Macrolides/Tetracyclines/Glycopeptides Flashcards
Macrolide Examples
Erythromycin
Clarithromycin
Azithromycin
Macrolide MOA
attach to the 23S rRNA on the 50S subunit of bacterial ribosome resulting in
inhibition of protein synthesis
Macrolide Killing??
Generally bacteriostatic; time dependent killing
Bacteria resistance to macrolides
- Change to the binding site
methylation of the rRNA receptor
Inactivating enzymes (able to produce some enzyme that can mess with macrolide causing it to be inactive)
Active efflux (drug actively pumped out so cannot attach at the ribosome)
Macrolides spectrum of activity
Gram positive – pneumococci, streptococci and corynebacteria (reserved for penicillin allergic patients)
M pneumoniae
Chlamydia trachomatis –> STI
C. pneumophilia
Bordatella pertussis –> Whooping cough (beta-lactams ineffective)
Campylobacter jejuni –> Stomach/gut
Helicobacter pylori –>Stomach/gut
Erythromycin Route of Admin
IV or Oral
Adverse Effects of Erythromycin
Gi
Increased liver function tests (LFTs)
Cholestatic hepatitis – increased with estolate and pregnancy (dark urine and jaundice)
Drug Interaction Erythromycin
QT prolongation/cardiac arrhythmias particularly when combined with CYP 3A inhibitors –> Have to be alert for drug interactions
Clarithromycin and Azithromycin Spectrum of Activity
Just Azithro covers……
Active against staph and strep
- Enhanced against:
L. pneumophilia (pneumonias) , Chlamydia trachomatis (STI), Chlaydiophila pneumoniae, Moraxella catarrhalis, H. influenzae (azithro), Mycobacterium avium complex and other mycobacteria
Clarithromycin and Azithromycin are useful for some…..
MRSA
Clarithromycin and Azithromycin have lower rates of….
G.I. adverse effects
Azithromycin is unique because….
Long half-life leads to long intracellular concentrations
5 days of azithromycin = 10days of therapy
Long periods of sub-inhibitory concentrations may lead to more resistance
Uses of Macrolides include…
Upper respiratory tract infections
Sexually transmitted infections
Acne –> effective
Macrolide Drug Interactions. Which one has the least interactions?
Significant number of DI especially with erythromycin and clarithromycin
Fewer with azithromycin (if pt is on. A lot of meds)
Erythromycin and clarithromycin are substrates and inhibitors of CYP 3A4
Long list of drugs that are metabolized by CYP 3A4, so E or C may increase the toxicity
Antiarryhthmics, antidepressants, benzodiazepines, anticonvulsants, statins (very common), anticonvuslasants, etc
Clindamycin MOA
same as macrolides
Clindamycin Spectrum
anaerobes, S. aureus including some MRSA as well as streptococci
Clindamycin Use. Is it the drug of choice for any infections? Why?
Used in patients with penicillin allergies or with resistant organisms
Not DOC for any infections
Oral or parenteral –> Can be used in serious and minor infections
Associated the most of antibiotic caused diarhhea worst culprit of Clostridium difficile infection
Clindamycin Adverse Effects and Counselling Tip
Nausea, vomiting, diarrhea
Rash
Elevated LFTs–> not the same degree of macrolides
Esophageal irritation –> pt. counselling –> always be taken with liquid or water –>sit upright after taking it for awhile
Associated with C. difficile diarrhea
Tetracycline Examples
- tetracycline
- minocycline
- doxycycline
Tetracycline MOA
inhibit binding of aminoacyl-tRNA to the 30S unit of ribosome thereby
inhibiting protein synthesis
Tetracycline killing
- Bacteriostatic
Tetracyclines spectrum of activity
active against many gram positive and negative organisms but high rates of resistance (e.g. E. coli, S. pneumoniae)
drugs of choice for rickettsiae, Bartonella, chlamydiae and M. pneumoniae
Nocardia –> less common
P. acnes
Adverse Effects of Tetracyclines and Contraindications
Gi upset (N, V, D)
Skin rashes
Photosensitivity
Yeast overgrowth –> vaginitis, skin inf (moist places), mouth inf
Deposited in bones and teeth; do not use in children < 8 years old (can cause discolouration of teeth as well as bone deformities)
Hepatitis
Tetracycline Drug Interactions + Counselling
Some anticonvulsants may reduce tetracycline levels ( phenobarbital, phenytoin, carbamazepine) –> May not get eves high enough to treat the infection
Divalent and trivalent cations reduce absorption ( iron, bismuth, calcium, magnesium, aluminum); separate doses
Counsel pt’s –> do not take with multivitamin
Doxyxycline has less binding to calcium so therefore do not need to counsel on not taking with milk, etc.
Increased INR and bleeding with warfarin –> Increased bleeding
Glycylcyclines Example
Synthetic analogue of tetracycline – tigecycline
Tigecycline Spectrum
Active against many gp and gn organisms including MRSA, S. pneumoniae and enterococci, Salmonella, Shigella and Acinetobacter; also anaerobes
Tigecycline eliminated through… and are for…
Eliminated through biliary tract and feces
Reserved for resistant organisms
Glycopeptides Example
Vancomycin
Glycopeptide MOA
– inhibits cell wall peptidoglycan synthesis
- Bactericidal
Glycopeptides resistance
- VRE, S. aureus (VISA)
Vancomycin Spectrum
gpc in particular enterococci, PRSP (penicillin resistant streptococcus pneumonaie) and MRSA (pt who is very ill with MRSA); active against clostridia, Clostrioides and some bacilli
Vancomycin is the DOC for
Vancomycin is the drug of choice for C. Diff Infection (any antibiotic can produce C. Diff but the more narrow the less chance of infection
Vancomycin Route of Admin
IV for serious infections
PO only for C. difficile; not orally absorbed
Adverse Effects of Vancomycin
Nephrotoxicity – especially in combination with nephrotoxins –> damage to the kidneys
Ototoxicity –> Manifests as hearing impairement; or imbalances (not usually)
Red-man syndrome (red-neck syndrome) –> person turns red, uncomfortable, associated with hypotension, pt fees nauseated, flushed, uncomfortable –> can be reduced by reducing the infusion rate
–> Need to keep in mind of infusion rate –> if to fast, every one will get RMS
- 500 mg infused over an hour –> long infusion rates
Granulocytopenia –> long term use
