Term
| Do Aminoglycosides cross into CSF? |
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Definition
| NO - not used to treat meningitis |
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Term
| What are features of aminoglycosides? |
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Definition
- Renally excreted - do not use in kidney disease
- Tx for AEROBIC gram(-). Only works through porins, which are not in gram(+)
- Cidal agents |
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Term
| What are the main side effects of aminoglycosides? |
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Definition
- Nephrotoxicity - most prevalent, retention in proximal tubules. Neomycin is the worst
- Ototoxicity - accumulates in otic fluid, increase permeability of hair cells, causing leakage and permanent death. Mg loss.
**Do not give in M. gravis - receptors less sensitive to Ach |
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Term
| What is the MoA of aminoglycosides? |
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Definition
Hydrophobic, go through porin channels. A pump in the periplasm that uses O2 to bring in sugars brings in the the drug
**Drug binds to ribosomes at 30s, stops translation. (specifically blocking the A site of 16S)
**Block: Ca/Mg, low pH, anaerobic environment |
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Term
| What are pleitropic effects of aminoglycosides? |
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Definition
| Increased membrane permeability and competition for sugars/energy disturbance |
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Term
| How does protein translation occur? |
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Definition
ribosomes pull mRNA apart, reading the codons. Each tRNA codes for a specific AA.
rRNA: A site, P site, E site. Bonding occurs between A and P sites. |
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Term
| How do bacteria become resistant to aminoglycosides? |
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Definition
- Mutation at the 16S subunit of 30S prevents binding - doesn't happen often
- Doesn't permeate outer membrane through porins or through O2 depended pump
- Enzyme inactivation*** - via N-acetyltransferases, O-adenyltransferases, and O-phosphotransferases. Happens often. |
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Term
| What is the spectrum of aminoglycosides? |
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Definition
- Aerobic gram(-): E. coli, P. aerug, Klebsiella, H. influenzae, enterobacteria, gonorrhea
- Select gram(+): synergism w/ Vanc and penicillins to treat E. faecalis or E. faecium, and Streptococci |
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Term
| How is streptomycin used? |
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Definition
- Streptomycin - 1 binding domain. The first TB tx.
- Endocarditis caused by enterococci: Penicillin + Streptomycin
- Y. pestis, the black plague
**An aminoglycoside, watch kidneys |
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Term
| How are gentamycin and tobramycin used? |
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Definition
- Gentamycin/Garamycin - gram(-), enterococci, Listeria (gram +). Not used alone for gram +, but a good synergist
- Tobramycin/Nebcin - Superior for P. aeruginosa. 1ST LINE: Ticarcillin + Tobramycin (T&T) |
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Term
| What AG is incompatible IV with beta lactams? |
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Definition
| Gentamicin, must use different bags or different arms |
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Term
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Definition
An aminoglycoside with bulky groups to inhibit enzymatic deactivation
Broadest spectrum, used in nosocomial gram(-) infections and also TB and MAC mycobacterium infections.
**May work where gent and tobramycin have failed |
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Term
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Definition
| A broad spectrum AGs, but P. aerug is resistant. Can be used for Enterococci. DO NOT USE IV. Used orally to wipe out gut bacteria for surgery |
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Term
| What are properties of tetracyclines? |
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Definition
- Accumulate in bones and teeth
- Chelates cations - avoid w/ metals
- Given orally
- Throw away at expiration - Fanconi syndrome |
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Term
| What is the MoA of tetracyclines? |
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Definition
A static agent that binds to the 30S subunit.
Water soluble, goes through porins. O2 pump to access cell. Mino and doxy are more lipophilic, get stuck in membranes
**At HIGH doses, inhibits mammalian 40S subunit. BAD. Also a teratogen. |
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Term
| What are mechanisms of tetracycline resistance? |
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Definition
- Low influx, higher efflux
- Decreased access to ribosome
- Enzymatic inactivation
**Widespread resistance |
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Term
| What are tetracyclines used for? |
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Definition
Specific indications only:
- Acne
- Lyme disease: B. burgdorferi
- RMSF: Rickettsia
- Chlamydia or gonorrhea
- Cholera
- Clostridium species: tetanus, C. diff, gangrene
- Add on for black plague, anthrax
**Not used for enterobacteria, gram(+) |
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Term
| What are AEs of tetracyclines? |
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Definition
- Category D in pregnancy
- Deposition to bone
- Hepatotoxicity
- Superinfections: C. albicans and C. diff |
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Term
| What drugs are tetracyclines? |
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Definition
- Tetracycline/Sumycin - 2nd choice for gonorrhea in a pen allergy. Most effective for H. pylori
- Minocycline/Minocin
- Doxycycline/Vibramycin
- Tigecycline/Tygacil - Affects CRE! Also Bacteroides, Staph, Strep. Overcomes resistance to other TETs |
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Term
| What is Rocky Mountain Spotted Fever? |
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Definition
Rickettsia rickettsii - tick bite transmission causes fever, HA, rash that can be fatal. Do not delay Tx
**Only alternate is chloramphenicol |
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Term
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Definition
A diarrheal disease caused by Vibrio cholerae - can lead to shock and death. Drinking water and eating shellfish
**B component of toxin binds to cells while A component enters cells. Binds to Gs, locking it into active. cAMP always on = efflux of water. |
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Term
| What is the MoA of macrolides? |
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Definition
| A lipophilic static agent that binds to the 23S P site of 50S, blocking extension of the tRNA. |
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Term
| How do bacteria become resistant to macrolides? |
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Definition
- Efflux by active pump, a common mechanism
- Methylation of the ribosome, preventing binding of the macrolide
- mutation of 23S subunit
**gram(-) intrinsically resistant due to lipophilicity. |
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Term
| What are AEs of macrolides? |
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Definition
| MANY drug interactions - 3A4 substrates. longer half life and toxicity for both drugs: Statins, CCBs, oral contraceptives |
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Term
| What is the spectrum of the macrolides? |
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Definition
- Primarily gram (+) organisms: NOT MRSA, Strep and Staph, S. perfringens, Listeria, B. anthracis
- 4 gram(-): H. influenzae, gonorrea, H. pylori***, Legionella, chlamydia
**drug of choice in H. pylori and legionella |
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Term
| What are the different types of erythromycin? |
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Definition
Erythromycin/E-mycin
Erythromycin Estolate/Ilosone
Erythromycin Ethylsuccinate/Eryped/EES
Deactivates in acidic environments, food reduces absorption. Prodrugs mask bitter taste |
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Term
| How is Clarithromycin/Biaxin used? |
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Definition
Structure increases lipophilicity and decreases ketal formation - Increased potency for H. influenzae.
**The drug of choice for H. pylori and M. pneumoniae |
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Term
| How does H. pylori cause ulcers? |
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Definition
- Secretion of urease creates a base cloud around the bacteria
- Evades host defenses
- VacA - vacuolation of luminal cells
**Decrease in somatostatin --> increase in gastrin |
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Term
| What are the standard therapies for H. pylori? |
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Definition
- Triple: PPI + Clarithromycin + Amoxicillin
- Quad: PPI + bismuth + Metronidazole + Tetracycyline |
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Term
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Definition
Has a long half life and very lipophilic
SYNERGISM w/ cephalosporins vs: Gonorrhea and M. pnemoniae.
**Less 3A4 side effects |
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Term
| What macrolide is a 'ketolide'? |
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Definition
Telithromycin/Ketek
ONLY used for multi-drug resistant S. Pneumoniae
**Many black box warnings |
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Term
| Which macrolid is approved to treat C. diff? |
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Definition
Fidaxomicin/Dificid
Actually inhibits bacterial RNA polymerase
**Less recurrence than with vancomycin |
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Term
| What are features of clindamycin? |
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Definition
- Binds to 50S subunit
- Used for Strep including agalactiae, MSSA, Bacteroides, ACNE, clostridium
- POTENT cause of C. diff |
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Term
| What does Linezolid/Zyvox cover? |
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Definition
Only gram(+) but resistant strains: MRSA, VISA, VRSA, VRE, Listeria, M. tuberculosis
**Inhibits binding of tRNA to 70S, displacement of ternary complex |
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Term
| What is Chloramphenicol used for? |
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Definition
- Very wide spectrum - Inhibits binding to A site, can also work on mammalian cells. TOXIC - aplastic anemia
- Alternate treatment for RMSF - Ricketsia |
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Term
| What is Synercid used to treat? |
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Definition
Quinupristin/Dalfopristin or Synercid - only used to treat MDR/Vanc resistant E. faecium, NOT E. faecalis
**IV only, resistance by hydrolysis and efflux. Quin blocks P site, Dalf binds A site --> inhibits translation
**3A4 effects |
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