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89 Cards in this Set

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MIC?
minimal inhibitory concentration
Frequency of bacterial mutation:

1 mutation per ___ cells
1 to 10^16 cells
Broad spectrum antibiotic therapy commonly causes what female problem
vaginitis
What pt should not receive bacteriostatic drugs?
immunosuppressed
3 Adaptations that lead to resistance
lipopolysaccharide coat changes to alter uptake

transport system is altered to remove drug from cell

metabolism changes to bypass the effect of the drug
What entities code for enzymes that inactivate antibiotics?
plasmids and transposons
Most common complaints about antibiotics
Diarrhea and nausea

bad taste
Best way to pick a drug?
Culture (and sensitivity)

C&S
Inhibitors of cell wall synthesis
ß-lactams
Polypeptides
Protein synthesis inhibitors
Aminoglycosides
Chloramphenicol
Clindamycin
Macrolides
Ketolide
Streptogramin
Oxazolidanone
Tetracyclines
Folate Antagonists
Sulfonamides
Trimethoprim
Others
Quinolones
Urinary tract antiseptics
Final step in synthesis of bacterial cell wall is a cross linking of adjacent peptidoglycan strands - this is called what?
transpeptidation
Penicillins and cephalosporins Structures are similar to what part of bacteria
the terminal portion of the peptidoglycan strands



Result is bacteria with structurally weakened cell walls and death
All contain a ß lactam ring (4)
Penicillins
Cephalosporins
Carbapenems
Monobactams (Aztreonam)
Most common mode of resistance to beta lactams is _______
plasmid transfer of the genetic code for ß lactamase
Specific ß lactamases
(2)
Penicillinase
Cephalosporinase
ß lactamase inhibitors (3)
Clavulanic acid
Sulbactam
Tazobactam
3 penicillins
Penicillin G
Penicillin V
Benzathin pen G
Penicillinase Resistant (5)
Methicillin
Cloxacillin
Dicloxacillin
Nafcillin
(MnO3)
Oxacillin
Aminopenicillins (2)
Amoxicillin
Ampicillin
Spectrum of Penicillins
narrow (gm-pos)
spectrum of aminopenicillins
broad (gm-pos and some gm-neg)
Extended Spectrum penicillins (5)
Azlocillin
Carbenicillin
Mezlocillin
Piperacillin
Ticarcillin
(Takes Care of Pseudomonas And Me!)
spectrum of extended spectrum penicillins
extended (gm-neg -- rarely gm-pos


active against pseudomonas
Penicillins:
Most can only cross the blood brain barrier if it is _____
inflammed


(use in meningitis)
Generally, oral absorption of penicillins are
a) adequate
b) poor
c) good
poor
Penicillins are excreted by active tubular excretion which can be blocked by concurrent administration of _______
probenecid (prolongs action)
3 types of hypersensitivity rxns with penicillins
Immediate
Accelerated
Late
symptoms of immediate reaction
pruritis,
paresthesia,
wheezing,
choking,
fever,
edema,
urticaria
immediate rxn is mediated by what immunological entity?
IgE
possible outcomes of immediate reaction to penicillin
hypotension, shock, death
when do Accelerated reactions happen timewise?
1-72 hrs
Accelerated reactions Consist mainly of _____
urticaria
Late reaction:
More common with_______
semisynthetics
Late reaction is mainly what problem?
skin rashes
time period of late reaction to penicillins
72 hours - weeks after administration
Penicillins: Adverse Reactions
Serious skin reactions
Multiforme erythrema
Stevens Johnson Syndrome
TEN
Toxic Epidermal Necrolysis (TEN)
Cephalosporins: First Generation (2)
Cefazolin
Cephalexin
Spectrum of cephalosporins
Narrow spectrum (similar to broad spectrum penicillins)
Are cephalosporins Sensitive to ß lactamases?
yes
Cephalosporins: Second Generation (3)
Cefaclor
Cefamandole
Cefoxitin
Spectrum of second gen Cephalosporins
Increased activity toward gram negative organisms
Diff from 1st gen?
Increased stability
Cephalosporins: Third Generation (3)
Cefotaxime
Ceftazidime
Ceftriaxone
Spectrum of 3rd gen
Broader spectrum than previous generations
3rd gen diff from 1st and 2nd
More resistant to ß lactamases
Cephalosporins: Fourth Generation (2)
Cefepime
Cefpirome
spectrum of 4th gen
Gram positive and gram negative activity
Effective against Pseudomonas aeruginosa
Also gram negative organisms with multiple drug resistance patterns
Which Cephalosporins penetrate the CNS?
Third and some second generation drugs
(treat meningitis)
Cephalosporins used in the treatment and prophylaxis of infections in hospitalized patients
Third generation
Cephalosporins targeted at organisms with multiple-drug resistance
Fourth generation
Cephalosporins and bleeding: comment
Can interfere with vitamin K (increased bleeding)
Comment on allergies and cephalosporins and penicillins
Some cross-allergy with penicillins
Cephalosporins: do not drink alcohol with cephs.... why?
Disulfiram-like reaction:

Block alcohol oxidation
Acetaldehyde accumulates
Carbapenems (3)
Imipenem
Ertapenem
Meropenem
Carbapenems are administered how?
All administered iv
Imipenem is hydrolyzed by renal ______ in the kidney to a toxic metabolite (and has no antimicrobial activity)
dipeptidase
Why must cilastatin be administered with imipenem?
Cilastatin inhibits dipeptidase so must be administered with imipenem
______ is stable to dipeptidase -does not require coadministration of cilastatin
Meropenem
Monobactams (1)
Aztreonam
Spectrum of monobactams
Narrow spectrum
Aerobic gram negative bacteria including Pseudomonas
Ineffective against gram positive bacteria
monobactams ß lactamase sensitivity?
Highly resistant to ß lactamases
Non ß Lactam Drugs: Cell Wall Synthesis Inhibitors (5)
Vancomycin and teicoplanin
Bacitracin
Fosfomycin
Daptomycin
How do Vancomycin and teicoplanin
Inhibit cell wall synthesis?
by preventing polymerization of the linear peptidoglycans
Spectrum of Vancomycin and teicoplanin
Only effective against gram positive organisms
Bad things about Vancomycin and teicoplanin
Poorly absorbed orally
Dose related ototoxicity (tinnitus, high tone deafness, hearing loss)
Red man syndrome
What drug is this?

Mixture of polypeptides that inhibit cell wall synthesis
Binds to lipid carrier that transports cell wall precursors
Used topically due to serious nephrotoxicity
Bacitracin
What drug is this?

Inhibits one of the first steps in the synthesis of peptidoglycan (enolpyruval transferase)
Used for treatment of UTIs
Fosfomycin
What drug is this?

Binds to membrane of bacteria and causes depolarization
Loss of membrane potential results in death
Daptomycin
What kind of drug is this?

Major route of resistance is blockade of drug from entering the cell
Protein Synthesis Inhibitors

Require binding to intracellular protein (ribosomal subunit) so must enter the cell
Aminoglycosides (7)
Kanamycin
Gentamicin
Amikacin
Neomycin
Netilmicin
Tobramycin
Streptomycin
Spectrum of Aminoglycosides
Broad spectrum antimicrobials but anerobic bacteria are generally resistant
Drug enters bacteria through oxygen dependent transport system
Anerobes do not oxygen dependent metabolism
How are aminoglycosides administered?
Poorly absorbed from GI tract
Most must be administered parenterally

coadministration of penicillins
Why coadministration of penicillins with aminoglycosides?
Usually require a transport mechanism or coadministration of penicillins
Penicillins create cell wall abnormalities that allow aminoglycosides to penetrate the cell
Bad things about aminoglycosides
Narrow margin of safety
Ototoxicity
-Cochlear (auditory)
-Symptoms: tinnitus, deafness, high frequency hearing loss
-Due to selective destruction
of outer hair cells in organ
of Corti
-Vestibular (vertigo)
Nephrotoxicity
-Due to rapid uptake of drug
by proximal tubular cells and
subsequent death
-Acute nephrotoxicity is
reversible
Neurotoxicity
-Due to blockade of
presynaptic release of
acetylcholine at neuromuscular
junction (some postsynaptic
blockade can also occur)
-Symptoms: weakness and
respiratory depression
Tetracyclines (5)
Tetracycline
Chlortetracycline
Oxytetracycline
Demeclocycline
Minocycline - Acne in small white people
DOXYCYCLINE
Can you use expired tetracyclines?
no - degrades to renal toxic compound
How do tetracyclines work?
Accumulate in cytoplasm by an energy dependent transport system which is not present in mammalian cells
How do bacteria get resistant to tetracyclines?
Resistance occurs when bacteria mutate to prevent entry of the drug into the cell
Spectrum of Tetracyclines
Broad spectrum (gram positive and negative organisms, anerobes)
Use tetracyclines to treat what specific diseases?
Rickettsial diseases (Rocky Mountain spotted fever)
Chlamydial diseases
Cholera
Lyme disease (spirochetes)
Mycoplasma pneumonia
Why not eat food with tetracycline?
Form insoluble chelates with calcium, magnesium and other metals
Avoid antacids
Does not occur with doxycyline and minocycline
Why is teetracycline not recommended in children and pregnancy?
Deposited in teeth and bones
why not sunbath with tetracycline?
Photosensitivity
Macrolides (5)
Clarithromycin
Azithromycin
Dirithromycin
Erythromycin
Troleandomycin
Macrolides treat what diseases?
Mycoplasma infections
Pneumonia
Legionnaires’ disease
Chlamydial infections
Diptheria
Pertusis
most common side effect of macrolides?
GI upset


motilin agonist
useful for macrolide resistance organisms
Telithromycin

(Ketolides)