2. Topics covered
Introduction
3 D Structure
Inhibitors (Drugs)
Classification of drugs
Mechanism of action
Derivatives
References
3. Gyrase:
DNA gyrase is an essential
bacterial enzyme that catalyzes the ATP-
dependent negative super-coiling of
double-stranded closed-circular DNA
It belongs to the class
Topoisomerase
Topoisomerases are isomerase
enzymes that act on the topology of DNA.
4. Bacterial DNA gyrase is the target of
many antibiotics, including nalidixic
acid, novobiocin, and ciprofloxacin.
Here the Inhibitors such as
Quinolones mainly against Gram
negative bacteria
Due to their action on DNA gyrase
While action on Topoisomerase IV on
Gram positive bacteria
7. Inhibitors ~2 main
classification
Quinolones ,particularly
fluroquinolones with their broad
antimicrobial activity are used in
disease causing oraganisms.
Fluroquinolones are the drugs that are
chemically related to nalidixic acid and
has fluorine in their chemical structure.
8.
9. Quinolones
The quinolones are a family of
synthetic broad-spectrum antibiotic
drugs.
Quinolones, and derivatives, have also
been isolated from natural sources
(such as plants, animals and bacteria)
and can act as natural antimicrobials
and/or signalling molecules.
11. Nalidixic Acid
4-quinolone derivaive
Effective against G-ve bacteria __
E.coli , shigella , many strains of
proteus
Relatively ineffective against G+ve
bacteria due to development of
resistance
Readily absorbed in GI tract
Serum level of the drug usually low
80 % eliminated thru, urine span of
8hrs
12. Fluroquinolones
The fluorine in the chemical structure
called fluoroquinolones
Chemically related to nalidixic acid
This fluorine increases the activity of
spectrum
Highly effective orally
Bactericidal with broad spec
13. Effective against bacteria which are
resistant to beta lactum and
aminoglycoside
They are also safe to use
14. Fluroquinolones Generations
Generation Name Oral bioavl. T half Indications
2 Class I Norfloxacin 30 – 40 % 3- 4 hrs UTI, Prostatitis
Lomefloxacin 90 % 6 – 8 hrs
2 Class II Ofloxacin
Ciprofloxacin
60-70
95
3. 3 to 4.9
5 to 7
UTI, Typhoid,
Gonorrhea,
Gastroentiritis,
skin ,
soft tisue
infections
Pefloxacin 90 8-13
3rd Gen Levofloxacin
Sparfloxacin
Gemifloxacin
>90
70
6-8 Preferred in
community
acquired
Pneumonia
Moxifloxacin 90 7
15.
16. These Fluroquinolones also effective
against Legionella, brucell, chlamydia
and mycoplasma pneumoniea
Mycobacterium tuberclosis and
M.avium complex
Quinolones such as ciprofloxacin are
potent liver enzyme inhibitors and can
reduce the metabolism of warfarin,
theophilline and sulfonylurease
17. Therapeutic uses
Quinolones..
Urinary tract infections, even when
caused
by multifrug-resistant bacteria, intestinal
and
biliary tract infections, soft tissue
infections,
18.
19. A/E
Adverse effects include…
GI Toxicity : nausea, diarrhoea
CNS Toxicity: dizziness, headache
mildly,
Tendon and cartilage damage :
rupture of shoulder, hand, achilles
tendons