Protein Synthesis Inhibitors Flashcards
What is the most common bug responsible for community acquired pneumonia?
atypical?
CAP- strep pneumo
atypical- mycoplasma
What was methicillin made for?
What makes MRSA so interesting?
Methicillin was made to kill bugs resistant to beta lactams (beta lactamase doesn’t hurt methicillin)
It is interesting because MRSA is resistant to methicillin which typically works against resistant bugs!
Why is mycoplasma pneumoniae resistant to penicillins and cephalosporins?
Because it lacks a peptidoglycan wall!
-these drug inhibit cell wall synthesis, no wall, no effect
Where do protein synthesis inhibitors exert their antimicrobial effects?
By targeting the bacterial ribosome within the cell, not the cell wall
Buy AT 30s
CELL at 50s
Aminoglycosides-change shape of 30s subunit–> mRNA read incorrectly
Tetracycline- binds to 30s subunit and prevents attachment of tRNA molecule to mRNA
Chloramphenicol- binds to 50s subunit and inhibits formation of polypeptide bond when making polypeptide chain
Erythromycin- binds to 50s subunit and stops ribosome movement along mRNA (can’t read info on mRNA chain)
Lincomycin- 50s
cLindamycin-50s
*all lead to protein synthesis inhibition
Adverse Effects of Tetracyclines
- deposition in bone and dentition
- stained teeth and stunted bone growth
- gastric discomfort; controlled if taken with food other then dairy
- phototoxicity (severe sunburn)
- ototoxicity (dizziness, N/V)
Tetracycline Resistance
resistant to one tetracycline=resistant to all.
-bug decreases influx pump of abx and develops efflux pump to eject abx out of cell.
Absorption of Tetracycline
-Doxycycline
adequetly but not completely absorbed after oral ingestion. Dairy decreases absorption, can cross placental barrier and concentrate in fetal bone and dentition
Doxycycline- can eat dairy with the med, otherwise same absorption as tetracycline.
Distribution:
- Tetracycline
- Doxycycline
conc. in liver kidney spleen skin and tissues undergoing calcification (teeth & bones).
Excretion of Tetracycline and Doxycycline
- Tetra: released in bile, reabsorbed from intestines to be excreted by the kidneys
- Doxy: released in bile and excreted by the feces.
CI of Tetracycline
- *pregnant women
- *breast-feeding
- *Children under 8 yo
- Caution if impaired renal function (except doxycycline)
- Caution if impaired liver function
- Caution in SLE
Routes of Administration of Tetracyclines
Oral
IV
IM– not recommended d/t pain and inflamm.
What are tetracyclines especially useful for? What are they NEVER used for?
- useful in STIs, atypical pneumonia, exacerbations of chronic bronchitis, acne vulgaris,
- NEVER use for skin infections b/c of decreased activity against staph aureus.
What is the drug of choice for mycoplasma pneum. and chlamydiae, rickettsiae (rocky mtn spotted fever), and lyme disease
DOXYCYCLINE!!!
What is the drug of choice for acne vulgaris but rarely used for anything else?
Minocycline
What is used in the tx of Syndrome of Inappropriate Anti-diuretic hormone?
-Demeclocycline b/c of its inhibiting action of ADH
What is the most common macrolide?
-Azithromycin
MOA of Macrolides?
bind irreversibly to a site on 50S subunit or bacterial ribosome inhibiting translocation steps of protein synthesis.
Macrolide Erythromycin is effective against the same organisms as Penicillin G, why would we choose this drug over a penicillin?
-use this w/ penicillin allergy.
Macrolide Resistance
- most strains of staphlyococci in hospitals most are resistant to erythromycin
- Clarithromycin and azithromycin show cross resistance w/ erythromycin
Macrolid Resistance Mechanism
- alteration in binding site of ribosome
- manifestation of efflux pump to get drug out of cell
- enzymatic inactivation
Macrolide Absorption, DIstribution, Metabolism, and Excretion
Erythromicin Absorption
- destroyed by gastic acid, needs enteric coat.
- adequately absorbed orally
- Clarithromycin and Azithromycin Absorption
- stable in stomach acid and readily absorbed
Distribution for All:
-widely distributed in tissues except CSF.
Metab:
Erythro: cytochrome P450, metabolized in liver.
Clarithromycin metabolized in liver
Azithromycin: doesnt have many interaction w/ other meds.
Excretion:
Erythro & Azithro: concentrated in bile
Clarithro: kidney as well as liver (dose needs to be adjusted in renal pt)
Adverse Effects of Macrolides
- GI distress including diarrhea, especially in erythro*** leading to poor pt compliance. Azithro and Claritho are very well tolerated (no GI upset)
- Ototoxicity- transient deafness at high dose
- Prolonged QT w/ erythro and clarithro (rare)
Why is Azithromycin chosen for tx much more often than erythro and clarithro?
fewer adverse effects and drug interactions
for most part dont have to worry about adjustment in pt w/ kidney and liver disease
long half life= easy to use and better compliance.
azithromycin tastes good
