Antibacterial Chemotherapy Flashcards
1
Q
- very selective toxicity, bactericidal in growing, proliferating cells
- primarily used for gram (+)
- mechanism of action: covalent binding to transpeptidases/PBPs, inhibition of transpeptidase reaction, activation of murein hydrolases
A
penicillins
2
Q
absorption of penicillins?
A
oral-though many are acid sensitive
parenteral- IV or IM
depot- benzathina penicillin G
3
Q
distribution of penicillins?
A
good to most tissues and fluids, exlcusing pleural/pericardial/synovial
poor penetration to eye, prostate, CNS (except in meningitis)
4
Q
excretion of penicillins?
A
-tubular through organic acid secretory system, blocked by probenecid
5
Q
penicillins have __________ cell killing, where ______ above MBC relates to efficacy
A
time dependent
time
6
Q
penicillins primaryily used against gram positives?
A
Pen G and Pen V
7
Q
anti staph penicillins?
A
nafcillin, methicillin, isoxazolyl pencillins (ox-, clox-)
beta lactamase resistant
8
Q
extended spectrum penicillins with increased gram (-) activity?
A
ampicillin, amoxacillin, ticarcillin, piperacillin, mezlocilli
9
Q
anti pseudomonal penicillins effective against proteus and pesudomonas?
A
ticarcillin, piperacillin, mezlocillin
10
Q
problem with anti pseudomonal penicillins?
A
rapid emergence of resistance with pseudomonas, so use in combo with aminoglycosides or fluoroquinolones
11
Q
adverse effects of penicillins?
A
- ampicillin rash, self limiting
- hypersensitivity reaction: rapid onset, not dependent on therapeutic dose
- seizures in high doses
12
Q
resistance to penicillins due to?
A
- inaccessible PBPs: gram negatives, MRSA
- Beta lactamase resistant: plasmid mediated, use beta lactamase resistant penicillins (nafcillin, oxacillin, cloxacillin)
- co administer beta lactamase inhibitor (clavulanic acid, sulbactam, tazobactam)
13
Q
- structure and function similar to penicillins
- less sensitive to beta lactamases
- broader spectrum of activity
- poor oral absorption
- renal toxicity
- secondary ICWS
A
cephalosporins
14
Q
- generally greater gram (-) activity
- 2nd generation less gram (+) activity
- less beta lactamase sensitivity
- cephalosporine resistant (especially 4th generation-cefepime)
- less toxic to patient, better distribution to CNS
A
cephalosporins
15
Q
cefazolin and cephalexin (oral) are ______ generation cephalopsporins with _______ spectrum
A
1st generation
narrow
16
Q
cefuroxime (oral), cefotetan, cefaclor (oral) are _______ generation cephalopsorins with _________ spectrum
A
second generation
intermediate
17
Q
cefotaxime, ceftriaxone, ceftazidime, cefdopoxime (oral) are _______ generation cephalosporins with ________ spectrum
A
3rd generation
broad
18
Q
cefepime is _______ generation cephalosporin with _________ spectrum
A
4th generation
broad
19
Q
adverse effects of cephalosporins?
A
- local irritation from injection
- renal toxicity-tubular necrosis, interstitial nephritis, may be enhanced by aminoglycosides
- cefotetan and cefoperazone have disulfiram effect, give with vitamin K b/c bleeding and platelet disorders
- hypersensitivity - 1% cross reaction with penicillins
20
Q
- gram negative activity, virtually inactive against gram (+) or anaerobes
- becta lactamase resistant
- crosses blood brain barrier
- no cross reactivity in penicillin sensitive patients
A
aztreonam (a monobactam)
21
Q
- broad spectrum, anaerobes
- beta lactamase resistant
- pseudomonas: rapid resistance, use with aminoglycosides
- IV only
- crosses BBB
- inactivated by renal dipeptidase, co administer Cilastatin
- cross reative with penicillins, incidence low
A
imipenem (carbapenem)
22
Q
- inhibits transglycosylation
- bactericidal for gram positive
- IV for systemic use (MRSA), oral for C diff
- IV cleared through kidney- enhances oto and renal toxicity of aminoglycosides
- red man or redneck syndrome- histamine release
A
vancomycin
23
Q
- ICWS, broad spectrum
- inhibits cytoplasmic step in cell wall precursor synthesis
- active uptake by G6P
- oral
- actively excreted by kidney
- approved for single dose therapy of UTI
- synergistic with beta lactams, aminoglycosides, fluoroquinolones
A
fosfomycin
24
Q
- markedly nephrotoxic
- topical antibiotic only
A
bacitracin
25
- basic peptides, act as detergents
- active against gram negatives, except proteus and neisseria
- limited to topical use due to systemic toxicity (esp. renal)
- salvage therapy for highly resistant acinetobacter, pesudomonas, and enterobacteriae
polymixin B and E (colistin) , membrane active drugs
26
- target is different in pathogen than host
| - substantially less selective toxicity than with ICWS
inhibitors of protein synthesis (IPS)
27
- reversible binding to 30S subunit, bacteriostatic, selectivity based on bacterial uptake
- oral, chelate metal ions so don't admin with food/milk/antacids
- well distributed except CNS, concentrates in teeth, bone, liver, bile, kidney
- cross placenta, excreted in milk
tetracyclines
28
- broad spectrum
- mycoplasma, chlamydia, rickettsiae
- Lyme disease
tetracyclines
29
adverse effects of tetracyclines?
- GI irritation
- superinfections-pseudomonas, proteus, clostridia, candida
- impaired liver function
- photosensitization
- calcium chelation: deposit in teeth and bones, discoloration, growth retardation, deformity
30
resistance to tetracyclines?
- decreased uptake due to efflux pumps
- altered ribosomal proteins or RNA
- common in pseudomonas, proteus
- indiscriminate use/overuse
31
- new generation of tetracyclines, no affected by efflux pump
- slight increased risk of death
tigecycline
32
- macrolide antibiotics
- GI absorption but acid labile , enteric coating or esters
- also IV
- crosses placenta
- excreted in bile
- half life 1-5 hours (except one)
- bacteriostatic or bacteriocidal depending on dose
erythromycin, clarithromycin, azithromycin
33
clinical uses of macrolide antibioitics?
- gram (+), some gram neg and mycobacteria
- backup for penicillins in pen-sensitive patients
- azithromycin and clarithromycin broader spectrum
- mycoplasma pneumonia, legionnaire's, chlamydia
34
adverse effects of macrolide antibiotics?
- GI
- microsomal enzyme inhibition- drug/drug interactions, oral anticoags, digoxin, antihistamines
- hepatotoxicity-esp with erythromycin estolate, cholestatic jaundice
35
resistance to macrolide antibiotics?
- staph resistant, some strep and pneumo
- altered methylated rRNA, efflux pump, esterase which hydrolyzes erythromycins
- methylation and efflux pumps
36
- minimal P450 based interactions
| - tissue levels 10-100X plasma levels, 1/2 life 2-4 days
macrolide antibiotics
37
clarithromycin and mycobacterium active against _______ in AIDS patients
avium intracellulare
38
- ketolide, semi synthetic macrolide
- oral
- metabolized in liver
- poor substrate for efflux pump
- once daily dosing
- respiratory tract infections (CA-pneumonia, bronchitis, sinusitis)
- inhibits CYP3A4
- QT prolongation
telithromycin
39
- bactericidal-irreversible inactivation of 30S ribos
- multiple effects on translation: misreading of mRNA, interfere with initiation, break up polysomes
- poor oral absorption, given IV
- no significant host metabolism
- glomerular filtration, very high concentrations in proximal tubules
- concentration dependent killing
aminoglycosides
40
- use concentration dependent killing
- peak serum concentration relates to extent of killing
- higher peak values result in increased efficacy and decreased development of resistance
aminoglycosides, fluoroquinolones
41
clinical uses for aminoglycosides?
- non resistant gram (-) infections (Ecoli, proteus, pseudomones)
- pseudomonas: gentamicin > tobramycin > amikacin
- streptomycin and getamicin are older, use older first
42
related to aminoglycosides, used for penicillin resistant gonococci?
spectinomycin
43
adverse effects of aminoglycosides?
- nephrotoxicity: high concentrations in renal cortex, usually reversible
- ototoxicity: loss of vestibular/auditory function, may be reversible
- neuromuscular blockage: common during surgery, myasthenia gravis
44
resistance to aminoglycosides?
- increased bacterial metabolism through adenylation/acetylation/phosphorylation
- alteration in bacterial uptake
- altered ribosomal protein
45
- reversible inhibitor of protein synthesis: bacteriostatic, broad spectrum
- pharmacokinetics: CNS levels=serum levels
- plasmid mediated resistance, slow development
- adverse effects: GI following fungal superinfection, anemia due to bone marrow suppression, aplastic anemia, usually irreversible and fatal, gray baby syndrome
chloramphenicol
46
clinical use of chloramphenicol?
- powerful antibacterial, use limited by toxicity and resistance
- typhoid fever, rocky mountain spotted fever
47
- lincosamide- antibiotic, bacteriostatic
- well absorbed and distributed, except CNS
- useful against bacteroids fragilis, other anaerobes
- MRSA, endocarditis prophylaxis
- GI upset, C diff superinfections, hepatotoxic
clindamycin
48
- peptide macrolactones
- IV, potent CYP3A4 inhibitor
- block sites affected by macrolides and clindamycin
- approved for use against vanco resistance enterococcus faecium, MRSA
- no cross resistance with other IPS
streptogramins (quinupristin, dalfopristin)
49
- prevents formation of 70S ribosome (unique), no cross resistance with other IPS
- bactericial against streptococci, bacteriostatic against staph and enterococic
- primary indication: vancomycin resistant E. faecium (limit to multi drug resistant gram + infections)
- bone marrow suppression, thrombocyopenia
linezolid (oxazolidinone)
50
- PABA analogs, competitive inhibitor of dihydrofolate synthesis
- bacteriostatic
- oral, topical for burns
- acetylation yields inactive metabolite
- excreted in urine
sulfonamides
51
- topical for burns
- opthalmic
- UTIs
- ulcerative colities
- adverse: allergic reactions , Stevens Johnson
- resistance: overproduction of PABA
sulfonamides
52
- dihydrofolate reductase inhibitors
- treat UTI, usually combined with sulfonamide
- used for pneumocystic pneumonia, complicated UTI, many others
- combo is bactericidal
tremethoprim
53
adverse effects of trimethoprim?
anti folate effects: megaloblastic anemia, leukopenia, granulocytopenia, treat with folinic acid
54
- fluoroquinolones: fluorinated analogs of nalidixic acid
- excreted in kidney, blocked by probenicid
- DNA gyrase inhibitors
ciprofloxacin, levofloxacin, ofloxacin
55
clinical use of fluoroquinolones?
- gram(-) in GI and urogenital tract infections, some gram (+)
- respiratory, skin, soft tissue infections, esp for multi drug resistant organisms
56
adverse effects of fluoroquinolones? resistance?
- connective tissue disorders
| - altered DNA gyrase, decreased permeability, plasmid mediated protection
57
- oxidative stress
- 50% active drug excreted in urine
- treats UTIs, effective at ph < 5.5
- occasional hemolytic anemia
- all pesuodomonas, proteus resistant
nitrofurantonin
58
- blocks synthesis of mycolic acids for mycobacterial cells wall, bactericidal in growing cells only
- TB prophylaxis or chemotherapy
- hepatotoxic, peripheral and central neuropathy (use pyridoxine B6)
- resistance: katG in mycobacterium
isoniazid (INH)
59
- inhibits bacterial RNA synthesis
- inducer of microsomal enzymes, hepatotoxic, orange color to body fluids
- anti mycobacterial chemo
rifampin
60
- inhibits synthesis of mycobacterial cell wall glycan
| - dose dependent optic neuritis, decreased acuity, loss of red green sight
ethambutol
61
- blocks membrane function of mcyobacterium
- gouty arthritis
- contraindicated in pregnancy
pyrazinamide
62
- used for M.leprae
- sulfone, concentrates in skin, muscle, liver, kidney
- hemolysis, methemoglobinemia common
dapsone
