L29- Protein Synthesis Inhibitors I Flashcards
(37 cards)
list the protein synthesis inhibitors
- tetracyclines
- glycylcyclines
- aminoglycosides
- macrolides
- chloramphenicol
- clindamycin
- streptogramins
- linezolid
- mupirocin
Protein Synthesis Inhibitors:
- bacterio-(static/cidal)
- (2) MOA
- (3) MOA’s effects that are basis for AEs
1- bacteriostatic (mostly, aminoglycoside is only bacteriocidal)
2- binds bacterial ribosome (70S = 50S + 30S) —- differs from eukaryotic ribosome (80S = 60S + 40S)
3- binds mammilian mitochondrial ribosome (due to resemblance to bacterial ribosome) => AEs
______ is the only bacteriocidal protein synthesis inhibitor
aminoglycosides
list tetracyclines
- doxycycline
- minocycline
- tetracycline
Tetracycline MOA:
- enters bacteria via (1) in order to concentrate drug intracellularly
- binds (ir-/reversibly) to (3) in order to prevent (4) process
1- passive diffusion + energy dependent transport
2- reversibly
3- 30S subunit of ribosome
4- attachment of aminoacyl tRNA
______ antibiotic works by binding 30S subunit of ribosome in order to prevent tRNA attachment
tetracyclines (T for tRNA)
describe the prevalence and mechanisms of resistance to Tetracyclines
-widespread resistance (due to overuse)- usually plasmid related
1) impaired influx OR inc efflux via plasmid-encoded protein pump
2) bacterial protein production to interfere with binding to ribosomes
3) enzymatic inactivation
Tetracyclines are most commonly used to treat (1) and (2)- (3) is also a popular use of tetracyclines.
1- severe acne
2- rosacea
3- empiric therapy for CA-pneumonia
Tetracycline (monotherapy) is the drug of choice for….. (hint- 7)
- chlamydia
- Mycoplasma pneumoniae (CA-pneumonia)
- Lyme disease
- Cholera
- Anthrax prophylaxis
- Rickettsia (Rocky Mountain Spotted Fever)
Tetracycline is used in combination therapy for the following conditions….
- H. pylori
- Malaria prophylaxis and Tx (doxycycline)
- Tx of plague, tularemia, brucellosis
Tetracycline Pharmacokinetics:
- (1) describe general oral bioavailability among the tetracyclines
- accumulates in (2) tissues
- (3) main route of elimination, (4) is the exception
1- variable — doxycycline is lipid soluble, therefore parenterally admin. preferred
2- liver, kidney, spleen, skin
3- urine
4- Doxycycline –> bile
Tetracycline AEs:
- (1) common AEs
- (2) are the main contraindications due to (3) AEs
- (4) are seen with doxycycline and minocycline
- (5) via renal accumulation
- (6) via skin accumulation
1- n/v/d or superinfections
2- pregnancy, children <8y/o (crosses into placenta and breast milk — teratogen)
3- discoloration and hypoplasia of teeth (via Ca binding), stunting of growth, fatal hepatotoxicity in pregnant Pts (high doses + partial hepatic insufficiency in pregnancy)
4- dizziness, vertigo
5- exacerbation of renal dysfunction
6- photosensitive
list the glycylcyclines
tigecycline
Glycylcyclines:
- effective against (1) bacteria
- (2) describe resistance
(tigecycline)
1- broad-spectrum: MDR Gram+, some Gram- and some anaerobes
2- little resistance — efflux pumps only in Proteus and Pseudomonas spp.
describe clinical use of glycylcyclines
(tigecycline)
Last Chance Antibiotic: inc risk of mortality seen when treating serious infections
-complicated skin, soft tissue, intra-abdominal infections
Glycylcyclines:
- (1) route of administration
- (2) describe distribution
- (3) route of elimination
(tigecycline)
1- IV
2- excellent tissue and intracellular penetration
3- biliary / fecal elimination
Glycylcyclines:
- (1) AEs
- (2) contraindications
1- well tolerated — similar AEs to tetracyclines: n/v/d
2- pregnancy, children <8y/o
list the Aminoglycosides
- amikacin
- gentamicin
- tobramycin
- streptomycin
- neomycin
Aminoglycosides:
- (1) is a unique feature in comparison to the activity of all other protein synthesis inhibitors
- (2) describe general clinical use
1- bacetiocidal (all others are bacteriostatic)
2- mostly replaced by safer antibiotics — associated with serious toxicities
describe the unique feature of pharmacodynamics with Aminoglycosides (hint: time v [drug])
Postantibiotic effect + Concentration-dependent killing = once daily dose
1) concentration dependent killing = more [drug] => better killing power VS. time-dependent where duration, not drug amount, affects killing power
Aminoglycoside MOA:
- (1) entry of (2) bacteria only
- binds (ir-/reversibly) to (4) leading to inhibition of initiation complex, causing (5) and (6)
1- passively and actively (O2 dependent)
2- aerobic Gram- bacteria
3- irreversible (covalent bond)
4- 30S ribosomal subunit
5- misreading of mRNA
6- blockade of translocation
describe the mechanisms of Aminoglycoside resistance
1) plasmid-associated synthesis of enzymes –> drug modification and inactivation via acetylation, phosphorylation, adenylation
2) dec drug accumulation
3) change in receptor protein on 30S ribosomal subunit (alteration or deletion via mutation)
Aminoglycosides are the drug of choice for…..
Note- always empiric therapy and always in combination
*infective endocarditis w/ vancomycin
Aminoglycoside Pharmacokinetics:
- (1) route of administration
- (2) describe distribution
- (3) route of elimination
1- parenteral (once daily) —- except neomycin is topical
2- well-distributed everywhere: including CSF, bronchial secretions, *renal cortex and *inner ear
3- urine (reduce dose in renal insufficiency)
