Ribosomal Agents Flashcards
30s ribosome
spectinomycin, aminoglycan, tetracyclines
50s ribosome
Chloramphenicol, macrolides, lincosamides, strettogramins, linezolid
Spectinomycin MOA
- Inhibit initiation complex
- bacteriostatic
- bind to 30s subunit
- Parenteral
- Only indication = Gonorrhea
Aminoglycosides Examples
Streptomycin, gentamicin, tobramycin, Neomycin, Amikacin, Netilmicin
Aminoglycosides MOA & MOR
- Bind to 30s subunit
- Prevents initiation AND causes misreading of codon
- bactericidal
- O2 dependent –> needs high pH and aerobic conditions»better activity at high pH
- Resistance = group transferases (acetyl-,adenyl-, phospho-)
If there is resistance to gentamicin, what agent would you use?
Amikacin
Aminoglycosides adverse effects
-OTOTOXICITY
-NEPRHOTOXICITY (must monitor renal function)
(same toxicity as vancomycin)
- Neuromuscular blockade
- Skin reactions
Aminoglycosides indications
AEROBIC gram -
usually combine with beta-lactam
Tetracycline examples
Tetraycline, Doxycycline, MInocycline, Tigecycline, Demeclocycline
Tetracyclines MOA & MOR
- Bind to 30s subunit
- Inhibit binding of aminoacyl-tRNA
- Resistance: efflux protein pump
Tetracyclines indications
- Broad spectrum antibiotics ( gram - & gram +)
- Respiratory ifx (atypical): Mycoplasma, Legionella, Chlamydophila
- Bronchitis: H. flu, pneumococcus
- *Rickettsiae,
- *STDs!! (chlamydia, PID, ureaplasma, chancroid)
- *Lyme disease
- *Acne
- Drug resistent falciparum malaria (doxy)
Chloramphenicol MOA & MOR
- 50s subunit
- inhibit peptidyl transferase
- Resistance: acetyltransferase
Chloramphenicol adverse effects
- gray baby syndrome
- Bone marrow suppression (dose-dep)
- Aplastic anemia
- Decreased iron incorporation into Hgb
- Rare hypersensitivity
Chloramphenicol Indications
- Broad spectrum (but not for staph or pseudomonas)
- typhoid fever (if other unable to use other tx)
- MENINGITIS & Brain Abscess (only if other agents can’t be used)
- Bac conjunctivitis (topical)
- Oral meningitis tx when IV can’t be used
Macrolides Examples
Erythromycin, claritrhomycin, azithromycin, Telithromycin
Macrolides MOA & MOR
- Binds to 50s
- prevents translocation
- Resistance: Methylation (use Telitrhomycin in such cases)
Macrolide adverse effect
- GI problems
Macrolides are oral agents
Macrolide indications
- broad spectrum
- respiratory ifx
Lincosamides examples
lincomycin, clindamycin
Lincosamides MOA & MOR
- Bind to 50s subunit
- prevent translocation
- Resistance methylation
Lincosamides Indications
- anaerobic ifx
- aerobic gram +
Streptogramins MOA & MOR
-Binds to 50s
-Prevents translocation
-Bactericidal
Resistance = methylation
-Example = synercid
Streptogramins indications
PRSP, MRSA, VRSA, VRE tx
Linezolid MOA & MOR
- bactericidal
- Unique site binding to 50s (23s)
- Inhibits initiation AND translocation
- No cross resistance ( resistance only with mutation of 23s binding site)
Linezolid Indications
PRSP, MRSA,VRA, VRE tx
Enterococci tx
not active against G- or anaerobes
only topical or oral aminoglycoside antibiotic
Neomycin–b/c of high nephrotoxicity
all others parenteral
second line drug for tx of drug resistant TB
Streptomycin
Tetracylines adverse effects
absorption inhibited by milk, antacid, Ca+, Iron (metals)
- CONTRAINDICATED: renal failure and pregnant women & children
- teeth discoloration and concentration in bones
- GI effects
- Hepatotoxicity
- Doxy –> esophageal ulcerations, photosensitivity
- Tetra, Mino–> pre-renal azotemia
- Mino –> Vertigo
Erythromycin Indications
Treatment for:
- *Legionnaire’s disease
- *Mycoplasma pneumonia
- *Chlamydia ifx
- *Corynebacterium diphtheria
- *Bordatella pertussis
- *Campylobacter Enteritis
- Use w/ neomycin for surgical bowel prep
This drug exacerbates Myasthenia gravis
Telithromycin
This drug is associated with pseudomembranous colitis
Clindamycin
Mupirocin MOA
formely called pseudomonic acid
- topical ointment
- Interfers w/ bac RNA & protein synthesis
Rifampin
Cheif use for tx of TB
- Also for staph ifx involving bone and prosthetic devices
- ALWAYS combined with another antimicrobial
- Reddish discoloration of urine
Rifaximin Indications
- prevention and therapy of traveler’s diarrhea due to non-invasive E. coli
- Px/tx of hepatic encephalopathy (dec ammonia production by gut bac)
- Tx of refractory C. diff colitis
This class has minimal protein binding and cleared unchanged into urine by glom. filtration
Aminoglycosides
Aminoglycoside distribution
- Low in CNS, Sputum, Bile, and Prostate
- Excellent in urine
this drug can be taken orally to decrease gut flora before GI surgery or in liver failure
Neomycin
Initial DOC for serious aerobig gram neg rod infections
Gentamicin, tobramycin, amkacin
(can be swapped with drugs w/ less toxicity later when org ID/sensitivity is known)
-Good to give w/ beta lactams for synergy, spectrum (hit gram +), and resistance issues
Aminoglycoside with highest nephrotoxicity
Neomycin
Aminoglycoside with highest vestibular toxicity
Streptomycin
FYI: Balance probs–provide enough light to compensate visually
Aminoglycoside with highest Cochlear toxicity
Neomycin
Factors that increase risk of aminoglycoside nephrotoxicity
- Severe infection
- Decreased renal blood flow (e.g. in spetic shock, dec cardiac output)
- Dehydration, diuretic use
- Underlying renal dz
Average half-life for aminoglycosides
2-3 hrs
50-110 hours in anephric!
Spectinomycin half-life
1-2 hours
Short-acting Tetracycline
Tetracycline O, IV
T1/2=8hrs
Long-Acting Tetracyclines
Doxycycline O, IV (T1/2=18 hrs)
Minocycline O, IV (T1/2=16 hrs)
This class of drugs is metabolized by liver, concentrated in bile, but excreted by kidneys
Tetracyclines
except Doxy: excreted mainly in poop
First class of glycyclines-derivatives of minocyclines
Tigecycline
This drug is IV only, has half-life of 36 hours, and primarily cleared by liver
Tigecycline
Tigecycline MOA
- Binds to 30S
- Inhibits protein synthesis
- STATIC
Tigecycline Spectrum
Very broad spectrum
- All Gram + (even MRSA & VRE)
- Most Gram -, bu NOT pseudomonas and proteus
- Most anaerobes
- Atypical orgs: mycoplasma, mycobacteria, but NOT Legionella
Tigecycline Indications
- Complicated skin and soft tissue infections
- Complicated intra-abdominal infections
Tigecycline Toxicity
- N & V
- Contraindicated in preg & young kids (like tetracyclines)
T1/2 Erthromycin
1.4 hrs
Erythromycin oral preparations
- E. Base
- E. Ethylsuccinate (EES)
- E Estolate
- E. Stearate
Erythromycin pharmacokinetics
- Wide distribution EXCEPT in CNS & Eye
- Much is metabolized in liver
- Some excreted in bile
- 10% excreted in urine
Erythromycin Spectrum
- Similar to pen G (good substitute in allergic pts)
- AVOID in serious infections
- Good for Strep, Staph (non-MRSA), pen-sensitive anaerobes
- NOT good for GC or Syph
Erthromycin toxicity
- GI upset
- Cholestatic hepatitis (mimics gallbladder attack)
- Phlebitis
- Cardiac rhythm disturbances
- Drug interactions (drugs met by liver)
- Hypersensitivity uncommon
Clarithromycin indications
- Similar to erythro and azithro but mainly for RESPIRATORY infections (concentrates in resp tissues)
- atypical mycobac infection (esp m. avium)
Clarithomycin Toxicity
- Same as erythromycin except…
- Less GI
- Bad taste in mouth
- Contraindicated in preg
- Possibly cardiac rhythm
- Drug interactions
This macrolide has a half-life of three days when taken orally
Azithromycin
Now also available in IV
Azithromycin Indications
- H. Flu & Moraxella catarrhalis (ear infections)
- Chlamydia (single dose tx)
- Mainly resp infections
- Atypical mycobac infections (m. avium)
Azithromycin Toxicity
- Mild GI
- Possible cardiac rhythm
- Tinnitus/deafness (high doses)
- Drug interactions
Telithromycin Indications
- Mild-moderate COMMUNITY-onset pneumonia (not bronchitis, otitis, or sinusitis) b/c of severe toxicity
- S. pneumo (resistant strains too)
- E. Faecalis
- S. aureus
Telithromycin Toxicity
- Mainly GI (taken orally)
- Drug interactions: CYP 450 3A4
- Rare Fatal hepatotoxicity (met by liver)
- MG exacerbation
- Contraindicated in pts w/ MG or liver dz
Clindamycin pharmacokinetics
-T1/2= 2.5 hrs
-Oral, IM, IV, Topical
-Cleared mainly by liver and intestine
-Wide distribution, but no CNS, eye, and ? prostate
» Gets into BONE and works in abscesses!!
Clindamycin indications
- MRSA skin/soft tissue infections
- DOC for Anaerobic infections
- staphylococcal osteomyelitis
- Acne (topical)
- Pen alternative for staph, strep, anaerobes
- NOT FOR AEROBIC GRAM (-)
Clindamycin Toxicity
- Hypersenstivity
- Mild hepatotoxicity
- GI upset
- Pseudomembrane colitis
Mupirocin Indications
- Topical tx of superficial skin infections due to staph and strep (Impetigo)
- Nasal application for S. aureus carriage (esp MRSA)
Mupirocin Toxicity
Local irritation
This drug has a half-life of 5 hrs and does not need to be adjusted in renal failure
Linezolid
(largely met in liver, excreted in urine)
Oral and IV administrations
Linezolid Toxicity
- SEROTONIN Syndrome when taken w/ antidepressants
- Inc BP when taken w/ adrenergic agents or high tyramine
- mild GI
- occasional thrombocytopenia & neutropenia
- Also, super expensive :(
Rifaximin MOA
- Drug related to rifampin
- Blocks RNA synth: Binds to beta sub-unit of RNA polymerase
Rifaximin Toxicity
- Minimal/sim to placebo
- Preg Category C (teratogenic in rats)
Chloramphenicol Pharmacokinetics
- Oral or IV
- T1/2= 2-3 hr (doubles in renal failure)
- Inactivated in liver and excreted in urine
- Great distribution, even in CNS!!
