Dr Sun - Antibiotics Pt 1

Penicillin contains highly unstable bicyclic system - 4 membered ________ fused to 5 membered _________

B-lactam with 5 membered thiazolidine

A lactam is considered a _________________

Cyclic amide

Under acidic conditions, penicillin reacts with what to break to the b-lactam ring? What group makes Penicillin V orally available?

Water breaks b-lactam ring

Electron-withdrawing (phenoxymethyl) group at acylamido side chain to reduce nucleophilicity → weaker nucleophile → less likely to react with b-lactam carbonyl

With anti-staphylococcal penicillins - which 2 (Same) groups provides beta lactamases resistance, but more acid sensitive

2 ortho-methoxy groups

How does the bulky R group of methacillin affect polarity? GN affinity?

Increases hydrophobicity and decreases penetration to GN bacteria

**Which functional groups present in dicloxacillin make this drug resistant to acidic degradation and beta lactamase?

Addition of electron withdrawing (isooxazole) group to the bulky R group of penicillin improves acid stability and improves b-lactamase resistance

**Which functional groups present in amoxicillin make this drug orally available with increased spectrum?

The hydrophilic NH2 group (acid stability, GN) and the phenolic group (oral)

Piperacillin contains which functional group?

Urea

***** What was the first boron-based, cyclic boronic acid beta-lactamase inhibitor approved by the FDA

Vaborbactam → BLI do not contain acylamino side chain

***What is an example of a monobactam? It is an alternative to which drug? GP/GN/anaerobic activity?

1. Aztreonam - not fused to another ring

2. Aminoglycosides - less toxic

3. No GP or anaerobic activity

***How imipenem is classified?

Created from thienamycin. It is a carbapenem, does not contain thiazolidine or dihydrothiazine ring.

Differences in ring between Penicillins and Cephalosporins?

1. Thiazolidine ring - Penicillin

2. Dihydrothiazine - Cephalosporins

Cefuroxime contains what two groups?

Furan and Ketoxime

**** Which structures are common to 3rd generation cephalosporins?

2-amino thiazole and oxime moiety

Which functional group enhances pseudomonal activity in 3rd gen cephalosporins?

Dimethyl acidic acid

What group distinguishes cefepime from earlier generations?

Methylpyrrolidinium group - zwitterionic charge that quickens GN penetration for Pseudomonas

**Which functional group is involved in anti-MRSA activity in ceftaroline? Which functional group increases solubility?

1. 1,3 thiazole ring → MRSA

2. Phosphono group → Solubility

***Which functional group of cefiderocol is involved in chelation of iron?

Chlorocatechol

***What is the MOA of vancomycin compared to penicillin? It is considered a ________

Binds to substrate of transglcocylase/transpeptidase (d-Ala-d-Ala) of lipid II - preventing the action of both enzymes

A glycopeptide

***What type of antibiotic is ortiavancin? What group makes it have a long MOA?

Semisynthetic lipoglycopeptide containing a large, hydrophobic 4-chlorobiphenylmethyl group detached to disaccharide

Prolonged MOA

***The _______ ring is a core and highly reactive component of fosfomycin → irreversibly inhibits cell _______ synthesis

1. Epoxide ring → cell wall synthesis

Polymyxin and colistin are _________ antibiotics → targetting cell ________ and are restricted to what (GP/GN)?

1. Cyclic lipopeptide

2. Cell membrane

3. GN bacteria

Daptomycin is a _____________ antibiotic that targets the cell _____ and is restricted to ______ bacteria

1. Cyclic lipopeptide

2. Cell membrane

3. Gram positive