Quinolones Metronidazole

Quinolones, metronidazole

Inhibitors of bacterial nucleic acid synthesis
Quinolones
 Bactericidal
 Concentration-dependent bacterial killing.
 Effective against gramnegative organisms:
 Pseudomonas species ,enterobacteriacea, haemophilus influenzae, Moraxella catarrhalis, legionellaceae, chlamydia, and gonorrhea

Generations of Quinolones

First Generation
Nalidixc Acid (NegGram)
 G-ve Bacteria like Escherichia coli
 No systemic effect
 Urinary Tract Infection (UTI)
Second Generation
Fluoroquinolones
Ciprofloxacin
Lomefloxacin
Norfloxacin
Ofloxacin
Pefloxacin
 Systemic effect
 G-ve > G +ve Bacteria


Third Generation
Levofloxacin
Moxifloxacin
 (Enhanced activity against G+ve) … Lower respiratory Tract Infection
Fourth Generation (Anaerobes)
 Clinafloxacin
 Gemifloxacin
 Trovafloxacin (Removed from clinical used)

Mechanism of Action Quinolones

Impairment of bacterial nucleic acid synthesis by inhibiting the replication of bacterial DNA
 In Gram Negative bacteria these drug inhibit the enzyme DNA gyrase (topoisomerase II)
 In Gram Positive bacteria these drug Inhibit the enzyme topoisomerase IV during bacterial growth and reproduction.
 Can cause cell death by inducing cleavage of the DNA.

Clinical uses of Quinolones

1. Urinary tract infection
2. Acute cystitis in females
3. Chronic bacterial prostatitis
4. Lower respiratory tract infection
5. Acute sinusitis
6. Skin infection
7. Bone and joint infection
8. Infectious diarrhea
9. Uncomplicated gonorrhea
Adverse reactions of Quinolones
1. Nausea, vomiting, and diarrhea (most common).
2. Phototoxicity
3. prolong QT interval
4. Liver toxicity: Trovafloxacin (life-threatening).
5. Risk of permanent damage to the joints (Arthropathy)
Note: Avoided in pregnancy, in nursing mothers, and in children under 18 years of age. In adults, fluoroquinolones can infrequently cause ruptured tendons.


Metronidazole:
 For treating amebic infections; it kills the E. histolytica trophozoites
 For the treatment of amebiasis, it is usually administered with a luminal amebicide, such as iodoquinol or paromomycin.
 For treating infections caused by Giardia lamblia , Trichomonas vaginalis, anaerobic cocci, and anaerobic gramnegative
Bacilli
 It is the drug of choice for the treatment of pseudomembranous colitis
Mechanism of action of metronidazole
 The nitro group of metronidazole is able to serve as an electron acceptor, forming reduced cytotoxic compounds that bind to proteins and DNA, resulting in cell death.

Pharmacokinetics of metronidazole

 Completely absorbed after oral administration
 Well distributed
 Metabolism by mixed-function oxidase, followed by glucuronylation.
 The parent drug and its metabolites are excreted in the urine
 Phenobarbital, enhances the rate of metabolism
 Cimetidine, inhibits the rate of metabolism.
Adverse effects
 Gastrointestinal tract, including nausea, vomiting, epigastric distress, An npleasant, metallic taste is often experienced. Other effects include oral moniliasis (yeast infection of the mouth) and, rarely
 Neurotoxicologic problems, such as dizziness, vertigo, and numbness or paresthesias in the peripheral nervous system.
 If taken with alcohol, a disulfiram-like effect occurs


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