Tetracycline and Aminoglycosides Flashcards
What is a ribosome?
A large nucleoprotein complex that catalyzes the ordered polymerization of amino acids
What directs the ribosome to order the amino acids?
An mRNA template (mRNA translation)
How can drugs target bacterial ribosomes while not affecting human ribosomes?
Structural difference (70s prokaryote vs. 80S Eukaryote)
What are the 3 steps of protein synthesis?
- Initiation
- Elongation
- Termination
Which step of protein synthesis do most current protein synthesis inhibitors target?
Elongation
How to aminoglycosides inhibit protein synthesis?
Promote premature termination
Tetracyclines are named according to what?
The number of fused rings
Tetra = 4
Doxy = 2
Mino = 1
How do tetracyclines inhibit protein synthesis?
Bind to the 30S ribosomal subunit and inhibit binding of amino acylated tRNA to A site of ribosome
What helps tetracycline along in its effect on bacteria?
Bacteria concentrate tetracyclines inside the cell, eukaryotes and resistant bacteria do not
Are tetracyclines bactericidal?
No, bacteria start to grow again once the patient stops taking tetracycline.
What is the spectrum of activity for tetracycline?
Broad Spectrum: G+, G-, aerobe, anaerobe, atypical bacteria (rickettsiae, mycoplasma, Chlamydia)
Of Tetracycline, Doxycycline, and Minocycline: which has the lower bioavailability and higher risk of superinfection in the gut?
Tetracyclines
What inhibits the absorption of Tetracyclines?
divalent cations (Ca, Mg, Al, Fe). Think of Tetracycline binding to bone. Do not take w/ milk. Take 1-2 hrs prior to a meal. Tetracycline is a potent chelator
Of tetracycline, doxycycline and minocycline: which are the most lipophilic and are therefore more easily distributed?
Tetracycline and Doxycycline
What is a characteristic of tetracyclines that is useful in the treatment of adults with periodontal disease?
Concentrate in gingival crevicular fluid
Of Tetracycline, doxycycline, and minocycline: which has the shortest halflife and therefore must be dosed more often during the day?
Tetracycline (4/day)
Minocycline and doxycycline (2/day)
Of tretracycline, doxycycline, and minocycline: which is eliminated unchanged in the urine?
Tetracycline (whereas minocycline and doxycyclines undergo hepatic
metabolism and excretion as well as renal excretion)
When is tetracycline contraindicated?
In pregnant women and children less than 8. Uptake and concentrates in developing bones and teeth.
What are 3 common side effects of tetracycline?
Staining of teeth and altered rates of bone growth
GI disturbances
Phototoxic skin reactions
Is teeth staining reversible or irreversible?
Is it dose dependent or non-dose dependent?
Irreversible/permanent and dose dependent
What is the superinfection and its symptoms that can be caused by tetracycline (doxycycline has reduced risk)?
Colitis due to superinfection by C.diff (main symptom: bloody stools)
What can be a rare side effect from treating a meningococcal infection with minocycline?
Vestibular toxicity: dizziness, vertigo
What do doxycycline and minocycline do in the blood and what consideration must be made?
Depress plasma prothrombin. If patient is on anticoagulation therapy, dosing may need to be reduced
Why not use a tetracycline with a penicillin?
Tetracycline is bacteriostatic. Will reduce amount of cell wall synthesis targets for penicillin reducing its bacteriocidal effectiveness
Tetracyclines are Drugs of choice for the treatment of what infections?
Mycoplasma pneumonia
Rickettsia (Rocky Mountain Spotted Fever)
Borrelia (Lyme’s Disease)
Chlamydia (Chlamydia pneumonias/vaginitis)
Vibrip(Cholera)
Combo therapy for H.pylori ulcer
Acne
Gonorrhea and syphilis in penicillin allergic
What drug is commonly used for the eradication of the meningococcal carrier state (treating people who have come in close contact with someone who has meningitis)?
Minocycline
What is Periostat?
Doxycycline (20mg tab bid, p.o.). Systemic therapy of advanced periodontal disease for up to 1 year?
What is Arestin?
Topical minocycline to be placed in periodontal pocket for up to 3 weeks release
What other periodontal problem can tetracyclines be used to treat (as an alternative to penicillin)?
ANUG
Protein synthesis inhibitor that is isolated from streptomyces soil bacteria?
Chloramphenicol
What is the major side effect associated with chloramphenicol?
Aplastic anemia
Aplastic anemia associated with chloramphenicol is an example of what
idiosyncratic toxicity (characteristic peculiarity[internet definition for idiosyncratic])
Though Chloramphenicol is similar to tetracycline in its spectrum of activity, how is it different (mechanism of action)?
Binds to 50S bacterial ribosome and inhibits ribosomal peptidyltransferase
What is the Gray Baby Syndrome?
Neonate symptom that showed infants do not have mature hepatic drug metabolizing system (Chloramphenicol requires hepactic metabolism)
What character of chloramphenicol makes it useful in treating bacterial meningitis?
Lipophilic and crosses blood brain barrier
What are 2 blood dyscrasias associated with chloramphenicol?
- Predictable, dose dependent depression of bone marrow cell proliferation
- Non-predictable, non-dose dependent risk of aplastic anemia that can occur even months after off Chloramphenicol
What is the good thing about the depressed bone marrow cell depression caused by chloramphenicol?
it goes away once chloramphenicol is stopped
When is chloramphenicol indicated for treatment?
In severe systemic infections not treatable with less- toxic drugs. E.g. Cephalosporing resistant typhoid (S. typhi) or Meningitis and pneumonia caused by H.influenza or B. fragilis
Aminoglycosides are important for treating what bacteria?
Gram negative bacilli aerobes
Pseudomona (P. aeruginosa)
How must aminoglycosides be administered?
parenteral (outside alimentary, normally IV or IM [internet definition])
Do aminoglycosides have a high or low therapeutic index?
Low Therapeutic Index, so monitoring.
Aminoglycoside spectrum (broad vs narrow) and activity (bacteriostatic vs bacteriocidal) is what?
Narrow spectrum (focus on gram negative aerobes) Bacteriocidal
Are aminoglycosides useful against anaerobes?
No
What is the aminoglycoside mechanism of action?
Bind bacterial ribosome 30S subunit and inhibit protein synthesis
What are 3 effects caused by aminoglycosides binding the 30S bacterial ribosome?
- Accumulation of initiation complexes (streptomycin monosomes)
- Misread mRNA = wrong amino acid inserted
3 Premature protein release from mRNA
Why are Aminoglycosides poorly absorbed if taken orally?
Due to their large size
Can aminoglycosides cross cell membranes?
No
How are aminoglycosides excreted?
Unchaged, rapidly by kidney (glomerular filtration)
What are 2 toxicities associated with aminoglycosides?
Ototoxicity
Nephrotoxicity
How is aminoglycoside toxicity avoided?
Longer interval, monitored dosing, not in patients with impaired kidney function
What makes bacteria resistant to aminoglycosides?
Aminoglycoside-metabolizing enzyme acquired from plasmids
What are some systemic infections that are treated by aminoglycosides?
Klebsiella Proteus E.coli Enterobacter Pseudomonas aeruginosa Serratia
Why are aminoglycosides NOT used at abscess sites?
Because abscesses have anaerobes against which aminoglycosides are ineffective
Name 2 infections where aminoglycosides are administered along with penicillin?
Meningitis
Enterococcal endocarditis
What is a prototype aminoglycoside?
Gentamicin
What aminoglycoside is used in skin ointments or to sterilize bowel prior to GI surgery?
Neomycin
What aminoglycoside is used in pseudomonal infections?
Tobramycin
What 2 aminoglycosides that are back up drugs for gram negative drug resistant infections?
Amikacin
Netilimicin
