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37 Cards in this Set

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Bactericidal Antibiotics: Concentration dependant
These are classified as Type I, Concentration Dependant effect w/ SIGNIFICANT PAE (post antibiotic effect)


Lipopeptide daptomycin, aminoglycosides, ketolides, fluoroquinolones, nitroimidazole, rifamycin

Bactericidal Antibiotics: Time dependant
These are classified as Type II, time dependant effect w/ NO PAE.

beta lactams (NONE FOR GRAM -), glycopeptides (vancomycin action on Gram Pos Rods -- it's bacteriostatic against Gram Pos Cocci).
Bacteriostatic Antibiotics
These are Type III, time dependant with moderate to prolonged PAE.

glycopeptides (Gram Pos Cocci), oxazolidinones, tertracycline, glycylcycline chloramphenicol, macrolides, lincosamine, sulfonamides

some beta-lactams have some PAE effect (none for Gram Neg though).
Glycopeptide Antibiotics: VANCOMYCIN
STATIC: Gram Pos Cocci
CIDAL: Gram Pos RODS (incl penicillinase producers and methicillin-resistant strains)
Glycopeptide Antibiotics: VANCOMYCIN... Mech of Action
Binds D-Ala-D-Ala terminus of Murine monomer, and prevents Transglycosylase from attaching disaccharide subunits to pre-existing cell wall. (NO THE NEW NAM-NAG ISN'T ABLE TO JOIN THE PREXISTING CHAIN)

Inhibition by binding the SUBSTRATE (unlike PCN which binds the enzyme)

not effective against Gram Neg
Glycopeptide Antibiotics: VANCOMYCIN... Mech of Resistance
acquisition of van HAX gene, allows it to replace the terminal D-ala with D-lactate, so vancomycin cannot bind to the end of the pentapeptide chain.
Glycopeptide Antibiotics: VANCOMYCIN... Pharmcokinetics
Poorly absorbed from GI, orally used to treat pseudomembranous colitis and Staphylococcal enterocolitis

Pri renal elimination.

No cross resistance or sensitivty to beta lactams, so can be used in these individuals to treat SERIOUS STAPHYLOCOCCAL AND STREPTOCOCCAL infections.
Glycopeptide Antibiotics: VANCOMYCIN... Adverse effects
RED MAN SYNDROME (hypersensitivity rxn: skin flushing, nephro, ototoxicity, neutropenia, tissue necrosis if given IM.
Glycopeptide Antibiotics: TEICOPLANIN
Since glyopeptide antiobitics are time dependant, and w/out much PAE, TEICOPLANIN is a good drug because:

extended Half-Life of elimination, Once daily dosing, fewer side effects (NO OTOTOXICITY), no tissue necrosis after IM.
Beta Lactams
Includes Penicillins, cephalosporins, carbapenemes, monobactam

Bactericidal: so requires actively growing infection
Beta Lactams: Mechanism of action
inhibition by binding the ENZYME (Transpeptidase)

This inhibits synthesis of crosslinks between repeating disaccharide subunits of cell wall.
- These bind the enzyme by mimicing the structure of D-alanyl-D-alanine substrate for transpeptidase.

The second way it works is by activating or disinhibiting autolytic enzymes which normally function to breakdown the cell wall during cell growth and division.

Both result in weakning of cell wall and osmotic pressure outwards causes rupture of the microorganism.
Beta lactams: Mech of Resistance
4 ways:

1. incrase penicillinase acitivity

2. decrease affinity for PCN binding protein (PBPs) through mutations.

3. decrease cell membrane permeability so drug can't get in.

4. active efflux of the drug out the cell.
Beta lactam: Strategy to overcome pencillinase depenant resistance?
introduce beta lactams and 'sucidice inhibitors' of pencillinase (beta lactamase) i.e.


UNASYN: ampicillin plus SULBACTAM

ZOSYN: pipericillin plus TAZOBACTAM
Beta lactams: ADVERSE EFFECTS (except Monobactams)
allergic rxn (drug's polymers and metabolites react with bacterial and tissue proteins to form antigenic conjugates).

Diarrhea (kids and children)

Cardiovascular effects due to fluid overload secondary to salts present in drug

CNS especially in renal failure pts (due to GABA inhibition: cause hallucinations and convulsions)

COAGULATION DEFECTS: esp w/ CARBENICILLIN AND TICARCILLIN (anti-pseudomonals). It inhibits platelet activation and conversion of fibrinogen to fibrin.
beta lactam: Structure: significance of the B ring
the B ring is active center of the drug, site of pencillinases, site of formation of major antigenic determinants
beta lactam: Structure: significance of the R group
acid stability, sensitivity to pencillinase acitivty, antibacterial spectrum and potency.
Beta lactams: Pharmacokinetics
good distro except CSF, PCNs organic acids so ionized at physio pH. Therefore, provided as Na or K salts.

Pri Elim: renal secretion of unmetabolized drug (short half life).

Hepatic metab not important for elimination but metabolites generated are important for generation of hypersensitivity reactions.
Beta Lactams: Natural PCNs: PCN G and V
natural compounds, has 6-aminopenicillanic acid nucleus composed of thaizolidine ring fused to a beta-lactam ring
Beta Lactams: Natural PCNs: PCN G
PCN G: most active against BROAD spectrum, GRAM POS, non-pencillinase producers. PCN G is acid labile, so only 1/3 oral dose is absorbed

Esp active against Neisseria and some anaerobes

blood levels extended by: delaying absorption by combining with PROCAINE or BENZATHINE (v. effective against SYPHILIS); OR delay elimination by adminstration of PROBENECID, competivite blocker of tubular secretin of organic acids.
Testing for PCN Hypersensitivity?
Skin testing: challenge with Pre-Pen to predict 95% of IgE mediated hypersensitivtiy. So, NEG test doesn't guarantee absne of anaphylactic response.
Beta Lactams: PCNase resistant PCNs
Think: i MET NAsty OXen

METhicillin, NAfcillin, OXacillin, clOXacillin, diclOXacillin
Beta Lactams: PCNase resistant PCNs: Pathogen spectrum
Initial therapy for beta lactamase producing gram positive coccal infection.


Ideal for beta lactamase producing Staph aureus and staph epidermis

NOT active against Gram Negative
Methicillin resistance (MRSA)
related to failure to bind PCN binding proteins.

These organisms are likely to be resistant to other PCNs and Cephalosporins
think i AM extended

AMpicillin, AMoxicillin

First PCN effective against Gram Negative (makes sense: it's there long enough to penetrate the Gram Negative. Also due to decrease susceptibility to Gram neg PCNases) These are more susceptible to Gram Pos PCNases though.

Amoxicillin more completely absorbed.

Active against: E. coli, P. mirabilis, H. influenza, Salmonella, Shigella, and Neisseria.
beta lactams: Antipseudomonal PCNs
think 'pseudo-CARs have tail PIPES'

Extended via carboxylation: CARbenicillin, tiCARcillin; extend range to Pseudomonas aeruginosa, Proteus and Enterobacter. ; OFTEN RESERVED FOR PULMONARY INFXN.


Extended through N-acyl derivaation: PIPEricillin
beta lactams: Cephalosporins
similar action as PCNs, but wider range of activity due to alteration of R groups, PCNase resistance and pharmakokinetics.
Cephalosporins: First Gen

A is the first letter in alphabet, so First Gen

narrow spectrum, Gram Pos

NO active infection, SURGICAL PROPHYLAXIS, does not penetrate CNS

No mrsa, no gram neg
Cephalosporin: Second Gen
Increased activity against Gram Negative, decreased activity against Gram Pos

CEFOTETAN and CEFOXITIN: Bacterioides fragilis (G-) and other anaerobic organisms, PROPHY during abd surgery

CEFUROXIME: H influenza, K pneumoniae (used in community acquired pneumonia), CROSSES BBB, use IV

LORACARBEF: aka carbacephem, acitivity comparable to amoxicillin/clavualante combo (Augmentin)
Cephalosporin: Third Gen

Highly active against Gram NEG enteric bacteria

BROADER spectrum: both Gram Neg and Pos.

CEFTRIAXONE: N gonorrhea, B burgdorferi (Lyme Dz)

CEFTAZIDIME, CEFOPERAZONE: indicated for Multi-drug resistant GRAM NEG ifxn esp. P. aeruginosa.
Cephalosporins: Fourth Gen
CEFEPIME: similar to ceftazidime in activity against P. aeruginosa, and other gram Neg;

better than Third gen against GRAM POS due to resistance to chromosomally encoded Beta lactamase

Cephalosporin Adverse effects
BLEEDING: (cefoperazone and cefotetan) due to hypothrombinemia, thrombocytopenia, Vit K deficiency

Bleeding common in ELDERS

nephrotoxicity esp. in combo with aminoglycosides

superinfection: wipe out enteric bacteria

Hypersensitivity (same as PCN)

Disulfiram-like Alcohol reaction w/ methylthiotetrazole group. Increased acetal dehydrogenase
Carbapenems: Imipenem
extremely broad spectrum, resistant to beta lactamase, rapidly hydrolyzed by RENAL dipeptidase so given in COMBO with CILASTATIN (dipeptidase inhibitor) as PRIMAXIN

NOT resistant to metallo-beta-lactamases,

Cross allergencities to PCN.

CNS seizures and renal toxicities
Carbapenems: Meropenem
similar to imipenem but less susceptible to renal tubule dipeptidase (doesn't require cilastin)

Less nephrotoxic than imipenem
Monobactam (aztreonam)
excellent activity against Gram Neg bacteria, poor Gram Positive

little cross-allergenicity with other beta lactam antibiotics (THE ONLY ONE)

Can be used in some cases instead of aminoglycosidases.
Lipopeptide antibiotic: Daptomycin
inhibition of cell membrane potential by forming membrane channels in Ca-dependant manner resulting in depolarization of the membrane inhibiting protein, DNA and RNA synthesis.
Lipopeptide antibiotic: Daptomycin... Pathogen spectrum
used for complicated skin and skin structure infections by aerobic, Gram Positive incl. resistant gram pos bacteria, also isolates resistant to methicillin, vacomycin, and linezolid (BIG GUN)

synergizes with oxacillin against MRSA.

Bactericidal against VRE (vancomycin resistant enterococci)
Lipopeptide antibiotic: Daptomycin... Pharmcokinetics
IV only (IM causes tox to muscle), excreted by Kidney (dose adj req'd for renal insufficiency)

Adv effects: irritation to site of injectin, skeletal muscle pain and weakness, increase CPK, renal failure.