Protein Synthesis Inhibitors Flashcards
Tetracylines
tetracycline, doxycycline, minocycline, demeclocycline
Aminoglycosides
amikacin, gentamicin, neomycin, streptomycin, tobramycin
Macrolides
azithromycin, clarithromycin, erythromycin, fidaxomicin
Other synthesis inhibitors
clindamycin and linezolid
What subunits does a bacterial ribosome have?
50s and 30s
What subunits does a human ribosome have?
60s and 40s
What is different about mitochondrial ribosomes?
mammalian mitochondrial ribosomes are closer to bacteria, so drugs targeting it may cause toxic effects
Which drugs inhibit protein synthesis at the 30s ribosome?
tetracyclines and aminoglycosides
Which drugs inhibit protein synthesis at the 50s ribosome?
macrolides and “others” + chloramphenicol
Which group of drugs have adverse effects on the teeth?
tetracyclines
What is the tetracycline MOA?
reversibly bind the 30s subunit to prevent binding of tRNA which prevents the addition of new amino acids to the growing peptide chain
Are tetracyclines bacteriostatic or bactericidal?
bacteriostatic
Which two tetracyclines are longer lasting?
doxycycline and minocycline
What do tetracyclines treat?
broad spectrum, gram - and , chlamydia!
How does resistance to tetracyclines come about?
mutation preventing organism from taking in the drug, plasma encoded efflux of drug, enzymatic inactivation, or producing proteins that prevent binding to ribosome
What does tetracycline bind to?
calcium, aluminum, iron, magnesium
What reduces the bioavailability of tetracycline?
dairy products– avoid antacids and iron supplements as well
What tissues does tetracycline bind to?
tissues undergoing calcification
Which tetracycline can penetrate CSF but is not effective for CNS infections?
minocycline
T/F tetracyclines cross the placenta and bind fetal bones and teeth
true– contraindication!
Who should you not prescribe tetracycline to?
pregnant/breastfeeding women
Describe the elimination of tetracycline
gets concentrated in the liver, secreted into bile, reabsorbed into the intestine and excreted in urine
T/F doxycycline is excreted by the kidney
false, good for patients with renal disease
What are the adverse effects of tetracycline?
gastric discomfort, effects on calcified tissues, photo-toxicity, vestibular issues, and pseudotumor cerebri
What are tetracyclines effects on calcified tissue?
discoloration and hypoplasia of teeth in children, can stunt growth, avoided in children under 12
What are tetracyclines effects on the vestibular system?
it concentrates in endolymph in the ear and can cause vertigo
What is pseudotumor cerebri?
effect of tetracycline, idiopathic intracranial hypertension, pt symptoms are headache and blurred vision with a swollen appearance to the optic nerve (bilaterally)
What are three superinfections that can result from tetracyclines?
candida (yeast), resistant staph, colitis
Summarize the four main contraindications of tetracyclines
only doxycycline for those with kidney problems, NO pregnant women, no children under 12, inhibits warfarin (blood thinner) clearance
What is a 50 mg or less dose of doxycycline for?
anti-inflammatory effects that work on soft tissue inflammation and do not encourage bacterial resistance to larger dose
What is the MOA of aminoglycosides?
bind 30s ribosome proteins and interfere with initiation complex by causing misreading of mRNA
Are aminoglycosides bacteriostatic or bactericidal?
bactericidal
Which two aminoglycosides often cause allergies?
gentamicin and neomycin
What is true of the absorption of aminoglycosides?
oral absorption is inadequate because of highly polar structure
How are aminoglycosides administered?
IV, IM, topically
What are aminoglycosides used against?
gram - including pseudomonas, with some gram +
What can an aminoglycoside be combined with to improve the spectrum?
b-lactam or vancomycin
What are two causes of aminoglycoside resistance?
decreased uptake of drug, plasmid associated synthesis of enzyme
Describe the aminoglycoside distribution?
inadequate CSF penetration, low tissue penetration, high concentration in renal cortex and inner ear, all cross the placenta
What is the elimination of aminoglycosides?
no host metabolism, rapidly excreted into urine
What are four main adverse effects of aminoglycosides?
ototoxicity, nephrotoxicity, neuromuscular paralysis, allergic reactions
What is ototoxicity?
an adverse effect of aminoglycosides with deafness that may be irreversible, orally will affect the fetus
How does aminoglycoside neuromuscular paralysis occur?
after very large doses it causes decrease in acetylcholine release and in post-synaptic sensitivity to acetylcholine
Are topical aminoglycosides likely to become resistant?
no
What is the MOA of macrolides?
bind to the 50s ribosomal subunit to block peptidyltransferase center and prevent amino acid chain elongation… can also inhibit formation of 50s
What is a good macrolide alternative to PCN?
erythromycin
Which macrolide is effective against H. influenzae
clarithromycin
Which macrolide is best for respiratory infections and chlamydia?
azithromycin (1000 mg once)
What are three mechanisms of macrolide resistance?
inability to take up antibiotic/efflux pump, decreased affinity of 50s subunit, and presence of plasmid associated enzyme
T/F macrolides are well absorbed orally
true
Which macrolide should not be given via IV for thrombophlebitis risk?
erythromycin
T/F macrolides only diffuse into one tissue type
false, distributes well into fluids and tissues
Which macrolide has a long half life and high V?
azithromycin
What is true of erythromycin and telithromycin metabolism?
extensively metabolized and inhibit oxidation of many drugs, interact with P450
Which organ excretes macrolides?
kidney
What are three macrolide adverse effects?
GI problems, acute hepatitis with jaundice, ototoxicity
Which macrolide primarily produces ototoxicity in high doses?
erythromycin
What are two contraindications of macrolides?
hepatic dysfunction, arrhythmia
T/F macrolides inhibit hepatic metabolism of many drugs
true via P450
What is the MOA of clindamycin?
same as erythromycin, bind 50s
What is clindamycin used to treat?
MRSA, abdominal anaerobic infections
T/F clindamycin has poor absorption to CSF
true
What is linezolid used to treat?
resistant gram + organisms like MRSA
What is the MOA of linezolid?
inhibits formation of ribosomal complex by binding 50s subunit near the interface with 30s
T/F linezolid has no cross-resistance with other drug classes
true
Linezolid vs vancomycin for MRSA
linezolid is noninferior to vancomycin for MRSA pneumonia but is not used for MRSA bacteremia
What are important pharmacokinetic principles of linezolid?
completely absorbed orally, high V, no interaction with P450, renal and nonrenal excretion
What are three adverse effects of linezolid?
thrombocytopenia, anemia, optic and peripheral neuropathy
What are contraindications for linezolid?
caution with MAOIs and SSRIs due to case reports of serotonin syndrome
