OFKA ( Ofloxacin )
OFLOXACIN
Ofloxacin belongs to Fluoroquinolones
group of Antimicrobials i.e. – These are the quinolones
having one or more Fluorine substitution in their structure.
Ofloxacin belongs to the first generation Fluoroquinolones.
Other
members of the 1st generation Fluoroquinolones
are- Norfloxacin, Ciprofloxacin & Pefloxacin.
Mechanism of Action -:
Ofloxacin inhibits the enzyme Bacterial DNA gyrase,which nicks double standard
DNA introduces negative super coils and then repeals the nicked ends.
The
DNA gyrase consists of; two A
subunits and two B subunits, A subunit consist of nicking of DNA while B
subunit introduces -ve super coils and then A subunit
repeals the stands.
Ofloxacin binds to A subunit with
high affinity and interfere with it’s strand cutting & repealing function.
In Gram+
bacteria the major target of Ofloxacin action is a
similar enzymes Topoisomerase.
In
place of DNA gyrase or Topoisomerase
4 enzyme the mammalian Cells passess an Topoisomerase 2 , which has very low affinity for Fluoroquinolones (Ofloxacin)-
Hence less toxicity to the host Cells.
Spectrum of action -:
Intermediate
between Ciprofloxacin & Norfloxacin in activity
against gram-ve Bacteria, but it is comparable to or
more potent than Ciprofloxacin for gram+ve Organisms.
Good
activity against Chlamydia and Mycoplasma.
Other
susceptible organisms include – Enterobacter , E.coli, H.influenzae, K.pneumonae, N.gonorrhoea,
Proteus, Pseudomonas aeruginosa, Staph.aureus,
Step.pneumonae, Step.pyogens,
anaerobes such as Bacteroides spp.
Clostridium spp, Gardnerella
vaginelis, Peptostreptococcus
spp. etc.
It
also inhibits M.tuberculosis & it is highly
active against M.leprae.
Pharmacokinetics -:
It
is relatively lipid soluble. Oral bioavailability is higher ,
attains higher plasma concentrations.
Food
does not interfere with it’s absorption.
It
is excreted largely unchanged in urine. Dose needs to be reduced in renal
failure
Adverse effects -:
Ofloxacin has good safety records. Side effects occur in
<10% cases but are generally mild.
Gastrointestinal – nausea, vomiting, bad taste, anorexia.
CNS
effects – dizziness, headache, restlessness, insomnia, impairment of
concentration. Seizers are rare, occur only at high doses.
Skin hypersensitivity – rashes, pruritis,
urticaria etc.
Interactions -:
Better
than other 1st generation Fluroquinolones
which increase plasma concentration of Theophylline,
Caffeine and Warferin due to inhibition of their metabolism.
Antacids,
sucralfates and iron salts given concurrently reduce
the absorption of Ofloxacin.
NSAIDS
may enhance the CNS toxicity of Ofloxacin.
INDICATIONS (USES) -:
CHRONIC BRONCHITIS AND OTHER
RESPIRATORY / ENT INFECTIONS.
GI INFECTIONS.
SKIN & SOFT TISSUE INFECTIONS.
URNARY TRACT INFECTION & UROGENITAL INFECTIONS.
TYPHOID
GONORRHOEA
OFKA -OZ ( Ofloxacin
+ Ornidazole)
ORNIDAZOLE
Ornidazole is a member of Nitromidazole
gp. Of antiamoebic
drugs.
Ornidazole is active against Protozoa & Anaerobic
bacteria.
Mechanism of Action -:
Selectively toxic to anaerobic micro-organisms.
After
entering the cell by diffusion it’s nitro group is
reduced by certain red ox Proteins operative only in anaerobic microbes to
highly reactive nitro radical which exerts cytotoxicity
by damaging DNA & other critical molecules.
Aerobic
environment attenuates cytotoxicity of Ornidazole by inhibiting it’s
reductive activation.
Pharmacokinetics -:
Ornidazole is almost completely absorbed from the small
intestine.
It
is widely distributed in the body attaining therapeutic concentration in
vaginal secretions, semen, saliva and CSF (cerebro
spinal fluid).
Compared
to Metronidaole, it is slowly metabolized in Liver
& excreted in urine.
Plasma
½ life is 12-14 hours
Adverse effects -:
Adverse
effects are generally mild & transient and mostly non serious.
Nausea,
anorexia, metallic taste, abdominal cramps are the most common. Occasionally diarrhea
may be seen.
Less
frequent side effects are – Headache, glossitis,
dryness of mouth, dizziness, rashes & transient neutropenia.
Prolonged
administration may cause CNS neuropathy and CNS effects. Seizures occur after
very high doses.
Thrombophelebitis of injected vein if solution is not
well diluted.
Contraindications -:
Neurological
disorders
Blood
dyscrasiae
1st
Trimester of pregnancy
chronic alcoholism
Hypersensitivity to Ornidazole or
other Nitromidazoles.
Interactions -:
A disulfiram like intolerance to alcohal
occurs.
Phenobarbitone, Rifampicin
may reduce it’s therapeutic effects.
Cimetidine can reduce it’s
metabolism.
Concomitant
use of oral anticoagulants may increase the risk of hemorrhage.
INDICATIONS (USES) -: