Quinolones & Fluoroquinolones : One of the most important member of quinolone group of antibiotic was Nalidix Acid.The Problem with this compound was that it was narrow spectrum and it has moderate gram negative activity but it has no gram positive activity.Apart from this issue the nalidix acid was poorly distributed in the body.so with the passage of time scientists added flourine with mother compound i.e Nalidix acid so “a group of antibiotics which are flourinated analogues of nalidix acid are called fluoroquinolones”
why they are so important ?
A)Very Good Oral Absorption.
B)Very good distribution means deep peneteration in the tissues very effiently.because of their deep penetretion they can kill intracellular organisms.e.g chlamydia,TB,Legionella,brucella.
C)Newer agents are very broad spectrum.
D)They have high potency.
E)They are very well tolerated (Very safe drugs compare to other antibiotic drugs)
Mechanism of action of quinolones :
These drugs are bactericidal But the question is how they kill the bacteria ?
They are working on enzymes called topoisomerases or DNA Gyrase.
Quinolones and fluoroquinolones inhibit bacterial replication by blocking their DNA replication pathway. DNA is the core genetic material of the cells, and is responsible for proper functioning of the cell. During protein synthesis and DNA replication, the double-stranded DNA needs to unwind into a single stranded structure, which allows for complementary base pairing to occur and synthesis of mRNA to procede. Normally This unwinding of DNA in the bacteria is done by enzymes in the bacteria called DNA gyrase or DNA topoisomerase. DNA gyrase is a topoisomerase II type enzyme that unwinds the DNA by introducing negative supercoils and can also help relax positive supercoils. Quinolones and fluoroquinolones inhibit this enzyme by binding to the A-subunit of the enzyme due to which the bacteria is unable to replicate or even synthesize proteins.
When we give the patient a fluoroqinolones they approach the topoisomerase enzyme and work on ligase point and make it dysfunctional.
Initially the quinolone and fluoroquinoles first and second generation drugs were best work on gram negative bacteria.but the newer group work on both gram negative and gram positive .
Classification of quinolones and fluoroquinolones
The first generation i.e Nalidix acid is only quinolone other 3 classes are flouroquinolones.All Other compounds are the derivaties of nalidix acid.Following are some classes of quinolones and fluoroquinolones ;
- (A)First Generation e.g Nalidix acid
- (B)Second Generation e.g Ciprofloxacin (Ciproxin) ,Norfloxacin and ofloxacin.
Norfloxacin don’t absorb very well and they are not used most commonly While ciprofloxacin is the most commonly used drug in this class.
- (C)Third Generation E.g Levofloxacin
- (D)Fourth Generation : Moxifloxacin
Spectrum of activity:
- 1)First Generation Nalidix acid is moderatly effective (Not very effective) against gram negative bacteria.This drug is not used these day because of poor distribution in the body so it is use in rare uncomplicated urinary tract infections.because this drug is eliminated from the body through renal system and it concentrate into urinary system.
- 2)Second Generation
They become more efficient against gram negative as compare to Nalidix acid.And Also have some less gram positive coverage but keep in mind it doesn’t work on sptreptococcus pnemoneia.
Ciprofloxacin (Ciproxin) is also effective against atypical organism like chalymdia,mycoplasma both of these organism cause respiratory tract infections.
Means second generation has expanded its spectrum from moderate to more effective against gram negative bacteria some added benefits to gram positive bacteria and to atypical organisms.
Uses / Indications
- Where not to use this antibiotic ?
Don’t use this antibiotic more often because of the development of resistant strain and due to over usage, ciprofloxacin is failing against bacteria because of development of resistance.
Every doctor know there is one resistance type of organism i.e MRSA (Methicillin resistance staphylococcus aureus )it is resitant to many other antibiotic and the latest news is even ciprofloxacin (Ciproxin) is failing on this .
Don’t use this drug in Pneumococcus and Enterococcus infections .
- Where to Use Ciprofloxacin ?
A)GIT :Its very effective in traveller diarhea caused by toxic ecoli.
B)Ciprofloxacin is more effective in cystic fibrosis due to infection by pseudomonas auregenosa.
Usually flouroquinolones is contraindicated in children under the age of 18 because in animal model it is approved that flouroqinolones can damage the cartilages and they can produce arthropathy so it should not be used in pregnant women.
- 3)Third Generation: Levofloxacin
Good against gram negative but has more activity against gram positive including streptococcus pnemoniea means levofloxacin can be used in pnemonia and that is why this is also called respiratory quinolones .
Levofloxacin is also effective against chlamydia ,mycoplasma and atypical pnemonia.
DON’T Use this antibiotic
if you are allergic to this drug or other drugs of this class like ciprofloxacin,norfloxacin,moxifloxacin.
- Avoid taking antacids, vitamin or mineral supplements, sucralfate (Carafate), or didanosine (Videx) powder or chewable tablets within 2 hours before or after you take levofloxacin.
- Before taking levofloxacin, tell your doctor if you have muscle weakness,kidney or liver disease,or trouble breathing,seizures,joint problems, diabetes, myasthenia gravis, a history of head injury of brain tumor, a condition called pseudotumor cerebri, a personal or family history of Long QT syndrome,low levels of potassium in your blood,or if you have ever had an allergic reaction to an antibiotic.
- Levofloxacin may cause swelling or tearing of a tendon, especially in the Achilles’ tendon of the heel. These effects may be more likely to occur if you are over 60, or if you have had a kidney,heart, or lung transplant.
if you take steroid medication, Stop taking levofloxacin and call your doctor at once if you have sudden pain, swelling, tenderness, stiffness.
- Levofloxacin is used to treat bacterial infections that cause bronchitis or pneumonia,means that action of this drug is more extended against pneumococci and also used to treat people who have been exposed to anthrax or plague.
- Levofloxacin is also used to treat bacterial infections of the sinuses,skin,kidneys, bladder, or prostate.4)Fourth Generation.Moxifloxacin
Levofloxacin and moxifloxacin both are called respiratory quinolones .
Its spectrum of activity further broaden against gram positive cocci and gram positive bacilli .
Moxifloxacin can kill the anaerobic organisms and this can be used in mixed infection .
- Moxifloxacin is used to treat a variety of bacterial infections. It works by stopping the growth of bacteria.
- Moxifloxacin is used to treat bacterial infections, including:
community-acquired pneumonia,throat, sinus, and lung infections,stomach infections ,skin infections
Related Article: Important information About Mefenamic Acid