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Pharmacology – Antimicrobials -Sulfonamides

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Pharmacology – Antimicrobials -Sulfonamides Drug Drug Class Mechanism of Action Indications Adverse Effects Specific Uses Sulfamethoxazole + Trimethoprim (Cotrimoxazole): PCP in AIDS Patients (DoC) Sulfadoxine + Pyrimethamine: Malaria Sulfadiazine + Pyrimethamine: Toxoplasmosis Sulfasalazine: PABA Analog Bacteriostatic Agents Against: (Sulfapyridine + 5-Aminosalicylic Acid): Bacteria Use PABA to Synthesize Folic Acid Gram + and Gram - Bacteria: Ulcerative Colitis and Rheumatoid Arthritis Crystalluria: Folic Acid is Essential for Purine/Pyrimidine Synthesis S. Pyogenes ------------------------------------------------- Hematuria and Renal Failure (Tx: Sodium Bicarbonate) ------------------------------------------------------ E. Coli Sulfacetamide: Hypersensitivity: Inhibit Dihydropteroate Synthase Enterobacter Spp. Eye Infections Skin Rashes Conjuctivitis or Adjuvant for Trachoma --> Folic Acid Synthesis Inhibition Toxoplasma Folic Acid Synthesis Inhibitors Fever Mafenide: Sulfonamides ---------------------- P. Jiroveci Bacteriostatic Exfoliative Dermatitis Used in Burn Dressing Well Absorbed from GIT Vibrio Cholera Stevens Johnson Syndrome Causes Burning/Pain/Metabolic Acidosis Cross BBB Nocardia Phototoxicity Silver Sulfadiazine: Metabolized by Acetylation and Glucuronidation in the Chlamydia Hemolysis in G6PD Deficiency Active Against Bacteria/Fungi Liver ---------- Kernicterus (In Newborns) Used in Burn Dressings and Ulcers Acetylated Derivative is Insoluble in Urine POOR Anaerobe Activity (Less Toxicity than Mafenide) Causes Crystalluria Pseudomonas is Intrinsically Resistant ------------------------------ Resistance: Overproduction of PABA Production of Folic-Acid Synthesizing Enzyme (Dihydropteroate Synthase) that has LOW AFFINITY For Sulfonamides Impair Permeability to Sulfonamides Inhibits Dehydrofolate Reductase Patients Allergic to Sulfa Drugs Results from Reduced Cell Permeability, Prevents Dihydrofolate --> Tetrahydrofolate Concentrates in Prostatic Fluid and Folic Acid Synthesis Inhibitors Bone Marrow Suppression Overproduction of Dyhydrofolate Trimethoprim Prevents Synthesis of Purine and DNA Vaginal Fluid Acute Bacteriostatic Enterocolitis Reductase, or Production of an Altered ------------------------------------------------------------------------- UTI Reductase with Reduced Drug Binding Drug is Weak Base and Attracked to Acidic Fluids Prostatitis Methicillin Resistant Strains Combination of Trimethoprim + Sulfamethoxazole NOT NOSOCOMIAL INFECTION Fixed Dose Ratio: 5:1 (S:T) E. Coli (UTI) Plasma Concentration: 20:1 (Maximum Synergy) Salmonella (Typhoid Fever) ---------------- Shigella (Bacterial Diarrhea) Folic Acid Synthesis Inhibitors Cotrimoxazole Sulfamethoxazole: Respiratory Tract Infections Decreases Resistance Bacteriocidal Inhibits Dihydropteroate Synthase (No Mycoplasma) Trimethoprim: Toxoplasma Inhibits Dyhydrofolate Reductase Pneumocystic Carinii Causes the Sequential Blockage of Folate Metabolism DoC: Nocardia DoC: P. Jiroveci Gram - Bacteria: E. Coli Proteus Klebsiella Limited Use: Shigella Rapid Resistance Quinolones Bactericidal Does not Achieve Systemic Limited Therapeutic Utility Nalidixic Acid Direct Acting Nulceic Acid Inhibits DNA Gyrase (Topoisomerase II) Anti-Bacterial Levels Adverse Effects: Synthesis Inhibitors Inhibits DNA Synthesis High Concentration in Urine Seizures -- Hemolysis in G6PD Deficiency Lethal to Urinary Pathogens (Urinary Antiseptic) Useful in LOWER UTIs Bacteriocidal Concentration-Dependent Killing Post-Antibiotic Effect ---------------------------------------------------------- Topoisomerases: Change the Configuration of DNA by Nicking and Re- Both Gram + and - Antacids Impair Absorption Sealing Mechanisms. FQs Chelate Cations NSAIDs Enhance the CNS Toxicity of FQs Contraindicated: Fluroquinolones INHIBIT the RE-SEALING STEP. Delay Activity Seizures are Reported Pregnancy and Children ------------------------------------------ (Take 2 hours Before/4 Hours After ------------------------------------------------------------------------ (Inhibition of Chondrogenesis) Inhibit Topoisomerase II/IV Meal) GI Distress Resistance: Inhibits DNA Synthesis ------------------- Fluoroquinolones Cartilage Damage, Tendonitis Mutations in DNA Gyrase and Topoisomerase II (DNA Gyrase): Typhoid Fever Direct Acting Nulceic Acid Rupture of the Achilles' Tendon Topoisomerase IV Prevents the Relaxation of Positively Supercoiled DNA UTIs (Not Moxifoxacin) Synthesis Inhibitors Phototoxicity ----- that is Required for Normal Transcription and Replication Gasteroenteritis CNS: Drug Interactions: Topoisomerase IV: Skin, Soft Tissue, Bone Infections Insomnia Dizziness P450 Inhibitors Interferes with Separation of Replicated Chromosomal (Not Norfloxicin) Headache Seizures (Increased Concentrations of DNA into the Respective Daughter Cells during Cell Anthrax (DoC: Ciprofloxacin) Liver Failure (Trovafloxacin, Pefloxacin) Theophylline, Warfarin) Division Chlamydia Prolonged QT ------------------------ Urethritis Cervicitis Oral, Well Absorbed Metabolized in Liver High Tissue Penetration --------------------------- Inhibited by Probenecid Excellent: Gram - Moderate: Gram + Fluoroquinolones E. Coli Drug Interactions: Resistance: Ciprofloxacin Direct Acting Nulceic Acid Same as Above Salmonella Typhi Inhibition of Metabolism of: Aminoglycoside Acetyltrasnferase Synthesis Inhibitors H. Influenzar Neisseria Vibrio Cholera Theophylline and Warfarin Can Inactive Drug Most Potent: Pseudomonas DoC: Anthrax Fluoroquinolones Least Active Norfloxacin Direct Acting Nulceic Acid Same as Above Used in Complicated/Uncomplicated Synthesis Inhibitors UTIs Prostatitis Enhanced Gram + Activity Excellent Against Anaerobes Trovafloxacin: Fluoroquinolones Trovafloxacin Moxifloxacin: Can be used normally in renal patients (B. Fragilis) Not Used - Liver Toxicity Direct Acting Nulceic Acid Moxifloxacin (Other FQs: Reduce Dose) Levo, Gemi, Moxi: Moxifloxacin: Synthesis Inhibitors Respiratory FQ's: Poor Activity Against Peusomonas Gram + and Atypical RTIs FQs: Ciprofloxacin: Co-Trimoxazole Most Common Classs of Antibiotics Acute Nitrofurantoin: Nitrofuraontoin, Amoxicillin, or a Cephalosporin: (Trimethoprim and Fosfomycin: Prescribed for UTI, but They SHOULD NOT Uncomplicatted 5 Days Nitrofurantoin: Do not Give during 3rd trimester or later Seulfamethoxazole): Single Dose for Pregnancy Women be used as First-Line Agents or Empiric Cystitis Alternative with Lower Rate of Resistance for E. Coli Only due to risk of hemolytic anemia in the newborn 3 Days Treatment of Acute Uncomplication Cystitis (Due to Resistance) Ceftriaxone: Acute Ciproflocazin Cotrimoxazole: Single IV Injection Uncomplicated or Anterative if Uropathogens are Suscepible Followed by: Pyelonephritis 5 Days of Levofloxavin 7-14 Days of Oral Anti-Microbial In Patients with Indwelling Urinary Catheters or Anatomic/Function Abnormalities Alternatives: of the Urinary Tract Fluoroquinolones: (First Choice) Cotrimoxazole Complicated UTIs: --------------- Ciprofoxacin Amoxicillin + Clavulanac Acid Caused by: Alternative: Levofoxacin 3rd Gen Cephalosporins Antibiotic-Resistant Gram - Bacilli (Cefdinir Ceftibuten) MRSA Vancyomycin-Resistant Strains.
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