Nalidixic acid

Nalidixic acid is the first member of Quinolone class of drugs. It was introduced in mid 1960s. It is active against gram negative bacteria, specially coliforms: E.coli, Proteus, Klebsiella, Enterobacter, Shigella but not Pseudomonas. It acts by inhibiting bacterial DNA gyrase and is bactericidal. Resistance to nalidixic acid develops rather rapidly.

Pharmacokinetics:

Nalidixic acid is absorbed orally, highly plasma protein bound and partly metabolized in liver: one of the metabolites is active. It is excreted  in urine with a plasma t1/2 of 8 hours. Concentration of the free drug in plama and most tissues attained with the usual doses is non-therapeutic for systemic infections (MIC values for most susceptible bacteria just approach the 'break point' concentration). However, high concentration in urine (20-50 times that in plasma) is lethal to the common urinary pathogens.

Adverse effects:

These are relatively infrequent, consist mostly of g.i upset and rashes. Most important toxicity is neurological-headache, drowsiness, vertigo, visual disturbances, occasionally seizures (specially in children). Prolonged use has produced parkinsonism like symptoms, leucopenia and biliary stasis. Phototoxicity is rare. Individuals with G-6PD deficiency may develop haemolysis.

Contraindications:

Nalidixic acid is contraindicated in infants.

Dose:

0.5-1g TDS or QID

Uses:

1. Nalidixic acid is primarily used as a urinary antiseptic, generally as a second line drug in recurrent cases or on the basis of sensitivity reports. Nitrofurantoin should not be used concurrently-antagonism occurs.

2. It has also been employed in diarrhea caused by Proteus,E.coli, Shigella or Salmonella, and has a special place in ampicillin resistant Shigella enteritis.

G-6PD: Glucose-6 Phosphate dehydrogenase

t 1/2: Half-life

TDS: Thrice a day

QID: Quarter in die (Four times a day)

Quinolones

These are entirely synthetic antimicrobials having a quinolone structure that are active primarily against gram negative bacteria, though newer fluorinated compounds also inhibit gram positive ones. The first member Nalidixic acid introduced in mid 1960s had usefulness limited to urinary and g.i. tract infections because of low potency, modest blood and tissue levels, limited spectrum and high frequency of bacterial resistance. A breakthrough was achieved in the early 1980s by fluorination of the quinolone structure at position 6 and introduction of a piperazine substitution at position 7 resulting in derivatives called fluoroquinolones with high potency, expanded spectrum, slow development of resistance, better tissue penetration and good tolerability.