Study about the Ciprofloxacin

 

Ciprofloxacin

·    ·Is an example of a fluoroquinolone. Is not ototoxic.

·    ·Ciprofloxacin & moxifloxacin are the only quinolones available for parenteral use.

·    ·Used in ocular infections.

·    ·Metabolized in liver and highly dependent on kidneys for excretion.

What to learn?

·      ·Clinical uses

·      ·  Classification

·     ·  Mechanism of action

·     ·Pharmacokinetics

·    ·   Drug interaction

·    · Contraindication

·     · Side effects

·     ·Toxicity

 Clinical uses

1. Urinary tract infections (G-bacteria)

2. Osteomyelitis due to P. aeruginosa

3. Gonorrhoea

4. Travellers’ diarrhoea- ciprofloxacin commonly used

5. Tuberculosis

6. Prostatitis

7. Community- acquired pneumoniae

8. Diabetic foot infections (P. aeruginosa)

9. Anthrax

  Classification:-

1^st generation:

·     Drug:- Nalidixic acid, Oxalinic acid, Pipemidic acid.            

·     Characteristic features:-

   Active against some Gram-negative bacteria.

   Highly protein bound drugs.

   Short half-life.

·     Structure:-

Nalidixic acid

  

   2^nd Generation:- 

·    Drug:- Norfloxacin, Enoxacin, Ciprofloxacin, Ofloxacin, Lomefloxacin.

·    Characteristic features:-  

Protein binding (50%)

Longer half-life than previous agents.

Improved activity against Gram-negative bacteria.

·    Structure:-

Norfloxacin

 3^rd Generation:- 

·    Drug:- Temafloxacin, Sparafloxacin, Grepafloxacin

·    Characteristic features:-  

Active against Gram-positive bacteria.

Also active against Gram-positive bacteria.

·    Structure:- 

Temafloxacin

Mechanism of action

·    Interfere with bacterial topoisomerase II (DNA gyrase) & topoisomerase IV.

v  the enzymes involved in the supercoiling of DNA that is necessary for the duplication, transcription & repair of bacterial DNA.

 

                              Pharmacokinetics

·    Well absorbed orally with bioavailability 80-95%, almost equal to IV.

·    Half life 3-10 hours

·    Oral absorption impaired by divalent actions(Antacids containing Mg. Ca or Al).

·    Most of fluoroquinolones eliminated by renal mechanism so adjustment required in patients with creatinine clearance <50 ml/min.

·    Limited CSF penetration.

 Drug interaction

·    Ciprofloxacin and ofloxacin can increase the serum levels of theophylline by inhibiting its metabolism.

·    Third and fourth generation fluoroquinolones, may raise the serum levels of warfarin, caffeine, and cyclosporine.

·    Ciprofloxacin listed 36 different drug interactions.

·    12 new interactions were added to the GenMedRx database with these drugs found from PubMed, Stockley's, and BNF.

·    Ciprofloxacin: levothyroxine, duloxetine, zolmitriptan.

·    Levofloxacin: cimetidine, lithium, amiodarone.

·    Fluoroquinolones: antidiabetics, NSAIDs, probenecid, magnesium containing drugs, sucrafate, didanosine.

Contraindication

·    Hypersensitivity to Ciprofloxacin Hydrochloride other quinolones, or   any inactive component of the preparation.

·    Concomitant administration with Tizanidine is contraindicated.

·    Children/adolescents, pregnancy and lactation.

Side effects

·    Nausea, vomiting & diarrhoea

·    CNS effects-confusion, insomnia, headache, dizziness & anxiety.

·    May damage growing cartilage

·    Tendenitis (rare but more serious)

·    Hepatotoxicity-rare

·    Phototoxicity-avoid excessive sunlight

·    Gastric disturbances

·    Photosensitive rashes

·    Occasional neurotoxicity

Toxicity

·     Patients experiencing an overdose may present with nausea, vomiting, abdominal pain, crystalluria, nephrotoxicity, and oliguria. Ciprofloxacin overdose typically leads to acute renal failure. An overdose may progress over the next 6 days with rising serum creatinine and BUN, as well as anuria. Patients may require prednisone therapy, urgent haemodialysis, or supportive therapy. Depending on the degree of overdose, patients may recover normal kidney function or progress to chronic kidney failure.

·    The oral LD50 in rats is >2000mg/kg.

·    2/8 in vitro tests and 0/3 in vivo tests of mutagenicity of ciprofloxacin have yielded a positive result.

·    Oral doses of 200 and 300 times the maximum recommended clinical dose in rats and mice have shown no carcinogenicity or tumorigenicity.