Antibacterial Agents III: Protein Synthesis Inhibitors Flashcards
Clindamycin penetrates most tissues well, especially ____, but not well into ____.
bone; CSF
Pts with myasthenia gravis or that take other neuromuscular blocking agents can have respiratory arrest after taking ______.
aminoglycosides
What is the mechanism of action for Linezolid?
binds to the 23s portion of the 50s ribosome to inhibit early phase protein synthesis
What is the mechanism of resistance in the aminoglycosides?
chemical mods to the abx that prevents uptake and ribosomal binding (plasmid mediated)
Where do the aminoglycosides accumulate?
the renal cortex and inner ear
_____ are VERY TOXIC!
Aminoglycosides
Why do ventricular arrhythmias occur with macrolides?
they prolong the QT interval
What are the mechanisms of chloramphenicol resistance?
emergence of mutant strains impermeable to drug; inactivation of bacterial enzymes
Why does chloramphenicol cause gray baby syndrome?
immature hepatic and renal fxn leads to toxic accumulation of the drug
What impairs the absorption of tetracyclines?
milk products, Al, Ca, Mg, and Fe salts
Tx for Borrelia burgdorferi Lyme disease (early)?
doxycycline
Quinupristin/Dalfopristin inhibits cytochrome 3A4, which may cause increased plasma levels of _____ (6).
- benzodiazepines cisapride 2.. calcium channel blockers 3. carbamazepine 4. cyclosporine 5. HMG CoA reductase inhibitors 6. HIV protease inhibitors
Name 3 tetracyclines.
- tetracycline 2. doxycycline 3. minocycline
Azithromycin is not metabolized; its high tissue penetration and slow release allows _____ dosing.
once-daily
_____ in aminoglycoside use is usually reversible when the drug is discontinued.
Renal toxicity
How should clindamycin be taken?
food doesn’t affect it
Tx for Chlamydia trachoma, C.A. pneumonia, urethritis?
azithromycin
Which tetracyclines have the best bioavailability?
minocycline, doxycycline
How do antacids and iron supps interact with tetracyclines?
decrease bioavail of the tetracyclines by forming insoluble salts
_____ has limited use in the US and is only used for severe infections.
Chloramphenicol
Tx of Strep pneumonia (C.A. and nosocomial)?
Linezolid, Quinupristin/Dalfopristin
Tx for C. diptheriae diptheria?
erythromycin
Avoid _____ if leukopenias, anemia, or thrombocytopenia present bc of bone marrow tox.
chloramphenicol
Why does admin of aminoglycosides have to be so carefully monitored?
they are subject to wide variation of pharmacokinetics, even in pts with healthy kidney function, and have a narrow therapeutic index
What is Telithromycin/Ketek?
a ketolide Abx derived from erythromycin
Describe the hepatotoxicity via macrolides.
reversible acute cholestatic hepatitis
Name 6 drugs that can be toxic in combination with a macrolide.
theophylline, warfarin, methylprednisolone, cyclosporine, SSRIs, benzodiazepines
Why is there some selective toxicity with tetracyclines?
mammalian cells have an active efflux mechanism preventing accumulation of drugs, and lack active transport of drugs into the cell
Tx of Enterococci (including VRE) bacteremia, endocarditis?
Linezolid, Quinupristin/Dalfopristin
Tx for Enterococci bacteremia, endocarditis, intra-abd infections?
gentamycin + penicillin or vancomycin
What drug can cause gray baby syndrome?
chloramphenicol
______ is metabolized in the liver and excreted in the bile.
Erythromycin
What is the mechanism of action of clindamycin?
inhibits protein synthesis by binding to the 50s ribosome- prevents translocation of peptidyl tRNA and peptide bond formation
How do the tetracyclines work?
reversibly bind to 30s ribosome to prevent access of aminoacyl-tRNA to site
Aminoglycosides have ____ killing and a _____ which allows their admin in a single, large daily dose.
concentration-dependent; postantibiotic
What are the adverse affects of Linezolid?
minor GI, thrombocytopenia, drug interaction with MAO and SSRI
Choose: The macrolides ARE/ARE NOT excreted in breast milk and ARE/ARE NOT ok to use in breastfeeding women.
ARE; ARE
When should Telithromycin/Ketek be prescribed?
ONLY in community acquired pneumonia due to Strep. pneumoniae
Choose: Chloramphenicol is BACTERIOCIDAL/BACTERIOSTATIC.
normally static, but cidal against bacteriodes, H. influenzae, N. meningitidis
How is Linezolid metabolized/distributed/excreted?
nonenzymatic oxidation; well-perfused tissues; renally
Tx for Chlamydia trachoma, C.A. pneumonia, urethitis?
doxycycline
Name 6 general adverse rxns for the tetracyclines.
- teeth and bone 2. GI upset 3. photosensitivity 4. yeast/candida overgrowth 5. liver/kidney toxicity 6. drug interactions
Aplastic anemia, although rare, can be fatal and appears weeks to months post-_____ treatment.
chloramphenicol
What drugs does Linezolid interact with?
MAOs, SSRIs
Choose: Linezolid is BACTERIOSTATIC/BACTERIOCIDAL.
static
Tx for Richettsia rocky mtn spotted fever, Q fever?
doxycycline, chloramphenicol
Which tetracycline is choice for pts with renal disease or for breastfeeding mothers?
doxycycline
_____ should be used to treat severe anaerobic infections.
Clindamycin
Tx for Strep and Pneumococci pneumonia and pharyngitis?
any macrolide
Tx for Myco. avium pneumonia?
clarithromycin, azithromycin
Name 3 adverse rxns for clindamycin.
- pseudomembranous colitis 2. GI upset or skin rashes 3. impaired liver function, neutropenia (rare)
Aminoglycosides have concentration-dependent killing and a postantibiotic effect which allows their admin in a ______.
single, large daily dose
Azithromycin and clarithromycin accumulate in higher concentrations in _____ and ____.
certain tissues (skin, lungs, tonsils, cervix, sputum); macs
Tx for Bacillus anthracis anthrax?
doxycycline
Tetracyclines can lead to disturbance of normal gut flora, leading to ____ and _____.
thrush, vaginitis
Tx for MRSA localized cutaneous infection?
clindamycin
Tx for Strep. pneumonia, pharyngitis?
clindamycin
What are the s/s of gray baby syndrome?
vomiting, abnormal respirations, cyanosis, vasomotor collapse and ashen-gray color
Tx for Myco. tuberculosis Tb?
streptomycin + anti-Tb drugs
Is clindamycin bacteriocidal or bacteriostatic?
static, but can be cidal against certain orgs and high concentrations
Which of the macrolides causes the most GI upset? How?
erythromycin; directly stimulates gut motility
How do the aminoglycosides work?
inhibits initiation of protein synthesis by interacting with mRNA on the 30s ribosome- breaks up the polysomes, misreads the code
Why does chloramphenicol have a diminished selective toxicity?
it inhibits mammalian mitochondrial protein synthesis in the bone marrow
Tx for Bacteriodes fragilis intra-abd. and brain abscesses?
clindamycin, chloramphenicol
Choose: Macrolides are BACTERIOSTATIC/BACTERIOCIDAL.
bacteriostatic at normal concentrations
Tx for Salmonella typhi typhoid fever?
chloramphenicol
_______ inhibits metabolism of phenytoin, oral anticoagulants, and 1st gen oral hyperglycemic agents.
Chloramphenicol
What is the absorption, distribution, metabolism, and excretion of chloramphenicol?
rapid and complete from GI tract; widely distributed in all tissues and fluids, inc CNS and CSF; metabolized by glucuronidation or reduction except in fetus and neonate; excreted in breast milk
Tx for H. pylori peptic ulcers?
tetracycline
______ have concentration-dependent killing and a postantibiotic effect which allows their admin in a single, large daily dose.
Aminoglycosides
How should each of the macrolides be taken?
- erythromycin = depends on salt form 2. clarithromycin = doesn’t matter- food may help absorb 3. azithromycin = take on empty stomach
Tx for H. influenzae URI/bronchitis?
azithromycin, clarithromycin
Tetracyclines should be used with caution in pts with ____.
impaired liver function
Tx for Vibrio cholera cholera?
doxycycline
How does resistance to the macrolides occur?
methylation of the 50S ribosome, preventing binding of drug
Tx for Myco. pneumoniae C.A. pneumonia?
any macrolide
How does resistance to tetracyclines work?
- changes in protein receptors or transporters 2. produce proteins to block and protect the ribosome
_____ penetrates most tissues well, especially bone, but not well into CSF.
Clindamycin
What are the important drug interactions with Quinupristin/Dalfopristin?
inhibits cytochrome 3A4
____ is short-acting (t1/2 of 6-8 hours); ____ and _____ are long-acting (t1/2 of 16-18 hours).
tetracycline; doxycycline, minocycline
What are the macrolides?
- erythromycin 2. clarithromycin 3. azithromycin
What is the mechanism of action for Quinupristin/Dalfopristin?
inhibits bacterial protein synthesis by binding to the 50S ribosome to inhibit elongation
Tx for Clost. perfringens gas gangrene, food poisoning?
clindamycin
Tx for Pseudo. aeruginosa (any)?
gentamycin, tobramycin, amikacin
Does tetracycline cross into the placental/fetal circulation?
yes
Tetracycline is short-acting (t1/2 of ____); doxycycline and minocycline are long-acting (t1/2 of _____).
6-8 hours; 16-18 hours
Aminoglycosides are _____ at low concentrations and _____ at high concentrations (clinically).
bacteriostatic, bactericidal
Tx for Prop. acnes acne?
minocycline, doxycycline, clindamycin
Which drug requires oxygen and is therefore ineffective in anaerobic organisms?
aminoglycosides
Name the 6 aminoglycosides.
- streptomycin 2. tobramycin 3. gentamycin 4. amikacin 5. kanamycin 6. neomycin
How are the aminoglycosides absorbed, distributed, metabolized, and excreted?
highly polar, so not sig. absorbed after oral admin- use IM- distributed into extracellular fluid- excluded from CNS but accumulates in the renal cortex and inner ear; not metabolized; excreted thru kidneys
Tx for H. influenzae otitis media, C.A. pneumonia?
doxycycline
Tx of Staph (including MRSA) complicated skin infections?
Linezolid, Quinupristin/Dalfopristin
______ should be avoided in pregnancy and breastfeeding because it cannot be conjugated by the fetal and neonate liver, causing toxicity.
Chloramphenicol
Tx for MSSA osteomyelitis?
clindamycin
Pts with myasthenia gravis or that take other neuromuscular blocking agents can have _____ after taking aminoglycosides.
respiratory arrest
What happens when an aminoglycoside and penicillin are given together?
the aminoglycoside is inactivated
Clarithromycin is ____ eliminated.
renally
What is the distribution of the macrolides?
widely except brain and CSF; crosses placenta
Tx for H. influenza meningitis?
chloramphenicol
How do the macrolides work?
inhibit protein synthesis by binding to the 50s subunit and block translocation of peptidyl tRNA and peptide bond formation
Tx for E. coli, Klebsiella, Serratia, Proteus, Enterobacter UTIs, lower RIs, bacteremias, post-surg bowel sterilization, wound infections?
neomycin
Chloramphenicol inhibits metabolism of ____, ____, and _____.
phenytoin, oral anticoagulants, and 1st gen oral hyperglycemic agents
What is the main adverse rxn for clindamycin?
pseudomembranous colitis
______ is not metabolized; its high tissue penetration and slow release allows once-daily dosing.
Azithromycin
_____, although rare, can be fatal and appears weeks to months post-chloramphenicol treatment.
Aplastic anemia
How is Quinupristin/Dalfopristin administered?
IV only
Which drugs interact negatively with tetracyclines?
- antacids and iron supps 2. phenytoin/barbs/carbamazipines 3. oral anticoagulants
How do the aminoglycosides get into the bacterium?
active transport
Tx for Staph. aureus cutaneous infections, pneumonia, food poisoning?
doxy, tigecycline
How do the tetracyclines affect bones and teeth?
temporarily depresses bone growth and permanently discolors teeth
How is clindamycin metabolized and excreted?
metabolized by the liver, then into biliary excretion- also excreted into breast milk
Erythromycin is metabolized in the ____ and excreted in the ____.
liver; bile
Name 5 adverse rxns to chloramphenicol.
- bone marrow tox 2. gray baby syndrome 3. GI upset 4. oral or vaginal candidiasis 5. drug interactions
Tx for Legionella community-acquired pneumonia?
azithromycin
How is Quinupristin/Dalfopristin metabolized and excreted?
hepatic conjugation rxns; biliary excretion into the feces
Tx for Moraxella catarrhalis otitis media, c.a. pneumonia?
doxycycline
______ is renally eliminated.
Clarithromycin
What drug do the aminoglycosides interact with?
the β-lactams and penicillin
Why are the macrolides only selectively toxic?
they don’t bind to the 60S ribosome
Where is tetracycline metabolized and excreted?
concentrated in the liver, secreted into bile, excreted into the urine (except doxycycline and minocycline)
How does chloramphenicol work?
reversible binding of the 50S ribosome, blocking peptidyl transferase action and incorporation of aas in to the newly formed peptide
Tx for N. meningitides meningitis?
chloamphenicol
Which macrolides can potentially cause toxicity via drug-drug interactions and why?
erythromycin, clarithromycin- inhibit CYP450- increase plasma drug levels
Tx for H. pylori peptic ulcer disease?
clarithromycin plus PPI or H2 antagonist
____ and ____ accumulate in higher concentrations in certain tissues and macs.
Azithromycin; clarithromycin
How is Linezolid administered?
orally, food doesn’t matter
What are the common side effects of Quinupristin/Dalfopristin?
infusion site irritation, arthralgia/myalgia, GI upset, skin rashes
_____ in aminoglycoside use is irreversible and happens at high frequency in elderly pts and those with impaired renal function.
8th nerve damage
What must be monitored in aminoglycoside-receiving pts?
- plasma drug conc 2. 8th cranial nerve function 3. kidney function
Tx for Myco. pneumoniae C.A. pneumonia?
doxycycline
______ and _____ should only be used for life-threatening infections.
Linezolid and Quinupristin/Dalfopristin
What are the 4 main adverse rxns of macrolides?
- GI upset 2. hepatotoxicity 3. ventricular arrhythmias 4. inhibition of CYP450 causing drug/drug interactions
Choose: Tetracyclines are BACTERIOCIDAL/BACTERIOSTATIC.
bacteriostatic
Linezolid and Quinupristin/Dalfopristin should only be used for _____.
life-threatening infections
How should tetracycline be administered?
on an empty stomach
What sensitivity rxns can occur with aminoglycoside use?
contact dermatitis, skin rashes, bone marrow depression
Tx for B. pertussis whooping cough?
any macrolide
Macrolides enter the cell via ____.
passive diffusion
