Lecturer notes on veterinary pharmacology and toxicology for B.V.Sc & A.H Seventh semester student for educational purpose.This lecturer notes will be useful for all the veterinary students. Please send your comments,jibachhashah@gmail.com,mob.9845024121

1. QUINOLONES
Dr. Jibachha Sah
M.V.Sc (Veterinary Pharmacology)
Lecturer, College of Veterinary Science,
NPI, Bhojad, Chitwan, Nepal
SEVENTH SEMESTER !
Course Title: Veterinary Pharmacology &
Toxicology(Chemotherapy)
Course Code: VPT-413
Lecture notes

2. CONTENTS
1.INTRODUCTION AND HISTORY
2.MECHANISM OF ACTION
3.CLASSIFICATION OF FLUOROQUINOLONES
4.ANTIMICROBIAL ACTION AND RESISTANCE
5.PHARMACOKINETICS AND DRUG INTERACTIONS
6.TOXICITY AND ADVERSE EFFECTS
7.CLINICAL APPLICATION
8.Summary

3. Introduction
and History
01
First entirely man made synthetic antibiotic/antibacterial agents.
History
●They were developed from structural, modification of chloroquine
(1939)
● Nalidixic acid was the first quinolones introduced in 1967 for treating
GIT and UTI followed by its congener’s oxolonic acid flumequine
● In 1980’s fluorination of quinolone structure at 6th position and
addition of piperazine moeity(a part or functional group of a molecule) led to
development of fluoroquinolones
congener’s ; A thing of the same genus, species, or kind;

4. Limited Use
●Narrow spectrum - Only Enterobacteriaceae
● Low potency - Short half life
● High plasma protein binding - low tissue level
● Toxicity related to CNS
Advantage
●High potency
● Better tissue penetration
● Long half life
● Slow development of resistance
● Better oral bioavailability
● Extended spectrum

5. MECHANISM OF ACTION
●Inhibit the activity of DNA gyrase - an enzyme which controls the supercoiling of DNA - converts
released Covalently closed circular DNA to a superhelical form by energy dependent strand breakage
and resealing.
● DNA gyrase - contains two sub units which controls nicking and resealing - necessary to prevent
excessive supercoiling during transcription and other DNA unwinding process.
● Fluoroquinolones
● binds to the DNA gyrase of exonuclease - digests DNA - Bactericidal action.
● Bactericidal action is rapid and concentration dependent

6. CLASSIFICATION OF FLUOROQUINOLONES
●First generation Quinolones
Eg: Nalidixic acid, Oxolinic acid, flumequine
● Second generation Quinolones
Eg: Ciprofloxacin, Danofloxacin, Enrofloxacin, Norfloxacin
● Chemistry
Basic structure of 4- pyridine 3-carboxylic acid moiety

7. ANTIMICROBIAL ACTION AND RESISTANCE
●High activity towards Gram negative aerobes and against Gram positive aerobes
● The second generation Quinolones are active against Mycobacteria (Ciprofloxain and ofloxacin),
Mycoplasma, Rickettsia and inactive against anaerobes
Resistance
● Resistance development is slow for second generation. Single step mutation at low frequency
● Mutation in A subunit of DNA gyrase.
● Efflux pump (
● Plasmid mediated resistance - not described

8. PHARMACOKINETICS AND DRUG INTERACTIONS
●Better absorbed after oral administration in monogastrates, preruminant and absorption is poor in
ruminants but better in parenteral administration.
● Lipophilic, low degree of ionisation, well distributed in tissues -Bone, cartilage, prostrate, CSF etc.
● High Concentration - Liver, bile,urinary tract
● Partially metabolised in liver and excreted in urine and bile.
● Urinary drug concentration exceeds serum conc, hence low dose is sufficient in UTI
Drug Interaction
● Additive effect - Betalactam, Aminoglycosides, Macrolides
● Antagonistic - Nitrofurans, Chloramphenicol and rifampin
● Fluoroquinolones+ Metronidazole - extended spectrum
● Enzyme inhibitor - interferes with the metabolism of Theophylline, warfarin, cimetidine etc.
● Food and antacids interfere with the absorption
● Complex with metallic ions - Fe++, Mg++, Ca++

9. TOXICITY AND ADVERSE EFFECTS
●Relatively safe drug
● Human - Nausea, upper gastrointestinal tract discomfort, headaches and dizziness
● Skin rashes and photosensitivity - less common
● Neurotoxic - sometimes prone for CNS convulsions
● Pregnancy - embryonic loss and maternal toxicity

10. Dogs
● Cartilaginous erosion leading to permanent lameness in young animals. Hence not
recommended for pups less than 8 months in small breed and 18 months in large
breeds (some time within 1hr of administration)
Horses
● Not recommended because of arthralgic effect
Administration
● Monogastrates and preruminants – Oral
● Ruminants - Parenteral
● Dose of Enrofloxacin - 2.5 to 5mg/kg x 24hr

11. CLINICAL APPLICATION
●Human- Urinary tract infection, STD, bacterial enteritis, pneumonia, septicaemia due to Gram negative
aerobic organisms.
●Also in meningitis, prostatitis, Rickettsia, Mycoplasma and Mycobacteria infections
●Veterinary - Gram negative infections
.
Cattle, sheep and goat Pneumonia
● Mycoplasma bovis and pasteurella
● E.coli and salmonella enteritis
● E.coli septicaemia
● Mycoplasma, Rickettsia, chlamydia.

12. Swine
●Swine Pneumonia of various origin
● E.coli diarrhoea, salmonellosis, Mastitis Metritis Agalactia syndrome.
Horses
● Not in young and growing horses.
Dogs and cats Adult
● Urinary tract infection, respiratory tract infection, osteomyelitis, skin and wound infection.
Poultry
● Enrofloxacin 50 ppm in water - Mycoplasma, E.coli, Fowl cholera, salmonellosis, Erysipelas and
Bordetella.
● Enrofloxacin - specific for veterinary use.
● Weak activity to anaerobes.