| Fluoroquinolones Therapeutic Uses | 1 Respiratory Tract Infection. (Levo, Spar, Ofloxacin)
2 Typhoid (Cipro, Ofloxacin)
3 Furunculosis
4 Tuberculosis
5 Osteomyelitis (Ciprofloxacin)
6 UTI (Norfloxacin 4-6 weeks)
7 Conjunctivitis
8 Bacillary Dysentery (Nor, Cipro, Trallver's-cotrimoxaz)
9 Otitis Media
10 Leprosy
11 STD. Except Syphilis 2nd line -> (Cipro, Oflo, Gatifloxacin)
12 Meningitis (2nd line Drugs) |
| Synthetic antibacterial agents that are
highly effective in the tx of many
types of infectious diseases.
They are used against a variety of
gram negative as well as positive
pathogens | QUINOLONES |
| Synthetic antibacterial patterned after NALIDIXIC ACID, a
napthyridine derivatived introduced for the tx of UTI in 1963. | 1-Ethyl-1,4-dihydro-7-methyl-4-oxo-1,8-naphthyridine-3-carboxylic acid |
| Isosteric heterocyclic groupings | a. Quinolones (Norfloxacin, Ciprofloxacin, Lomefloxacin)
b. Napthyridines (nalidixic acid, enoxacin)
c. Cinnolines (cinoxacin) |
| tx for serious systemic infections
all members of the group have 6-fluoro
substituent in common, and cyclic basic
amine moiety at C-7
First manmade antibiotics | Fluoroquinolones |
| SAR OF QUINOLONES
1 Study shows that __ moiety is essential for antibacterial activity
2 The __ must be annulated with aromatic ring
3 Isosteric replacements of __ for carbon atoms at positions __ leads to retention of antibacterial activity
4 Introduction of substituents at position __ greatly reduces or abolishes activity
But substitutions at position __ at annulated ring produce good effects
5) __ group at position C5 increases activity
6) __ substitution at position 6 significantly enhance activity
7) __ substitution at position 1 is essential for activity | 1) 1,4-dihydro-4-oxo-3-pyridinecarboxylic acid
2 Pyridone system
3 Nitrogen,
2,5,6 and 8
4) 2,
5,6,7 and 8
5) Amino
6) Fluorine
7) Alkyl substitution |
| MOA of Quinolones
1 In gram negative
2 In gram positive | 1 Inhibition of DNA Gyrase
2 Inhibition of Topoisomerase IV |
| MOA of Fluoroquinolones
1 In gram negative
2 In gram positive | 1 Decrease permeability
2 Efflux pump, Mutation of enzymes |
| 1 From chloroquine in 1939 to __ in 1962
2 Synthesis intermediate found to display antibacterial activity | 1 Nalidixic acid
2) 7-chloroquinoline |
| 1 Limited usefulness as a drug
- Narrow antibacterial spectrum (Enterobacteriaceae)
- Short half life (1.5HR)
- High protein binding 90%
2 Modify naphthyridone into quinolone __,
Shows reduced protein binding
3 Shows weak but broad Gram negative activity
4 Shows Longer Half Life | 1 Nalidixic Acid
2 Oxolinic acid
3 Flumequine
4 Pipemidic acid |
| 1 Broader gram negative activity
Less protein binding 50%
Longer half life (3-4 h)
2 Tricyclic compound, Flumequine but morpholine ring
3 From ofloxacin: Cyclopropyl to increase potency | 1 Norfloxacin
2 Ofloxacin
3 Ciprofloxacin |
| 1 Piperazine
2 Cyclopropyl
3 Methyl
4 Morpholine | 1 Norfloxacin
2 Ciprofloxacin
3 Pefloxacin
4 Ofloxacin |
| 1 Active form of ofloxacin
2 Pure (-) isomer | 1 (-) S isomer
2 Levofloxacin |
| 1) 1-Ethyl-1,4-dihydro-4-oxo[1,3]dioxo[4,5g]cinnoline-3-carboxylic acid
2) 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid
3) 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperainyl)-1,8-naphthyridine-3-carboxylic acid
4) 1-cyclopropyl0-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid) | 1 Cinoxacin (Cinibac)
2 Norfloxacin (Noroxin)
3 Enoxacin (Penetrex)
4 Ciprofloxacin (Cipro) |
| 1) 9-fluoro-2,3-dihydro-3-methyl-10(4-methyl-1-piperaziny
l)-7-oxo-7H-pyrido[1,2,3-de]-1,4,-benzoxacine-6-carboxylic acid
2) 1-ethyl-6,8-difluoro-1,4-dihydro-7-(3-methyl-1-piperaziny
l)-4-oxo-quinolinecarboxylic acid
3) (cis)-5-amino-1-cyclopropyl-7-(3,5-dimethyl)-1-piperazinyl)-6,8-difluoro-1,4-dihydro-4-oxo-quinolinecarboxylic acid | 1 Ofloxacin (Floxin)
2 Lomefloxacin (Maxaquin)
3 Sparfloxacin |
| 1 Fluoroquinolone Uses | 1 Opthalmic infections,
2 Respiratory Infections,
3 Infections of bones, joints & soft tissues,
4 GI & Abdominal infections,
5 Prostatitis (UTI &STD ) |
| Fluoroquinolone
1 Routes
2 Mechanism
3 Adverse Effects | 1 ORAL, IV
2 Inhibits DNA Gyrase and Topoisomerase IV
Bactericidal
3 Tendon rupture, Category C pregnancy, Seizures, Dizziness, Confusion, Photosensitivity |
| Fluoroquinolones: For Sexually Transmitted Diseases
1 A single dose of a fluoroquinolone such as __ or __ is effective treatment for sensitive strains of __
2 But increasing resistance to fluoroquinolones has made __ the first-line agent | 1 ofloxacin, ciprofloxacin, N.gonorrhoeae
2 Ceftriaxone |
| Fluoroquinolones: Bone, Joint, and Soft Tissue Infections
1 Fluoroquinolones in combination with an agent with antianaerobic activity are a reasonable choice for __
2 Fluoroquinolones have been used for the treatment of chronic __ | 1 Diabetic Foot Infections
2 Osteomyelitis |
| Current Use of Fluoroquinolones
1 Wide range of Infections. Pneumonias, bone infections, diarrhea, Skin infections and urinary tract infections. Not good for methicillin resistant Staphylococcus Aureus.
2 Better for UTI. Effective against Gram-negative (including pseudomonas aeruginosa) and Gram-positive UTIs and prostatitis, but not systemic infections.
3 UTIs an bronchitis caused by Haemophilus influenzae or Moraxella catarrhalis.
__ Is not effective against pseudomonal bacteremia
__ Is recommended for STDs
4 Overcomes the problems with S. pneumoniae acute bacterial sinusitis; mild to moderate community acquired pneumonia | 1 Ciprofloxacin
2 Norfloxacin
3 Lomefloxacin, Enoxacin
4 Moxifloxacin |
| Fluoroquinolones Therapeutic Uses | 1 Respiratory Tract Infection. (Levo, Spar, Ofloxacin)
2 Typhoid (Cipro, Ofloxacin)
3 Furunculosis
4 Tuberculosis
5 Osteomyelitis (Ciprofloxacin)
6 UTI (Norfloxacin 4-6 weeks)
7 Conjunctivitis
8 Bacillary Dysentery (Nor, Cipro, Trallver's-cotrimoxaz)
9 Otitis Media
10 Leprosy
11 STD. Except Syphilis 2nd line -> (Cipro, Oflo, Gatifloxacin)
12 Meningitis (2nd line Drugs) |
