral sx, often exacerbated by cold

persistent= >14d, daily activities effected (writing, buttoning, swallowing), sx may improve on drug d/c

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

taxane MOA -3

A

M phase specific:

Bind to micotubules, Stabilizes polymerization, prevents Microtubule to Tubulin breakdown;

(niche for cabazitaxel is poor affinity for p-gp->?less drug resistance, activity in D resistant cells)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

taxane DLT -1

A

leukopenia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

taxane ADR -6

WHAT IS INF RX DIFFERENCE?

A

hypersensitivity rxn (P, premed (rare for D)),

allopecia,

cardiac tox (P),

PN,

mucositis (P),

peripheral edema (D, pre and post med)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

taxane administration issues -4

A

P cremophor hypersensitivity rxn- premed dex 20, diphen 50, ranit 50 iv

administer prior to platinums to reduce myelosuppression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

nab-albumin paclitaxel administration issues -1

A

does not contain cremophor->less hypersensitivity reactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

taxane DAs -3

A

hepatic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

epothilones (ie. ixabepilone) MOA -3

A

M phase specific.

similar to taxanes but distinct microtubule binding. activity in paclitaxel-resistant cell lines.

poor p-gp substrates->?overcome resistance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

epothilones (ie. ixabepilone) DLT -2

A

leukopenia

PN

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

epothilones (ie. ixabepilone) ADR -6

A

anemia,

thrombocytop,

diarrhea,

fatigue,

myalgia,

alopecia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

epothilones (ie. ixabepilone) admin issues -1

A

premed with diphen 50, ranit iv 50 (or cimet iv 300)

no steroid needed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

miscellaneous tubulin agent (ie eribulin) MOA -2

A

marine macrolide halichondrin B, synthetic,

inhibits tubulin polymerization

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

miscellaneous tubulin agent (ie eribulin) ADR -2

A

neutropenia,

neuropathy (less than vincristine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

miscellaneous tubulin agent (ie eribulin) DA -2

A

both renal and hepatic dose adjustments

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

antimetabolite general MOA (4pts)

A

1 compete for binding sites on enzymes

S phase specific:

inhibit cell growth and proliferation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

folate antagonist (methotrexate and pemetrexed) MOA -3

A

S phase specific:

inh conversion of FA to tetrahydrofolate by inh enzyme dihydrofolate reductase

-> blocks thymidylate and purine synthesis which inhibits DNA synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

folate antagonist (methotrexate and pemetrexed) DLT -2

A

leukopenia

thrombocytopenia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

folate antagonist (methotrexate and pemetrexed) ADR -5

A

watch third spacing

renal tubular necrosis (high doses),

pulmonary pneumonitis,

alopecia,

stomatitis, mucositis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

leucovorin rescue -4

A

initiate with 42 hours

MOA: reduced folate, enters cell by passive diffusion thus high doses needed

po bioavailability good <35mg, above that ranges 5-50%

t 1/2=3hr

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

pemetrexed premeds -3

A

folic acid and vitamin b12

reduce myelosuppression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

methotrexate DDI (3pts)

A

1 highly protein bound drugs may displace MTX from albumin and inc tox (ie. sulfonamides, salicylates, phenytoin, tetracycline)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

purine analogue thioguanine (6-TG) and mercaptopurine (6-MP) MOA -2

A

S cycle specific.

structural analogues of guanine that are incorporated into DNA.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

thioguanine (6-TG) and mercaptopurine (6-MP) DLT -2

A

leukopenia and thrombocytopenia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

thioguanine (6-TG) and mercaptopurine (6-MP) ADRs -4

A

liver tox and jaundice (much higher with 6-MP),

stomatitis, mucositis,

rash,

N/V

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

mercaptopurine (6-MP) DDI -2

A

metabolized by xanthine oxidase.

75% dose reduction with allopurinol.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

other purine analogues names (3pts) and ADR

A

cladribine, fludarabine, pentostatin

unique myelosuppression of t-helper cells->often requires abx px

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

pyrimidine analogues names (2pts) and MOA -4

A

S cycle specific.

cytarabine and gemcitabine.

structural analogues of nucleosides cytidine and deoxycytidine.

inhibit DNA polymerase.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

pyrimidine analogues DLT -2

A

leukopenia and thrombocytopenia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

pyrimidine analogues ADR -9

A

for high dose araC: excess BM depression, CNS tox, conjunctivitis (steroid eye gtts)

N/V,

mucositis,

diarrhea,

flu-like sx,

rash,

TLS (often give with allopurinol)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

“false” pyrimidine analogues names (2pts) and MOA -5

A

1inhibit formation of base thymidine by inhibiting enzyme thymidylate synthase (rate limiting step).

S cycle specific.

5-FU and capecitabine.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

“false” pyrimidine analogues DLT -5

A

5-FU: leukopenia and thrombocytopenia.

anemia (bolus inf),

HFS and diarrhea (continuous inf)

cape: HFS,

diarrhea

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

“false” pyrimidine analogues ADR -7 (3+4)

A

5-FU: skin discoloration,

nail changes,

photosensitivity,

neurologic tox

cape: N/V,

fatigue,

rash

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

hypomethylating pyrimidine analogues names (2pts) and MOA. -5

A

S cycle specific.

azacytidine and decitabine.

direct incorporation into DNA, inhibit DNA methyltransferase.

hypomethylation of DNA->cell differentiation and apoptosis.

ALSO covalent bonds of drug-DNA methyltrasferase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

hypomethylating pyrimidine analogues DLT -1

A

myelosuppression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

hypomethylating pyrimidine analogues ADR -2

A

mild GI tox

infx’s

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

bleomycin MOA -2

A

binds to DNA producing single and double stranded DNA breaks through the generation of free radicals

indx: testicular, hodgkins, NHL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

bleomycin DLT -1

A

fatal lung disease

MAX DOSE is 400 units!!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

bleomycin ADR

A

hyperpigmentation,

rashes,

fever,

rare allergic rxns

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

omacetaxine MOA -3

A

inhibits protein translation preventing the initial elongation step of protein synthesis.

protein synthesis and tumor growth inhibited independent of BCR-ABL binding (can use in T315I mutation)

indx: resistant CML

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

omacetaxine ADR -10

A

thrombocytopenia,

inc risk of hemorrhage,

anemia, neutropenia, lymphop

diarrhea, N,

fatigue,

asthenia, 
inj site rxn,
 pyrexia,
 infx,
hyperglycemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

antiestrogens - tamoxifen MOA -2

A

inhibits nuclear binding of estrogen to estrogen receptor.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

antiestrogens - tamoxifen ADR -8

A

menopausal sx (hot flashes, N/V),

vaginal bleeding,

bone pain,

menstrual irregularities,

HA,

depression.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

antiestrogens - nonspecific aromatase inhibitor name (1pt) and MOA -4

A

aminoglutethimide:

“medical adrenalectomy”,

inhibits cholesterol->pregnenolone conversion.

inhibits production of estradiol BUT ALSO glucocorticoids, mineralcorticoids, and androgens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

antiestrogens - nonspecific aromatase inhibitor ADRs -5

A

neuro - lethargy, nystagmus, dizziness

N/V,

leukopenia, thrombocytop

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

antiestrogens - nonsteroidal aromatase inhibitor name (3pts) and MOA -3

A

anastrazole, letrazole, and exemstane

selective inhibition that block both testosterone-> estradiol AND androstenedione->estrone conversion.

DO NOT BLOCK gluco-,mineralo-corticoids or androgen formation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

antiestrogens - nonsteroidal aromatase inhibitor ADR -5

A

GI disturbances,

hot flashes,

thromboembolic events,

wt gain,

edema

83
Q

luteinizing hormone-releasing hormone analogs (2pts) names and MOA -8

A

goserelin and leuprolide

competitive binding to hypothalamus receptor

  • > initial surge in FSH and LH
  • > stimulate adrenal gland, testes, ovaries
  • > surge in E and T production which stimulate down regulation of receptor via negative feedback loop
  • > decrease in further LH
  • > decrease in androgen AND estrogen production.

T reduced ~75% by day 14, then ~100% by day 28

84
Q

luteinizing hormone-releasing hormone analogs and antagonists=GnRH antagonist ADR (7pts)

A 
hot flashes, 
impotence, 
reduced libido, 
GI disturbances (N/V/ constipation), 
injection site pain, 
gynecomastia, 
peripheral edema
#tumor flare: from initial T increase->bone pain (treat with antiandrogens prior to Tx OR use degarelix)
85
Q

luteinizing hormone-releasing hormone antagonists = gonadotropin releasing hormone antagonist (1pt) names and MOA. -6

A

NO tumor flare.

Degarelix

blocks GnRH receptors in anterior pituitary

  • > decrease FSH and LH release
  • > decrease in androgen and estrogen production

T reduced ~90% in 24hours

86
Q

antiandrogens name (3pts) and MOA and use -3

A

flutamide 250tid, bicalutamide 50qd, nilutamide 300qd x1mo,150qd

nonsteroidal, competitively Inh binding of androgens (T) to peripheral R,

use in combo with LHRH analogs

87
Q

antiandrogen ADR (7pts)

A

gynecomastia,

hot flashes,

inc LFTs,

N/V,

diarrhea,

visual disturbances

88
Q

abiaterone MOA -4

A

selective, irreversible Inh of CYP17.

blocks pregnenolone and progesterone

-> androgens DHEA and androstenedione (these are further converted to T and DHT downstream.

DO NOT significantly affect hydrocortisone levels

89
Q

abiaterone administration -3

A

250mgx4 daily = 1000mg WITH pred 5bid

1hr before or 2hr after meals

90
Q

abiaterone DA’S -2

A

child-pugh class B= reduce to 250qd

if hepatoxic develops, ALT/AST >5x ULN or billi >3x HOLD and reduce dose

91
Q

abiaterone ADR -15

Know serious adr

A 
joint swelling of discomfort, 
hypoK,
 edema, 
muscle discomfort, 
hot flush,
 diarrhea, 
UTI, 
cough,
 htn,
 arrythmia,
 urinary frequency, 
nocturia,
 dyspepsia,
 URI
SERIOUS: CHF, arrhythmias, liver tox, adrenal insuff
92
Q

abiaterone DDI

A

CYP2D6 Inh

CYP3A4 substrate

93
Q

misc hormonal agents - enzalutamide MOA -3

A

Inh nuclear translocation of the androgen R, DNA binding, and coactivator recruitment.

greater affinity for receptor.

No known agonistic effects.

94
Q

misc hormonal agents - enzalutamide ADR -13

A 
asthenia,
 diarrhea, 
arthralgia,
 muscle pain,
 hot flashes,
 peripheral edema, 
infx, 
HA, 
dizziness, 
spinal cord compression,
 hematuria,
 htn
RARE: seizure
95
Q

misc hormonal agents - enzalutamide DDI -2

A

CYP3A4, 2C9, 2C19 inducer (warfarin)

CYP3A4, 2C8 substrate

96
Q

misc hormonal agents - estramustine MOA

A

thought was alkylating agent linked to estradiol BUT seems to work via Inh of microtubule assembly and disassembly.

give 1hr before or 2hr after food

97
Q

misc hormonal agents - estramustine ADR (6pts)

A 
N/V, 
edema,
 CV tox,
 thromboembolic events,
 gynecomastia
98
Q

monoclonal Ab MOA (4pts)

A

antibody dependent cellular cytotoxicity (ADCC)
CDCC - complement dependent
??

99
Q
  • zumab
  • ximab
  • umab
  • momab
A 
zumab= humanized
ximab= chimeric
umab= human
momab= murine
100
Q

alemtuzumab MOA and indx -3

A

CD52 on malignant lymphocytes (binding induces cell lysis)

#CD52 also on nml lymphocytes, monocytes, NK cells, some 
granulocytes, some nml bone marrow cells
101
Q

alemtuzumab administration -3

A

3mg, then 10mg, then 30mg as tolerated

102
Q

alemtuzumab ADR -3

A

serious, prolonged, sometimes fatal heme tox (avg neutropenia duration 28d, thrombocyto 21d),

infusion related rigors,

hypotension

103
Q

brentuximab vedotin MOA -2 and indx -3

A

CD30 antibody linked to monomethylauristatin (MMAE) which Inh microtubule polymerization

104
Q

brentuximab vedotin ADR. -15

A 
neutrop,
 PN, 
fatigue, 
N, 
anemia, 
URI, 
diarrhea, 
pyrexia, 
rash, 
thrombocytop, 
cough, 
V

SERIOUS: progressive multifocal leukoencephalopathy (PML), TLS, steven’s johnson

105
Q

brentuximab vedotin dose and administration issues -2

A

1.8mg/kg q3wk up to 16c

premed for infusion rxns

106
Q

rituximab MOA. -3

A

CD20 binding and apoptosis

107
Q

rituximab ADR -5

A 
infusion rxns (fever, chills/rigors, hypot, N) (premed), 
TLS, 
mucocutaneous rxns,
 hepatitis B reactivation, 
PML
108
Q

ofatumumab MOA -3 and indx -1

A

ADCC

109
Q

ofatumumab dose and administration issues -4

A

300mg D1, 2000mg D8 weekly x7, then 4 wks later 2000mg q4wk x4 doses

110
Q

ofatumumab ADR -6

A 
infusion rxns (fever, chills/rigors, hypoT, N), 
neutrop, 
thrombocytop, 
bacterial or fungal infx, 
hepatitis b reactivation, 
PML
111
Q

ibritumomab tiuxetan MOA -3 indx -1

A

CD20.

chelate tiuxetan binds to In-111 and Y-90.

beta emission from Y-90 induces cellular damage by formation of free radicals.

CLL

112
Q

ibritumomab tiuxetan dosing and DA -4

A

step 1- ritux 250

step 2- 7-9d later, 2nd ritux 250 prior to 0.4mCi/kg Y-90 irbitumomab

REDUCE to 0.3 if plt 100-149k

HOLD if plt <100k

113
Q

ibritumomab tiuxetan ADR -2

A

thrombocytop (61%),

neutrop

114
Q

tositumomab MOA -4 indx -1

A

ritux refractory FL

CD20 antibody LINKED to I-131

gamma XRT->imaging purposes

beta XRT->cytotoxic

115
Q

tositumomab ADR -4

A

hypersensitivity rxn (anaphylaxis),

prolonged and severe neutrop and thrombocytop (nadir 4-7wks, 30d duration),

preg category X (I-131 can damage fetal thyroid tissue),

secondary malignancies (8%)(MDS, AML)

116
Q

tositumomab administration issues -2

A

premed APAP, diphen

thyro-protective regimen at least one day prior to tx

117
Q

ipilimumab MOA -3

A

may also antagonize CTLA-4 on regulatory T cells to limit their ability to suppress the antitumor T cell effector response

CTL4, a negative regulator of T cell function

-> Inc T-cell stimulation and antitumor reaction

118
Q

ipilimumab dose -1

A

3mg/kg over 90 min q3wk x4

119
Q

ipilimumab ADR -3

A

skin, liver, GI, pituitary (endocrinopathy) GVHD,

neuropathy

most during tx, but also weeks to months after

120
Q

trastuzumab MOA

A

binds to Her-2/neu oncogene (25% of breast CA)

-> antibody dependent cellular cytotoxicity (ADCC)

IHC 2-3, FISH (+)

121
Q

trastuzumab dose - 1

A

qwk schedule: 4mg/kg week 1, then 2mg/kg q3wk schedule: ??

122
Q

trastuzumab ADR -5

A

CHF,

infusion related sx

Others: rash,

myelosuppression,

GI tox (diarrhea)

123
Q

pertuzumab MOA. -3

A

Her-2 receptor on extracellular domain blocking ligand dependent HER2, HER3 ligand dimerization.

124
Q

pertuzumab dosing -1

A 
840mg load then 420mg q3w
flat dosing (not wt or BSA-based)
125
Q

pertuzumab ADR (10pts)

A 
diarrhea,
 N, 
alopecia, 
rash, 
neutrop,
 fatigue, 
PN,
embryo-fetal tox, 
LV dysfunction, 
infusion related rxn
126
Q

cetuximab MOA -4

A

cell surface epidermal growth factor receptor (EGFR-1) preventing EGF and TGF-alpha binding and signal transduction.

Blocks PI3K-Akt-mTOR and STAT 3/5 (survival) and Ras-Raf-MEK-MAPk (proliferation) pathways.

127
Q

cetuximab dose -1

A

400mgm2 load then weekly 250

128
Q

cetuximab ADR (9pts)

A 
infusion related rxns required dose mods,
 skin rash,
 asthenia/malaise, 
diarrhea, 
N/V, 
interstitial lung dz,
 hypoMg
129
Q

panitumumab MOA -2

A

EGFR-1 (same as cetux)

IgG2

130
Q

panitumumab dose -1

A

6mg/kg q2wk

131
Q

panitumumab ADR (4pts)

A

skin rash,

infusion related rxns,

interstitial lung dz,

hypoMg

132
Q

bevacizumab MOA -4

A

binds to VEGF ligand-> prevents binding to receptor.

133
Q

bevacizumab dose and administration issues -2

A

usually 5mg/kg q2wk

134
Q

bevacizumab DLT (3pts)

A

HTN,

bleeding episodes,

thrombotic events (MI, PE, DVT)

135
Q

bevacizumab ADR -3

A

rare perforation of bowel,

proteinuria

Wound healing

136
Q

VEGF diagram

A

SEE PG 776

137
Q

erlotinib and gefitinib MOA -3

A

EGFR-TKI (blocks intracellular phosphorylation)

138
Q

erlotinib and gefitinib indications

A

E 1st or 2nd line NSCLC, panc, maintenance NSCLC

139
Q

erlotinib and gefitinib ADR -6

A 
diarrhea,
 rash (MAY BE IMPORTANT), 
acne, 
dry skin, 
N/V
#RARE but serious: interstitial lung dz (1%, but 33% fatal in these cases)
140
Q

erlotinib and gefitinib DDI -2

A

CYP3A4 substrate

increased INR with warfarin

141
Q

lapatinib MOA and dose -3

A

MBC in combo with cape

TKI of both EGFR and Her-2

142
Q

lapatinib ADR (5pts)

A

diarrhea (common),

dec LVEF,

QT prolongation,

rash,

HFS

143
Q

lapatinib DDI -2

A

CYP3A4 and 2C8 inhibitor

144
Q

lapatinib DA -1

A

hepatic

145
Q

imatinib, dasatinib, nilotinib, bosutinib, ponatinib MOA -5

A

Bcr-Abl TKI -> apoptosis of Bcr-Abl (+) cells

146
Q

imatinib, dasatinib, nilotinib, bosutinib, ponatinib drug resistance -2

A

1 Bcr-Abl point mutation ->dec binding (dependent resistance)

147
Q

imatinib, dasatinib, nilotinib, bosutinib, ponatinib DLT -1

A

myelosuppression (mostly leukop and thrombocytop)

148
Q

imatinib, dasatinib, nilotinib, bosutinib, ponatinib ADR (7pts) -ponatinib additional ADR (3pts)

A 
N/V, 
fluid retention, 
elevated transaminases or bili, 
muscle cramps, 
fever, 
bleeding
#P peripheral and arterial thrombosis,
 severe and fatal hepatotox, 
pancreatitis (monitor LFTs, serum lipase)
149
Q

imatinib, dasatinib, nilotinib, bosutinib, ponatinib DA -1

A

hepatic (mostly)

150
Q

imatinib, dasatinib, nilotinib, bosutinib, ponatinib DDI

A

CYP3A4 substrate and inhibitors

Nilotinib without food

151
Q

CYP3A4 and general DDI -3

A

inducer (phenytoin)

inhibitor (cimetidine, itraconazole)

substrates (simvastatin, cyclosporine)

152
Q

sunitinib MOA, indx and dose -3

A

refractory GIST, advanced RCC

multi-R TKI: PDGFR, EGFR, stem cell factor R, others

153
Q

sunitinib ADR -12

A

common:
diarrhea, N/V,
stomatitis, dyspepsia,
skin discoloration

others:
 fatigue, 
HTN, 
bleeding, 
swelling, 
mouth pain, 
taste disturbance, 
CHF
154
Q

sunitinib DDI. -1

A

CYP3A4 substrate

155
Q

sorafinib MOA and dose -3

A

multi-R TKI: PDGFR, VEGFR, stem cell factor R, raf/mek pathway kinases

156
Q

sorafinib ADR -4

A

common: diarrhea

others: rash,
HTN,
HFS

157
Q

sorafinib DA -1

A

HFS

158
Q

sorafinib DDI. -2

A

CYP3A4, UGT1A9 substrate (increases AUC of SN-38)

159
Q

pazopanib MOA and dose

A 
#multi-R TKI: PDGFR, VEGFR, c-Kit, IL-2 R inducible T-cell kinase, leukocyte-specific protein tyrosine kinase, transmembrane, glycoprotein R TK
#adv RCC, adv STS
#800mg qd without food
160
Q

pazopanib ADR

A

common: diarrhea
others: HTN, inc LFTs, prolonged QT, arterial thrombosis, hemorrhagic events, proteinuria, hypothyroidism

161
Q

axitinib MOA

A 
#multiR TKI: similar to pazopanib with enhanced potency and selectivity to all VEGFR, minor against PDGFR and c-KIT
#adv RCC
#5mg q12h
162
Q

axitinib ADR

A

diarrhea, rash, HFS, bleeding, thrombotic events, HTN, hepatotox, hypothyroidism, proteinuria, GI perforation, fatigue
RARE: PML

163
Q

axitinib DA and DDI

A

hepatic - decrease for Childs-Pugh B

CYP3A4 substrate

164
Q

vandetanib MOA and dose

A 
VEGFR, EGFR, RET TK
#progressive medullary thyroid CA
#300mg qd
165
Q

vandetanib ADR

A

black box: QT prolongation (monitor lytes, EKG)

others: skin rxns, stevens-johnson, ILD, ischemic c/v events, hemorrhage, CHF, diarrhea, hypothyroidism, HTN, RPLS

166
Q

vandetanib DA and DDI

A

renal: CrCl <50 reduce to 200

167
Q

cabozantinib MOA and dose

A 
#multi-R TKI: most important rearranged during transfection receptor (RET), VEGFr-2, and MET membrane R
#progressive medullary thyroid CA
#140mg qd
168
Q

cabozantinib ADR (23pts)

A

black box: hemmorrhage, fistulas, GI perforation
others: diarrhea, stomatitis, HFS, weight loss, dec appetite, N, fatigue, oral pain, hair color changes, dysgeusia, HTN, abd pain, constipation, inc LFTs, proteinuria, lymphop, neutrop, thrombocytop, hypoCa, hypophos

169
Q

cabozantinib DDI

A

CYP3A4 substrate

170
Q

regorafenib MOA and dose

A 
#multi-kinase inh: VEGFR, c-KIT, RET, RAF1, BRAF, PDGFR, fibroblast growth factor R (FGFR)
#colon CA
#160mg daily D1-21 of 28days, take with low fat breakfast
171
Q

regorafenib ADR

A

black box: hepatotoxicity

others: asthenia, fatigue, dec appetite, HFS, diarrhea, mucositis, wt loss, infx, htm, dysphonia, hemorrhage

172
Q

regorafenib DDI

A

CYP3A4 substrate

173
Q

bortezomib and carfilzomib MOA and dose

A 
#Inh 26S proteasome, which is a intracellular protease responsible for protein catabolism. IkB accumulates which leads to increased inhibition of NF-kB (transcription factor). NF-kB decreases expression of adhesion molecules and various growth, survival and angiogenic factors.
#C irreversible and rapid binding (use in bortezomib resistance, after 2 tx including bortezomib)
#B MM, mantle cell
174
Q

bortezomib DLT

A

thrombocytop or neuropathies (PN dec with SQ admin)

175
Q

bortezomib ADR (5pts)

A

thrombocytop, fatigue, PN, TLS, neutrop

176
Q

carfilzomib ADR (13pts)

A

fatigue, anemia, thrombocytop, N, diarrhea, dyspnea, pyrexia, inf related rxns
RARE: cardiac arrest, MI, CHF, hepatotox, TLS

177
Q

bortezomib and carfilzomib dose and admin issues

A 
#C 20mg/m2 1st C, then 27mg/m2 subsequent C, D1-2, 8-9, 15-16 of 28d cycle
premed with Dex
#B 1.3mg/m2 D1,4,8,15 q21d OR D1,8,15,22 q35d
178
Q

temsirolimus and everolimus MOA

A 
#Inh mTOR signaling pathway-> cell cycle arrest, dec expression of proteins VEGF, PDGF, transforming growth factor (TGF) and others involved in angiogenesis and cell growth
#adv RCC (T 1st line, E post TKI failure)
179
Q

temsirolimus and everolimus dose and admin issues and DDI

A

both CYP3A4 substrates

#T 25mg iv weekly (diphen premed)
#E 10mg qd
180
Q

temsirolimus and everolimus ADR

A

common: rash, asthenia, mucositis, N, edema, anorexia

lab abnormalities: anemia, hyperglycemia, hyperlipidemia, hypertriglyceridemia, inc LFTs, inc SCr, lymphop, hypophos, thrombocytop, leukop

MGMT: treat both hyperglycemia and hyperlipidemia

181
Q

crizotinib MOA and dose

A

EML4-ALK fusion oncogene TKI (blocks activation downstream Ras pathway, which inhibits apoptosis)

182
Q

crizotinib ADR

A

severe: pneumonitis, hepatotox, QT prolongation

183
Q

crizotinib DA and DDI

A

HOLD or REDUCE for hepatotox, QT prolongation, or myelosuppression

184
Q

vemurafenib MOA and dose

A 
#Inhibits MAP kinase signaling pathway through inhibition of mutated BRAF (V600E) -> prevents downstream activation of MEK and ERK
# metastatic melanoma
#960mg bid
185
Q

vemurafenib ADR

A

24% SQUAMOUS CELL CANCER

common: arthralgia, rash, alopecia, fatigue, photosensitivity rxn, N, pruritis, skin papilloma

186
Q

vemurafenib DDI

A

CYP3A4 substrate and inducer

CYP1A2 moderate Inh

CYP2D6 weak Inh

increases warfarin levels

187
Q

thalidomide and lenalidomide MOA

A 
#not fully understood
#immune modulation (inc T-helper cells)
#cytokine inhibition (TNF-alpha)
#antiangiogenesis
188
Q

thalidomide dose

A

pharmacies and prescribers need to enroll in STEPS program

189
Q

lenalidomide dose

A

patients, pharmacies, prescribers need to enroll in RevAssist

190
Q

thalidomide ADR

A

common: somnolence/drowsiness, constipation, dizziness/orthostatic, hypotension, rash, PN

RARE: neutrop

SERIOUS: teratogenicity (pregnancy test)

191
Q

lenalidomide ADR

A

common: neutrop, thrombocytop, thrombotic issues

MUCH less somnolence, PN than thalidomide

192
Q

ziv-aflibercept MOA, indx, and dose

A

soluble recombinant fusion protein designed to block angiogenesis. fused VEFR-1 and -2 immunoglobulin domains to Fc portion of human IgG1. Blocks VEGF and PIGF by “trapping” ligands before they get to transmembrane receptors.

#colon CA in combo with FOLFIRI after oxal-based regimen progression
#4mg/kg IV q2wks
193
Q

ziv-aflibercept ADR

A

black box: hemorrhage, GI perf, compromised wound healing

others: neutop, diarrhea, proteinuria, inc transaminases, stomatitis, fatigue, thrombocytop, htn, wt loss, dec appetite, epistaxis, abd pain, dysphonia, SCr inc, HA, arterial thrombotic events, fistula formation

194
Q

vismodegib dose and MOA

A

Hedgehog signaling pathway inhibitor. Pathway abnormally activated in solid tumors. Binds to SMO.

#basal cell carcinoma that is untreatable with surgery or XRT
#150mg qd
195
Q

vismodegib ADR

A

black box: embryo-fetal death and severe birth defect (hedgehog pathway used in nml tissue here)

others: muscle spasms, alopecia, dysguesia, ageusia, wt loss, fatigue, n/v/d, dec appetite, constipation, arthralgia

196
Q

vismodegib DDI and donating blood

A

AVOID pgp inhibitors and drugs that alter gastric pH

197
Q

denileukin difitox MOA

A

recominant protein of IL-2 receptor + diptheria toxin fragments A and B. binds with high affinity to IL-2 receptors on T-lymphocytes, is internalized into cell by fragment B, then fragment A is cytotoxic

198
Q

denileukin difitox admin issues

A

premed with pred 20 or dex iv 8 to lower hypersensitivity rxns

199
Q

denileukin difitox ADR

A

capillary leak sx (hypotension, edema, hypoalbuminemia) occurs within 2 wks and get worse with each infusion. hypersens rxns, flu-like sx

200
Q

vorinostat MOA

A

histone deacetylase (HDAC) inhibitor. leads to accumulation of acetylated histones which induces cell cycle arrest or apoptosis

201
Q

vorinostat ADR

A

PE, VTE, n/v/d, dose related thrombocytop and anemia

202
Q

RENAL DOSE ADJUSTMENTS

A

see pg 790

203
Q

HEPATIC DOSE ADJUSTMENTS

A

see pg 791

BCOP (32 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions