Protein Synthesis inhibitors Flashcards
(48 cards)
Aminoglycosides mechanism
Block association of 50S subunit with 30S-m RNA complex (static)
ii. Misreading of code-incorporation of wrong amino acid. (cidal)
Linezolide(50S) mechanism
Block association of 50S subunit with 30S-m RNA complex (static)
The drugs that prevent Amino acid interaction with the acceptor site
Tetracycline(30S)
Streptogramin(50S)
Block the attachement of aminoacyl t RNA to acceptor site(static)
Chloramphenicol act by
Blocking Formation of peptide bonds
Mechanism of Chloramphenicol
Inhibit activity of peptidyl transferase(-static)
Macrolide & Clindamycin(50S)
work by
Blocking Translocation
Mechanism: Inhibiting peptidyl t RNA from acceptor to donor site(static)
Name Tetracyclines
TETRACYCLINE
DEMECLOCYCLINE
DOXYCYCLINE - Lipid soluble, lyme disease. Most affective.
Tetracyclines chelate metal ions—Ca2+, Al3+, Fe2+, Mg2+
Not absorbed therefore..
do not administer with food, milk, antacids, etc.
Tetracyclines are concentrated in
Concentrates in teeth, bone, liver (bile), kidney
Tetracyclines can cross the
cross the placenta and are excreted in milk
All tetracylines are excreted through urine except
Doxycycline
Tigecycline useful for?
Treatment of complicated skin and skin structure infections caused by susceptible organisms, including:
Methicillin-resistant Staphylococcus aureus
Vancomycin-sensitive Enterococcus faecalis
Treatment of complicated intra-abdominal infections
New approved tetracycline analog
Tigecycline
Adverse Effects of Tetracyclines
- G.I.T.: N/V, diarrhea are the most common (superinfection, alters intestinal flora)
- Bone and Teeth: Tetracyclines concentrate in growing teeth and bone. Their use by pregnant women or children under 8 yrs of age may cause discoloration of teeth and hypoplasia of the enamel, resulting in yellow-brown or gray mottling of front teeth.
- Liver & Kidney: TCNs may cause potentially severe Nephrotoxicity (except Doxycycline) and Hepatotoxicity in the form of fatty degeneration.
- Phototoxicity (don’t go in the sun otherwise you’ll get rashes) , Demeclocycline leading to erythema, and exacerbating the sunburn.(classic V-neck shaped bright red rashes in the sun exposed area
Resistance to Tetracyclines is by
Decreased uptake of tetracyclines– efflux pumps are major mediators.
Tetracyclines have become resistant because of
Indiscriminate use/overuse of tetracyclines
(clinical and agricultural) has fostered the emergence of resistance
Chloramphenicols (50s) are both
Bacteriostatic
Broad spectrum
Adverse affects of Chloramphenicols
Anemia due to bone marrow depression (Dose Dependant)
Aplastic anemia
Probably idiosyncratic reaction (genetic)
Not strictly dose- and time-related, but more common with prolonged use
USUALLY IRREVERSIBLE AND FATAL
Gray Baby syndrome
Newborns and infants are poor glucuronidator’s (H.Influenzae induced Meningitis)
Chloramphenicols inhibit the metabolism of drugs by?
Inhibits CYTP450
Chloramphenicol are used to treat
Typhoid fever & Rocky Mountain spotted fever in children & meningitis in both adult & chidren ; ace-in-the-hole drug
Some Macrolides are
Anything with THRO ERYTHROMYCIN BASE ERYTHROMYCIN ESTERS AZITHROMYCIN CLARITHROMYCIN
Macrolide adverse affects
1) GI distress –due to direct stimulation of motilin receptor by all macrolides - CAUSE INCREASED Peristalsis –most common (exception Clarithromycin).
2) Hepatotoxicity–Especially with erythromycin estolate
Cholestatic jaundice
3) Blocks CYP450 but not azithromycin
4) QT prolongation (erythromycin
Telithromycin used in
Macrolide resistant Streptococcus pneumoniae
Azithromycin is good because
Minimal P450-based interactions (excreted by kidney)
Tissue levels 10-100 x plasma levels; t ½ = 2 - 4 days
Active against Mycobacterium avium-intracellulare in AIDS patients (an exception where bacteriostatic is used in an immunocompromised condition-Hence very high dose required )
Only macrolide safe in Pregnancy.
