M6 - Fluoroquinolones and Penicillins

7-chloroquinoline precursor

chloroquine

7-chloroquinoline binding effect

Less protein binding

Nalidixic acid origin

7-chloroquinoline

First quinolone

Nalidixic acid

Flumequine precursor

Nalidixic acid

Pipemidic acid precursor

Nalidixic acid

Norfloxacin precursor

Nalidixic acid

Flumequine activity type

Weak broad Gram (-)

Pipemidic acid feature

Longer half-life

Norfloxacin spectrum

Broader Gram (-)

Norfloxacin protein binding

50%

Norfloxacin half-life

3-4 hours

Norfloxacin structure

6-fluoro-7-pyrimidino-quinoline

Pefloxacin precursor

Norfloxacin

Pefloxacin ring addition

Methyl

Pefloxacin half-life

11 hours

Ofloxacin precursor

Pefloxacin

Ofloxacin ring addition

Morpholine

Ofloxacin structure type

Tricyclic

Ofloxacin half-life

6 hours

Ciprofloxacin precursor

Norfloxacin

Ciprofloxacin ring addition

Cyclopropyl

Ciprofloxacin potency

Increased

Longest 1st gen half-life

Pefloxacin

Ofloxacin mixture type

Racemic

Levofloxacin form

(-) isomer

1st gen examples

Cinoxacin, Nalidixic acid

2nd gen examples

Norfloxacin, Ciprofloxacin

3rd gen examples

Levofloxacin, Sparfloxacin

4th gen examples

Moxifloxacin, Gemifloxacin

1st gen spectrum

Gram (-), not Pseudomonas

2nd gen spectrum

Gram (+/-), includes Pseudomonas

3rd gen spectrum

Extended Gram (+), atypicals

4th gen spectrum

Gram (+/-), anaerobes

Fluorine addition gen

2nd generation

Removed in 1999

Trovafloxacin

Removed from use

Gatifloxacin

MIC definition

Minimum Inhibitory Concentration

Lower MIC effect

Higher potency

R5 NH2 effect

Gram (-) activity

R5 CH3 effect

Gram (+) activity

R7 Piperazine effect

Gram (-) activity

R7 Pyrimidine effect

Gram (+) activity

R7 attachment effect

Increase half-life

X8 Methoxy effect

Increase potency

X8 Naphthyridone effect

Gram (+), anaerobe

X8 Halogen effect

Increase potency

R1 Cyclopropyl effect

Increase potency

R1 Difluorobenzene effect

Anaerobe potency

Virulence definition

Microbe damage ability

Antibacterial regimen

21 doses t.i.d.

What do antibiotics inhibit?

Microorganism growth

Antibiotics effective concentration

Low

Antibiotic dosing requirement

Convenient schedule

Antibiotic removal requirement

Rapid metabolism

Penicillin mechanism

Inhibit cell wall synthesis

Effect of cell wall inhibition

Spheroplast formation

Most vulnerable bacterial state

Spheroplast

PBP 1a & 1b function

Peptidoglycan synthesis

PBP 1 inhibition effect

Spheroplast, lysis

PBP 2 function

Rod shape maintenance

PBP 2 inhibition effect

Ovoid forms

PBP 3 function

Septum formation

PBP 3 inhibition effect

Filamentous bacteria

PBPs 4-6 function

D-Ala-D-Ala hydrolysis

PBPs 4-6 inhibition effect

Not lethal

Autolysins function

Create wall nicks

Penicillin source organisms

Penicillium notatum, chrysogenum

Crystalline penicillin storage

Moisture-free

Hygroscopic penicillin form

Crystalline salts

Water-soluble penicillin salts

Na, K

Depot therapy salts

Organic base salts

Core beta-lactam feature

Beta-lactam ring

Beta-lactam ring degradation

Inactivates antibiotic

Penicillin template

6-aminopenicillanic acid

Inactive hydrolysis product

Penicilloic acid

6-APA stability medium

Neutral, alkaline

6-APA acidic reaction

Decarboxylation

Electron-withdrawing group effect

Acid stability

Bulky group effect

Penicillinase resistance

Polar group effect

Hydrophilicity

Steric hindrance function

Block beta-lactamase

Thiazolidine ring type

5-membered saturated

Penicillin ring system

Bicyclic

Bicyclic ring effect

Increased activity

Carboxylic acid function

Binds PBPs

Form reducing activity

Alcohol or ester

Penicillin PBP target

Lysine residues

What degrades Penicillin G orally?

Gastric acid

Penicillin G stability

Acid-labile

Penicillin G administration route

IV

Penicillin G salt property

More lipophilic

Penicillin V modification

Electronegative oxygen

Penicillin V stability

Acid-stable

Penicillin V administration route

Oral

Methicillin resistance feature

Bulky groups

Methicillin stability

Acid-labile

Nafcillin resistance feature

Steric hindrance

Nafcillin stability

Acid-labile

Isoxazoyl penicillin features

Bulky, EWG