Lecture 15 Sulfonamides, Trimethoprim and Flouroquinolones

Sulfonamides, Trimethoprim, &
Fluoroquinolones
Sulfonamides
Weak acids
Short acting Intermediate long
sulfisoxazole sulfamethoxazole sulfadoxine
Mechanism of action
• The sulfonamides are bacteriostatic inhibitors of folic acid synthesis. As
antimetabolites of PABA, they are competitive inhibitors of
dihydropteroate synthase
Mechanism of resistance
• decreased intracellular accumulation of the drugs
• increased production of PABA by bacteria
• decrease in the sensitivity of dihydropteroate
synthase to the sulfonamides
. Clinical Use
Simple urinary tract infections Oral (eg, triple sulfa, sulfisoxazole).
Ocular infections Topical (eg, sulfacetamide)
Burn infections Topical (eg, mafenide, silver sulfadiazine)
Ulcerative colitis, rheumatoid arthritis Oral (eg, sulfasalazine).
Toxoplasmosis Oral sulfadiazine plus pyrimethamine (a
dihydrofolate reductase inhibitor) plus
folinic acid
Toxicity(Hyper Girl Dig grave of her Hyper Neigbour)
Hypersensitivity Allergic reactions, including skin rashes
and fever, occur commonly
Gastrointestinal Nausea, vomiting, and diarrhea
Drug interactions Sulfonamides can displace bilirubin from
plasma proteins, with the risk of
kernicterus in the neonate if used in the
third trimester of pregnancy
Hematotoxicity Acute hemolysis may occur in persons
with glucose-6-phosphate dehydrogenase
deficiency,aplastic
anemia,granulocytopenia and
throbocytopenia
Nephrotoxicity Sulfonamides may precipitate in the urine
at acidic pH, causing crystalluria and
hematuria
Trimethoprim
Weak base
Mechanism of action
• Trimethoprim is a selective inhibitor of bacterial dihydrofolate
reductase that prevents formation of the active tetrahydro
form of folic acid
• trimethoprim most commonly results from the
production of dihydrofolate reductase that has a
reduced affinity for the drug
Toxicity
• Bone marrow suppression
• megaloblastic anemia
• Leukopenia
• granulocytopenia.
• These effects are usually ameliorated by

supplementary folinic acid
Co-Trimoxazole
• Trimethoprim compounded with sulfmethoxazole is
called Cotrimoxazole.
• Synergism:greater effect than individual

• Decrease emergence of resistance
Clinical action and toxicity is almost same
• It is most important for UTI(mainly caused by Ecoli)
• Most common infection in AIDS in pneumocystis jiroveci… we will use co

trimethoxazole
• DOC for nocardia

• 2nd DOC for salmonella,shigella and vibrio
• Can be used for MRSA and listeria
Fluoroquinolones
1st 2nd generation 3rd generation 4th generation
Naldixic acid Norfloxacin Gemifloxacin Trovafloxacin
Ciprofloxacin Moxifloxacin Gatifloxacin
Ofloxacin Levofloxacin
sparofloxacin
Gram –ve bacteria Gram –ve including Same as 2nd Same as 3rd
but not pseudomomonas generation but generation and
pseudomonas and some gram +ve extended gram –ve they are broad
spectrum anaerobics
• Dosage reductions are usually needed in renal dysfunction
except for moxifloxacin which is eliminated partly by hepatic
metabolism and also by biliary excretion.
• Use of moxifloxacin in urinary tract infections is not

recommended
Mechanism of action
• The fluoroquinolones interfere with bacterial DNA synthesis by inhibiting
topoisomerase II (DNA gyrase), especially in gramnegative organisms
• They block the relaxation of supercoiled DNA that is catalyzed by DNA gyrase, a
step required for normal transcription and duplication.
• topoisomerase IV, especially in grampositive organisms

• Inhibition of topoisomerase IV by fluoroquinolones interferes with the separation
of replicated chromosomal DNA during cell divisio
Like aminoglycosidesand
streptogramins, the fluoroquinolones
exhibit postantibiotic effects, whereby
bacterial growth continues to be
inhibited even after the plasma
concentration of the drug has fallen
below the minimum inhibitory
concentration of the bacterium
• Efflux pumps(M Tuberculosis, S Aureus ,S Pneumoniae)
• changes in porin structure (in gram-negative bacteria)
• Changes in sensitivity of target enzymes due to point
mutations in receptors
• Mutations in quinolones resistance determining region of
gyrA(gene that encode DNA gyrase) in gonococc
Clinical use
• Anthrax - Ciprofloxacin(Uses as prophylaxis)
• Cipro and ofloxacin in single doses have been used as alternatives to ceftriaxone or
cefixime in Gonorrhoea
• 7 day course of treatment of ofloxacin is required to eradicates Chlamydia
trachomat
• Levofloxacin is effective against Beta lactum resistant antibiotics against
communityu acquired pneumoniae
• Fluoroquinolones have also been used in the meningococcal carrier state, in the
treatment of tuberculosis Salmonella typhi DOC is
• in prophylactic management of neutropenic patients ciprofloxacin
Inchildren(ceftriaxone/az
ithromycin
Inadults
..Flouroquinolones
Contra-Indications
• pregnancy and lactation
• In children under Use for Treatment of
pseudomonal infection
• QT prolongation complicated with cystic
fibrosis in children
Toxicity(The Good Clinical Liver Practitioner
Tendonitis Mostly Achilles tendon

GIT disturbance Nausea vomiting Diarrhea
Cartilage damage arthropathy
Phototoxicity Lomefloxacin and pefloxacin
Abnormal liver function test
Grepafloxacin was Most important

Getifloxacin is Sparo,Moxi,Gemi,le
withdrawn from clinical
drug interaction vo and Gati floxacin
contraindicated in use in the United
States because of with cause QT
diabetics
serious cardiotoxicity theophylline prolongation
Pirofloxacin cause
ototoxicity

Lecture 15 Sulfonamides, Trimethoprim and Flouroquinolones

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Sulfonamides, Trimethoprim, &

• These effects are usually ameliorated by

• Synergism:greater effect than individual

• It is most important for UTI(mainly caused by Ecoli)

• Most common infection in AIDS in pneumocystis jiroveci… we will use co

• DOC for nocardia

• Use of moxifloxacin in urinary tract infections is not

• topoisomerase IV, especially in grampositive organisms

Tendonitis Mostly Achilles tendon

Grepafloxacin was Most important

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