Protein Synthesis Inhibitor MedChem Flashcards
1
Q
Aminoglycosides
A
- All contain inositol derivatives (amino sugars)
- All bind to 30S subunit
- Recent evidence that this induces ROS
- Derived by fermentation of various soil microorganisms
- Often use site-specific delivery to avoid systemic toxicity
2
Q
Aminoglycoside Effect on Ribosome
A
- Inhibit initiation of translation, bacteria is unable to produce proteins at all
- Cause misreading of mRNA leading to inactive or unstable proteins
- Inactive/unstable proteins then have to be degraded and active ones need to be synthesized, costly energy wise
3
Q
Kanamycin
A
- Doesn’t follow rule of 5
- Inhaled for lumenal lung infections
- Parenteral for systemic infection
- Ocular for conjunctival infection
- Mixture of different, similar compounds with antibacterial activity
- Glycosidic bonds resistant to hydrolysis
4
Q
AG + Routes
A
- Tobramycin: IV/IM, inhaled for CF, eye drops
- Streptomycin: IV/IM, inhaled off label
- Amikacin: inhaled liposomal suspension
5
Q
AG Modification
A
- Inhibited by R-factor enzymatic modification at functional groups
- Usually acetylation at amine and either adenylation or phosphorylation at hydroxyls
- These modifications weaken their binding to bacterial ribosomes by multiple routes
6
Q
Macrolides
A
- 14-member cyclic ester that is heavily substituted with oxygen
- Two hydroxyls are further substituted with a sugar and aminosugar moiety
- Ester hydrolysis occurs after absorption, acid sensitive EC prevents this
- Acid-induced decomposition leads to the formation of an intramolecular ketal
7
Q
Erythromycin
A
- Mixture of different active agents like Kanamycin
- Molecular structure modified along with use of EC to prevent ketal formation (acid-stable)
8
Q
Azithromycin
A
- Also utilizes modified structure to stop potential for ketal formation
- Unusually long half life (more amines), high compliance
- Concentrates in acidic sites (inflamed/infected) and is retained for long periods of time in these sites
- Neutralizes lysosomes by accumulating so much in them
9
Q
Fidaxomicin
A
- Approved for C. Diff in 2011
- No oral absorption
- Selective for C. Diff
- Many more hydroxyls (7), unsaturated macrolide
10
Q
Lincosaminides
A
- Contain thiomethyl aminooctoside, amide linked to N-methyl pyrrolydiylcarboxylic acid derivative
- Concentrates well in bones so commonly used in orthopod surgery
- Binds at similar site to macrolides on 50S ribosome
11
Q
Clindamycin
A
- Prototypical lincosaminide drug
- Metabolized to two bioactive metabolites: clindamycin sulfoxide and N-demethylclindamycin
12
Q
Tetracyclins
A
- Contain four fused 6-membered rings
- Substitutions on rings B-D provide the range of compounds
- Act on 30S ribosome unit to inhibit addition to protein chain
- Given orally, also a polymer-based periodontal formulation
- Major feature: binding to polyvalent cations (Al+3, Ca+2) as quinolones
- Enolization on the bottom of the molecule is extensive
- Decreased solubility leads to fecal excretion instead of absorption in GI
13
Q
Tetracyclin Effects
A
- Insolubility of chelate leading to incomplete absorption of calcium, iron, aluminum
- Great affinity for calcium, so avoid in growing kids forming adult teeth since it leads to discoloration and weakening
14
Q
Tigecyclin
A
- New tetracyclin agent with more amines, lipophilic, and great half life
- Not acted on by efflux pumps to help overcome resistance
15
Q
Oxazolidones
A
- All contain key pharmacophore on page 15
- Binds to unique site on 50S
