Pharmacology Bacterial Infections/Lung Cancer Flashcards

1
Q

Treatment of Legionnaires

A

Azithromycin or Clarithromycin
Alt: quinolones (levofloxacin, ciprofloxacin, moxifloxacin)
Severe: Rifampin

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2
Q

Outpatient treatment for uncompliaction CAP

A

Macrolide or Doxycycline

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3
Q

Outpatient treatment of CAP with COPD

A

if recent steroids/abx - Fluoroquinolone or Augmentin, or Clarithromycin and Cephalosporin

no recent steroids/abx: Clarithromycin or Doxycycline

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4
Q

Nuring home CAP Treatment

A

Fluoroquinolone or Augmentin, or Clarithromycin and Cephalosporin

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5
Q

Hospital ward treatment CAP

A

Fluoroquinolone or Augmentin, or Clarithromycin/Azithromycin and Cephalosporin

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6
Q

ICU treatment CAP

A

3rd generation cephalosporin +/- macrolide or piperacillin/tazobactam or fluoroquinolone

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7
Q

Macrolides nomenclature and MOA

A

“MYCINs” 50s ribosomal inhibitor blocking translocation

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8
Q

Tetracyclines nomenclature and MOA

A

“CYCLINEs” 30s ribosomal inhibitor blocking protein synthesis

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9
Q

Fluoroquinolones nomenclature and MOA

A

“FLOXACINs” DNA gyrase inhibitor preventing DNA replication

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10
Q

Penicillins nomenclature and MOA

A

“CILLINs” block cell wall cross linking

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11
Q

Carbopenem nomenclature and MOA

A

meropenem - blocks cell wall cross linking

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12
Q

Cephalosporins nomenclature and MOA

A

“CEFs or CEPHs” inhibition of cell wall cross-linking

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13
Q

Aminogylcosides

A

gentamicin 30s ribosomal inhibitor

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14
Q

Macrolide resistance mechanism

A

ribosomal methylation and mutation of 23S rRNA; active efflux

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15
Q

Tetracyclines resistance mechanism

A

decreased entry into and increased efflux from; target insensitivity

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16
Q

Fluoroquinolones resistance mechanism

A

mutation of DNA gyrase; active efflux

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17
Q

Penicillins resistance mechanism

A

Drug inactivation (beta lactamase); altered peniciilin binding proteins (target insensitivity)

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18
Q

Cephalosporins resistance mechanism

A

decreased permeability of gram negative outer membrane (altered porins); active efflux

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19
Q

Aminoglycosides resistance mechanism

A

drug inactivation (amino glycoside modifying enzyme); decreased permeability of gram negative outer membrane; active efflux; ribosomal methylation

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20
Q

Drugs indicated for Nocosomial pneumonia

A

Imipenem/Cilastin, Aztreonam, Cetazidime, Vancomycin (IV only for staph aureus)

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21
Q

Alternative drugs for Nocosomial pneumonia

A

Meropenem, piperacillin/tazobactam, Cefepime

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22
Q

Drugs for Aspiration Pneumonia

A

Primary - clindamycin

alternative - ampicillin/sulbactam

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23
Q

Clindamycin MOA and Resistance

A

50s ribosomal inhibitor blocking translocation; resistance - methylation of binding site, enzymatic inactivation

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24
Q

Vancomycin MOA and resistance

A

binds D-alanyl-D-alanine terminus of the peptide precursor units, inhibiting peptidoglycan polymerase and transpeptidation reactions; resist - replacement of D-ala by D-lactate

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25
Q

Antibiotics with biliary elimination

A

azithromycin, doxycycline, erythromycin, ceftriaxone (+renal), clindamycin (+renal)

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26
Q

Amoxicillin and Ampicillin toxicity

A

cross reactivity with penicillin sensitivity; GI distress; maculopopular rash

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27
Q

Azithromycin toxicity

A

cholestatic jaundice; QT prolongation

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28
Q

Cefazolin, Cefepime, Ceftazidime, Ceftriaxone toxicity

A

complete cross reactivity with cephalosporins, partial cross reactivity with penicillin hypersensitivity; GI distress

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29
Q

Clindamycin toxicity

A

GI distress

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30
Q

Doxycycline toxicity

A

GI distress; teeth discolored; photosensitivity; decreased bone growth

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31
Q

Erythromycin toxicity

A

CYP3A4/pgp inhibitor; cholestatic jaundice; QT prolongation

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32
Q

Gentamicin toxicity

A

nephrotoxicity; ototoxicity; neuromuscular paralysis

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33
Q

Imipenem toxicity

A

Partial cross-reactivity with pen/ceph hypersensitivity; seizures

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34
Q

Levofloxacin toxicity

A

Tendon rupture in adults; cartilage damage in young children

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35
Q

Linezolid toxicity

A

bone marrow suppression; non specific MAO inhibitor

36
Q

Meropenem toxicity

A

partial cross reactivity with pen/ceph hypersensitivity; seuizures

37
Q

Piperacillin toxicity

A

partial cross reactivity with ceph hypersensitivity; decreased coagulaiton

38
Q

Vancomycin toxicity

A

nephrotoxic, ototoxic; Red Man’s syndrome

39
Q

Antibiotics to avoid or caution with breastfeeding

A

clarithromycin, linezolid, metronidazole, piperacillin

40
Q

Sulbactam, Clavulonic acid, Tazobactam MOA

A

used in combination with penicillin derivatives; these are all irreversible inhibitors of bacterial beta-lactamases

41
Q

Cilastin MOA

A

used in combination with Imipenem; it is a reversible, competitive inhibitor if renal dehydropeptidase-1 (DHP-1), an enzyme that breaks down imipenem to inactive but nephrotoxic metabolites

42
Q

Reason for not using Daptomycin for lung infections

A

It distributes to the lungs, but is inhibited by pulmonary surfactant so is ineffective against pulmonary infections

43
Q

Antibiotics for treatment of bronchitis

A

First line: Amox + Clauv, azithromycin, clarithromycin, doxycline (oral or IV)
Resist: Ciprofloxacin (oral or IV)

44
Q

Antibiotics for treatment of Lung Abscess

A

Clindamycin (esp. against Bacteroides); Metronidazole and Ceftriaxone for nocosomial infections

45
Q

Mechanisms of TKI resistance

A

Mutation in ATP binding site for TKIs, polymorphisms in apoptosis genes, downstream activation mutations (KRAS, BRAF)

46
Q

Lung cancer mutations more common in nonsmokers

A

EGFR, EML4-ALK fusions, HER2, hMSH2

47
Q

SCLC Treatment plan

A

metastasis occurs early so chemotherapy with radiation is only option

48
Q

NSCLC treatment plan

A

surgical resection if there has been no metastasis, can use adjuvant/neoadjuvant chemotherapy

49
Q

Standard chemotherapy for SCLC

A

Etoposide and cisplatin or carboplatin

50
Q

Standard chemotherapy for NSCLC

A

Cisplatin and paclitaxel, gemcitabine, docetaxel, vinorelbine, irinotecan, or pemetrexed
Add targeted therapy for those with targetable mutations

51
Q

Indications for Bevacizumab

A

patients with non-squamus, no brain metastases, no hemoptysis NSCLC

52
Q

Carboplatin and Cisplatin MOA

A

forms DNA intrastrand cross links and adducts

53
Q

Cyclophosphamide MOA

A

pro drug of active alkylating moiety

54
Q

Docetaxel MOA

A

microtubule stabilized inhibiting depolymerization

55
Q

Doxorubicin MOA

A

intercalator, free radical generator, topo II inhibitor

56
Q

Etoposide, VP-16 MOA

A

DNA-topo II complex stabilized

57
Q

Gemcitabine MOA

A

DNA polumerase inhibitor via incorporation of triphosphate form during DNA synthesis

58
Q

Ifosfamide MOA

A

intra and inter strand cross linker

59
Q

Irinotecan MOA

A

DNA topo I complex stabilized

60
Q

Paclitaxel MOA

A

Microtubule stabilizer inhibiting depolymerization

61
Q

Pemetrexed MOA

A

DHFR inhibitor

62
Q

Topotecan MOA

A

DNA-topo I complex stabilizer

63
Q

Vincristine Vinorelbine MOA

A

Microtubule inhibitor, tubules disintegrate into spiral aggregates/protofilaments

64
Q

Carboplatin Toxicity

A

allergic (platinum) reactives; dose related myelosuppression; cumulative anemia; N/V, blood chemistry dyscrasia, increased hepatic enzymes, BUN, creatinine

65
Q

Cisplatin Toxicity

A

Allergic reactions to platinum; dose related nephrotoxicity, myelosuppression, N/V. Siginificant Ototoxicity in children

66
Q

Cyclophosphamide Toxicity

A

Blood dyscrasias leading to anemia/infection; renal compromise, hemorrhages cystitis (take mesna for protection), N/V, rash, Amenorrhea/infertility, pulmonary fibrosis, secondary malignancies

67
Q

Docetaxel Toxicity

A

increased mortality in SCLC; edema (treat w/ steroids); contra with increased bilirubin/ALK/phos/SGOT/SGPT; neutropenia, dose limiting sensory neuropathyr

68
Q

Doxorubicin Toxicity

A

Myelosuppression, CHF, hepatic disease, secondary malignancies, extravasational necrosis, N/V

69
Q

Etoposide, VP-16 Toxicity

A

Myelosuppression, infection; dose limiting hematologic toxicity, N/V, diarrhea, alopecia

70
Q

Gemcitabine Toxicity

A

Myelosuppression, infection, arthralgia, drowsiness, fatigue, N/V, alopecia, snesory peripheral neuropathy

71
Q

Ifosfamide Toxicity

A

Alopecia, N/V, blood dyscrasia -> infection, neurotoxicity, heamturia renal failure

72
Q

Irinotecan Toxicity

A

Myelosuppression, diarrhea, asthenia, fever pain, weight loss

73
Q

Paclitaxel Toxicity

A

Taxane hypersensitivity, myelosuppression, myalgia and arthralgia

74
Q

Pemetrexed Toxicity

A

Myelosuppression and GI toxicities, especially with Cisplatin for NSCLC; elevated LFTs and serum creatinine

75
Q

Topotecan Toxicity

A

Myelosuppression and GI toxicities, hyperbilirubinemia

76
Q

Vinblastine and Vinorelbine toxicity

A

myelosuppression, neuropathic toxicity (less w/ vinorelbine); neutropenia (less w/ vinorelbine); intrathecal administration of vinca alkaloids is fatal

77
Q

Erlotinib MOA

A

Reversible inhibitor selective for EGFR; CYP 3A4 substrate; oral administration on empty stomach; smoking increases clearance

78
Q

Erlotinib Toxicity

A

Diarrhea, intersitial lung disease-type events, liver and or kidney problems, stomach/intestinal perforation, bleeding, corneal perforation/ulceration, conjunctivitis, hypertrichosis, rash

79
Q

Afatinib MOA

A

covalent inhibitor of EGFR, HER2, HER4; oral admin on empty stomach; Pgp substrate and inhibitor

80
Q

Afatinib Toxicity

A

Diarrhea, rash, pulmonary toxicity (~1% but 2% in Asians); less toxic than erlotinib

81
Q

Crizotinib MOA

A

reversible multi-kinase inhibitor, including ALK; oral admin on empty stomach; cyp3A4 substrate and Pgp substrate and inhibitor

82
Q

Crizotinib toxicity

A

GI issues, edema, QT prolongation, visual disorders, neutropenia, hepatic dysfunction, respiratory dysfunciton, uncommonly rash

83
Q

Bevacizumab MOA

A

humanized antibody that binds to VEGF preventing receptor activation; given by IV infusion

84
Q

Bevacizumab Toxicity

A

HTN, arterial thromboembolism, alopecia, GI issues, hemorrhage, asthenia, dizziness, HA, renal proteinuria, dyspnea, upper respiratory infections, Fistulas of GI, vagina, bladder, bronchopulmonary

85
Q

Treatment for adenocarcinoma with EGFR mutation

A

Erlotinib or Afatinib

86
Q

Treatment for adenocarcinoma with EML4/ALK translocation

A

Crizotinib

87
Q

Treatment for adenocarcinomas without known genetic subtype

A

Standard cytotoxic chemotherapy