Scribd Logo
Upload

Welcome to Scribd!

  • 62 views

    Sulfonamides: Miss Preeti Verma Assistant Professor Faculty of Pharmaceutical Sciences, Rama University, Kanpur, U.P

    Uploaded by

    Yash Singh
    This document provides information on sulfonamides and sulfamethoxazole-trimethoprim (cotrimoxazole). It discusses that sulfonamides were the first effective antimicrobials against bacterial infections. It classifies sulfonamides and describes their antibacterial properties, mechanisms of action, resistance, kinetics, adverse drug reactions, and individual drug uses. It also discusses the mechanism of action, antibacterial spectrum, resistance, adverse drug reactions and uses of cotrimoxazole.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd

    Sulfonamides: Miss Preeti Verma Assistant Professor Faculty of Pharmaceutical Sciences, Rama University, Kanpur, U.P

    Uploaded by

    Yash Singh
    62 views17 pages
    This document provides information on sulfonamides and sulfamethoxazole-trimethoprim (cotrimoxazole). It discusses that sulfonamides were the first effective antimicrobials against bacterial infections. It classifies sulfonamides and describes their antibacterial properties, mechanisms of action, resistance, kinetics, adverse drug reactions, and individual drug uses. It also discusses the mechanism of action, antibacterial spectrum, resistance, adverse drug reactions and uses of cotrimoxazole.

    Original Title

    lecture-5

    Copyright

    © © All Rights Reserved

    Available Formats

    PDF, TXT or read online from Scribd

    Did you find this document useful?

    Is this content inappropriate?

    This document provides information on sulfonamides and sulfamethoxazole-trimethoprim (cotrimoxazole). It discusses that sulfonamides were the first effective antimicrobials against bacterial infections. It classifies sulfonamides and describes their antibacterial properties, mechanisms of action, resistance, kinetics, adverse drug reactions, and individual drug uses. It also discusses the mechanism of action, antibacterial spectrum, resistance, adverse drug reactions and uses of cotrimoxazole.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    62 views17 pages

    Sulfonamides: Miss Preeti Verma Assistant Professor Faculty of Pharmaceutical Sciences, Rama University, Kanpur, U.P

    Uploaded by

    Yash Singh
    This document provides information on sulfonamides and sulfamethoxazole-trimethoprim (cotrimoxazole). It discusses that sulfonamides were the first effective antimicrobials against bacterial infections. It classifies sulfonamides and describes their antibacterial properties, mechanisms of action, resistance, kinetics, adverse drug reactions, and individual drug uses. It also discusses the mechanism of action, antibacterial spectrum, resistance, adverse drug reactions and uses of cotrimoxazole.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    of 17

    SULFONAMIDES

    Miss Preeti Verma


    Assistant Professor
    Faculty of
    Pharmaceutical
    Sciences,
    Rama University,
    Kanpur, U.P
    Sulfonamides
    • The first antimicrobials effective against Pyogenic
    Bacterial infections.
    • Derivatives of Sulfanilamide containing a “sufonamido
    “ring (SO2NH2).
    • Structurally and chemically related to p-aminobenzoic
    acid (PABA).
    • Structurally similar to many drugs – thiazides,
    acetazolamide, dapsone and sulfonylureas etc.
    • Physically – available as white powder, mildly acidic and
    form water soluble salts with bases.
    • However, indications and practical uses are very few
    these days.
    Sulfonamides - Classification
    • Short acting: Sulfadiazine,
    Sulfadimidine, Sulfacetamide
    • Intermediate acting: Sulfamethoxazole
    • Long acting: Sulfadoxine,
    Sulfamethoxypyrazine, Sulfadimethoxine
    etc.
    • Topically used: Mafenide, Silver
    sulfadiazine and Sulfacetamide
    • Ulcerative colitis: Sulfasalazine
    Sulfonamides – Antibacterial Property
    • Bacteriostatic against gm +ve and gm –ve bacteria
    • Bactericidal in urine
    • Susceptible organisms: Str. pyogens, H. influenzae, H.
    ducreyi, Callymatobacterium grannulomatosis, V.
    cholerae, Chlamydia, Actinomyces etc.
    – Few strains of Staph aureus, gonococci,
    meningococci, pneumococci, E. coli and Shigella
    • Chlamydiae: trachoma, lymphogrnuloma
    venereum., inclusion conjunctivitis. Also
    Actinomyces and Nocardia
    • Protozoa:
    – Plasmodium (Sulfadoxine + Pyrimethamine)
    – Toxoplasmosis (Sulfadiazine + Pyrimethamine)
    – PCP (Sulfamethoxazole + Trimethoprim = SXT)
    Sulfonamides – MOA
    Sulfonamides - Resistance
    • Many strains – S. aureaus, pneumococci,
    gonococci, meningococci, Strep. Pyogens, E.
    coli and Shigella
    • Mechanism:
    1. Production of increased amounts of PABA
    (Staph, Neisseria)
    2. Folate synthase enzyme has low affinity to
    sulfonamides
    3. Adopt alternative pathway of folate synthesis –
    structural changes in folate synthase (E coli) –
    encoded chromosomally and plasmid mediated
    • Resistant to one sulfonamide – resistant to all
    • No cross resistance
    Sulfonamides – Kinetics
    • Rapidly and completely absorbed from GIT
    • Extend of plasma protein binding differs (10 –
    95%)
    – Longer acting ones are highly plasma protein bound
    – Widely distributed – enters in serous cavity easily
    • Metabolized by non microsomal acetyl
    transferase in liver – slow and fast acetylators
    • Acetylated product – inactive excreted in urine
    (but, more toxic than parent) – crystalluria
    • Acetylated form accumulates in blood – toxic in
    renal faiure
    • Reabsorbed in tubule
    Sulfonamides - ADRs
    • Nausea, vomiting and epigastric pain
    • Crystalluria – alkanization of urine
    • Hypersensitivity (2 – 5%) – rashes,
    urticaria, drug fever. Exfoliative dermatitis,
    SJ syndrome (long acting ones)
    • Hepatitis
    • Haemolysis – G-6-PD deficiency
    • Kernicterus – displacement of bilirubin
    Individual Sulfonamides
    • Sulfadiazine: General purpose use – absorbed orally and
    rapidly
    excreted. More crystalluria. Preferred in meningitis.
    • Sulfamethoxazole: slower absorption and lower excretion.
    10 Hrs. half life. Combination with Trimethop
    • Sulfadoxine:Ultra-long acting >1 week. High protein bound –
    long excretion. Not suitable for Pyogenic infections – low
    plasma conc.. Used in Malaria, Pneumocystis jiroveci and
    toxoplasmosis
    • Sulfacetamide: Ophthalmic use – infections by bacteria,
    chlamydia, ophthalmia neonatorum etc
    • Mafendie: Atypical sulfonamide. Local application – inhibits
    variety of bacteria – active in presence of pus –
    pseudomonas and clostridia
    • Silver sulfadiazine: Bacteria, fungi, Pseudomonas. In burn
    cases
    Sulfonamides - Uses
    • Rarely used now a days systemically
    • UTI: caused by E. coli and P. mirabilis: Sulfisoxazole –
    1 gm 4 times daily
    • Malaria: sulfadoxine and pyrimethamine combination
    • Toxoplasmosis: sulfadiazine + pyrimethamine
    • In Combination with Trimethoprim: Cotrimoxazole
    • Ulcerative colitis: Sulfasalazine – 1-4 gm initially
    and 500 mg 6 Hrly.
    • Locally:
    – Sodium sulfacetamide: 10-30% ophthalmic solution in
    bacterial
    conjunctivitis, trachoma etc.
    – Mafenide acetate (1% cream) and Silver sulfadiazine 1%
    cream): Burn dressing and chronic ulcers
    Trimethoprim
    • Trimethoprim (trimethyl benzyl pyrimidine)
    is a diaminopyrimidine, chemically related
    to Pyrimethamine
    • Do not confuse: Clotrimazole
    (antiungal) - Cotrimoxazole is TMP –
    SMZ, but Sulfadoxine + Pyrimethamine is
    antimalarial
    • MOA: Sequential block of folate
    metabolism
    • Trimethoprim is 50,000 or more times
    more active against bacterial DHFRase
    enzyme than mammalian
    • So, no harm to human folate metabolism
    MOA OF TRIMETHOPRIM-SULFAMETHOXAZOLE
    PAB
    Sulfonamid
    A Tetrahydropteroic acid
    es synthetase

    Dihydrofolic acid

    Trimethoprim
    Dihyrofolate reductase
    1.Sulfamethoxazol
    e inhibits
    Tetrahydrofolic synthas
    dihydrofolate
    acid e.
    2.Trimethoprim
    Purine
    inhibits
    synthesis dihydrofolate
    reductase.
    DNA
    synthesis
    Cotrimoxazole – general points
    • Individually, both are bacteriostatic, but combination is –
    bactericidal
    • Both drugs have almost similar half lives (10 Hrs)
    • Maximum synergism if the organism is sensitive to both the
    agents
    • Optimal synergism is obtained at 20 (S) : 1 (T) concentration
    (MIC of both is reduced by 3 - 6 times)
    – This ratio is obtained at 5:1 dose ratio ( e.g. 800 mg:160 mg)
    – Because TMP has large Vd and enters many tissues – plasma
    conc. is low
    • But, TMP crosses BBB and placenta and SMZ not
    • TMP is more rapidly absorbed than SMZ
    • TMP is 45% plasma protein bound but SMZ is 65% bound
    • TMP is partly metabolized in liver
    Cotrimoxazole – antibacterial
    spectrum
    • Similar to sulfonamides
    • Additional benefits: Salmonella typhi,
    Serratia, Klebsiella Enterobacter, Yersinia
    and Pneumocystis jiroveci
    – Sulfonamides resistance strains of S. aureus,
    E. coli, gonococci, meningococci and H
    influenzae
    • RESISTANCE: Slow to develop
    – By mutational changes or plasmid mediated
    acquisition of a DHFRase enzyme having lower
    affinity for the inhibitior.
    Cotrimoxazole - ADRs
    • All adverse effects of sulfonamides – nausea,
    vomiting,stomatitis,rash etc
    • Folate deficiency (megaloblastic anaemia) – patients with
    marginal folate levels
    • Blood dyscrasias
    • Pregnancy: teratogenic risk, Neonatal haemolysis and
    methaemoglobinaemia
    • Patients with renal disease may develop uremia
    • Fever, rash and bone marrow hyperplasia
    • Elderly – risk of bone marrow toxicity from cotrimoxazole
    • Diuretics given with cotrimoxazole have produced a higher
    incidence of thrombocytopenia
    • Bone marrow hypoplasia among AIDS patients with
    Pneumocystis jiroveci infection
    Cotrimoxazole - Uses
    • Uncomplicated infection of the lower urinary tract infection
    – Cystitis (5 tablet dose)
    – chronic and recurrent urinary tract infections
    (including enterobacteriaceae) – 3-10 days
    • Respiratory tract infection – lower and upper, chronic
    bronchitis, facio-maxillary infections, otitis media due to
    gm+ve cocci and H influenzae etc
    • Typhoid
    • Bacterial diarrhoeas & dysentery: due to campylobacter,
    E coli, Shigella etc.
    • Pneumocystis jiroveci: Severe pneumonia - Prophylactic use
    in AIDS patients with neutropenia. Dose – DS tablet 4-6
    times 2-3 weeks
    • Chancroid – H. ducreyi
    • Alternative to penicillin in agrannulocytosis patients,
    scepticaemia etc.
    Thank you

    You might also like