PHARMACOTHERAPY OF

SULFONAMIDES & QUINOLONES

Pharmacotherapy of quinolones
✓ Higher potency
✓ Extended spectrum
✓ Slow development of resistance
✓ Better tissue penetration
✓ Good tolerability
 introduction
Family of synthetic broad spectrum antibiotics

The term quinolone(s) refers to potent synthetic chemotherapeutic

antibacterial agent

The first generation of the quinolones begins with the introduction of nalidixic
acid in 1962 for Rx of urinary tract infections in humans

Nalidixic acid was discovered by George Lesher & co-workers in a distillate

during an attempt at chloroquine synthesis

They prevent bacterial DNA from unwinding & duplicating

First Generation

Gram-negative

Second Generation

Gram-negative, some gram positive & mycobacteria

First-generation

✓ Nalidixic acid
✓ Norfloxacin
✓ Ofloxacin
✓ Ciprofloxacin
✓ Pefloxacin
Second-generation

✓ Levofloxacin
✓ Moxifloxacin
✓ Lomefloxacin
✓ Gemifloxacin
✓ Sparfloxacin
✓ Prulifloxacin
 moa
✓ Fluoroquinolones enter the cells by porins & target two enzymes:
DNA gyrase & topoisomerase IV

✓ DNA gyrase or topoisomerase IV helps in producing negative

super-helical twists

✓ When fluoroquinolones bind to these enzymes, it blocks the

activity of these enzymes & hence stops replication, transcription,
repair as well as recombination
 KEY FEATURES
✓ Rapid cidal
✓ Long post-antibiotic effect
✓ Low incidence of resistance
✓ Microbial flora spared
✓ Less active at acidic pH
✓ Active against many β-lactam and aminoglycoside resistant
bacteria
 resistance

Resistance to quinolones may develop during therapy via

mutations in the bacterial chromosomal genes encoding DNA
gyrase or topoisomerase IV, or by active transport of the drug
out of the bacteria
 resistance
In the recent there have been increasing number of cases of
resistance against fluoroquinolones due to many reasons such as

✓ Incomplete treatment with required doses & duration

✓ Over dosage
✓ Excessive & improper use of fluoroquinolones when not required

✓ Development of mutant strains of causative bacteria

 Adverse effects
✓ Nausea, vomiting & diarrhoea

✓ Headache, dizziness, insomnia, skin rash, occasionally

✓ Hepatotoxicity is rare

✓ Photosensitivity occurs with lamefloxacin & pefloxacin

✓ Fluoroquinolones may damage growing cartilage & cause an arthropathy

✓ They are not used in patients under 18 years of age

✓ Since fluoroquinolones are excreted in breast milk, they are contraindicated
for nursing mothers
 Therapeutic uses

Nalidixic acid is only second-line drug treating urinary infection with

gram negative bacilli (Bacillus coli, Bacillus proteus etc)
Fluoroquinolones are extensively used treating general infection

✓ Urinary tract infections, even when caused by multidrug-

resistant bacteria

✓ Intestinal & biliary tract infections

✓ Soft tissue infections

✓ Bone, joint & in intra-abdominal

✓ Respiratory tract infections

Ciprofloxacin & ofloxacin are effective for gonococcal infection,
including disseminated disease

They are occasionally used for treatment of tuberculosis &

atypical mycobacterial infections

They are suitable for eradication of meningococci from carriers

summary