Sulfonamides,

trimethoprim and
Quinolones
By
S. Bohlooli, PhD
School of Medicine, Ardabil University of Medical
Sciences

Antifolate drugs

Sulfonamides
Trimethoprim
Trimethoprim & Sulfamethoxazole
mixture

Sulfonamides: chemistry

Sulfonamides: mechanism
of action

Inhibition of
dihydropetroate
synthase

Sulfonamides:
antimicrobial activity

Gram positive and negative

bacteria
Nocardia, chlamydia trachomatis
Some protoza
Some enteric bacteria
Rickettisiae stimulated!

Sulfonamides: resistance

Overproduction of PABA
Low affinity dihydropetroate
synthase
Loss of permeability to
sulfonamides

Sulfonamides:
pharmacokinetics

Oral absorbable

Short
Medium
Long

Oral,
nonabsorbable
topical

Serum protein
bind

20 ~ 90%

Excreted into
urine

Pharmacokinetic Properties of Some

Sulfonamides and Trimethoprim

Sulfonamides: clinical uses

Oral absorbable agents

Sulfisoxazole, sulfamethoxazole

Sulfadiazine: toxoplasmosis
Sulfadoxine: long acting, in a combination for
treatment of malaria

Oral nonabsorbable agents

To treat urinary tract infection

Ulcerative colitis, enteritis, other inflammatory bowel

disease

Topical agents

Sulfacetamide: ophthalemic
Mafenide & silver sulfadiazine: topically

Sulfonamides: adverse
reactions

Cross allergenic sulfonamide drugs:

Urinary tract disturbances

Thiazide, furosemide, diazoxide, sulfonylurea

hypoglycemic agents, and others
Fever, skin rashes, exfoliative dermatitis,photosensivity,
urticaria, nausea, vomiting, diarrhea
Stevens-Johnson syndrom
Crystalluria, hemturia, obstruction

Hematopoietic disturbance

Hemolytic or aplastic anemia

Granulocytopenia, thrombocytopenia, leukmoid reaction
Hemolysis in G-6PDH deficient patients
Kernicterus in newborn of mothers have taken near the
end of pergnancy

Trimethoprim: chemistry

Trimethoprim: resistance

Reduced cell permeability

Overproduction of DHF reductase
Altered affinity of reductase

Trimethoprim:
pharmacokinetics

Usually given orally alone or in

combination with sulfamethoxazole
Mainly excreted into urine
More antibacterial activity in
prostatic and vaginal fluids

Clinical use

Oral trimethoprim

Oral trimethoprim-sulfamethoxazole

P jiroveci pneumonia, shigellosis, systemic salmonella

infection, complicated urinary tract infection,
Active against many respiratory pathogens

Intravenous trimethoprim-sulfamethoxazole

Acute urinary infection

Gram negative sepsis, pneumocystis pneumonia

Shigllosis, typhoid fever

Oral pryrimethamine with sulfanamide

With sulfadiazine in Leishmaniasis, toxoplasmosis

With sulfadoxine in malaria

Adverse effects

Megaloblastic anemia
Leukopenia, granulocytopenia
Can be prevented by folinic acid
The AIDS patients have high
frequency of unwanted reactions

DNA gyrase inhibitors

Fluoroquinolones
Nalidixic acid and cinoxacin

Fluoroquinolones:
chemistry

Fluoroquinolones:
chemistry-2

Fluoroquinolones:
antibacterial activity

Block of bacterial DNA synthesis by

Inhibiting topoisomerase II, IV

Gram positive & negative bacteria

Mycoplasma & clamydia, legionella
Some mycobacteria
Anaerobic bacteria

Fluoroquinolones:
resistance

Change in permeability
Loss of affinity

Fluoroquinolones:
pharmacokinetics

Well absorbed after oral

administration
Good distribution
Divalent cations impair absorption

Pharmacokinetic Properties of
Fluoroquinolones

Fluoroquinolones: clinical
uses

Urinary tract infection

Bacterial diarrhea

Even with multi-drug resistant organisms

Shigella, salmonella, toxigenic E. coli

Infections of soft tissues, bones and joints

Intra-abdominal and respiratory tract infections
Gonococcal infection
Chlamydial urethritis and cervicitis
Legionellosis
Tuberclusis and atypical mycobacterial infections

Fluoroquinolones: adverse
effects

Nausea, vomiting & diarrhea

Headache, dizziness, insomnia, skin rash,
abnormal liver test
Acute hepatitis & hepatic failure:
trovafloxacin
Photosensivity: lomefloxacin, pefloxacin
QT prolongation: sparfloxacin
Hyperglycemia or hypoglycemia
May damage growing cartilage: arthropathy
Tendinitis

Nalidixic acid & cinoxacin

Excreted too rapidly

Useful for urinary tract infections