Protein Synthesis Inhibitors Flashcards
What are the aminoglycosides and who are they effective against?
These are they mycins…gentamicin, tobramycin, neomycin, amikacin, streptomycin…NOT Erythromycin or Vancomycin
All given IV except for Neomycin which is topical in an ointment
Use against G- bacteremia or for UTI
Use with Vanco or PCN for bacterial endocarditis
Use for mycobacterial infections (TB…use IV streptomycin)
What are the targets of the Protein Syn Inhibitors
Target the bacterial ribosome only, leaving the euk ribosome unaffected
- Aminoglycosides and Tetracyclines–>30S
- Macrolides & Clindamycin, Chloremphenicol, Streptogrammins, Linezolid—>50S
What are the MOA of the aminoglycosides?
First they passively diffuse down the porin channel (remember they are for G- and they have the porins)
Then they have ACTIVE O2 DEPENDENT transport across the cell membrane. (This is inhibited by anaerobic and acidic conditions…so anaerobes are innately resistant).
Their uptake is enhanced by a cell wall syn inhib like PCN or vanco.
Once inside it irreversibly binds the 30S P site and causes a frameshift in reading code—>Bactericidal
What are the pharmokinetics of Aminoglycosides?
They have minimal absorption so must be given IV (except who…?)
Dose is based on weight and creatinine clearance (renal function) and usually given 2-3x/day with normal renal function
Monitor patients that are receiving this for days at a time bc this can start to affect the kidney, or those whose renal function is changing or deteriorating
For high CNS penetration, use a intrathecal (injection directly into the spinal canal or intraventricular (delivery of drug to CNS within an implanted catheter or pump)
What is the mechanism behind once daily dosing of Aminoglycosides
It is based on concentration dependent killing (also true of floroquins)
- As the amount of drug in the blood incr, so does the killing.
- Has a post antibiotic effect where the aminoglyc continues to work even after the measurable levels of it are barely there. Prob bc it is taken up into the bact cell
- TimeDependent Killing of Bacteria is characteristic of B lactams & Vanco
- -Bugs are killed as long as the plasma conc is above MIC, therefore these drug’s levels need to always be above this level btwn doses
What are the pros and cons of once daily aminoglyc dosing?
Pro: Convenient for Outpatients, Less toxic
Con: Unproven in bacterial endocarditis, pregnancy, burn patients, severe renal impairment
What are the causes and risk factors of Aminoglyc nephrotoxicity?
These drugs can cause ACUTE renal injury indicative by a rise in plasma creatinine concentration.
-Since they are filtered across the glom then filtered in the prox tubule, its these tubules that are damaged. Fortunately the prox tubules can regenerate and this damage is reversible, and renal function can be recovered.
Risk Factors: Prolonged Therapy, Frequency of Dosing Advanced Age, Comorbidities (diabetes, renal disease) Concomitant meds (loop diuretics, vanco, amphotericin) Elevated plasma drug concentrations
What is a way to avoid aminoglyc nephrotoxicity
Use once daily dosing bc renal cortical accumulation is way less with this method. Also, this method only requires a periodic TROUGH level
-If not, the serum peak and trough levels should be monitored closely.
Acute kidney injury can still occur either way
What is the irreversibly toxicity of Aminoglycs?
Ototoxicity.
It causes cochlear damage that may result in permanent hearing loss and damage to the vestibule as well (vertigo, ataxia, nystagmus)
Free radicals generated in the ear which damage sensory cells and neurons.
Gentamicin in particular damages hair cells so this is toxic to the vestibule only not cochlear. So GENTAMICIN WONT MAKE YOU DEAF, ONLY DIZZY OR OFF BALANCE
Audiometric testing used with aminogly use
What are the clinical uses for aminoglycs?
They are used for G- sepsis or bacteremias
Endocarditis with strep, enterococcus or staph
Often used in combo with other B lactams, esp for treating
-PSEUDOMONAS, LISTERIA, ENTEROCOCCUS
What kills Listeria?
Ampicillin with an Aminoglycoside
What is gentamicin used for?
Bugs:
Staph (only as a synergistic with PCN or vanco, not by itself) and G- (pseudomonas, Proteus, Enterobacter, Klebs, Serratia, Stenotrophomonas
-Has NO ANAEROBE activity (O2 dependent, remember?)
Only used for G+ as a synergistic or as a topical eye drop
-ie B lactams, vanco
What is Tobramycin used for?
Pseudomonas
Available as an inhaled solution for pseudomonas lung infections with CF patients
What is streptomycin used for?
First line IV treatment for TB
15% of gentamicin resistant enterococcus will be sensitive to streptomycin
What is amikacin used for?
Used for G- infection resistant to gentamicin and tobramycin
-bc amikacin is usu resistant to the group transferases that inactivate toby and geni
Treats mycobacterial infections (both atypical and resistant)
What is neomycin used for?
Used as a topical and bowel prep, and for hepatic encephalopathy
What is cefepime used for?
4th generation cephalo that does what 3rd gens do + have pseudomonas coverage. It also more resistant to lactamases
What are the 4 tetracyclines and how are they administered?
1) Tetracycline - PO QID (4 x/day)
2) Doxycline - PO (100% bioavailable) or IV
3) Minocycline - PO 100% bioavailable
4) Tigecycline - IV
How are the tetracycline eliminated?
Through the urine, others via biliary or fecal route
It goes thru enterohepatic circulation
What is the spectrum, bugs/infections that tetracyclines work against?
Spectrum: G+, G- Chlamydia and Mycoplasma Rickettsia and Borellia (Lyme disease) H. Pylori, Vibri, P Falciform
Common uses: MRSA, acne, atypical and community acquired pneumonia, chlamydia, Lyme Disease, Rocky Mountain Spotted Fever, H. Pylori, malaria prophylaxis
Use Demecyclocyline for SIADH which inhibits ADH in renal tubule…makes you pee it seems like
What is Tigecycline and what is it used for?
It is a broad spectrum that covers:
MRSA, VRE, Anaerobes
-NOT pseudomonas, Proteus, Providencia, and Morganella
-Use for skin and abdominal infection
- Has poor urine conc so DONT USE FOR UTI
- HAS poor blood conc so DONT USE FOR BACTEREMIA
What are the adverse effects of the tetracyclines?
Binds di and tri valent cations ie Ca2+ so dont take with food, esp dairy or vitamins.
In children will bind to the Ca in their teeth and turn them brown. So dont give to kids or pregnant women.
Also phototoxic
Irritates GI/Esophageal tract locally
What is the MOA of Erythromycin and what is its spectrum?
It binds to the 50S subunit
It is given orally or topical
Spectrum:
G+ organisms (Pneumococci, Strep, Staph)
Mycoplasma, Legionella
Chlamydia, Pertussis
What are the adverse effects of erythromycin?
GI Issues (n/v diarrhea) For this reason, it is used to treat motility disorders ie gastroparesis
Hepatoxicity (esp erythromycin estolate), and inhibitor of CYP450, increases theophylline, anticoagulants, cyclosporin
Increases digoxin level by increasing bioavailability
