Antibiotics: Pharmacology Flashcards
Which are the beta lactams
penicillins, cephalosporins, carbapenems, and beta-lactamase inhibitors
** all have the lactam ring
MoA of beta lactams : cell wall
impact cell wall synthesis via inhibition of the transpeptidation reaction
- Bind covalently and block PBP so that it can no longer remove terminal alanine; no cross linking occurring + peptidoglycan synthesis
**only kill cells that are actively growing
T or F: B lactams oral absorption is impaired by food
T - all except amoxicillin
— rest needed to be dosed 1-2 hours before or after a meal
Which beta lactams are acid stable
penicillin, amoxicillin, ampicillin and cloxacillin: can be given orally
Main SEs of Beta lactams
GI: N/V/D
Secondary opportunistic infections
- skin rash or hypersensitivity (cross reaction in class and across classes)
How does B lactam hypersensitivity occur
penicillin Ags are presented during metabolism to immune cells when bound to protein
- recognized as non-self and mount response against
What is the main mech of B-lactam R
Beta-lactamase: destroys beta lactam ring —- and therefore Abx activity
- included for penicllins, cephalosporins, carbapenems
2nd mech of R for beta lactams
modification of PBP (ex/ Strep. pneumo)
—- responsible for MRSA too
impaired penetration: gram - (more layers); efflux pumps (gram -)
B lactamase inhibitors include…
clavulanic acid and tazobactam
T or F: beta lactamase inhibitors have strong antibacterial activity on their own
F - they act as a suicide molecule and used in combo with beta lactam
—- distracts B-lactamase while beta lactam actually does its shit
** extends the penicillin activity too to include those with R because of beta lactamase production —- Beta lactam producing strands of S. aureus
What penicillins are b-lactamase inhibitors used in combo with
amoxicillin, ticarcillin, piperacilin
T or F: penicillin G is oral and V is IV
F - G is IV and V is oral
What are the anti-staphylococcal penicillins
Cloxacillin
- food impacts its absorption
What are the anti-pseudomonal penicillins
ticarcillin, piperacillin
What makes cephalosporins different than penicillins (structure)
beta lactam ring + 6C ring
penicillins: beta lactam ring + 5 C ring
T or F: penicillins tend to have a broader spectra than cephalosporins
F - cephalosporins is broader
T or F: all cephalosporins are prodrugs
F - some are prodrug esters
T or F: you can get cross sensitivity bw penicillins and cephalosporins
T - 1-5%
Special ADRs of cephalosporins
nephrotoxicity - high doses
disulfiram-like reactions: inhibit alcohol dehydrogenase so if drink get build up of acetaldehyde
What are the carbapenems
Include imipenem. meropenem and ertapenem
— same MoA: beta lactam
** imipenem is co-adminned with cola statin to prevent its breakdown in the kidney
SEs of carbapenems
N/V
seizures
cross reactivity with penicillins
T or F: Vanco is orally available
F - only IV unless treating GI shit
T or F: vancomycin targets the cell wall like Beta lactams
F - cell wall targeting but different MoA
binds to ala-ala terminal of peptidoglycan chain and prevents building
T or F: Vanco can’t penetrate gram - bacteria’s outer membrane
T == only impact gram +
Unique SEs of Vanco
IV admin shit
toxicities associated with ear and kidney
- rare and not seen in humans ; just animal models
Main mech of R to Vanco
mutation of target site (Ala-Ala) to Ala-Serine or Ala-lactate
What is Fosfomycin
Non-beta lactam cell wall agent
- inhibits the MurA enzyme that produces peptidoglycan by acting as a PEP analog
** inhibits earlier on the cell wall synthesis pathway
ADRs of fosfomycin
Nausea, diarrhea, headache, neutropenia, angioedema
What are the bacterial ribosomal parts
30S and 50S
human : 40S and 60S
- different enough that targeting is relatively selective for B
What is included in the protein synthesis inhibitors
Tetracyclines (doxy), marcolides, clindamycin
What is the general structure of tetracyclines
4 ring system that is hydrophilic
MoA of tetracyclines
inhibit protein synthesis by binding to the 30S subunit and blocking incoming tRNA
- slow/stop translation
T or F: Doxy is excreted in urine but also can undergo enterohepatic recycling
T
Tetracycline SEs
GI
photosensitivity
liver toxicity: high doses
renal toxicity: Fanconi syndrome (expired tetracyclines)
Vestibular Rxn - minocycline
When is it not safe to use tetracyclines
kids and pregnant people — chelate and bind to Ca
- accumulate in these areas and can impact bones and teeth
rxn related to dose: weight (not duration )
Doxy- only exception to this because decrease AFF to Ca
Main Mech of R to Tetracyclines
Drug Efflux (pump shit out)
MoA: Macrolides
protein synthesis inhibitors
- bind reversible to 50S unit and inhibit transpeptidation and translocation
What are the macrolides
azithromycin, clarithromycin and erthromycin
Which of the macrolides is the best absorbed
Clarithromycin
- Azithromycin is best on empty stomach and shouldn’t be taken with antacids
- Erythromycin: acid labile and needs enteric coat
What metabolizes the macrolides
CYP 3A4
Which macrolides inhibit P450 enzymes
Clarith + Erythro but not Az
SEs of Macrolides
GI: anorexia, N/V/D
fever, eosinophilia, rash
hepatotoxicity: erythromycin
QT prolongation
Which macrolide has the highest risk of QT prolongation
E> C> A
** more risk when already have long QT interval
T or F: there is one main mech of R for macrolides
F - they have just a shit ton
1) Reduce permeability (gram -) or active efflux (gram +)
2) destroy them via esterases
3) modification of ribosomal site (mutate target)
What is Clindamycin? MoA
not a macrolide; acts like one but chemically different
- MoA; binds to 50S and blocks (can have cross R bw macrolides and clindamycin; also will compete for same spot if coadmin)
SEs of Clindamycin
N, D
skin rash
impaired LFT
neutropenia
MoR for Clindamycin
Ribosomal access
- poor porin permeability (gram -)
no impact by efflux pumps in gram + — gram + can’t pump out*
decreased ribosomal binding: change target
What are the DNA targeting ABx
FQ
What are the FQs
Ciprofloxacin, norfloxacin, ofloxacin
Resp FQ: levofloxacin, moxifloxacin, gemifloxacin
— bactericidal
FQ: MoA
block DNA synthesis
1) Inhibt DNA gyrase/topoisomerase II: DNA can’t uncoil and relax
2) Block Topoisomerase IV: replicated DNA does’t separate properly into cells during division
** expressed in humans too but relatively selective for B>H by 100-1000
T or F: FQs are normally given orally
T
FQ: ADRs
GI
photosensitivity
headache, dizzy, drowsiness, insomnia
skin rash, abnormal LFTs
QT prolongation
cartilage and tendon damage: only seen in animal models
—— why not used in those younger 18 years or pregnant people
Main MoR for FQ
mutations in binding region of target enzyme
- mutation of gyrA subunit of DNA gyrase
others: change permeability, expression of proteins that protect DNA gyrase from FQ
MoA: Metronidazole
Nitro group on Abx is metabolized into toxic radical in anaerobic bacteria
— ferrodoxins reduce nitro group to radical to react with DNA and cause damage
** only impacted by aerobic bacteria, inhibited by O2 levels that are high
** once done its shit, gets regenerated and can repeat
DF for Metronidazole
IV, oral or suppository
SEs of Metronidazole
headache
N/V/D
dry mouth
disulfiram like effects
increased prothrombin time
Rare (CNS): ataxia and paresthesias
- associated with duration of therapy
Main MoR: Metronidazole
mutation that impairs production of nitro anion
- decrease O2 scavenging ability (can’t get rid of O2 as well in bacteria)
- decreased levels of ferredoxin
What is Fidoxamicin? MoA
Thicc boi that works against gram + and anaerobic bacteria
- binds to sigma subunit of RNA poly - inhibit it and transcription
** used for C. difficile
