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Renal 22 Sulfas
Bridges: Sulfonamides and Other Drugs for UTIs
Question | Answer |
---|---|
Drugs used in UTIs | Trimethoprom+sulfamethoxazole Fluorosuinolones Antiseptics |
Trimethoprom+sulfamethoxazole | 1st choice for uncomplicated cystitis Safe, effective, relatively inexpensive Increasing drug resistance a problem |
Fluoroquinolones | Tend to be over used Resistance developing Still a good choice |
Antiseptics | Nitrofurantion Useful in treating recurring UTIs |
Acute uncomplicated cystitis Treatment | 3 day course of trimethoprim+sufamethoxazole Increasing resistance of E.coli If resistance is >20%, use Fluoro. |
Acute uncomplicated pyelonephritis or complicated UTIs Treatment | Require longer Tx (7-14 days) Sometimes with other drugs |
Sulfonamides Clinical Uses | Single: Nocardiosis, Acute uncomplicated UTI Combo prep: TMP/SMX DoC for UTIs Toxoplasmosis |
Sulfonamides Oral Agents | Short acting: sulfisoxazole Intermediate acting: sulfamethoxazole |
Sulfonamides Topical agents | Opthalmic (bacterial conjunctivitis): Sodium sulfacetamide Burns: Silver sulfadiazine |
Sulfonamides Mechanism of Action | Work as antimetabolites Competitive inhibitors -Structural analof or PABA -Competes with PABA for dyhydropteroate synthetase Essential for folate production |
Sulfonamides Mechanism of Action (cont) | Folic acid needed for nucleic acid synthesis Bacteria cannon use exogenous folate Must be made from PABA |
Sulfonamides Resistance | Overproduction of PABA Lower affinity of enzyme for drug Decreased entry of drug Resistance is increasing Often resistant: -ococci |
Sulfonamides Pharmacokinetics | Drug-Drug interactions: Oral anticoagulants Sulfonylurea hypoglycemic agents Hydantion anticonvulsants Effects potentiated by sulfa Possible albumin displacement |
Sulfonamides Adverse Effects Urinary tract disturbances | Crystalluria, hematuria, obstruction Rarely problem w/ newer drugs Precipitates @ neutral/acidic pH High doses/low fluid intake Crystalluria: NaHCO3 |
Sulfonamides Adverse Effects Hematopoietic Disturbances | Acute hemolytic anemia: Sensitization *G6PD Deficiency* Agranulocytosis: Reversible |
Sulfonamides Adverse Effects Aplastic Anemia | Rare-direct myelotoxicity-can be fatal Profound anemia, granulocytopenia and thrombocytopenia Common with low bone marrow reserves (AIDS) |
Sulfonamides Adverse Effects Hypersensitivity reactions | More likely with longer acting agents Any type reaction... Rash~3% Rarely, potentially fatal, SJS |
Sulfonamides Adverse Effects Kernicterus | Increased risk if taken near end pregnancy -Newborn and premature infants -Avoid use in near term and nursing mothers Causes encephalopathy |
Trimethoprim Mechanism of Action | Antifolate Synergistic sequential blockade Competitive inhibitor of DHFR Selective Toxicity |
Tripethoprim Clinical Uses | Used in combo to treat several bacterial infxn Single agent: approved primarily for UTIs Initial Tx and prophylaxis Used to treat prostatitis |
Trimethoprim Resistance | Can result from: Reduced cell permeability Overexpression of DHFR Altered DHFR with ↓ drug binding **Most Common Mech** |
Trimethoprim Adverse Effects | GI-NV Dermatologic reactions -Maculopapular rash, puritus Folate deficiency impacting bone marrow |
Trimethoprim+Sulfamethoxazole TMP/SMX General | Fixed dose combo -Synergistic -aka Bactrim Combo minimizes resistance Combo usually bactericidal |
TMP/SMX Clinical Uses UTIs | Acute uncomplicated cystitis Prolonged suppression of chronic UTIs and recurrent UTIs in females Acute uncomplicated pyelonephritis in females Useful in complicated UTIs |
TMP/SMX Clinical Uses | Prostatis Pneumocystis jiroveci pneumonia -DoC for prophylaxis & Tx Enterocolitis from Shigella Traveler's diarrhea -DoC for prophylaxis & Tx |
TMP/SMX Clinical Uses (cont) | Otitis Media -Alt to amoxicillin Respiratory Tract Infections -H. influenzae |
TMP/SMX Adverse Reactions | Those associated with TMP and SMX |
Fluoroquinolones | Ciprofloxacin Levofloxacin Moxifloxacin Norfloxacin |
Fluoroquinolones Spectrum of Action | Excellent G- activity G+ activity depends on the drug Includes MSSA and MRSA H. influ, N. gonorrhea, Klebiella Weak antipseudomonal activity -Cipro has sig. pseudomonas |
Fluoroquinolones Mechanism of Action | Block bacterial DNA synth -Inhibits DNA gyrase and Topo IV -Only drug class that inhibits DNA synth Selective tox. Bactericidal |
Fluoroquinolones Ciprofloxacin | Active against G- including pseudomonas G+ (MSSA), S.pneumoniae N. gonorrhoeae UTIs & systemic infxn *First line for post anthrax* |
Fluoroquinolones Levofloxacin | Expanded activity against G+ to include Strep. pneumoniae Maintains activity against G- but only has weak pseudomonal activity |
Fluoroquinolones Moxifloxacin | Similar spectrum as levo but includes: E. faecalis Anaerobes Weak anti-pseudomonal activity |
Fluoroquinolones *Clinical Activity* | UTIs including MDR bugs Bacterial diarrhea Infxn of soft tissues, bones & joints Intra-abdominal and RTI including MDR bugs |
Fluoroquinolones *Clinical Uses* | Post-inhalation exposure to anthrax -Cipro Upper and lower RTIs -levo, moxi -Cipro often effective, not DoC |
Fluoroquinolones Resistance | ↑ problem from overuse Mechanisms -Change in drug binding region of enzyme -Change in permeability of organism |
Fluoroquinolones Pharmacokinetics | Well absorbed orally -Antacids impair absorption Norfloxacin -Low serum levels (Tx of UTIs) Most cleared renally -Dose adjustment |
Fluoroquinolones Adverse Effects | Extremely well tolerated NV (most common) *Achilles tendon rupture or tendinitis* *QTc prolongation* CNS: headache, dizziness |
Urinary Antiseptics | Oral agents with antibacterial activity in urine -rapidly excreted Use limited to UTIs Prolonged suppression of bacteriuria |
Nitrofurantoin | Prevention of UTIs Tx of uncomplicated UTIs Chronic UTIs Active against many strands of E.coli and entercocci Used in pts with other allergies |
Nitrofurantoin Mechanism of Action | Highly reactive species formed which damages DNA |
Nitrofurantoin Spectrum of Activity | Many G+ and G- Resistant species -Most species of Pseudomonas & Proteus -Many species of Enterobacter & Klebsiella |
Nitrofurantoin Pharmacokinetics | Good oral absorption Rapid metabolism and renal excretion -No systemic ABx activity -Only effective in urine -Eliminated by GF and secretion |
Nitrofurantoin Adverse Effects | NVD (most common) Hypersensitivity Reactions Hemolytic anemia in G6PD deficiency Acute pneumonitis (elderly) Urine turns a brown color |