Protein Synthesis inhibitors Flashcards
Which protein synthesis inhibitors are cidal and which are static?
- Aminoglycosides are cidal
- Tetracyclinies, Chloramphenicol, Macrolides, Lincosamides are static
Name a specific chloramphenicol drug. Why is this drug different from other chloramphenicols?
Florfenicol
* Not susceptible to acetyltransferase inactivation
* Does not cause irreversible aplastic anemia (may cause reversible anemia after prolonged usage)
Are aminoglycosides time or concentration dependent?
Concentration dependent
What is the mechanism of action of aminoglycosides?
Binds 30S ribosomal subunit and interferes with protein synthesis
What are the 3 types of toxicity associated with aminoglycosides?
Nephrotoxicity, Ototoxicity, Neuromuscular blockade
What is the spectrum of activity of aminoglycosides?
Mostly aerobic gram negatives
How does the microenvironment affect the efficacy of aminoglycosides?
- Inactive in acidic environment
- Most active in alkaline environment
- Bound by sediment in pus and inactivated
- Inactive in low O2 tension environment
What length of PAE do aminoglycosides have?
Long (concentration dependent)
What are the mechanisms of toxicity of aminoglycoside?
(3)
Drug preferentially accumlates in kidney tubules and chochlea (have the same membrane lipids), lysosome dysfunction. In neuromuscular blockade, effects of acetylcholine are reduced at neuromuscular junction.
Are toxicities from aminoglycosides reversible?
Kidney: YES Renal tubular cells can regenerate
Cochlea: NO
Neuromuscular: YES
How do you prevent aminoglycoside toxicity?
- Maintain hydration
- Ensure appropriate blood flow to the kidney
- Ensure maximum time below the trough conc
- Appropriate dosage and frequency
- Avoid other nephrotoxic agents
- Use combination therapies
What factors determine how you dose aminoglycosides?
- Age, Kidney health-> may need higher dose with longer spacing to reduce toxicity.
- Cotraindicated if animal needs anesthesia or other neuromuscular blockade agents
How do you monitor dosing of aminoglycosides?
Monitoring urinalysis for kidney function
Which bacteriostatic drug can also be cidal? Under what conditions?
Macrolides are bacteriostatic, but can be slowly bactericidal (time dependent action like blactams)
What is the mechanism of action of tetracyclines?
Binds 30S ribosomal subunit to inhibit protein synthesis
What is the “bonus effect” of tetracyclines?
Anti-inflammatory action
What is the mechanism of action of Chloramphenicols?
Inhibits 50S ribosomal subunit to disrupt protein synthesis
What are dosing restrictions of chloramphenicol?
BANNED IN FOOD
ANIMALS!!!!
What is the mechanism of action of Macrolides?
Inhibits 50S ribosomal subunit to disrupt protein synthesis
What is the mechanism of action of Lincosamides?
Inhibits 50S ribosomal subunit to disrupt protein synthesis
What sort of spectrum of activity do tetracyclines have? In general are there many resistant organisms?
- Wide spectrum of activity
- Many organisms have developed resistance
Which bacteriostatic protein synthesis drugs can/can’t you use together?
Don’t want to use 50S drugs together (Macrolides, Lincosamides, Chloramphenicol)
How do bacteria develop resistance to tetracyclines?
- Acquisition of efflux pump
- Ribosome protection proteins
- Enzyme inactivation
How do bacteria develop resistance to chloramphenicol?
Acquisition of a plasmid that encodes an enzyme (acetyltransferase) which inactivates chloramphenicol
How do bacteria develop resistance to Macrolides?
- Target modification (ribosome change)
- Production of methylase to decrease dug binding
- Enzymatic inactivation of drug
How do bacteria develop resistance to Lincosamides?
Same as macrolides
* Target modification (ribosome change)
* Production of methylase to decrease dug binding
* Enzymatic inactivation of drug
What are the important side effects of Tetracyclines?
Life threatening antibiotic induced colitis in horses!, Renal and hepatic toxicity at high doses, permanent tooth discoloration in young animals
What are the important side effects of Chloramphenicol?
Aplastic anemia in humans (banned in food animals)
What are the important side effects of Macrolides?
Life threatening colitis in adult horses, hyperthermia/respiratory distess in foals, Cardiovascular toxicosis except in cattle
What are the important side effects of Lincosamides?
GI ISSUES Life threatening colitis in hindgut fermenters (HOrses + SA), C. diff in humans, diarrhea in swine and cattle
What type of drug is Erythromycin? What is a specific side effect of Erythromycin?
Macrolide (static P S inhibitor)
GI upset due to prokinetic activity of Erythromycin on motilin receptors
What type of drug is Tilmicosin? What is a unique side effect of Tilmicosin?
Macrolide (50S P S inhibitor)
Accidental self injection of tilmicosin CAN BE FATAL!!!
What is the spectrum of activity of each bacteriostatic protein synthesis inhibitor drug? Are some better than others for certain bacteria?
Tetracyclines: wide spectrum, lots of resistance
Chloramphenicol: wide spectrum
Macrolides: Mostly Gram (+), Mycoplasma
Lincosamides: Mostly Gram (+), Mycoplasma, Toxoplasma
Macrolides accumulate in LUNGS
Lincosamides good for anaerobes
Tetracyclines rickettsia, spirochetes, protozoa, mycobacteria, anaerobic + aerobic
Distinguish unique pharmacokinetic properties of each bacteriostatic protein synthesis inhibitor drug
Tetracyclines: accumulate in bone and teeth
Chloramphenicol: Destroyed by rumen, accumulates in brain, cats long half life
Macrolides: accumulates in WBCs
Lincosamides: accumulates in WBCs
Erythromycin and tilmicosin: accumulate in lungs
Should you be cautious as the person administering any drugs? Why?
- Chloramphenicols: aplastic anemia in humans
- Tilmicosin Accidental self injection of tilmicosin CAN BE FATAL
What drugs bind the 30S ribosomal subunit?
Tetracyclines, Aminoglycosides
What drugs bind the 50S ribosomal subunit?
Macrolides (Erythromycin, Tilmicosin), Chloramphenicols (Florfenicol), Lincosamides
What type of drug is Tilmicosin? What is a unique use of Tilmicosin?
Macrolide (50S P S inhibitor)
Bovine and ovine respiratory disease
