Sulphonamides and Quinolones

antimicrobials

1. Sulfonamides/ Sulfa drugs Sulfonamides are the antibiotics that have structural similarity with p- aminobenzoic acid (PABA) containing sulphonamide (SO 2 NH 2 ) groups in their chemical structure. T hey have bacteriostatic action against gram + ve & gram – ve bacteria. e .g : Sulfadiazine, sulfamethoxazole , cotrimoxazole , trimethoprim MECHANISM OF ACTION Sulfonamides  compete with PABA which is an essential precursor  in the synthesis of folic acid, required for the synthesis of  DNA  and  RNA  in  bacteria. They inhibit bacterial folate synthetase and lead to impairment of DNA formation.

2. Sulfa drugs were discovered when a red dye called P rontosil had shown in-vivo antibacterial activity against streptococcal infection. Later it was found that prontosil was broken down in the body to release Sulfanilamide which was responsible for antibacterial action.

3. Sulphonamides Examples Dose 1. Short Acting (4-8h) Rapidly Absorbed Sulfadiazine Sulfisoxazole 0.5-1g q.i.d Child 150mg/kg (4-6 doses) 2. Intermediate acting (8-12h) Absorbed Slowly Sulfamethoxazole 1g b.i.d for 2 days then 0.5 g b.i.d 3. Long acting (7days) Sulfadoxine Sulfamethopyrazine (used in combination with Pyrimethamine in malaria) 4. Special Purpose sulphonamides Sulfacetamide sodium Sulfasalazine Silver sulfadiazine Eye drops 10%, 20%, 30% (eye infection) 2-4g in divided dose (ulcerative colitis) Cream 1% (for burns)

4. Trimethoprim-Sulfamethoxazole combination ( Cotrimoxazole ) Cotrimoxazole causes sequential blocking of purine synthesis (synergism). Trimethoprim inhibits dihydrofolate reductase enzyme so inhibits tetrahydrofolic acid synthesis. The combination is bactericidal. It is the combination of trimethoprim & sulfamethoxazole in the ratio 1:5.

5. Sulfonamides (MOA) Dihydropteridine + PABA Sulfonamides (PABA analogues) Sulfomethoxazole (Bacterial) Sulfadiazine (Bacterial) Sulfodoxine (Malarial) Dihydropteroic acid Synthetase Dihydropteroic acid Glutamate Dihydrofolic Acid Timethoprim (Bacterial) / Pyrimethamine (Malarial) Dihydrofolate Reductase Tetrahydrofolic Acid Nucleic Bases Amino Acids RNA DNA Proteins Folic Acid Dihydrofolate Reductase (Mammalian ) + Cotrimoxazole Cotrimazine Static Cidal Static

6. Triple sulfa It is the combination of 3 sulfonamides together. Triple sulfa is an antibacterial medication that fights bacteria in the body. Triple sulfa vaginal is used to treat vaginal infections caused by the bacteria Gardnerella vaginalis .

7. Therapeutic Use Toxoplasmosis ( infection caused by Toxo plasma gondii -Mild flu like infection ( Sulfadiazine + Pyrimethamine ) Nocardiasis ( infection caused by Nocardia ) Chronic infection on lungs, cutanious part etc. (High dose for prolonged period) Trachoma and Inclusion Conjuctivitis Lympho Granuloma Venereum (infection of genitals) and Chancroid (Sexual infection Disease) Malaria ( Pyrimethamine + Sulfadoxine ) Burn ( Silver sulfadiazine ) Urinary Tract Infection (UTI ) Upper respiratory tract infections

8. Contraindication Should not be given for Infants Renal impaired patients Pregnancy

9. Adverse Effects Abdominal Discomfort : Nausea, Vomoting , diarrhea etc. Hypersensitivity reaction : Allergy , Rash, Inflammation etc. Nephotoxicity : formation and deposition of crystalline aggregate in the kidney, Ureters and Bladder Hematopoietic Disorders : Aplastic Anaemia (Anemia due to deficiency of RBC), Thrombocytopenia, Granulocytosis (Decrease granulosyte in RBC), Bone marrow depression etc. Kernicterus : displacement of bilirubin in infant specially premature baby. These free bilirubin cross the BBB and becomes deposited in basal ganglia and sub-thalamic nuclei of brain which is leading to parkinsonism .

10. Doses Sulfadiazine: 500-1000 mg 8 hourly oral for adult and 150mg/kg/day for children Sulfadimidine : Initial 2 gm and then 1gm 6-8 hourly orally Sulfacetamide : Locally used as eye drop or eye ointment as the concentration of 10, 20 and 30% Sulfamethoxazole : 1gm BD for 2 days and then 0.5gm BD upto 10 days Silver Sulfadiazine: Used as a 1% cream topically in burning area

11. Quinolones / F luoroquinolones Quinolones are synthetic antibiotics having quinolone structure & broad spectrum antibacterial activity. The important quinolones are synthetic fluorinated analogs of nalidixic acid . Also known as floroquinolones , which have a fluoro group attached the central ring system. Examples: Ciprofloxacin , Levofloxacin , Ofloxacin , Norfloxacin , etc.

12. Classification The Quinolones are divided into generation based on their antibacterial spectrum. The earlier generation agents are generally narrow spectrum than the later ones. 1 st generation Nalidixic acid 2 nd generation Ciprofloxacin, Ofloxacin , Norfloxacin 3 rd generation Levofloxacin , Baclofloxacin 4 th generation Moxifloxacin , Gatifloxacin

13. Mechanism of Action Quinolones exert their antibacterial effect by preventing bacterial DNA from unwinding and duplicating. Fluroquinolones enter bacterial cells via porins and i nhibit bacterial DNA gyrase in many gram- ve bacteria or topoisomerase IV in many gram+ve bacteria. Thereby inhibiting DNA replication and transcription. Fluoroquinolones also cause the cessation of cellular respiration and disruption of membrane integrity.

14. Indications Urinary tract infections ( Norfloxacin and Ofloxacin ) Bacterial diarrhoea caused by shigella , salmonella, toxigenic E coli , and campylobacter . Ciprofloxacin is a drug of choice for prophylaxis and treatment of anthrax (infection by Bacillus anthracis ) Ciprofloxacin and levofloxacin are effective for gonococcal infection Ciprofloxacin, levofloxacin , or moxifloxacin is occasionally used for treatment of tuberculosis and atypical mycobacterial infections . Levofloxacin , gatifloxacin , gemifloxacin , and moxifloxacin , so-called respiratory fluoroquinolones , with their enhanced gram-positive activity and activity against atypical pneumonia agents ( eg , chlamydia , mycoplasma , and legionella ), are effective and used increasingly for treatment of upper and lower respiratory tract infections.

15. Ciprofloxacin eye drop 3mg/ml eye drops used for eye infections

16. Adverse Effects The most common effects are nausea, vomiting, and diarrhea. Occasionally, headache, dizziness, insomnia, skin rash, or abnormal liver function tests develop. Photosensitivity has been reported. Rarely, hallucinations, delirium, and seizures have occurred, predominantly in patients who also were receiving theophylline or NSAIDS. Leucopenia, eosinophilia , and mild elevations in serum transaminases occur rarely.

17. Contraindication and Precaution Pregnancy Quinolones should be used with caution in patients receiving class III ( amiodarone ) and class IA ( quinidine , procainamide ) antiarrhythmics . Fluoroquinolones may damage growing cartilage and cause an arthropathy . Thus, these drugs are not routinely recommended for patients under 18 years of age.