antibiotics med chem Flashcards
mutualistic relationship
both organisms benefit
opportunistic relationship
under normal conditions the microbe does not cause disease, but can if certain conditions are met
features of gram positive bacteria
- Outer peptidoglycan layer
- stains purple
features of gram negative bacteria
- out lipopolysaccharide layer
- porins provide channels through LPS
- stains pink
antibiotics that are from manmade sources
sulfa drugs
fluoroquinolones
linezolid
bacteriocidal
kills bacteria (technically all antibiotics are bacteriocidal at high doses)
bacteriostatic
inhibits growth of bacteria
sugar with the peptide attached for cross linking in peptidoglycan
NAM
amino acids needed to form cross-link
- D-Ala D-Ala on NAM
- pentaglycine chains linking the NAMs
steps of forming peptidoglycan cross-link
in cytoplasm
- synthesize NAM
- attach NAG and prenyl
- add peptide side chain
- flipping into periplasm
in periplasm
5. form crosslink
enzyme that makes crosslinks
transpeptidase
what facilitates transport of NAG and NAM into periplasm
bactoprenol
how does transpeptidation take place?
- penicillin binding protein has an active Ser that attacks the non-terminal D-Ala forming an ester bond
- Ester bond can be attacked by an amine in the pentaglycine chain via transpeptidation, forming a cross link
beta-lactam MoA
mimic D-Ala D-Ala to form a bond with PBP and prevent it from being used to make cross links, thus opening the cells wall
definition of a lactam ring
an intramolecular ring with an amine and a carboxylic acid linked with varying amounts of carbons (alpha=1, beta=2, and so on)
what part of beta-lactams mimics the D-Ala D-Ala peptide
the acidic withdrawing group on the lactam ring
Problems with beta lactams
- degraded by water and stomach acid due to its instability
- resistance via beta-lactamase, penicillinase, and other mechanisms
beta-lactamase function
hydrolysis of penicillins
location of beta-lactamase in gram positive bacteria
outside the peptidoglycan
location of beta-lactamase in gram negative bacteria
periplasmic space, between LPS and cytoplasmic membraine
general SAR of penicillins
- required S in ring
- ring system
- no substitution on ring
- “west end” has amide linkage
- aromatic or cyclic function in “west end” R group
- dimethyl on east end
penicillin G features
- early penicillin
- very Gm+ (no staph)
- little Gm-
- unstable when given orally
penicillin V features
- early penicillin
- very Gm+ (no staph)
- little Gm-
- given orally b/c of ether electron withdrawing group
early penicillins
Pen G
Pen V
methicillin features
- ortho groups prevent beta-lactamase attack
- ok GM+
- little GM-
- given IV
nafcillin features
- ortho groups prevent beta-lactamase attack
- ok GM+ (staph)
- little GM-
- given IV
oxacillins feature
- ortho groups prevent beta-lactamase attack
- ok GM+ (staph)
- little GM-
- given oral
penicillinase-resistant penicillins
- methicillin
- nafcillin
- oxacillins (oxacillin, cloxacillin, dicloxacillin)
ampicillin/amoxicillin features
- amino group good for passing through porins
- good Gm-
- good Gm+
- good substrate for beta-lactamase
- ineffective against pseudomonas
- given orally
broad-spectrum penicillins
ampicillin
amoxicillin
broad-spectrum penicillins for pseudomonas
carbenicillin
ticarcillin
carbenicillin features
- has alpha-acidic group
- broad Gm-
- reduced Gm+
- useful against pseudomonas
- given IV
ticarcillin features
- has alpha-acidic group
- broad Gm-
- reduced Gm+
- useful against pseudomonas
- given orally
broad spectrum ureido penicillin
piperacillin
piperacillin features
- has urea-like group linker
- piperazine ring gives great Gm- penetration
- resistant to Gm- beta-lactamases
- susceptible to Staph beta-lactamase
- given IV
- good for pseudomonas and anaerobes
clavulanic acid features
- similar structure to penicillins, except has O in place of S and unsaturated C-2
- given with other beta-lactams to deal with beta-lactamase resisitance
clavulanic acid MoA
irreversible inhibitor of beta-lactamase
penem drugs
thienamycin
imipenem
meropenem
ertapenem
penem features
- very broad Gm-
- PBP binder
- no S or O in lactam ring
- long N and S based chain from ring
- anaerobes
- pseudomonas
cilastatin features
- taken with imipenem to prevent degradation
- don’t give w/ drugs that have methyl on lactam ring
monobactam drug
aztreonam
aztreonam features
- no intramolecular ring attached to lactam
- sulfate EWG group
- PBP binder
- good Gm-
- pseudomonas
- given IV
features of cephalosporins
- 6 member ring attached to lactam
- “west end” like penicillin
- leaving group attached to 6 mem ring
- acidic group required on 6 mem ring
1st gen cephalosporin drugs
cefalexin
cefazolin
cefalexin features
- broad Gm+
- limited Gm-
- none for MRSA
- given orally, ampicillin like side chain
cefazolin features
- broad Gm+
- limited Gm-
- none for MRSA
- given IV/IM
2nd gen cephalosporin drugs
cefuroxime
cefoxitin
cefotetan
cefuroxime features
- broad Gm+
- ok Gm-
- some beta lactamase resistance
- prodrug required for oral, IV
cefoxitin features
- broad Gm+
- ok Gm-
- some beta lactamase resistance
- anaerobes
- has methoxy to protect from beta lactam
- IV
cefotetan features
- broad Gm+
- ok Gm-
- some beta lactamase resistance
- anaerobes
- toxic tetrazole group that can case BLEEDING
drug that can cause bleeding
cefotetan
3rd gen cephalosporin drugs
cefdinir
cefixime
ceftriaxone
ceftazidime
cefdinir features
- good Gm+
- broadest Gm- of cephalosporins
- some beta-lactamase resistance
- poor leaving group (double bonded C’s) makes it good for oral
cefixime features
- good Gm+
- broadest Gm- of cephalosporins
- some beta-lactamase resistance
- poor leaving group (double bonded C’s) makes it good for oral
ceftriaxone features
- good Gm+
- broadest Gm- of cephalosporins
- some beta-lactamase resistance
- no pseudomonas
- IV
ceftazidime features
- poor Gm+
- broadest Gm- of cephalosporins, including pseudomonas
- some beta-lactamase resistance
- given with avibactam
- IV
avibactam
suicide inhibitor of beta-lactamase, given with ceftazidime
why is MRSA resistant
uses PBP2a instead of usual PBP
ceftaroline fosamil features
- 5th gen cephalosporin
- active against PBP2a MRSA
fosfomycin features
- similar to phosphoenolpyruvate
- inhibits enolpyruvyl transferase which makes NAM sugar
- broad spectrum
- uses a Cys residue to work
how to get resistance to fosfomycin
change Cys to an Asp in enolpyruvyl transferase
2 subunits that make up the prokaryotic ribosome
30S and 50S
70S together
activity sites in ribosome
EPA
2 subunits that make up the eukaryotic robosome
40S and 60S
80S together
aminoglycosides MoA
bind to 30S subunit of the ribosome, blocking initiation of translation or promoting misreading of the code
nonsense mutation
mutation that stops function of the gene
aminoglycosides use
broad spectrum, but mostly Gm- including pseudomonas
aminoglycoside side effects
- ototoxicity (organ of corti; irreversible)
- kidney toxicity (proximal tubule; reversible)
- small therapeutic window*
aminoglycoside general structure
amine sugar that does not have an O in the ring;
is attached to a sugar
aminoglycoside drugs
streptomycin
gentamicin
tobramycin
amikacin
streptomycin use
- Gm-
- tuberculosis and plague
- lots of resistance
- oral
gentamicin use
- Gm-
- UTI
- bone/joint infection
gentamicin unique feature
can be given with beta-lactams, but they cannot be in the same solution or they will inactivate each other
tobramycin use
Gm-
pseudomonas
amikacin use
Gm-
pseudomonas
tuberculosis
(only aerobic infections)
quinolones MoA
inhibit DNA gyrase
quinolone structure features
- double ring, must have a double bond and ketone on right side
- can’t give with multivitamins or Ca because of chelation
quinolone drugs
nalidixic acid
ciprofloxacin
levofloxacin
moxifloxacin
nalidixic acid use
Gm-
UTI
not very potent so high doses are needed leading to AEs like rash and GI
ciprofloxacin use
- Gm-
- pseudomonas
- atypicals
- PO/IV
ciprofloxacin side effects
- possibly erosion of joints
- damaging in 1st trimester of pregnancy
- CNS effects b/c of GABA activity
levofloxacin use
- broad, improved Gm+ over other quinolones
- pseudomonas
- once a day dosing
- PO/IV
two targets in folate synthesis inhibition
- dihydropteroate synthesis (unique in bacteria)
- tetrahydrofolate reductase inhibitors
role of folates
used for methylation of nucleosides and synthesis of purines and AAs
sulfonamide MoA
inhibit dihydropteroate synthase
sulfonamides in pregnancy
avoid near term because of neonatal jaundice
general sulfonamide adverse effects
- crystalluria
- agranulocytosis
- aplastic anemia
- stevens johnson
- skin rashes
trimethoprim MoA
dihydrofolate reductase inhibitor
trimethoprim use
given with sulfamethoxazole because of their different targets in folate synthesis and similar half lives (11 hr)
Bactrim
sulfamethoxazole and trimethoprim
-used for Gm+ and Gm-
imiprenem and meropenem use
- Gm+
- Gm-
- pseudomonas
- anaerobes
what should we never treat enterococcus with
carbapenems or cephalosporins
ertapenem lacks what activity
pseudomonas
acinetobacter
enterococcus
Cefipime features
- Gm+
- Gm-
- psuedomonas
- no anaerobes (preferred over zosyn when none present)
- IV
ceftaroline features
- Gm+
- Gm- (no pseudomonas)
- MRSA
- IV
TMP/SMZ combo use
- Gm+
- Gm-
- MRSA
TMP/SMZ side effects
- GI
- rash
- hyperkalemia
