Quiz 3 - Smith - Antimicrobials II Flashcards
Difference b/t prokaryotic and eukaryotic ribosome.
Pro - 70 S = 30 S + 50 S
Eu - 80 S = 40 S + 60 S
*S is a Svedberg unit and is a fx of sedimentation rate, which is effected by both molecular weight and shape
What is dose-dependent selectivity?
At low pharmacological doses, antimicrobial PSI’s (Protein synthesis inhibitors) are MORE SELECTIVE for bacterial ribosomes, so LESS TOXIC
At higher doses, toxicity occurs due to reduced selectivity
-Both host and bacterial ribosomes are affected, esp mitochondria
—Chloramphenicol
–Tetracyclines
What does the A site do?
P site?
E site?
A - Holds AA to be added
P - Holds growing polypeptide chain
E - Exit site for tRNA
Tell me how translation works?
When appropriate tRNA is recognized, a peptide bond is formed b/t the AA in the P-site and the AA in the A-site
String of AAs at the P site transfers to the AA in the A site
Ribosome shifts down the mRNA one codon and process repeats
tRNA in the P-site is shifted to the E-site and ejected from the ribosome
Process continues until a stop codon is positioned in the A-site
What class are the following drugs in?
Gentamycin
Amikacin
Tobramycin
Streptomycin
Neomycin
Aminoglycosides
*Cephalosporins are typically used before these due to toxicity risks
How do aminogylcosides work?
Bind to the 30S subunit and change its shape which does 3 things
- Block initiation
- Early termination
- Misreading
*THEY TARGET THE 30S subunit
Tell me about streptomycin (IM, IV).
Oldest aminoglycoside
High level of bacterial resistance
Gentamycin (IV) - tell me about it.
MOST COMMONLY PRESCRIBED aminoglycoside
Tell me about amikacin (IM, IV).
Broadest spectrum
-Diarrhea
Tell me about tobramycin (IM, IV).
Excellent against Pseudomonas aeruginosa
Tell me about neomycin (Topical only).
Very toxic
Topical
Enema before bowel surgery
When should aminoglycosides be used?
Against aerobic G- infections, like Pseudomonas
*Prone to high toxicity rates
Once daily dosing is very common
T/F - Aminoglycosides are given IV or IM, mostly.
TRUE
NOT oral
*Exception is neomycin which is topical
**Risk of nephrotoxicity and ototoxicity is conc. Dependent
Aminoglycosides synergize greatly with what two other classes?
B-LACTAMS
VANCOMYCIN
Tell me about ototoxicity.
Correlates with the # of destroyed hair cells
- Usually irreversible
- Streptomycin is linked to vertigo and loss of balance
Tell me about nephrotoxicity.
Usually reversible
Dose-dependent
-Frequent plasma conc and kidney fx monitoring is essential
What are 4 adverse effects of aminoglycosides?
Ototoxicity
Nephrotoxicity
Neuromuscular paralysis
Teratogenic - Don’t give to pregnant women
*Also, contact dermatitis
What are the “at risk groups” of aminoglycosides?
Elderly
Impaired renal fx
Septic pts
Recent exposure to other aminoglycosides
-Post-antibiotic effect can occur
What 4 drugs are in the tetracycline family?
Tetracycline
Doxycycline
Minocycline
Tigecycline
T/F - Tetracylcine is good against acne.
TRUE
T/F - Tetracyclines are broad spec and affect G- and G+.
TRUE
What is the exception to the rule with these drugs?
Tigecycline
-Effective even in pts resistant to other TTCs
How do tetracyclines work?
Reversibly binds to 30S of bacterial ribosome blocking access of the amino acyl-tRNA to the mRNA-ribosomes complex’s acceptor site
What are the pharmacokinetics of tetracyclines?
Oral absorption altered by diary, iron supplements or antacids
DO NOT USE DURING PREGNANCY OR BREAST FEEDING
USED FOR TREATMENT OF ACNE VULGARIS
What are two oral adverse effects of tetracyclines?
Hairy tongue
Deposition in bone and primary dentition
What are some general adverse effects of tetracyclines?
GI upset
Disulfiram-like effect - Avoid alcohol use while taking tetracyclines- hungover
Headache
Vestibular problems - dizziness, nausea, vomiting
Tigecycline was developed for what?
To overcome tetracycline resistance in complicated skin, soft tissue, and intra abdominal infections
Know that this was created for those allergic to tetracyclines
Administered IV
Erythromycin
Clarithromycin
Azithromycin
Are all what?
Macrolides or ketolides
What is the mechanism of macrolides?
Irreversibly binds to the 50S subunit of bacterial ribosome to inhibit the translocation step of protein synthesis (From the A site to the P site)
BROAD SPEC
Cross resistant w/in class
Tell me what macrolides are used for?
URIs and CA-pneumonia
Good alternative for pts allergic to penicillin
Tell me about erythromycin.
Largely been replaced by clarithromycin and azithromycin for CA-pneumonia
Used for G+ bacteria, spirochetes, n gonorrhea, chlamydia, mycoplasma, legionella
Tell me about clarithromycin.
Same as erythromycin plus add’l activity against h influenzae and h pylori
Tell me about azithromycin.
Z-pack
Less active against staph and strep than erythromycin
More active against respiratory infections due to h influenzae, moraxella catarrhalis and mycobacterium (NTB)
LONGEST HALF-LIFE AND VOLUME OF DISTRIBUTION IN THIS CLASS
