inhibitors of protein synthesis Flashcards
name the eye ointment name of tetracyclines
terramycin
why are they called “tetracyclines”?
they are called tetracyclines because they have 4 rings that are fused to each other. in addition to this they have 4 R groups that impart activity to the structure.
what is the MOA of tetracyclines
they enter by passive diffusion and an energy dependant transport protein. they bind reversibly to the 30 S subunit of bacteria thereby inhibiting bacterial protein synthesis
name the tetracycline drugs
tetracycline capsules 250 mg
oxytetracycline terramycin eye ointment
doxyclycline doxydar capsules 200 mg and IV injection
minocycline minocin capsule 100,200 mg and IV injection
tetracyclines should not be taken with specific products? name them and give reason why?
tetracyclines should not be taken concomitantly with
dairy products, aluminium and magnesium antacids or iron preparations because it decreases the absorption of tetracyclines due to formation of non absorbable chelates.
describe the absorption of tetracyclines
they are absorbed adequately but incompletely orally
tetracyclines should be administered
a. with food
b. without food
b. without food
where do tetracyclines concentrate
in the liver, kidneys, spleen, skin and tissues undergoing calcification (teeth and bone)
do tetracyclines enter the CSF
yes but in inadequate therapeutic concentrations
do tetracyclines cross the placental barrier, where do they concentrate in foetus
yes, they concentrate in the fetal bone and dentition
how are tetracyclines excreted
they are secreted in the bile. reabsorbed in the intestine and excreted in the urine by glomerular filtration
which tetracycline would you recommend to a patient with compromised renal function and why? name the component excreted.
recommend doxycycline because it is preferentially excreted in bile via feces.
doxycycline glucoronide
only ____________ provides therapeutic concentrations in the CSF.
minocycline
any organism resistant to one tetracycline is resistant to all. true or false
true
give 2 reasons for resistance to tetracyclines?
inability of the drug to accumulate due to the R factor, energy dependant efflux pumps
enzyme modification of tetracycline binding site
what are the adverse effects of tetracyclines
GI disturbance staining of teeth hyperplasia bone deformities fatal hepatotoxicity phototoxicity superinfection
what are the CI of tetracyclines
pregnant women
first trimester : abnormal skeletal development of baby
2nd and 3rd trimester ; dental discolouration and maternal hepatotoxicity
lactating females : drug may pass to baby via breast milk leading to dental discolouration and abnormal skeletal development
renally impaired patients except doxyclycline
children under 8 yrs : dental discolouration and abnormal skeletal development
name the aminoglycoside drugs
- streptomycin (streptomycin sylfate injection)
- trobramycin (nebcin injection)
- netromycin/netilmicin (netromycin sulfate injection)
- neomycin (neomycin and bacitracin cream)
neospora ( gramicidin + neomycin) eye drops - amikacin (amikin) injection
- gentamycin, genticin ear and eye drops, garamycin sulfate inj. and garamycin eye drops
aminoglycosides have been the mainstays of treatment for?
the serious infections caused by aerobic gram negative bacilli.
aminoglycosides have a broad therapeuic index. true or false?
false. they have a narrow therapeutic index
why are aminoglycosides rarely used
due to their serious toxicities
aminoglyclosides are now replaced with :
a. vancomycin, bacitracin, penicillins
b. 3rd gen cephalosporins. fluroquinolones, imipenem/cilastatin
c. imipenem, cilastain, penicillins
b. 3rd gen cephalosporins, fluoroquinolones and imipenem/cilastatin
what is the MOA of aminoglycosides
aminoglycosides bind to the 30S ribosomal subunit leading to
a. inhibition of the initiation of protein synthesis
b. misreading of mRNA leading to abnormal proteins. or premature chain termination
aminoglycosides are
a. bacteriostatic
b. bactericidal
b. bactericidal
why do aminoglycosides not work against anaerobic micro organisms?
because anaerobes do not have an O2 dependant carrier system. susceptible organisms have an oxygen dependant system that tranports the antibiotic across the cell membrane.
what is the synergistic relationship between aminoglycosides and beta lactam?
beta lactam destroys the cell wall allowing aminoglycosides to enter and inhibit protein synthesis
what are the typical therapeutic indications of aminoglycosides
enterococcal infections : gentamycin/stretomycin + vancomycin/ other beta lactam
psuedomonas infection : tobramycin alone or tobramycin + antipseudomonal penicllin eg. piparcillin
name the macrolides
- erythromycin
erythrocin tablets, erythrocin syrup, erythromycin injection - clarithromycin, klacid tablets, klacid powder for suspension
- azithromycin, zithromax capsules, zithromax oral suspension
what is MOA of macrolides
they act by binding irreversibly to the 50 S subunit of bacterial ribosome and inhibiting the translocation step of bacterial protein synthesis
name the therapeutic indications of erythromycin
Used in oral infections, urethritis, respiratory tract diseases (including Legionella), skin infections, chronic prostatitis, diphtheria prophylaxis and carrier state, acne vulgaris.
clarithromycin is additional active against which organisms?
H. influenzae and intracellular pathogens such as chlamydia. legionella and ureaplasma
_____________ is used as treatment in H.pylori eradication regimen.
clarithromycin
azithromycin is not as effective as erythromycin against ________ and _________.
streptococci and staphylococci
if the bacteria is resistant to erythromycin, can we administed azithromycin/clarithromycin? why?
no because Both azithromycin and clarithromycin show cross resistance with erythromycin
name the adverse reactions of macrolides
epigastric distress
cholestatic jaundice
ototoxicity (transient)
what happens when azithromycin and clarithromycin eliminate the intestinal flora?
the intestinal flora that inactivates digoxin is eliminated hence this leads to digoxin toxicity.
describe the MOA of chloramphenicol
binds reversibly to 50S ribosmal unit of bacteria and inhibits peptidyltransferase enzyme
why does chloramphenicol cause bone marrow toxicity at high doses?
this is due to the similarity between the organelles and due to inhibition of mitochondrial protein synthesis
describe the antibacterial spectrum of chloramphenicol
Broad spectrum, effective against bacteria and other microorganisms including anaerobes (except chlamydia and pseudomonas)
describe the resistance towards chloramphenicol
- inability of the antibiotic to penetrate the enzyme
2. prescence of an enzyme that inactivates chloramphenicol
what are the adverse reactions of chloramphenicol
Hemolytic anemia in G6PD deficient patients Reversible anemia (dose related) Aplastic anemia (dose independent) hepatic enzyme inhibition gray baby syndrome
why does gray baby syndrome occur with chloramphenicol?
Occurs due to inability of the baby to glucuronidate chloramphenicol effectively if doses were miscalculated.
describe the MOA of clindamycin
They act by binding irreversibly to the 50S ribosomal subunit of bacterial ribosomes inhibiting the translocation step in bacterial protein synthesis.
describe the therapeutic indications of clindamycin
Used in bone and joint infections, peritonitis and endocarditis prophylaxis
infections caused by Bacteroides fragilis
in acne caused by Propionibacterium acnes
dental infections or prophylaxis prior to dental procedures
clostridium difficile is resistant to clidamycin. this might cause _____________.
pseudomembranous colitis
what is the resistance mechanism of clindamycin
- inability of the antibiotic to penetrate organism.
- decreased affinity for 50 s ribosomal subunit.
- plasmid associated synthesis of esterase enzyme.
