Quinolones and fluoroquinolones are a class of broad-spectrum antibacterial drugs. They work by inhibiting bacterial DNA gyrase and topoisomerase enzymes. While quinolones like nalidixic acid were the first discovered, fluoroquinolones like ciprofloxacin are more potent and have a broader range of activity. Fluoroquinolones are widely used to treat urinary tract, respiratory, gastrointestinal, skin and soft tissue infections. Adverse effects can include gastrointestinal issues and central nervous system effects. Their use is contraindicated in some groups like pregnant women and children. Some fluoroquinolones are being investigated for repurposing as anticancer agents and for

1. QUINOLONES
By Shubham Marbade
M.Pharm
Pharmacology

2. Quinolones
• Synthetic, broad spectrum and bactericidal.
• Effective after oral administration for wide variety of
infectious diseases,
• Play an increasingly important role in treatment of
multi-drug resistant bacterial infections.
• They are widely used because of their relative safety,
availability both orally & parenterally and their
favorable pharmacokinetics.

3. • Nalidixic acid was the first quinolone
discovered in 1960s and primarily used for
urinary tract infection.

4. Fluoroquinolones
• Wide variety of application and broad
spectrum antibiotic
• More potent than quinolones.
• Modified quinolones with one or more
fluorine atom in their structure.

5. Classification

6. PHARMACOKINETIC
• Rapidly and almost completely absorbed after
oral administration and are widely distributed in
body tissues.
• Peak serum levels are obtained within 1- 3 hours
of an oral dose of 400mg with peak levels ranging
from 1.1 ug/ ml for sparfloxacin to 6.4 ug/ml for
levofloxacin .
• Food does not impair oral absorption but may
delay.
• Bioavailability is > 50% for all agents and > 95%
for several.

7. • Half life s 3- 5 hours for norfloxacin and ciprofloxacin.
• The volume of distribution of quinolones is high with
concentration of quinolones n urine, kidney, lung, and
prostate tissue, stool, bile and macrophage and neutrophils
higher than serum levels.
• Concentration in CSF, bone and Prostatic fluid are lower than
in serum.
• The fluoroquinolones are also metabolized by hepatic
conjugation and glucuronidation. Dosage, peak serum levels,
percent protein binding, urine concentrations, and degree of
metabolism differ to varying degrees among the quinolones.

8. • It is excreted primarily in urine, both by
glomerular filtration and tubular secretion.
• Urinary and biliary concentrations are 10–50
fold higher than plasma.

9. Mechanism of action
• These agents targets DNA gyrase and
Topoisomerase IV.
• For Gram – ve bacteria DNA gyrase, and for
Gram + ve bacteria topoisomerase IV is
primary site for their activity.
• These drugs binds to A- subunit of DNA
gyrases and four subunits of
topoisomerase IV enzyme which are
responsible for unwinding of supercoiled
DNA for process of replication and
transcription.
• Thus it results in blockade of unwinding
and inhibition of replication.
• Synthesis of protein inhibited.
• inhibition of growth of bacteria and kills
bacteria.

12. Antibacterial spectrum
• Quinolones have broad spectrum antibacterial
activity against various Gram +ve and Gram
-ve bacterias including E. coli, Salmonella,
Sheigella, P. aeruginosa, Clamydia,
mycoplasma, Brucella, Mycobacterium,
legionella etc.

13. Antibacterial Resistance
• Resistance to the quinolones develops due to
mutation to bacterial chromosomal genes of
Gyrase A and Topoisomerase IV encoding
information to unwind Supercoiled DNA.
• No quinolone modifying or inactivating
activity has been seen to develop resistance.

14. Therapeutic Uses
1. Urinary tract infections: High cure rates, even in
complicated cases or those with indwelling
catheters/prostatitis, have been achieved.
ChronicPseudomonas infections respond less completely.
2. Gonorrhoea: Initially a single 500 mg dose was nearly 100%
curative in non-PPNG as well as PPNG infections, but cure
rate has declined in the recent years due to emergence of
resistance.
3. Chancroid: 500 mg BD for 3 days is an excellent alternative
to ceftriaxone/erythromycin.
4. Bacterial gastroenteritis: Severe cases due toEPEC, Shigella,
Salmonella and Campy. jejunirespond quickly. It has also
been used to reducestool volume in cholera.

15. 5. Typhoid: Ciprofloxacin is the first choice drug in
typhoid fever since chloramphenicol, ampicillin and
cotrimoxazole have become unreliable due to
development of resistance. A dose of 500–750 mg BD
for 10 days is recommended. Patients unable to take
the drug orally may be treated with 200 mg. i.v. 12
hourly in the beginning.
6. Bone, soft tissue, gynaecological and wound
infections: caused by resistant Staph. and
gramnegative bacteria: high cure rates have been
obtained but prolonged treatment with high doses is
required in osteomyelitis and joint infections.Used
along with clindamycin/ metronidazole (to cover
anaerobes) it is a good drug for diabetic foot.

16. 7.Respiratory infections: Ciprofloxacin can treat
Mycoplasma,, H. influenzae, Branh. catarrhalis and
some streptococcal and pneumococcal infections
besides gram-negative ones.
8.Tuberculosis It is now frequently used as acomponent
of combination chemotherapy against multidrug
resistant tuberculosis. Recently, even FQ-resistant TB
have arisen.
9.Gram-negative septicaemias: Parenteral ciprofloxacin
may be combined with a third generation
cephalosporin or an aminoglycoside.

17. • 10. Meningitis: Though penetration in CSF is
not very good, ciprofloxacin has been
successfully used in gram-negative bacterial
meningitis, especially that occurring in
immunocompromised patients or those with
CSF shunts.

18. Adverse Effects
• GI tract- (2–13%) these include nausea, vomiting,
diarrhea, and abdominal pain.
• CNS effects- (1–8%) such as drowsiness, weakness,
headache, dizziness, and in severe cases, convulsions
and toxic psychosis, have been reported.
• sparfloxacin and lomefloxacinv shows photosensitivity
included second-degree burns, discoloration and
sometimes permanent discoloration and scarring of
the skin due to halogen substitution on the eighth
position, as found in

19. • Adverse cardiovascular effects (6–7%; vascular
embolism, cardiac insufficiency, hypotension)
also occur with sparfloxacin. Sparfloxacin,
moxifloxacin, and gatifloxacin can exacerbate
QT prolongations.
• Fulminant hepatotoxicity associated
withtrovafloxacin has resulted in acute liver
failure, and the FDA has recommended
limiting therapy to life-threateninginfections.

20. • Allergic reactions (e.g., rashes, urticaria, and
eosinophilia) have been observed. These drugs
have occasionally been associated with
cholestatic jaundice, blood dyscrasias, hemolytic
anemia, hypoglycemia, and nephrotoxicity.
• Recently the use of ciprofloxacin for prophylaxis
protection against anthrax infection has been
associated with damage to muscle ligaments.

21. Drug Interactions
• All quinolones interact with multivalent cations,
forming chelation complexes resulting in reduced
absorption.
• Major offenders are antacids; vitamins containing
calcium and iron can also be problematic. All
fluoroquinolones interact with warfarin,
didanosine, and phenytoin, resulting in decreased
absorption or metabolism.
• Ciprofloxacin and other second-generation drugs
interact with theophylline by decreasing its
clearance, which leads to theophylline toxicity.

22. Contraindications
• The use of the quinolones in pregnant or
breastfeeding women and children whose
epiphysial plates have not closed is generally
contraindicated.
• Their use for treating young cystic fibrosis
children infected with Pseudomonas species is
an exception; the patient should be monitored
carefully for untoward effects.

23. • These drugs contraindicated in arrhythmia
because it prolong the heart's QT internal by
blocking voltage-gated potassium channels
lead to a life-threatening arrhythmia.

24. Nalidixic acid
• It is active against gram-negative bacteria, especially E.
coli, Proteus, Klebsiella, Enterobacter, Shigella but not
Pseudomonas. It acts by inhibiting bacterial DNA
gyrase and isbactericidal.
• Absorbed orally, highly plasma protein bound and
partly metabolized in liver. It is excreted in urine with a
plasma t½ ~8 hrs.
• Concentration of the free drug in plasma and most
tissues attained with the usual doses is non therapeutic
• for systemic infections.
• Dose: 0.5–1 g TDS or QID

25. Ciprofloxacin
• It is the most potent first generation FQ active against a
broad range of bacteria, the most susceptible ones are
the aerobic gram-negative bacilli, especially the
Enterobacteriaceae and Neisseria.
• It binds to divalents cations which decreases
absorption.
• Because of its good penetration into bone, orally
administered ciprofloxacin is a useful alternative to
parenterally administered antibiotics for the treatment
of osteomyelitis caused by susceptible organisms.
• Dose- 250, 500, 750 mg tab, 200 mg/100 ml i.v.
infusion, 3 mg/ml eye drops.

26. Levofloxacin
• It is the levoisomer of ofloxacin having improved
activity against Strep. Pneumoniae and some other
gram-positive and gramnegative bacteria.
• Oral bioavailability of levofloxacin is nearly 100%; oral
and i.v. doses are similar.
• The primary indication of levofloxacin is community
acquired pneumonia and exacerbations of chronic
bronchitis in which 87–96% cure rate has been
obtained.
• High cure rates have been noted in sinusitis, enteric
fevers, pyelonephritis and skin/soft tissue infections as
well.
• Dose- 500 mg tab, 500 mg/100 ml inj.

27. Trovafloxacin
• Trovafloxacin is a broad spectrum antibiotic inhibit the
uncoiling of supercoiled DNA in various bacteria by
blocking the activity of DNA gyrase and topoisomerase
IV.
• It was shown to be more effective against Gram-
positive bacteria than Gram-negative bacteria when
compared to previous fluoroquinolones.
• Gonorrhea in males and endocervical and rectal
gonorrhea in females as well as non gonoccocal
urethritis and cervicitis.
• Well-absorbed from the gastrointestinal tract after oral
administration and does not depend on concomitant
food intake. The absolute bioavailability is
approximately 88%.
• Dose- 300 mg iv and 100 mg tid

28. Repositioning to Anticancer agents
• Several FQs just like anyother anticancer drug have been shown to cause
cell cycle arrest primarily in S and G2phase of progression.
• Several studies reveals the ability of ciprofloxacin to induce S/G2-phase
arrest in bladder and prostate cancer cells. Similarly, enoxacin revealed its
ability to induce S/G2-phase in prostate cancer cells and G2/M-phase
arrest in breast cancer cells.
• Later on, few more studies showed similar S/G2-phase arresting effects of
other FQs like lomefloxacin, ofloxacin and levofloxacin in epidermoid
carcinoma and breast cancer cells respectively.
• Ciprofloxacin possesses the maximum efficacy in inducing apoptosis. It
shows potent anti-proliferative effect to induce apoptosis in bladder
cancer cells and then later on in prostate cancer cells.

29. Clinafloxacin
• Methicillin resistant Staphylococcus aureus
(MRSA) has developed numerous mechanisms of
virulence and strategies to evade the human
immune system which are difficult to treat
infections in human beings, and becoming
important cause of morbidity and mortality.
• Acts as novel inhibitors of bacterial efflux pump,
FtsZ, DNA gyrase, and topoisomerase IV and have
the potential to exert multiple mechanisms of
action.

30. Fluoroquinolones in treatment of TB
• Fluoroquinolones like moxifloxacin, gatifloxacin
and levofloxacin, are the most valuable second-
line anti-TB agents according to the current WHO
guidelines.
• These drugs are currently under clinical trial for
pulmonary tuberculosis and tuberculosis
meningitis.
• The aim of this study is to provide an alternative
to resistant drug to prevent failure of treatment
and emergence of drug resistance.

31. Delafloxacin in ABSSSI
• Delafloxacin is a novel anionic fluoroquinolone (FQ) approved for
treatment of acute bacterial skin and skin structure infections
(ABSSSIs) caused by a number of Gram-positive and Gram-negative
organisms including MRSA and Pseudomonas aeruginosa.
• It is more potent than other quinolones against Gram +ve bacteria
and Gram –ve bacteria.
• It is considered a dual-targeting FQ and displays nearly equivalent
affinity for DNA gyrase and topoisomerase IV.
• This property likely explains delafloxacin’s broad spectrum of in
vitro activity against both GN and GP bacteria

32. Delafloxacin in CABP
• Approved for use in adults for the treatment of
community-acquired bacterial pneumonia,
delafloxacin was shown in a phase III clinical trial
to be superior to moxifloxacin in patients with
CABP who also have chronic obstructive
pulmonary disease (COPD) or asthma as a
comorbidity, and in CAP patients who may have
severe illness.
• Additionally, delafloxacin appeared to be better
tolerated compared to commonly used FQs.

33. Levonadifloxacin
• It is a novel antibacterial agent belonging to
benzoquinolizine subclass of fluoroquinolones
which is under clinical development as a
parenteral formulation and its prodrug
alalevonadifloxacin as an oral option. Both the
drugs have been approved recently in India
based on phase III trial completed for ABSSSI.

34. Fluoroquinolones in catheter coating
• Antimicrobial catheter coatings were prepared by immobilizing
fluoroquinolones either with the use of linkers (covalent binding) or
by activating the polymer matrix with iodine/bromine (noncovalent
binding).
• The new antimicrobial coatings, obtained with the participation of
fluoroquinolone antibiotics in an uncomplicated way, are able to
protect the urinary catheters against bacterial infections during
catheterization.
• Since the ideal antibacterial material has not yet been found, there
is still a need to look for new ways of the prevention of catheter-
associated urinary tract infections

35. Sparfloxacin
• Ocular diseases affect a growing number of people across
the globe. Some pathological ophthalmic conditions, such
as glaucoma, diabetic retinopathy, or age-related macular
degeneration, cause severe visual impairment that can
ultimately lead to blindness.
• Nanosuspensions were prepared via a solvent diffusion
technique and loaded with sparfloxacin used against
bacterial conjunctivitis.
• The optimal formulation was the one based on N-
carboxymethyl CS nanosuspension in combination with
sustainable sparfloxacin release.

36. Antifungal activity
• Quinolones and Flouroquinolones displayed potential anti-fungal
activity and some of them could significantly increase the
susceptibility of antifungals.
• Metal complexes of Flouroquinolones with specified antimicrobial
activities, are a new entry in the field of bioinorganic.
• Zone of inhibition values of fluoroquinolones are compared with
parent drug.
• Some of them found to exhibit excellent potency against both
drug‐susceptible and drug‐resistant fungi where as some found to
show lesser or no antifungal behavior as compared to the parent
drug.

37. Bioprinting Technology
• liver bioengineering has picked up momentum in recent
years for the development of both artificial substitutes for
supporting repair/regeneration as well as in vitro hepatic
models for clinical and diagnostic application.
• Trovafloxacin is used to induce liver txicity at tissue level.
• Compared to conventional 2D models, trovafloxacin
treatment resulted in significant, dose-dependent toxicity
at clinically relevant doses (≤4 μM) in the developed 3D
models.

38. Sitafloxacin
• According to study carried out in Japan :
Sitafloxacin based therapy is a potent
candidate for third-line Helicobacter pylori
eradication treatment.
• The 7-day regimen with vonoprazan 20 mg
b.i.d., sitafloxacin 100 mg b.i.d., and
amoxicillin 750 mg b.i.d. or 500 mg q.i.d. is a
good option as the third-line H. pylori
eradication treatment

39. Immunomodulatory Effects of
Fluoroquinolones
• Immune responses are indirectly modulated
by FQs through suppressing pro-inflammatory
cytokines, such as interleukin 1 (IL-1), IL-6,
tumor necrosis factor-alpha (TNF-α), and
super-inducing IL-2, which tend to increase
both the growth and activity of T and B
lymphocytes. In addition, they affect the
development of immune responses by
influencing of expression of other cytokines
and mediators.

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