initiation, elongation, termination, disassembly
30s, 50s, combine into 70s, 20AA/sec
why do antimicrobials only target bacterial ribosomes
cause they don't bind to mammalian ribosomes
protein synthesis initiation step 1
binding of 30s subunit with initiation factor
protein synthesis initiation step 2
binding of mRna and fMet-tRNA (only in bacteria) to complete 30s initation complex
protein synthesis initiation step 3
binding of 50s subunit and release of initiation factor
protein synthesis elongation step 1
aminoacyl-tRNA is positioned in ribosome
protein synthesis elongation step 2
amino acid transferred to growing polypeptide chain
protein synthesis elongation step 3
whole assembly moves one position along
protein synthesis termination step 1
binding of release factor when it sees a stop codon
protein synthesis termination step 2
hydrolysis of peptidyl tRNA
protein synthesis termination step 3
irrev bind to 30S, interfere with tRNA attachment, distor codon reading, create fissue causing leakage of intracellular content
is aminoglycoside bactericidal
streptomycin, neomycin, kanamycin, tobramycin, amikacin, netilmicin
aminoglycoside against what kind of organisms?
gram + and - aerobic.
can aminoglycoside have anaerobic activity?
aminoglycoside active in low oxygen?
resistance occuring with aminoglycoside?
chromosomal mutation or plasmid uptake of enzymes that modify drug (gentamicin vs. amikacin)
aminoglycoside often used with others?
YA definitely combination therapy
how is aminoglycoside's absorption? routes of adm?
little oral abs, so usually given by IV/im
will aminoglycoside cross CSF?
ya with inflamed meninges
where is aminoglycoside most concentrated in
100x in kidney
how is aminoglycoside eliminated?
uncharged in kidney
aminoglycoside adverse rxn/interactions
nephrotoxicity, ototoxicity, neuromuscular (inihit presynaptic release of Ach, and postreceptor sites)
aminoglycoside combination therapy
with beta lactam antibiotics
thru outer cell wall of gram negative and through inner membrane of gram positive by energy dep pump
rev bind 30S, block AA charged tRNA to acceptor site of mRNA complex
antibacterial don't bind to mammalian ribosomes?
no because it can bind with tetracycline
tetracycline chelates something
drugs in the tetracycline group
tetracycline, doxycycline, minocycline
which of the tetracycline group drugs is most active? used with what?
minocycline used with renal insufficiency
what organisms does tetracycline target
gram positive, gram negative, atypical organisms (mycoplasma, chlamydia, rickettsiae) treats chronic bronchitis, myycoplasm pnumonia, gonorrhea, early lyme disease
resistance to tetracycline
ribosomal binding site modification, enzyme inactivation of drug, drug efflux
oral abs but unstable in acid
reduced with calcium or cations, better fasting state and upper GI. antacid/iron salt decrease abs
tetracycline protein binding
60-95% quite alot
tetracycline distribution. binding
CSF 10% and bind to bones, teeth so not used in pregnant women or <11yr olds
kidney, liver. up to 60% unchanged in urine
minocycline and doxycycline elimination
minocycline biotransformed. doxycyclin excreted in feces
tetracycline adverse rxn
GI disturbance, photosensitivity (doxycycline), brownish discolouration of tooth enamel, hepatotoxicity after iv tetracycline, fancoi like syndrome with tetracycline, hypersensitivity rxns rare,neurotoxicity with minocycline, antacid/iron salt decrease absorption
bind 50s, inhibit peptidyl transferase so prevent peptide bond formation
is Chloramphenical bactericidal?
NO it's bacteriostatic
chloramphenicol target what bacteria
aerobic bac except p aeruginosa. ALL anaerobic and atypicals
can chloramphenicol treat meningitis
yes, and also salmonella nad anaerobes in abscesses
how did resistance develop against chlroamphenicol
through acquired enzymes that inactivated the drug and limit cell wall permeability
chloramphenicol drug interactions/adverse rxn
aplastic anemia 1in40000
dose related hematopoitic depression and anemia
grey baby syndrome in neonates
inhibit cyp450 metabolism of phenytoin, oral hypoglycemics, anticoagulants
what increases the clearnce of chloramphenicol
what causes accumulation of chloramphenicol
bind to 50S, prevent transloaction of peptidyl tRNA, new tRNA can't access occupied acceptor site, so prevent extension of peptide
plamid encoded, 3 mechanisms (membrane permeability reduce, active efflux) (esterase production that hydrolyze macrolide)(modification of ribosomal binding site by chromosomal mutation or by macrolide inducible or constitutive methylase)
macrolide cross resistance
macrolide, lincosomide, streptogramins
drugs in the macrolide family
erythromycin, clarithromycin, azithromycin
gram postiive and atypical organisms (mycoplasm, chlamydia, rickettsia)
clarithromycin and azithromycin active against...
clarithromycin active against STAPH and STREP
clarithromycin used with what effect
with less GI effect
mycobacterium used in what kind of patients
best absorbed macrolide is ....
protein binding for macrolides
where is macrolide retained
liver, and spleen, low levels in CSF even with inflmaed meninges
excretion of macrolide
urine, bile, hepatic metabolism (demethylated)
cyp450 in erythro>clari??? not azithromycin
drug interactions with erythromycin
GI, hepatotoxic, thrombophlebitis after IV, ototoxicity
macrolide inhibit what
isozymes of CYP450,
drug interaction with terfenadine or astermizole: QT prolongation
linezolid, iv or po, 100% bioav, kills gram +, bacteriostatic
oxazolidinones adverse effects
rever inhibitor of monoamine oxidase, bone marrow suppression, GI, rash, no cross resistance, resistance with ribosome site modification by binding to 50S p site