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    Antifolate Drugs

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    Julia Ishak
    Antifolate drugs work by blocking folic acid synthesis, which is essential for DNA production in bacteria and other microorganisms. There are three major classes of antifolate drugs: sulfonamides, trimethoprim, and metronidazole. Sulfonamides are bacteriostatic and work by inhibiting the enzyme dihydropteroate synthase. Trimethoprim is often used in combination with sulfonamides due to their synergistic effect, and works by inhibiting dihydrofolate reductase. Metronidazole is an antiprotozoal drug that acts on anaerobic bacteria and protozoa. These drugs are commonly used to treat ur

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    Antifolate Drugs

    Uploaded by

    Julia Ishak
    52 views2 pages
    Antifolate drugs work by blocking folic acid synthesis, which is essential for DNA production in bacteria and other microorganisms. There are three major classes of antifolate drugs: sulfonamides, trimethoprim, and metronidazole. Sulfonamides are bacteriostatic and work by inhibiting the enzyme dihydropteroate synthase. Trimethoprim is often used in combination with sulfonamides due to their synergistic effect, and works by inhibiting dihydrofolate reductase. Metronidazole is an antiprotozoal drug that acts on anaerobic bacteria and protozoa. These drugs are commonly used to treat ur

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    Antifolate drugs work by blocking folic acid synthesis, which is essential for DNA production in bacteria and other microorganisms. There are three major classes of antifolate drugs: sulfonamides, trimethoprim, and metronidazole. Sulfonamides are bacteriostatic and work by inhibiting the enzyme dihydropteroate synthase. Trimethoprim is often used in combination with sulfonamides due to their synergistic effect, and works by inhibiting dihydrofolate reductase. Metronidazole is an antiprotozoal drug that acts on anaerobic bacteria and protozoa. These drugs are commonly used to treat ur

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as DOCX, PDF, TXT or read online from Scribd
    Download as docx, pdf, or txt
    52 views2 pages

    Antifolate Drugs

    Uploaded by

    Julia Ishak
    Antifolate drugs work by blocking folic acid synthesis, which is essential for DNA production in bacteria and other microorganisms. There are three major classes of antifolate drugs: sulfonamides, trimethoprim, and metronidazole. Sulfonamides are bacteriostatic and work by inhibiting the enzyme dihydropteroate synthase. Trimethoprim is often used in combination with sulfonamides due to their synergistic effect, and works by inhibiting dihydrofolate reductase. Metronidazole is an antiprotozoal drug that acts on anaerobic bacteria and protozoa. These drugs are commonly used to treat ur

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as DOCX, PDF, TXT or read online from Scribd
    Download as docx, pdf, or txt
    of 2

    ANTIFOLATE DRUGS

    ANTIFOLATE SULFONAMIDE TRIMETHOPRIM METRONIDAZOLE


    DRUGS
    OVERVIEW  Bacteriostatic - trimethoprim : - antiprotozoal drug
     Structure= p-aminobenzoic acid  inhibit bacterial dihydrofolic
    (PABA) reductase 50000x
     Properties ≠ based on diff  efficienct > than mammal
    substituent attached to amino / enzyme
    amino group -pyremethamine :
     inhibit protozoa dihydrofolic
    acid reductase> mammal
    - trimethoprime- combination w
    sulfonamide
     synergism-sequential blocking
    -combined form-bactericidal
    RESISTANCE  Mutation-overproduction of PABA  Reduced cell permeability
     Low-affinity-enzyme to  Overproduction dihyrofolate
    sulfonamide reductase
     Impermeability to sulfonamide  Altered reductase-
    MECHANISM  Block folic acid synthesis-  Anaerobes
    reversible  Bacteriodes
    OF ACTION  DNA production  Clostridium species

    PABA
    ↓←sulfonamide (competitive inhb w
    dyhydropteroate synthase)
    dihydrofolic acid
    ↓
    tetrahydfolic acid
    ↓
    Purines
    ↓
    DNA

    ACT ON 1. Gram + bac


    2. Gram – bac
    3. Nocardia
    4. Clamydia trachomatis
    5. Some protozoa
    6. Some enteric bact- E.coli,
    Klebsiella, salmonella,
    shigella, enterobacter

    PHARMACO- 3 major group: - Oral, IV : trimethoprim + - Oral : good


    - Oral absorbable sulfamethoxazole - Distribution : wide + CNS
    KINETICS - Oral non-absorbable - Absorbtion : trimethoprim-well - ROUTE : IV, oral,suppository
    - topical - Distribution : wide + CNS - METABOLISM: liver
    - Excretion : kidney
    IV sufonamide-rarely used xcept - Reduce dose in renal problem
    sulfomethazole- trimethoprim - Concentrated in prostatic and
    vaginal fluids
    Absorbtion : stomoch, SI
    Distribution : wide including CNS,
    placenta, fetus
    Metabolism : acetylation and
    sulfonamide- in urine
    Dose is reduced in renal failure

    CLINICAL Oral absorbable  Oral trimethoprim: acute  Anaerobec, mixed


    urinary tract infection intraabdominal infx
    USED  Rarely use- single antibiotic  Trimethoprime-  Vaginitis (trachomas)
     Sulfisoxazole n sulfamethoxazole : sulfamethoxazole:  Antibiotics associated
    UTI - P jiroveci pneumonia, enterocolitis
     Sulfadiazine + pyremathamine: shigellosis, salmonella  Brain abcess
    toxoplasmosis - UTI, prostatitis  Amoebiasis
     Sulfadoxine- long acting ( - Mycobacteria  Giardiasis
    ↑protein binding n tubular - Respiratory tract  Trichomoniasis
    absorbtion ) pathogen: pneumococus,
     Fansidar( sulfodoxine + HI, klebsiella
    pyremethamine): malaria  IV trimethoprim-
    ANTIFOLATE DRUGS

    - Oral non-absorbable sulfamethazole:


    - Severe pneumocystis
    Sulfasalazine pneumonia
     Salicyl-azo-sulfapyridine: - Gram –ve bacterial sepsis
    ulcerative colitis, enteritis, IBD - UTI
     Sulfasalazine: split by intestinal  Oral phyrimethamine +
    microflora to sulfapyridine + 5 sulfonamide
    aminosalicylate : anti- - Leishmaniasis
    inflammatory - Toxoplasmosis
    - Falcifarum malaria
    (fansidar)
    - topical
     Sodium sulfacetamide
    ophthalmic solution or
    ointment : bacteria
    conjuntivitis, trachoma
     Silver sulfadiazine: burn
    wound= prevent infectn

    ADVERSE 1. fever, skin rashes, exfoliative 1. Antifolate effect: 1. nausea, dry mouth, metallic
    dermatitis, photosensitivity, urticaria,  Megaloblastic anemia state in mouth
    EFFECT 2. nausea, vomiting, dirrhea  Leucopenia, granulocytopenia 2. dirrhea
    3. urinary tract problem 2. Sulfonamide- associated side effect 3. stomatitis
    - sulfonamide precipitates in urine in combine drug: 4, pheripheral neuropathy w
    - producing crystalluria, hematuria, n  Nausea, vomiting prolonged use
    obsruction in acid urine  Fever 5. disulfram- like effect
    -rx: alkalization of urine, adequate  Renal damage 6. seizure-rare- occur w IV
    hydration  CNS disturbance
    -nephrosis  AIDS patient >> prone to dvlp
    -allergic nephritis adverse effect
    4. Stevens- johnson syndrome
    5. hematopoietic disturbances
    - hemolytic
    - aplastic anaemia
    - thrombocytopenia
    - leukemoid rxn
    - Kernicterus in newborns
    OTHER - stomatitis Drug2 interaction:
    - conjunctivitis - ↑ warfarin effect
    ADVERSE - arthritis - ↑ elimination when used
    EFFFECT -hematopoeitic disturbances together
    - polyarteritis nodosa - cimetidine ↓ plasma
    - psychosis clearance
    - lithium toxicity

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