• Antibacterial agents that inhibit nucleic acid metabolisim

1.Direct inhibition:
- Quinolones
- Azoles { DNA inhibitor }
- Rifampicin { RNA inhibitor }

2. Indirect inhibition:
- Sulphonamides & trimethoprim.

• DIRECT INHIBITORS OF NUCLEIC ACID METABOLISIM

DNA inhibitors:
1-Quinolones:
e.g. A- Non fluorinated quoinolon : nalidixic acid & cinoxacin.
B - fluoroquoinolons: ciprofloxacin, norfloxacin, ofloxacin , pefloxacin,
gemifloxacin .

• Mechanisim of action of Quinolones

They act by inhibiting the bacterial DNA synthesis.so thes are bactericidals.
They are active against gr+ve & gr-ve but not active against anaerobics (while
gemifloxacin, Gatifloxacin and moxifloxacin appear to have some anaerobic coverage
).
The fluorinated quinolons are 50 times more active than nalidixic acid.they are
eleminated by kidney except for pefloxacin.
• Individual Fluorinated Quinolons
*Ciprofloxacin : its active against gr +ve & -ve bacteria.
Dose : 250 – 750 mg/12 hrs
Ciprofloxacin is a metabolic inhibitor of some drugs including:theophyllin , warfarin
.
*Norfloxacin : used for acute & chronic UTI.
Dose : 200- 400 mg/12hrs.

• Individual Fluorinated Quinolons

Levofloxacin (Levaquin), gatifloxacin (Tequin), and moxifloxacin (Avelox) are the
new fluoroquinolones exhibiting increased activity against gram positive organisms
compared with ciprofloxacin, including excellent activity against pneumococci, even
penicillin-resistant strains...
The newer agents have comparable activity against gram-negative organisms;
however, they demonstrate slightly lower activity than ciprofloxacin for
Pseudomonas aeruginosa.

• Adverse effects of quinolones

1. GI s.e.:N , V & dia..
2. C.N.S. :h.a., nausea & convulsions (is more common in pts. Using theophyllin or
NSAIDs or those with history of epilepsy).
3. Fluoroquinolons may damage growing cartilage & can cause arthropathy.
4. Allergic reactions.
 • Drug-interactions of quinolons

1- Medical preparations containing Al, Ca Mg, Zn salts & iron preparations all can
decrease the absorption of ciprofloxacin.
2- Sucralfate.
3- Opioid analgesics increase cipro.. metabolism.
4- Ciprofloxacin inhibit hepatic drug metabolism (theophyllin, warfarin,
glibenclamide and zolmitriptan) .

Precautions
 Treatment should be stopped if the patient experience tendon pain.
 Adequate fluid intake should be maintained because of the risk of crystal urea
.
 Doses should be reduced in patient with renal impairment .
 Ciprofloxacin should not be used in children.

Direct inhibitors of DNA synthesis

2. Azoles
they act by inhibiting bacterial DNA synthesis.
There are 3 clases of this group:
1- metronidazole & tinidazole: has antibacterial & antiprotozoal activity.
2-clotrimazol: antifungal.
3- albendazol: has antihelminthic activity.
• Metronidazole
Is a bacteriostatic, it has antibacterial activity against anaerobics including bactroids
& clostredium species.
It is metabolised by the liver.
Oral dose: 250 – 500mg /8hrs.
Tinidazole have the same uses and adverse effects of metro.. But has longer
duration of action

• Adverse effects of Metronidazole:

1 .Nausea ,vomitting & dia...

2. Dry mouth or metalic taste in mouth.

3 .Dizziness ,head ache & weakness.

4. Should be used with caution in pts with active disease of CNS because of its
potential neurotoxicity.
• Drug interactions of Metronidazole :
1. Metronidazole can inhibit the metabolisim of : -Warfarin.
- lithium.
2. While phenytoin , phenobarbiton can increase the clearance of metro..
3. Plasma levels of metro..can be elevated by cimetidine.
 • Inhibition of bacterial nucleic acid:
1.Direct inhibitors include:
a.Inhibitors of DNA synthesis: quinolones & azoles.
b. Inhibitors of RNA synthesis: Rifampicin.
2.Indirect inhibitors of bacterial nucleic acid synthesis:
- Sulphonamides & trimethoprim.
• Direct Inhibitors of RNA synthesis: Rifampicin
It is particularly effective against mycobacteria ,so it is used in combination with
other antituberculous drugs for T.B..rifampin can
inhibit the growth of gr+ve & gr-ve bacteria .
Rifampin is effective for chemoprophylaxis of meningeococcal infections and
meningitis due to H.influenzae.
• Adverse effects of Rifampicin
1.Allergic reactions.
2.thrombocytopenia.
3.hepatitis.
4.Red discoloration of urin , tears, and sputum.
5. Influenza like syndrome.

• Drug – interactions of Rifampicin

Rifampicin is a metabolic inducer of many drugs even for itself;:
- warfarin
- CCP
- Narcotic analgesics
- phenytoin
- antidiabetic agents.
- theophyllin
- ketokonazole
• Indirect inhibition of bacterial nucleic acid synthesis
Sulphonamides & trimethoprim
PABA DHF synthase DHF
DHF- reductase
THF

purine
DNA
• trimethoprim & sulphonamides
Both are bacteriostatic.
*resistance to sulphonamides is increasingly a problem.
*trimethoprim can exert a synergistic effect with sulfonamides.

Side effects of sulfonamides & trimethoprim

1- N, , V. & dia..
2- allergic reactions.
3- mental depression.
4- acute haemolytic anaemia.
 Inhibition of cytoplasmic membrane of bacteria
e.g. : Polymixin B. ,Nystatin, Amphotericin.
Polymixin B. : is an antibiotic primarily used for resistant gram negative infections.
Polymyxins bind to the cell membrane and alters its structure making it more
permeable. The resulting water uptake leads to cell death. Side effects include
neurotoxicity and acute renal tubular necrosis.

• NYSTATINS
it is antifungal drug,this agents will bind to ergosterol that is found in the sensitive
fungi & increasing its permeability allowing the leakage of a variety of small
molecules.
It is used for prophylaxis & treatment of superficial candidiasis.
*nystatin is too toxic for systemic use, so not available for parantral use.
• Amphotericin
It has same mechanism of action of nystatin.
It is the d. of choice for fungal systemic infections but renal impairment limits its use.
• Resistance to Antibiotics
Intrinsic resistance
Some bacteria are intrinsically resistant to certain of the antibiotics. Example: Gram-
positive bacteria are much less susceptible to polymixins than Gram-negative
bacteria.
Acquired resistance
Many bacteria acquire resistance to one or more of the antibiotics to which they were
formerly susceptible.

• Requirements for Successful Antimicrobial Therapy

Clinical Diagnosis
Microbiologic Diagnosis
Culture and Susceptibility Testing
Appropriate Selection of Antimicrobial Agents
Correct Dosage and Route of Administration