Pharmacology Bacterial Infections/Lung Cancer Flashcards
Treatment of Legionnaires
Azithromycin or Clarithromycin
Alt: quinolones (levofloxacin, ciprofloxacin, moxifloxacin)
Severe: Rifampin
Outpatient treatment for uncompliaction CAP
Macrolide or Doxycycline
Outpatient treatment of CAP with COPD
if recent steroids/abx - Fluoroquinolone or Augmentin, or Clarithromycin and Cephalosporin
no recent steroids/abx: Clarithromycin or Doxycycline
Nuring home CAP Treatment
Fluoroquinolone or Augmentin, or Clarithromycin and Cephalosporin
Hospital ward treatment CAP
Fluoroquinolone or Augmentin, or Clarithromycin/Azithromycin and Cephalosporin
ICU treatment CAP
3rd generation cephalosporin +/- macrolide or piperacillin/tazobactam or fluoroquinolone
Macrolides nomenclature and MOA
“MYCINs” 50s ribosomal inhibitor blocking translocation
Tetracyclines nomenclature and MOA
“CYCLINEs” 30s ribosomal inhibitor blocking protein synthesis
Fluoroquinolones nomenclature and MOA
“FLOXACINs” DNA gyrase inhibitor preventing DNA replication
Penicillins nomenclature and MOA
“CILLINs” block cell wall cross linking
Carbopenem nomenclature and MOA
meropenem - blocks cell wall cross linking
Cephalosporins nomenclature and MOA
“CEFs or CEPHs” inhibition of cell wall cross-linking
Aminogylcosides
gentamicin 30s ribosomal inhibitor
Macrolide resistance mechanism
ribosomal methylation and mutation of 23S rRNA; active efflux
Tetracyclines resistance mechanism
decreased entry into and increased efflux from; target insensitivity
Fluoroquinolones resistance mechanism
mutation of DNA gyrase; active efflux
Penicillins resistance mechanism
Drug inactivation (beta lactamase); altered peniciilin binding proteins (target insensitivity)
Cephalosporins resistance mechanism
decreased permeability of gram negative outer membrane (altered porins); active efflux
Aminoglycosides resistance mechanism
drug inactivation (amino glycoside modifying enzyme); decreased permeability of gram negative outer membrane; active efflux; ribosomal methylation
Drugs indicated for Nocosomial pneumonia
Imipenem/Cilastin, Aztreonam, Cetazidime, Vancomycin (IV only for staph aureus)
Alternative drugs for Nocosomial pneumonia
Meropenem, piperacillin/tazobactam, Cefepime
Drugs for Aspiration Pneumonia
Primary - clindamycin
alternative - ampicillin/sulbactam
Clindamycin MOA and Resistance
50s ribosomal inhibitor blocking translocation; resistance - methylation of binding site, enzymatic inactivation
Vancomycin MOA and resistance
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
Antibiotics with biliary elimination
azithromycin, doxycycline, erythromycin, ceftriaxone (+renal), clindamycin (+renal)
Amoxicillin and Ampicillin toxicity
cross reactivity with penicillin sensitivity; GI distress; maculopopular rash
Azithromycin toxicity
cholestatic jaundice; QT prolongation
Cefazolin, Cefepime, Ceftazidime, Ceftriaxone toxicity
complete cross reactivity with cephalosporins, partial cross reactivity with penicillin hypersensitivity; GI distress
Clindamycin toxicity
GI distress
Doxycycline toxicity
GI distress; teeth discolored; photosensitivity; decreased bone growth
Erythromycin toxicity
CYP3A4/pgp inhibitor; cholestatic jaundice; QT prolongation
Gentamicin toxicity
nephrotoxicity; ototoxicity; neuromuscular paralysis
Imipenem toxicity
Partial cross-reactivity with pen/ceph hypersensitivity; seizures
Levofloxacin toxicity
Tendon rupture in adults; cartilage damage in young children
Linezolid toxicity
bone marrow suppression; non specific MAO inhibitor
Meropenem toxicity
partial cross reactivity with pen/ceph hypersensitivity; seuizures
Piperacillin toxicity
partial cross reactivity with ceph hypersensitivity; decreased coagulaiton
Vancomycin toxicity
nephrotoxic, ototoxic; Red Man’s syndrome
Antibiotics to avoid or caution with breastfeeding
clarithromycin, linezolid, metronidazole, piperacillin
Sulbactam, Clavulonic acid, Tazobactam MOA
used in combination with penicillin derivatives; these are all irreversible inhibitors of bacterial beta-lactamases
Cilastin MOA
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
Reason for not using Daptomycin for lung infections
It distributes to the lungs, but is inhibited by pulmonary surfactant so is ineffective against pulmonary infections
Antibiotics for treatment of bronchitis
First line: Amox + Clauv, azithromycin, clarithromycin, doxycline (oral or IV)
Resist: Ciprofloxacin (oral or IV)
Antibiotics for treatment of Lung Abscess
Clindamycin (esp. against Bacteroides); Metronidazole and Ceftriaxone for nocosomial infections
Mechanisms of TKI resistance
Mutation in ATP binding site for TKIs, polymorphisms in apoptosis genes, downstream activation mutations (KRAS, BRAF)
Lung cancer mutations more common in nonsmokers
EGFR, EML4-ALK fusions, HER2, hMSH2
SCLC Treatment plan
metastasis occurs early so chemotherapy with radiation is only option
NSCLC treatment plan
surgical resection if there has been no metastasis, can use adjuvant/neoadjuvant chemotherapy
Standard chemotherapy for SCLC
Etoposide and cisplatin or carboplatin
Standard chemotherapy for NSCLC
Cisplatin and paclitaxel, gemcitabine, docetaxel, vinorelbine, irinotecan, or pemetrexed
Add targeted therapy for those with targetable mutations
Indications for Bevacizumab
patients with non-squamus, no brain metastases, no hemoptysis NSCLC
Carboplatin and Cisplatin MOA
forms DNA intrastrand cross links and adducts
Cyclophosphamide MOA
pro drug of active alkylating moiety
Docetaxel MOA
microtubule stabilized inhibiting depolymerization
Doxorubicin MOA
intercalator, free radical generator, topo II inhibitor
Etoposide, VP-16 MOA
DNA-topo II complex stabilized
Gemcitabine MOA
DNA polumerase inhibitor via incorporation of triphosphate form during DNA synthesis
Ifosfamide MOA
intra and inter strand cross linker
Irinotecan MOA
DNA topo I complex stabilized
Paclitaxel MOA
Microtubule stabilizer inhibiting depolymerization
Pemetrexed MOA
DHFR inhibitor
Topotecan MOA
DNA-topo I complex stabilizer
Vincristine Vinorelbine MOA
Microtubule inhibitor, tubules disintegrate into spiral aggregates/protofilaments
Carboplatin Toxicity
allergic (platinum) reactives; dose related myelosuppression; cumulative anemia; N/V, blood chemistry dyscrasia, increased hepatic enzymes, BUN, creatinine
Cisplatin Toxicity
Allergic reactions to platinum; dose related nephrotoxicity, myelosuppression, N/V. Siginificant Ototoxicity in children
Cyclophosphamide Toxicity
Blood dyscrasias leading to anemia/infection; renal compromise, hemorrhages cystitis (take mesna for protection), N/V, rash, Amenorrhea/infertility, pulmonary fibrosis, secondary malignancies
Docetaxel Toxicity
increased mortality in SCLC; edema (treat w/ steroids); contra with increased bilirubin/ALK/phos/SGOT/SGPT; neutropenia, dose limiting sensory neuropathyr
Doxorubicin Toxicity
Myelosuppression, CHF, hepatic disease, secondary malignancies, extravasational necrosis, N/V
Etoposide, VP-16 Toxicity
Myelosuppression, infection; dose limiting hematologic toxicity, N/V, diarrhea, alopecia
Gemcitabine Toxicity
Myelosuppression, infection, arthralgia, drowsiness, fatigue, N/V, alopecia, snesory peripheral neuropathy
Ifosfamide Toxicity
Alopecia, N/V, blood dyscrasia -> infection, neurotoxicity, heamturia renal failure
Irinotecan Toxicity
Myelosuppression, diarrhea, asthenia, fever pain, weight loss
Paclitaxel Toxicity
Taxane hypersensitivity, myelosuppression, myalgia and arthralgia
Pemetrexed Toxicity
Myelosuppression and GI toxicities, especially with Cisplatin for NSCLC; elevated LFTs and serum creatinine
Topotecan Toxicity
Myelosuppression and GI toxicities, hyperbilirubinemia
Vinblastine and Vinorelbine toxicity
myelosuppression, neuropathic toxicity (less w/ vinorelbine); neutropenia (less w/ vinorelbine); intrathecal administration of vinca alkaloids is fatal
Erlotinib MOA
Reversible inhibitor selective for EGFR; CYP 3A4 substrate; oral administration on empty stomach; smoking increases clearance
Erlotinib Toxicity
Diarrhea, intersitial lung disease-type events, liver and or kidney problems, stomach/intestinal perforation, bleeding, corneal perforation/ulceration, conjunctivitis, hypertrichosis, rash
Afatinib MOA
covalent inhibitor of EGFR, HER2, HER4; oral admin on empty stomach; Pgp substrate and inhibitor
Afatinib Toxicity
Diarrhea, rash, pulmonary toxicity (~1% but 2% in Asians); less toxic than erlotinib
Crizotinib MOA
reversible multi-kinase inhibitor, including ALK; oral admin on empty stomach; cyp3A4 substrate and Pgp substrate and inhibitor
Crizotinib toxicity
GI issues, edema, QT prolongation, visual disorders, neutropenia, hepatic dysfunction, respiratory dysfunciton, uncommonly rash
Bevacizumab MOA
humanized antibody that binds to VEGF preventing receptor activation; given by IV infusion
Bevacizumab Toxicity
HTN, arterial thromboembolism, alopecia, GI issues, hemorrhage, asthenia, dizziness, HA, renal proteinuria, dyspnea, upper respiratory infections, Fistulas of GI, vagina, bladder, bronchopulmonary
Treatment for adenocarcinoma with EGFR mutation
Erlotinib or Afatinib
Treatment for adenocarcinoma with EML4/ALK translocation
Crizotinib
Treatment for adenocarcinomas without known genetic subtype
Standard cytotoxic chemotherapy