ID- Pharmacology Flashcards
What is the MOA of B-lactam antibiotics
- inhibits cell wall synthesis by binding covalently to the active sites of PBPs to inhibit the transpeptidation reaction
What does the absorption of penicillin depend on? Which can be given orally? With food? Without food?
Depends on acid stability
Oral: Penicillin V, amoxicillin, ampicillin & cloxacillin
Amox–> ONLY one to give with food
The rest without food
What is the most serious ADRs of penicillins? Explain its mechanism? Common side effects? dose-dependant?
Hypersensitivity
- Antigens are presented during penicillin metabolism when they are transiently bound to a protein –> results in hapten that is identified by non-self by the immune system
Common: uticaria, fever
Not dose-dependant
What is the primary mechanism of B-lactam resistance
B-lactam inactivation by B-lactamase
What are the B-lactam inhibitors?
MOA?
Clavulanic acid, sulbactam, tazobactam
MOA
- high affinity for catalytic site of B-lactamases –> inhibit hydrolysis of B-lactam
What does adding clavulanic acid to amoxicillin add to the spectrum?
Targets strains of STAPH. AUREUS and some gram-negative (better H. flu, better Proteus mirablis, + klebsiella pneumo)
What are the anti-staphylococcal penicillins?
Nafcillin, methicillin, cloxacillin
What are the anti-pseudonomal penicillins? what else does it target
ticarcillin, pippercillin
- targets gram-negative aerobes
What are some ADRs of cephalosporins
Sensitizing
Nephrotoxicity (at high doses)
What is the MOA of vancomycin?
Targets cell wall (not b-lactam)
- binds the Ala-Ala terminus of the peptidoglycan pentapeptide (instead of PBP)
How to administer vancomycin
IV
- oral for GI infections
Main Spectra of vancomycin
only gram-pos
- does not penetrate outer membrane of gram-negative bacteria
What are serious toxicities with vancomycin?
- in ear and kidney
- increase the risk of aminoglycoside nephrotoxicity
What is the resistance associated with vancomycin? Innate and acquired?
Innate (natural): to gram-neg
Acquired:
- altered cell wall precursors by switching the 2nd Ala group to lactate or serine
- binds less vancomycin
Fosfomycin MOA?
non b-lactam cell wall agent
-1. PEP analog –> inhibits MurA enzyme (needed for peptidoglycan cell wall synthesis)
2. Decrease the ability of bacteria to interact with the urinary tract epithelium
What are the protein synthesis inhibitors of bacteria? (4)
- Aminoglycosides
- Tetracyclines
- Macrolides and clindamycin
- linezolid
Which ribosomes do bacteria use for protein synthesis? Which do mammals?
30S + 50S
mammals: 40S + 60S
What is the MOA of tetracyclines?
bind to 30S subunit and block binding of incoming tRNA
- results in non-functional proteins and wrong AA addition
What is the metabolism of tetracycline?
Excreted into urine, bile, some enterohepatic recycling
What are the ADRs of tetracyclines
Gi
photosensitization
Liver toxicity (large doses)
Renal toxicity
What are toxicities of tetracyclines? exception?
calcium chelation (related to dose)
- tetracyclines bind to and damage growing bones and teeth
Exception: doxycyclines
What is the primary resistance mechanism of tetracyclines
Drug efflux pumps
Explain what each efflux pumps work in?
Tet AE
Tet K
Tet M
Tet AE: in gram-neg bacteria
Tet K: in staphlyococci against tetracyclines
Tet M: in gram positive
Which tetracycline is less susceptible to efflux pumps? why? Exception
Tigercycline
- bc of bulky side chain
except Proteus bacteria + pseudomonas
What are the macrolides (3)
erythromycin
clarithromycin
azithromycin
What is the MOA of macrolides
bind reversibly to the 50S ribosomal subunit
- inhibits transpeptidation/translocation steps in protein information
What are PK notes for each
erythromycin
clarithromycin
azithromycin
erythromycin: must be enteric coated
clarithromycin: best absorbed
azithromycin: empty stomach
What is the order of half-lives of macrolides
Azith > clarithromycin > erythromycin
Explain the resistance that macrolides experience (4)
- Reduced permeability of cell membrane (in gram neg)
- Active efflux (in gram-pos)
- Esterases production –> hydrolyze macrolides
- Target modification of 50S
What is the MOA of clindamycin
Same as macrolide
(bind reversibly to the 50S ribosomal subunit
- inhibits transpeptidation/translocation steps in protein information)
What is the resistance of clindamycin? What is the difference between this and macrolides
- Reduced permeability of cell membrane (gram-neg)
- Target modification of 50S
NOT AFFECTED BY EFFLUX PUMP (gram-pos)
What are the DNA-targeted antibiotics? (3)
- Fluroquinolone
- sulfonamide
- Trimethorprim
What are the bactericidal fluoroquinolones and respiratory fluoroquinolones?
Bactericidal
- cipro
- norfloxacin
- ofloxacin
Respiratory
- levofloxacin
- gemifloxacin
- moxifloxacin
What is the MOA of fluoroquinolones
Block DNA synthesis by inhibiting 2 bacterial enzymes
- Topoisomerase II
- prevents relaxation of DNA so that normal transcription/translation does not occur - Topoisomerase IV
- prevents separation of replicated chromosomes into daughter cells
What is the unique toxicity associated with fluoroquinolones
Cartilage damage (not recommended for patients under 18)
What are the resistance mechanisms of fluoroquinolones? (3)
- Target enzyme mutation (gyrA subunit of Topoisomerase II)
- Change in permeability
- Proteins that protect from Topoisomerase II
What is the MOA of metronidazole?
The nitro group on metronidazole is reduced –> highly reactive nitro radical anion –> affects DNA
- O2 inhibits metronidazole
(made for anaerobes)
What is metronidazole toxicity associated with? reason?
Associated with duration of therapy
What are resistance notes of metronidazole?
- Mutations that impair the production of nitro radical anion
- Decreased oxygen-scavenging (increase O2 in the cells = bad)
What is fidoxamicin used against?
macrolytic antibiotic against gram-positive and anaerobic bacteria
- used for C. difficile infections
Oral
MOA of fidoxamicin?
Binds the sigma subunit of RNA polymerase
- more selective for bacteria
What is the MOA of oeltamivir/zanamivir?
Neuraminidase inhibitors
- interact with neuraminidase and causes a conformational change; this inhibits the enzyme’s activity
- results in the virus aggregating at the cell surface and reduced spread
