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Pharmacology FINAL (2nd sem) > B: 32-37 > Flashcards

B: 32-37 Flashcards

1
Q

Antimetabolites

A
  • CCS (S-phase)
  • pyrimidine antimetabolites:
    • 5FU: inhibits thymidylate synthase, its metabolites incorporates into dna and rna
      • FDUMP : into DNA
      • 5UTP : into RNA
    • cytarabine : activated to cytosine- arabinoside inhibor of DNA polymerases
      • most specific to S-phase out of all antimetab
    • Capecitabine: activated to 5FU
      • oral
  • Folate antimetabolite:
    • Methotrexate : inhibits DHFR
    • Pemetrexed :
  • Purine antimetabolite
    • 6-mercaptopurine : inhibits denovo purine synthesis
      • low oral bioava
      • activated by Hypoxanthine-guanine phosphoribosyl transferase to toxic metabolites
    • thioguanine: inhibits denovo purine synthesis
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2
Q

Which drug reduces the toxic effect of Methotrexate?

A

Leucovorin rescue= folinic acid ( rescue therapy: decrease toxic effect)

after administering MTX for 36-48 hrs its terminated before severe toxicity of GI and bone marrow cells –> leucovorin –> accumulates more in normal cells –> rescue of normal cells bcz it bypasses DHFR step in folic acid system

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3
Q

Fluorouracil indic.

A
  1. Breast cancer
  2. GI cancer
  3. Head & neck
  4. HCC
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4
Q

Methotrexate special SE

A

Pulmonary fibrosis and infiltrates

folate defiency

mucositis, diarhhea

hepatotoxicity

alopecia

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5
Q

Methotrexate indication

A
  1. Breast cancer
  2. Bladder carcinoma
  3. Choriocarcinoma
  4. Head & neck
  5. Primary CNS lymphoma
  6. Non-hodkin lymphoma
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6
Q

6MP indic

A

CML
AML

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7
Q

Cytarabine ind

A
  1. AML
  2. Non-hodgkin lymphoma
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8
Q

capecitabine ind

A
  1. Breast( metastatic disease resistant to 1st line)
  2. Colon c
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9
Q

pemetrexed ind

A
  1. Non–small cell lung c
  2. mesothelioma
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10
Q

5FU toxicity

A
  • ACUTE
    • nausea
    • mucositis
    • diarhhea
  • chronic
    • myelosuppression
    • neurotoxicity
    • alopecia
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11
Q

Hepatoxicity side effect occurs with which anti-metabolite?

A
  • MTX: antifolate
  • 6MP: purine antimeta
  • cytarabine: pyrimidine antimetabolite
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12
Q

Alklyting agents

A

Alkylation agents are CCNS drug (CELL CYCLE NON SPECIFIC)

They form reactive molecular species which alkylate nucleophillic groups on DNA bases (Alkalates Guanine N7)

  • Cyclophosphamide- requires hepatic p450 activation,
    • forms DNA cross-links resulting in - of DNA syn & function
  • Cisplatin-
    • cross links DNA strands with platinum
  • Oxaliplatin- for colon cancer
  • Dacarbazine-
    • ​ needs CYP450 for hodgkin lymphoma
  • Temozolomide-
    • ​prodrug: activation in physiologic pH (not hepatic)
    • for Glioblastoma!
  • Bleomycin-
    • complexes with Fe and O2 –> free radicals–> DNA strand termination
    • Anti-tumor antibiotic
    • CCS (G2 phase)
  • Actinomycin D=dactinomycin:
    • ​anti-tumor antibiotic​
    • Inhibits DNA dep-RNA pol, at high doses inhibits DNA SYN

DOCTor!!! ABC!!!

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13
Q

Which is for CNS tumors?

A

Temozolomide

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14
Q

Give Cyclophosphamide with

A

Mesna to protect the bladder from arecolin

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15
Q

Cyclophosphamide indication

A
  1. Breast c
  2. Ovarian c
  3. Non-hodgkin lymphoma
  4. Chronic lymphocytic leukemia (CLL)
  5. neuroblastoma

immunosuppressive therapy

CycLo-circle as in breast, ovaryy, CLL

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16
Q

Cyclophosphamide SE

A
  • myelosupression
  • SIADH
  • HC hemorrhagic cystitis
  • alopecia
  • cardiac dysfunction
  • pulmonary toxicity
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17
Q

Cisplatin ind

A
  1. Testicular c
  2. bladder c
  3. ovarian c
  4. lung c

cis all circular organs exp lung

cis - bladderrr

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18
Q

Cisplatin SE

A

Neurotoxicity ( Ototoxicity , peripheral
Nephrotoxic

nausea, vomit

NOT ass with myelosupp

*prevent nephrotoxicity by amifostine (free radical scavenger) and saline infusion

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19
Q

Oxaliplatin ind

A

colon cancer (advanced stage)

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20
Q

oxaliplatin SE

A

Neurotoxicity

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21
Q

Dacarbazine ind

A
  • hodgkin lymphoma
  • melanoma
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22
Q

Dacarbazine SE

A

Nausea, vomit

Alopecia

skin rash

phototoxicity

myelosupp

Flu-like syndrome

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23
Q

Which alkalyting agent is a prodrug

A

temozoloamide

activation in physiologic pH (not hepatic)

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24
Q

Temozoloamide ind

A

CNS TUMORS

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25
Q

SE of temozoloamide

A

nausea vomit

myelosupp

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26
Q

Bleomycin ind

A
  • CCS drug!!! ( G2 phase)
  • Anti-tumor antibiotic
  1. Hodgkin lym
  2. testicular c
  3. lymphoma
  4. SCC
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27
Q

bleomycin mechanism

A
  • mixture of glycopeptides
  • generates free radical which bind dna –> strand breaks + inhibit dna synthesis
  • CCS drug (G2 phase)
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28
Q

bleomycin pharmacokinetic

A
  • parenterally
  • inactivated by tissue amino-peptidases
  • but some renal clearance.

complexes with Fe and O2 > free radicals > DNA strand termination

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29
Q

bleomycin SE

A
  • pulmonary fibrosis
  • pneumonitis
  • hypersensitivity rxn
  • mucocutaneous rxn
    • alopecia
    • hyperpigmentation
    • blister
    • hyperkeratosis
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30
Q

Alkylation agents are CCS OR CCNS drugs?

A

ALL are CCNS

expect for bleomycin

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31
Q

Dactinomycin ( actinomycinD) ind

A

CCNS

Antitumor antibiotic

  1. wilms tumor
  2. Ewing sarcoma
  3. rhabdomyosarcoma
  4. Gestational choriocarcinoma
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32
Q

Dactinomycin SE

A

Nausea, vomit

myelosuppresion

alopecia

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33
Q

Topoisomerase inhib.

A
  • Etoposide, teniposide-
    • induces DNA breaks through inhibition of Topo 2
    • CCS (late S phase, early G2 phase)
    • Semi-synthetic derivatives of plant alkaloid- podophyllotoxin
  • Irinotecan, topotecan-
    • DNA damage by inhibiting Topo 1 ( function: cuts and religates DNA strands)
    • CCS (S phase)
    • Semi-synthetic derivative of more toxic campthothecin
  • Doxorubicin, Daunorubicin, epirubicin-
    • intercalate between DNA bp’s, inhibits Topoisomerase 2
    • Oxygen frree radicals bind to dna causing strand break
    • CCNS (anthracyclin)
    • Anti-tumor Antibiotic (anthracyclins)

Topo inhibitors make DNA DIE! (dOXO)

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34
Q

Doxorubicin indications

A
  1. Breast cancer
  2. Ovarian c
  3. lymphoma
  4. myelomas
  5. sarcoma
  6. thyroid c
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35
Q

Doxirubicin toxicities

acute / chronic

A
  • acute:
    • nausea
    • arrythmias
  • chronic
    • alopecia
    • myelosupp
    • cardiomyopathy (CMP) and heart failure
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36
Q

what drug is given to protect against doxorubicin cardiotoxicity?

A

Dexrazoxane = inhibitor of iron-mediated free radical generation

may protect against dose-dep form of cardiotoxicity

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37
Q

administration of doxorubicin, daunorubicin?

metabolism

excretion

A

I.V

metabolised in liver

products excreted in bile and urine

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38
Q

irinotecan mechanism

pharmacokinetic

A

Inhibit topoisomerase 1 resulting in dna damage

CCS (S-PHASE)

Irinotecan is prodrug converted in liver to active form sn-38

Eliminated in bile and feces

genetic variation affects its metabolism (UGT1A)

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39
Q

Irinotecan ind

A

metastatic colorectal c

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40
Q

irinotecan SE

A

nausea, vomit, diarhhea

myelosupp(chronic)

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41
Q

etoposide mechanism

A
  • CCS (late S-phase, early G2)
  • derivative of podophyllotoxin
  • inhibits topoisomerase 2 –> dna damage
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42
Q

etoposide ind

A
  • Lung cancer
  • non-hodgkin lymphoma
  • gastric c
  • germ cell
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43
Q

etoposide pharmacokinetic

A
  • oral, distributes well
  • eliminated via kidney (dose reduction in pts with renal impairment)
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44
Q

etoposide se

A

acute: nausea, vomit
chronic: myelosupp, alopecia

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45
Q

Microtubule inhib.

A
  • Vinca alkaloid
    • Vincristine, Vinblastine
        • inhibit. polym. ALL. Cristine is unstable
      • Interfere with microtubule assembly, resulting in impaired mitosis
  • Taxane:
    • Docetaxel, paclitaxel
      • Interferes with microtubule disassembly, resulting in impaired mitosis
      • enhance polym. Breast Lung Overian. DOCtors who pay TAXes stabilize the economy

VIN and CRISTINE went to the DOC to pay TAX

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46
Q

Vincristine mechanism

A
  • interferes with microtubule assembly –> block formation of mitotiic spindle –> impaired mitosis
  • CCS (M phase)
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47
Q

vincristine pharmacokinetic

A
  • parrenterally
  • penetrate most tissue except CSF
  • Cleared mainly via biliary excretion
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48
Q

vincristine ind

A
  1. acute lymphoid leukemia (ALL)
  2. Hodgkin lymphoma
  3. Non-hodgkin lymphoma
  4. wilms tumor
  5. neuroblastoma
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49
Q

vincristine SE

A

acute : none

chronic:

  • neurotoxic with peripheral neuropathy
  • paralytic ileus
  • myelosupp
  • alopecia
  • IADH secretion (inappro adh)
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50
Q

Docetaxel mechanism

A
  • CCS (M-phase)
  • interferes with microtubule diassembly (mitotic spindle)
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51
Q

docetaxel, paclitaxel pharmacokinetic

A

I.V

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52
Q

docetaxel ind

A

Solid tumors

  • Breast
  • Ovarian
  • lung
  • Gastro-esophageal
  • prostate
  • bladder
  • head & neck
53
Q

docetaxel toxicity

A

Neurotoxicity

Bone marrow depression

54
Q

Hormonal agents

A

Prednisolone for ALL and Lymphomas
Tamoxifen- Estrogen antagonist in breast and CNS , SERM. breast cancer (estrogen sensitive)
Anastrazole- aromatase inhib.
Goserelin- GnRH agonist , inhibits LH/FSH due to desens.
Degarelix- GnRH antagonist for prostate cancer
Bicalutamibe- androgen receptor inhibitor prostate. Bi for 2 testicles
Octreotide- Somatostatin analog

DOG or BAT?

55
Q

prednisolone mechanism

A
  • Activates GC-R alters gene transcription
56
Q

prednisolone indic

A
  • inflammatory conditions
  • organ transplant
  • hematologic cancers (leukemia, lymphoma)
57
Q

pharmacokinetic prednisolone

A
  • duration of activity is longer than pharmacokinetic half-life of drug owning to gene transcription effect
58
Q

prednisolone toxicity

A
  • adrenal suppression
  • growth inhibition
  • muscle wasting
  • osteoporosis
  • salt retension
  • glucose-intolerance
  • behavioral changes
59
Q

tamoxifen mechanism

A
  • Estrogen antagonist in breast & CNS
  • Estrogen agonist in liver & bone
  • SERM (selective estrogen modulator)

blocks the binding of estrogen to estrogen-sensitive cancel cells in breast.

60
Q

tamoxifen ind

A
  • Prevention and adjuvant treatment of hormone-responsive breast cancer
61
Q

tamoxifen administration

62
Q

tamoxifen SE

A
  • HOT FLUSHES
  • thromboembolism
  • endometrial hyperplasia (agonist effect in endometrium)
  • vaginal bleeding
  • nausea, vomit
63
Q

anastrazole mechanism

A
  • aromatase inhibitor ( catalyzes conversion of andro-stenedione to estrone)
64
Q

anaztrazole indication

A
  • advanced breast cancer
65
Q

anastrazole toxicity

A
  • nausea
  • diarrhea
  • hot flushes
  • bone, back pain
  • dyspnea
  • peripheral edema
66
Q

Goserelin, leucoprolide mechanism

A
  • GnRH agonist
  • synthetic peptide
  • if administered in constant doses to maintain stable blood levels, they inhibit release of pituitary LH and FSH –> both androgen and estrogen synthesis decreases
67
Q

goserelin ind

A
  • prostate c
  • breast
  • leiomyoma
  • endometriosis
68
Q

goserelin SE

A
  • headache, nausea
  • injection site rxn
  • symptoms of hypogonadism with continuous treatment ( impotence in male)
69
Q

Degarelix mech

A
  • GnRH antagonist: alters release of FSH, LH –> decreased testestorone synthesis
70
Q

degarelix ind

A

prostate c

71
Q

degarelix se

A

headache, vomit

nausea

72
Q

Bicalutamide mech

A
  • Androgen receptor antagonist (ANTI-ANDROGEN)
73
Q

Bicalutamide IND

A
  • prostate c
74
Q

Bicalutamide SE

A
  • gynecomastia
  • hot flush
  • impotence
  • hepatotoxic
75
Q

octreotide mech

A
  • Somatostatin receptor agonist
    • inhibits release of GH, glucagon, insulin , gastrin
76
Q

octreotide ind

A
  • acromegaly
  • endocrine tumors:(hormone-secreting tumor)
    • carcinoid
    • gastrinoma
    • glucagonoma
    • isulinoma
    • VIPoma
  • acute control of bleeding esophageal varices
77
Q

octreotide pharmacokinetic

A
  • SC
  • I.V
  • IM (long acting injection)
78
Q

octreotide SE

A
  • GI
  • gallstone
  • bradycardia
  • cardiac conduction anomalies
79
Q

Small molecule signal transduction inhib.

A
  • Tyrosine kinase inhibitors
    • Imatinib- TK inhib. BCR-ABL for CML. C-kit
    • Lapatinib- TK inhib. HER2 Lap of breast like lack of breast
    • Sunitinib- TK inhib.
    • Ibrutinib- TK inhib like hebrew
  • EGFR inhibitors
    • Gefitinib, Erlotinib- EGFR antag. NSCLC
  • mTOR inhibitor
    • ​Everolimus- mTOR inhib for renal cancer. renal cancer and mTOR for EVER
  • proteosome inhibitors (reversible inhibition of 26S)
    • Bortezomib for MM
  • Crizotinib- ALK inhib. Cris speaks Hebrew
  • Dabrafenib(BRAF)+Trametinib for Melanoma Dabra is on the tram and there is a lot of sun
  • Tretinoin- AML and Acne. All trans retinoic acid

orally active

once/daily

Hepatic p450 metabolism

Act intracellularly

act on mutated, constitutivly active receptors that no longer reply on ligand binding

80
Q

imatinib mechanism

A

Tyrosine kinase inhibitor

  • inhibits bcr-abl tyrosine kinase (commonly expressed in CML ass with philadelphia chromosome translocation) and other tyrosine kinases
  • C-kit tyrosine kinase inhibitor
81
Q

imatinib ind

A
  • CML ( + philedelphia chromosome translocation)
  • gastrointestinal stromal tumor ( + Ckit tyrosine kinase)
82
Q

imatinib SE

A
  • acute
    • nausea
    • vomit
  • chronic
    • Fluid retention with ankle and periorbital edema,
    • diarrhea,
    • myalgias,
    • congestive heart failure
83
Q

Gefitinib, erlotinib mechanism

A

EGFR inhibitors (inhibit tyrosine kinase domain)

84
Q

Gefitinib, erlotinib ind

A
  • Gefitinic : Non-small-lung cancer (2nd line)
  • erlotinib:
    • Non small lung cancer (2nd line)
    • pancreatic c (combination therapy)
85
Q

Gefitinib, erlotinib SE

A

rash (acne like)

diarhhea

86
Q

lapatinib mechanism

A

Tyrosine kinase inhibitor ( HER2/neu and EGFR pathways)

87
Q

lapatinib indication

A

breast cancer (HER2 positive)

88
Q

lapatinib SE

A
  • rash
  • diarrhea
89
Q

sunitinib mech

A

it’s a small molecule that inhibits TK receptors.

Tyrosine kinase receptor inhibitor ( PDGF-R , VEGF-R)

  • metabolised by CYP3A4
  • elimination: hepatic
90
Q

sunitinib ind

A

renal cell carcinoma

imatinib-resistant GIST

91
Q

sunitinib SE

A
  • diarhhea, nausea, vomit
  • hypertension
  • bleeding complications
  • fatigue
92
Q

Ibrutinib mech

A
  • Tyrosine kinase inhibtor ( Brutons tyrosine kinase in B-cells)
93
Q

ibrutinib ind

A
  • CLL
  • waldenstrom macroglobulinemia
  • Mantle cell lymphome
  • marginal zone lymphoma
94
Q

ibrutinib SE

A
  • URTI
  • sinusitis
  • myelosupp
95
Q

Crizotinib mech

A
  • ALK kinase inhibitor
  • ROS1 oncogene inhibitor
96
Q

crizotinib ind

A

Non small lung cancer

97
Q

crizotinib SE

A

Nausea, vomit, diarhhea

98
Q

Bortezomib mechanism

A
  • proteosome inhibitor: Reversibly inhibits chymotrypsin-like activity of the 26S proteasome
    • ( inhibition result in downregulation of NF-Kbeta signalling pathway)
99
Q

Bortezomib indication

A

multiple myeloma

100
Q

Bortezomib SE

A
  • acute:
    • hypotension
    • edema
    • GI
  • chronic
    • peripheral neuropathy
    • cardiac dysfunction
101
Q

Dabrafinib and trametinib mechanism

A
  • Dabrafenib : BRAF inhibitor
  • trametinib : MEK inhibitor

USED IN COMBINATION

102
Q

Dabrafinib and trametinib(combo) ind

103
Q

Everolimus mechanism

A
  • mTOR-inhibitor
  • Derivative of sirolimus (rapamycin)
104
Q

everolimus ind

A
  • renal cancer
  • neuroendocrine tumors
105
Q

everolimus SE

A

stomatitis

infections

diarhhea

106
Q

T-retinoin - ATRA (all-trans retinoic acid) mechanism

A
  • vitamin A (retinol ) derivative
  • Differenciating agent: promotes differenciation of promyelocytes (used as adjunct to chemo)
107
Q

T-retinoin ind

A
  • AML (M3 type) acute promyelocytic leukemia
  • Acne (topical)
108
Q

T-retinoin SE

A
  • Differenciation syndrome :
    • fever
    • ARDS
    • pleural effusion
    • pericardial effusion
    • AKI
  • CNS symptoms
109
Q

Large molecule signal transduction inhib.

A
  • Trastuzumab-(emtasnsin) Anti HER2 trust me i cure breast cancer. but cardiotoxic
  • Panitumumab- anti EGFR. colon. Eating panir
  • Rituximab- Anti CD20. CLL, Hodgkins
  • Bevacizumab- Anti VEGF for colon. colon be evacuated from cancer
  • INF-a for CML, T cell lymphoma, hairy cell leukemia
  • Aldesleukin stimulates T cells for renal cancer. Aldes like aldostrom which works in renal
  • Pembrolizumab activates T cell for melanoma. pembrol sounds like a pimple that rolls on your skin

TiP! dont go to RIBA Pal

110
Q

Trastuzumab-(emtansin) mechanism of action

A
  • Monoclonal antibody
  • GF receptor inhibitor
    • Inhibits binding of EGF”epidermal GF” to HER2/neu growth receptor. “ trust me i cure breast cancer. but cardiotoxic”
111
Q

Trastuzumab-(emtansin) indication

A
  • GF receptor inhibitor
    1. HER2/neu receptor positive breast cancer
112
Q

Trastuzumab SE

A
  • Acute: Nausea, vomit, chills, fever, headache
  • Cardiac dysfunction including heart failure
113
Q

Panitumumab, cetuximab mechanism of action

A
  • Anti-EGFR
  • fully Human monoclonal ANTIBODY
114
Q

Panitumumab indication

A
  • Refractory metastatic colorectal cancer

NOTE: mutated K-RAS tumors are resistant

115
Q

Panitumumab, cetuximab SE

A
  • nausea, vomit
  • diarhhea
  • hypomagnesemia
116
Q

Cetuximab mechanism, indication, SE

A
  • Chimeric monoclonal antibody
    • GF-r inhibitor ( directed to EC domain of EGFR)
  • used in COMBO with
      • irinotecan+ oxaliplatin for: metastatic colon cancer
    • +radiation : head & neck cancer
  • SE: skin rash, hypersensitivity infusion reaction
117
Q

Rituximab mechanism and indication

A

Anti CD20 antibody (cell surface antibody) binds to CD20 in

Non-Hodgkins B cell lymphoma –> complement-mediated lysis, direct cytotoxicity, apoptosis

CLL,

118
Q

Rituximab SE

A
  • Hypersensitivy rxn 3: serum sickness
  • Myelosuppression
  • Infusion-related rxn: 50% of patients
  • fever
  • lymphopenia
119
Q

Beva

120
Q

Bevacizumab- mechanism & indication

A
  • Monoclonal antibody
  • Anti VEGF
    • Inhibits binding of VEGF to its receptor, resulting in inhibition of tumor vascularization
  • Indication:
    • Colorectal c
    • Breast c
    • Non-small cell lung c
    • Renal cancer
121
Q

Bevacizumab SE

A
  • Acute
    • HTN
    • infusion rxn
  • chronic:
    • Arterial thrombo-embolic event
    • GI peroforation
    • wound healing complications
    • proteinuria
122
Q

Interferon-alpha mechanism , indication

A
  • Endogenous glycoproteins with
    • anti-neoplastic,
    • immunosupp
    • & antiviral actions.
  • Indication:
    • CML
    • Hairy-cell leukemia
    • T-cell lymphoma
123
Q

Interferon-alpha SE

A
  • Myelosuppression
  • Neurotoxic
124
Q

Aldesleukin Mechanism, indication

A
  • IL-2 recombinant protein
  • stimulates growth and differenciation of T cells
  • Renal cancer
  • Melanoma
125
Q

Aldesleukin SE

A

diarrhea

hypotension

126
Q

Pembrolizumab mechanism

indication

A
  • Humanized monoclonal Ab ( IgG4 isotype)
  • Immunomodulator (check point protein modulator)
  • Antibody binds PD-1 receptor of lymphocytes ( programmed cell death protein 1) –> T-cell activated (prevent co-inhibitory signal)
  • activates T cell for melanoma. “pembrol sounds like a pimple that rolls on your skin”
  • Non-small lung cancer
127
Q

Pembrolizumab SE

A
  • Injection site rxn
  • pneumonitis
  • inflammation of endocrine glands
128
Q

RA Tx.

A

Rituximab with Methotrexate

129
Q

Antimetabolites are CCS or CCNS?

Pharmacology FINAL (2nd sem) (37 decks)

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