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Renal 22 Sulfas

Bridges: Sulfonamides and Other Drugs for UTIs

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
Created by: bcriss